what is synthesis and thesis

Persuasive Writing In Three Steps: Thesis, Antithesis, Synthesis

April 14, 2021 by Ryan Law in

Great writing persuades. It persuades the reader that your product is right for them, that your process achieves the outcome they desire, that your opinion supersedes all other opinions. But spend an hour clicking around the internet and you’ll quickly realise that most content is passive, presenting facts and ideas without context or structure. The reader must connect the dots and create a convincing argument from the raw material presented to them. They rarely do, and for good reason: It’s hard work. The onus of persuasion falls on the writer, not the reader. Persuasive communication is a timeless challenge with an ancient solution. Zeno of Elea cracked it in the 5th century B.C. Georg Hegel gave it a lick of paint in the 1800s. You can apply it to your writing in three simple steps: thesis, antithesis, synthesis.

Use Dialectic to Find Logical Bedrock

“ Dialectic ” is a complicated-sounding idea with a simple meaning: It’s a structured process for taking two seemingly contradictory viewpoints and, through reasoned discussion, reaching a satisfactory conclusion. Over centuries of use the term has been burdened with the baggage of philosophy and academia. But at its heart, dialectics reflects a process similar to every spirited conversation or debate humans have ever had:

• Person A presents an idea: “We should travel to the Eastern waterhole because it’s closest to camp.”
• Person B disagrees and shares a counterargument: “I saw wolf prints on the Eastern trail, so we should go to the Western waterhole instead.”
• Person A responds to the counterargument , either disproving it or modifying their own stance to accommodate the criticism: “I saw those same wolf prints, but our party is large enough that the wolves won’t risk an attack.”
• Person B responds in a similar vein: “Ordinarily that would be true, but half of our party had dysentery last week so we’re not at full strength.”
• Person A responds: “They got dysentery from drinking at the Western waterhole.”

This process continues until conversational bedrock is reached: an idea that both parties understand and agree to, helped by the fact they’ve both been a part of the process that shaped it.

Dialectic is intended to help draw closer to the “truth” of an argument, tempering any viewpoint by working through and resolving its flaws. This same process can also be used to persuade.

Create Inevitability with Thesis, Antithesis, Synthesis

The philosopher Georg Hegel is most famous for popularizing a type of dialectics that is particularly well-suited to writing: thesis, antithesis, synthesis (also known, unsurprisingly, as Hegelian Dialectic ).

• Thesis: Present the status quo, the viewpoint that is currently accepted and widely held.
• Antithesis: Articulate the problems with the thesis. (Hegel also called this phase “the negative.”)
• Synthesis: Share a new viewpoint (a modified thesis) that resolves the problems.

Hegel’s method focused less on the search for absolute truth and more on replacing old ideas with newer, more sophisticated versions . That, in a nutshell, is the same objective as much of content marketing (and particularly thought leadership content ): We’re persuading the reader that our product, processes, and ideas are better and more useful than the “old” way of doing things. Thesis, antithesis, synthesis (or TAS) is a persuasive writing structure because it:

• Reduces complex arguments into a simple three-act structure. Complicated, nuanced arguments are simplified into a clear, concise format that anyone can follow. This simplification reflects well on the author: It takes mastery of a topic to explain it in it the simplest terms.
• Presents a balanced argument by “steelmanning” the best objection. Strong, one-sided arguments can trigger reactance in the reader: They don’t want to feel duped. TAS gives voice to their doubts, addressing their best objection and “giv[ing] readers the chance to entertain the other side, making them feel as though they have come to an objective conclusion.”
• Creates a sense of inevitability. Like a story building to a satisfying conclusion, articles written with TAS take the reader on a structured, logical journey that culminates in precisely the viewpoint we wish to advocate for. Doubts are voiced, ideas challenged, and the conclusion reached feels more valid and concrete as a result.

There are two main ways to apply TAS to your writing: Use it beef up your introductions, or apply it to your article’s entire structure.

Writing Article Introductions with TAS

Take a moment to scroll back to the top of this article. If I’ve done my job correctly, you’ll notice a now familiar formula staring back at you: The first three paragraphs are built around Hegel’s thesis, antithesis, synthesis structure. Here’s what the introduction looked like during the outlining process . The first paragraph shares the thesis, the accepted idea that great writing should be persuasive:

Next up, the antithesis introduces a complicating idea, explaining why most content marketing isn’t all that persuasive:

Finally, the synthesis shares a new idea that serves to reconcile the two previous paragraphs: Content can be made persuasive by using the thesis, antithesis, synthesis framework. The meat of the article is then focused on the nitty-gritty of the synthesis.

Introductions are hard, but thesis, antithesis, synthesis offers a simple way to write consistently persuasive opening copy. In the space of three short paragraphs, the article’s key ideas are shared , the entire argument is summarised, and—hopefully—the reader is hooked.

Best of all, most articles—whether how-to’s, thought leadership content, or even list content—can benefit from Hegelian Dialectic , for the simple reason that every article introduction should be persuasive enough to encourage the reader to stick around.

Structuring Entire Articles with TAS

Harder, but most persuasive, is to use thesis, antithesis, synthesis to structure your entire article. This works best for thought leadership content. Here, your primary objective is to advocate for a new idea and disprove the old, tired way of thinking—exactly the use case Hegel intended for his dialectic. It’s less useful for content that explores and illustrates a process, because the primary objective is to show the reader how to do something (like this article—otherwise, I would have written the whole darn thing using the framework). Arjun Sethi’s article The Hive is the New Network is a great example.

The article’s primary purpose is to explain why the “old” model of social networks is outmoded and offer a newer, better framework. (It would be equally valid—but less punchy—to publish this with the title “ Why the Hive is the New Network.”) The thesis, antithesis, synthesis structure shapes the entire article:

• Thesis: Facebook, Twitter, and Instagram grew by creating networks “that brought existing real-world relationships online.”
• Antithesis: As these networks grow, the less useful they become, skewing towards bots, “celebrity, meme and business accounts.”
• Synthesis: To survive continued growth, these networks need to embrace a new structure and become hives.

With the argument established, the vast majority of the article is focused on synthesis. After all, it requires little elaboration to share the status quo in a particular situation, and it’s relatively easy to point out the problems with a given idea. The synthesis—the solution that needs to reconcile both thesis and antithesis—is the hardest part to tackle and requires the greatest word count. Throughout the article, Arjun is systematically addressing the “best objections” to his theory and demonstrating why the “Hive” is the best solution:

• Antithesis: Why now? Why didn’t Hives emerge in the first place?
• Thesis: We were limited by technology, but today, we have the necessary infrastructure: “We’re no longer limited to a broadcast radio model, where one signal is received by many nodes. ...We sync with each other instantaneously, and all the time.”
• Antithesis: If the Hive is so smart, why aren’t our brightest and best companies already embracing it?
• Thesis: They are, and autonomous cars are a perfect example: “Why are all these vastly different companies converging on the autonomous car? That’s because for these companies, it’s about platform and hive, not just about roads without drivers.”

It takes bravery to tackle objections head-on and an innate understanding of the subject matter to even identify objections in the first place, but the effort is worthwhile. The end result is a structured journey through the arguments for and against the “Hive,” with the reader eventually reaching the same conclusion as the author: that “Hives” are superior to traditional networks.

Destination: Persuasion

Persuasion isn’t about cajoling or coercing the reader. Statistics and anecdotes alone aren’t all that persuasive. Simply sharing a new idea and hoping that it will trigger an about-turn in the reader’s beliefs is wishful thinking. Instead, you should take the reader on a journey—the same journey you travelled to arrive at your newfound beliefs, whether it’s about the superiority of your product or the zeitgeist-changing trend that’s about to break. Hegelian Dialectic—thesis, antithesis, synthesis— is a structured process for doing precisely that. It contextualises your ideas and explains why they matter. It challenges the idea and strengthens it in the process. Using centuries-old processes, it nudges the 21st-century reader onto a well-worn path that takes them exactly where they need to go.

Ryan is the Content Director at Ahrefs and former CMO of Animalz.

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How to Synthesize Written Information from Multiple Sources

Shona McCombes

Content Manager

B.A., English Literature, University of Glasgow

Shona McCombes is the content manager at Scribbr, Netherlands.

Learn about our Editorial Process

Saul Mcleod, PhD

Editor-in-Chief for Simply Psychology

BSc (Hons) Psychology, MRes, PhD, University of Manchester

Saul Mcleod, PhD., is a qualified psychology teacher with over 18 years of experience in further and higher education. He has been published in peer-reviewed journals, including the Journal of Clinical Psychology.

On This Page:

When you write a literature review or essay, you have to go beyond just summarizing the articles you’ve read – you need to synthesize the literature to show how it all fits together (and how your own research fits in).

Synthesizing simply means combining. Instead of summarizing the main points of each source in turn, you put together the ideas and findings of multiple sources in order to make an overall point.

At the most basic level, this involves looking for similarities and differences between your sources. Your synthesis should show the reader where the sources overlap and where they diverge.

Unsynthesized Example

Franz (2008) studied undergraduate online students. He looked at 17 females and 18 males and found that none of them liked APA. According to Franz, the evidence suggested that all students are reluctant to learn citations style. Perez (2010) also studies undergraduate students. She looked at 42 females and 50 males and found that males were significantly more inclined to use citation software ( p < .05). Findings suggest that females might graduate sooner. Goldstein (2012) looked at British undergraduates. Among a sample of 50, all females, all confident in their abilities to cite and were eager to write their dissertations.

Synthesized Example

Studies of undergraduate students reveal conflicting conclusions regarding relationships between advanced scholarly study and citation efficacy. Although Franz (2008) found that no participants enjoyed learning citation style, Goldstein (2012) determined in a larger study that all participants watched felt comfortable citing sources, suggesting that variables among participant and control group populations must be examined more closely. Although Perez (2010) expanded on Franz’s original study with a larger, more diverse sample…

Step 1: Organize your sources

After collecting the relevant literature, you’ve got a lot of information to work through, and no clear idea of how it all fits together.

Before you can start writing, you need to organize your notes in a way that allows you to see the relationships between sources.

One way to begin synthesizing the literature is to put your notes into a table. Depending on your topic and the type of literature you’re dealing with, there are a couple of different ways you can organize this.

Summary table

A summary table collates the key points of each source under consistent headings. This is a good approach if your sources tend to have a similar structure – for instance, if they’re all empirical papers.

Each row in the table lists one source, and each column identifies a specific part of the source. You can decide which headings to include based on what’s most relevant to the literature you’re dealing with.

For example, you might include columns for things like aims, methods, variables, population, sample size, and conclusion.

For each study, you briefly summarize each of these aspects. You can also include columns for your own evaluation and analysis.

The summary table gives you a quick overview of the key points of each source. This allows you to group sources by relevant similarities, as well as noticing important differences or contradictions in their findings.

Synthesis matrix

A synthesis matrix is useful when your sources are more varied in their purpose and structure – for example, when you’re dealing with books and essays making various different arguments about a topic.

Each column in the table lists one source. Each row is labeled with a specific concept, topic or theme that recurs across all or most of the sources.

Then, for each source, you summarize the main points or arguments related to the theme.

The purposes of the table is to identify the common points that connect the sources, as well as identifying points where they diverge or disagree.

Step 2: Outline your structure

Now you should have a clear overview of the main connections and differences between the sources you’ve read. Next, you need to decide how you’ll group them together and the order in which you’ll discuss them.

For shorter papers, your outline can just identify the focus of each paragraph; for longer papers, you might want to divide it into sections with headings.

There are a few different approaches you can take to help you structure your synthesis.

If your sources cover a broad time period, and you found patterns in how researchers approached the topic over time, you can organize your discussion chronologically .

That doesn’t mean you just summarize each paper in chronological order; instead, you should group articles into time periods and identify what they have in common, as well as signalling important turning points or developments in the literature.

If the literature covers various different topics, you can organize it thematically .

That means that each paragraph or section focuses on a specific theme and explains how that theme is approached in the literature.

Source Used with Permission: The Chicago School

If you’re drawing on literature from various different fields or they use a wide variety of research methods, you can organize your sources methodologically .

That means grouping together studies based on the type of research they did and discussing the findings that emerged from each method.

If your topic involves a debate between different schools of thought, you can organize it theoretically .

That means comparing the different theories that have been developed and grouping together papers based on the position or perspective they take on the topic, as well as evaluating which arguments are most convincing.

Step 3: Write paragraphs with topic sentences

What sets a synthesis apart from a summary is that it combines various sources. The easiest way to think about this is that each paragraph should discuss a few different sources, and you should be able to condense the overall point of the paragraph into one sentence.

This is called a topic sentence , and it usually appears at the start of the paragraph. The topic sentence signals what the whole paragraph is about; every sentence in the paragraph should be clearly related to it.

A topic sentence can be a simple summary of the paragraph’s content:

“Early research on [x] focused heavily on [y].”

For an effective synthesis, you can use topic sentences to link back to the previous paragraph, highlighting a point of debate or critique:

“Several scholars have pointed out the flaws in this approach.” “While recent research has attempted to address the problem, many of these studies have methodological flaws that limit their validity.”

By using topic sentences, you can ensure that your paragraphs are coherent and clearly show the connections between the articles you are discussing.

As you write your paragraphs, avoid quoting directly from sources: use your own words to explain the commonalities and differences that you found in the literature.

Don’t try to cover every single point from every single source – the key to synthesizing is to extract the most important and relevant information and combine it to give your reader an overall picture of the state of knowledge on your topic.

Step 4: Revise, edit and proofread

Like any other piece of academic writing, synthesizing literature doesn’t happen all in one go – it involves redrafting, revising, editing and proofreading your work.

Checklist for Synthesis

•   Do I introduce the paragraph with a clear, focused topic sentence?
•   Do I discuss more than one source in the paragraph?
•   Do I mention only the most relevant findings, rather than describing every part of the studies?
•   Do I discuss the similarities or differences between the sources, rather than summarizing each source in turn?
•   Do I put the findings or arguments of the sources in my own words?
•   Is the paragraph organized around a single idea?
•   Is the paragraph directly relevant to my research question or topic?
•   Is there a logical transition from this paragraph to the next one?

Further Information

How to Synthesise: a Step-by-Step Approach

Help…I”ve Been Asked to Synthesize!

Learn how to Synthesise (combine information from sources)

How to write a Psychology Essay

Synthesis Essays: A Step-by-Step How-To Guide

A synthesis essay is generally a short essay which brings two or more sources (or perspectives) into conversation with each other.

The word “synthesis” confuses every student a little bit. Fortunately, this step-by-step how-to guide will see you through to success!

Here’s a step-by-step how-to guide, with examples, that will help you write yours.

Before drafting your essay:

After reading the sources and before writing your essay, ask yourself these questions:

• What is the debate or issue that concerns all of the writers? In other words, what is the question they are trying to answer?
• On what points do they agree?
• On what points do they disagree?
• If they were having a verbal discussion, how would writer number one respond to the arguments of writer number two?

In a way, writing a synthesis essay is similar to composing a summary. But a synthesis essay requires you to read more than one source and to identify the way the writers’ ideas and points of view are related.

Sometimes several sources will reach the same conclusion even though each source approaches the subject from a different point of view.

Other times, sources will discuss the same aspects of the problem/issue/debate but will reach different conclusions.

And sometimes, sources will simply repeat ideas you have read in other sources; however, this is unlikely in a high school or AP situation.

To better organize your thoughts about what you’ve read, do this:

• Identify each writer’s thesis/claim/main idea
• List the writers supporting ideas (think topic sentences or substantiating ideas)
• List the types of support used by the writers that seem important. For example, if the writer uses a lot of statistics to support a claim, note this. If a writer uses historical facts, note this.

There’s one more thing to do before writing: You need to articulate for yourself the relationships and connections among these ideas.

Sometimes the relationships are easy to find. For example, after reading several articles about censorship in newspapers, you may notice that most of the writers refer to or in some way use the First Amendment to help support their arguments and help persuade readers. In this case, you would want to describe the different ways the writers use the First Amendment in their arguments. To do this, ask yourself, “How does this writer exploit the value of the First Amendment/use the First Amendment to help persuade or manipulate the readers into thinking that she is right?

Sometimes articulating the relationships between ideas is not as easy. If you have trouble articulating clear relationships among the shared ideas you have noted, ask yourself these questions:

• Do the ideas of one writer support the ideas of another? If so, how?
• Do the writers who reach the same conclusion use the same ideas in their writing? If not, is there a different persuasive value to the ideas used by one writer than by the other?
• Do the writers who disagree discuss similar points or did they approach the subject from a completely different angle and therefore use different points and different kinds of evidence to support their arguments?
• Review your list of ideas. Are any of the ideas you have listed actually the same idea, just written in different words?

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How to Write a Synthesis Essay

4-minute read

• 31st May 2023

Are you writing a synthesis essay? This is a paper that combines information from a variety of sources to form a new idea. Essentially, you’re synthesizing existing concepts and arguments to create something original.

As a student, you’ll probably have to write a synthesis essay at some point. Read on for our step-by-step guide on how to write one effectively.

Step 1. Define Your Idea or Argument

If you haven’t done so already, decide on a topic to write about. Read up about it using a variety of credible sources and make detailed notes while you research. Make sure you keep track of the sources you decide to pull information from so that you can cite them properly later.

Make a list of key points from your research. Once you have a good selection of material to work with, start developing your own idea or argument. This will be the focus of your essay.

Step 2. Create an Outline

Synthesis essays generally follow this format: an introduction, a handful of main body paragraphs, and a conclusion. It’s a good idea to come up with an essay plan before you start writing so that you can keep things organized while you work.

The outline is mainly helpful for deciding what to include in your body paragraphs. Decide what supporting points (and counterarguments ) from your research you want to include, and which order you want to discuss them in. You should have enough information to flesh out one paragraph for each point.

Step 3. Write Your Introduction

In your introduction, you should open with something that hooks the reader and captures their attention. Then, state your argument or idea (i.e., your thesis statement) and briefly summarize the material you’ll be including in your essay. You should also include any relevant background information here.

Step 4. Write the Body Paragraphs

Using your outline, discuss each point from your source material in more depth, devoting a body paragraph to each. Explain the information from the outside source, including appropriate citations, and discuss how it connects with your idea.

It’s a good idea to mostly focus on points that support your argument, but you should also include a paragraph with a counterargument or two. This means discussing a perspective that doesn’t necessarily align with your idea, and then explaining why your argument still works.

Step 5. Tie It All Together With a Conclusion

The conclusion should leave the reader feeling convinced of your idea. Restate your point clearly and summarize the main points you’ve discussed. You could also offer any concluding reflections on the topic.

Different Types of Synthesis Essays

While you can follow our steps for any type of synthesis essay, yours will probably fall under one of two categories: explanatory or argumentative.

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Argumentative essays are as they sound – they present an argument. With an argumentative essay, you’ll take a more definitive stance on something and use your supporting material to persuade the reader.

Explanatory essays don’t necessarily take a side one way or the other. Rather, they focus on developing and explaining a concept thoroughly. Knowing which type of essay you’re writing will help you to gather more effective source material for your purpose.

Cite Your Sources

Since synthesis essays are particularly dependent on outside material, it’s especially important that you cite your sources correctly. Familiarize yourself with your referencing system before you start researching so you know what information you need to keep track of, and include appropriate citations whenever you use someone else’s work.

At the end of the essay, you’ll need to compile your sources into a reference list following the requirements of your style guide.

Summary: Writing a Synthesis Essay

Hopefully, this post has helped you to feel more confident in writing a synthesis essay. Choose a topic first, do your research, keep track of your sources, and develop an argument or idea. From there, you can organize your thoughts into an outline and get to writing!

Once you’ve created a first draft, make sure you send it our way! We’ll check it for errors in grammar, spelling, referencing, and more. Try it out for free today.

Frequently Asked Questions

What is a synthesis essay.

A synthesis essay gathers ideas and viewpoints from several different sources and ties them together to form a new concept.

How long is a synthesis essay?

Synthesis essays usually follow the five-paragraph format, with an introduction, three main body paragraphs discussing different points, and a conclusion.

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How to Write a Synthesis Essay

Last Updated: April 7, 2024 Fact Checked

This article was co-authored by Christopher Taylor, PhD . Christopher Taylor is an Adjunct Assistant Professor of English at Austin Community College in Texas. He received his PhD in English Literature and Medieval Studies from the University of Texas at Austin in 2014. There are 11 references cited in this article, which can be found at the bottom of the page. This article has been fact-checked, ensuring the accuracy of any cited facts and confirming the authority of its sources. This article has been viewed 1,120,359 times.

Writing a synthesis essay requires the ability to digest information and present it in an organized fashion. While this skill is developed in high school and college classes, it translates to the business and advertising world as well. Scroll down to Step 1 to begin learning how to write a synthesis essay.

Examining Your Topic

• Argument synthesis: This type of essay has a strong thesis statement that presents the writer's point of view. It organizes relevant information gathered from research in a logical manner to support the thesis' point of view. Business white papers known as position papers often take this form. This is the type of synthesis essay that students will write during the AP test.
• Review: Often written as a preliminary essay to an argument synthesis, a review essay is a discussion of what has been written previously on a topic, with a critical analysis of the sources covered. Its unstated thesis is usually that more research needs to be done in that area or that the topic problem has not been adequately addressed. This type of paper is common in social science classes and in medicine.
• Explanatory/background synthesis: This type of essay helps readers understand a topic by categorizing facts and presenting them to further the reader's understanding. It does not advocate a particular point of view, and if it has a thesis statement, the thesis is a weak one. Some business white papers take this form, although they are more likely to have a point of view, if understated.

• Example of a broad topic narrowed down into a reasonable synthesis essay topic: Instead of the broad topic of Social Media, you could discuss your view on the effects texting has had on the English language.
• If you've been assigned a topic as part of a class, make sure you read the prompt carefully and fully understand it.

• Keep in mind that it's better to do three sources well than to do five sources incompletely.
• Annotate each source by writing notes in the margins. This allows you to keep track of your train of thought, developing ideas, etc.

• Example: Texting has had a positive impact on the English language as it has helped the millennial generation create their own form of the language.

• If you wish to take on a claim by an opponent of your idea, and to poke holes in it, you should also find some ideas or quotes that go against your thesis statement, and plan ways to disprove them. This is called a concession, refutation, or rebuttal, which can strengthen your argument if you do it well.
• Example : For the thesis statement listed above, excellent sources would include quotes from linguists discussing the new words that have developed through 'text-speak', statistics that show the English language has evolved with almost every generation, and facts that show students still have the ability to write with the use of grammar and spelling (which your opponents would bring up as the main reason texting has had a negative effect on the English language).

Outlining Your Essay

• The introductory paragraph: 1. An introductory sentence that acts as a hook, capturing the reader's interest. 2. Identification of the issue you will be discussing. 3. Your thesis statement.
• The body paragraphs: 1. Topic sentence that gives one reason to support your thesis. 2. Your explanation and opinion of the topic sentence. 3. Support from your sources that backs up the claim you just made. 4. Explanation of the significance of the source(s).
• The conclusion paragraph: 1. State further significance of your topic from the evidence and reasons you discussed in the essay. 2. A profound thought or thoughtful ending for your paper.

• Example/illustration. This may be a detailed recount, summary, or direct quote from your source material that provides major support for your point of view. You may use more than one example or illustration, if your paper calls for it. You should not, however, make your paper a series of examples at the expense of supporting your thesis.
• Straw man. With this technique, you present an argument opposed to the argument stated in your thesis, then show the weaknesses and flaws of the counter-argument. This format shows your awareness of the opposition and your readiness to answer it. You present the counter-argument right after your thesis, followed by the evidence to refute it, and end with a positive argument that supports your thesis. [5] X Research source
• Concession. Essays with concessions are structured similar to those using the straw man technique, but they acknowledge the validity of the counter-argument while showing that the original argument is stronger. This structure is good for presenting papers to readers who hold the opposing viewpoint.
• Comparison and contrast. This structure compares similarities and contrasts differences between two subjects or sources to show the facets of both. Writing an essay with this structure requires a careful reading of your source material to find both subtle and major points of similarity and difference. This kind of essay can present its arguments source-by-source or by points of similarity or difference.

• Summary. This structure presents summaries of each of your relevant sources, making a progressively stronger argument for your thesis. It provides specific evidence to support your point of view, but usually omits presenting your own opinions. It's most commonly used for background and review essays.
• List of reasons. This is a series of sub-points that flow from the main point of your paper as stated in its thesis. Each reason is supported with evidence. As with the summary method, reasons should become progressively more important, with the most important reason last.

Writing Your Essay

• Your essay should have an introductory paragraph that includes your thesis , a body to present evidence that supports your thesis, and a conclusion that summarizes your point of view.

• Lengthy quotes of three lines or more should generally be set off as block quotes to better call attention to them. [7] X Trustworthy Source Purdue Online Writing Lab Trusted resource for writing and citation guidelines Go to source

Finalizing Your Essay

• Ask someone else to proofread your paper. The saying “two heads are better than one” still holds true. Ask a friend or colleague what would they add or remove from the paper. Most importantly, does your argument make sense, and is it clearly supported by your sources?

• Read the paper aloud to guarantee that you don't accidentally add in or take out words when reading in your head.
• If you can, get a friend or classmate to proofread your essay as well.

• Example of citing in an AP synthesis essay: McPherson claims “texting has changed the English language in a positive way--it has given a new generation their own unique way to communicate” (Source E).
• For college essays, you'll most likely use MLA format. Whichever format you use, be consistent in its use. You may also be asked to use APA or Chicago style.

• Example title: : English and the iPhone: Exploring the Benefits of 'Text-Speak'

Outline Template

Community Q&A

• Just as your title should fit your essay instead of writing your essay to fit the title, your thesis, once chosen, should direct your subsequent research instead of subsequent research altering your thesis � unless you find you've adopted an unsupportable thesis. Thanks Helpful 21 Not Helpful 8

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• ↑ https://success.uark.edu/get-help/student-resources/synthesis-paper.php
• ↑ https://www.unr.edu/writing-speaking-center/student-resources/writing-speaking-resources/mapping-a-synthesis-essay
• ↑ https://www.bgsu.edu/content/dam/BGSU/learning-commons/documents/writing/synthesis/planning-synthesis-essay.pdf
• ↑ https://writingcenterofprinceton.com/synthesis-essays-a-step-by-step-how-to-guide/
• ↑ https://owl.excelsior.edu/argument-and-critical-thinking/logical-fallacies/logical-fallacies-straw-man/
• ↑ https://writingcommons.org/section/rhetoric/rhetorical-stance/point-of-view/third-person-point-of-view/
• ↑ https://owl.purdue.edu/owl/research_and_citation/mla_style/mla_formatting_and_style_guide/mla_formatting_quotations.html
• ↑ https://owl.purdue.edu/owl/general_writing/the_writing_process/proofreading/steps_for_revising.html
• ↑ https://owl.purdue.edu/owl/general_writing/the_writing_process/proofreading/proofreading_suggestions.html
• ↑ https://www.edhs.org/ourpages/auto/2010/5/17/41759867/Synthesis%20Essay%20Introduction.pdf
• ↑ https://writing.umn.edu/sws/assets/pdf/quicktips/titles.pdf

About This Article

To write a synthesis essay, start by coming up with a thesis statement that you can support using all of the sources you've read for your essay. For example, your thesis statement could be "Texting has had a positive impact on the English language." Once you've got your thesis, go through your sources to find specific quotes, facts, and statistics that back up your claim. Structure your essay so it has an introduction that includes your thesis statement, a body that includes your arguments and evidence, and a conclusion that wraps everything up. For more tips on structuring your synthesis essay, read on! Did this summary help you? Yes No

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148 Synthesis

A synthesis will need to:

• Summarize and analyze.
• Show relationships and make connections.
• Make argumentative points with research.

What do we mean by synthesis? Where analysis calls on us to break an artifact  down into individual parts, synthesis requires us to make connections between those parts or—in most academic writing—among sources, topics, or events (just to name a few possibilities). A common type of synthesis in academic writing, for example, is a literature review in which the researcher-writer collects, compares, and shows connections or differences among different scholarly sources as well as gaps in the research. With academic writing foremost in mind, Lumen Learning defines synthesis as “analysis across sources,” adding that “what you write in reaction to the work of others should use synthesis to create new meaning or to show a deeper understanding of what you learned.” The idea is not just to summarize but to make connections. That feature is what makes synthesis so important: it’s critical thinking in action.

For example, in a movie review, you might first identify, summarize, and analyze key parts of the film, such as genre, plot, and specific techniques like suspense, background music, or humor. You might also find, summarize, and evaluate other critiques of the film. Synthesis relies on these skills, asking you to point out relationships between film elements, compare other critiques, note what’s missing or unexamined, then draw new, hopefully insightful conclusions of your own. Lumen Learning suggests, “… look for connections and patterns …[and] themes among your sources.” The idea is to connect ideas and show relationships from source to source. sources.” In other words, look for similarities, differences, and gaps. What did other critics or scholars say about a particular topic? On what points do they differ? Where do they agree? What have they missed?

In fact, we synthesize all the time but may not realize we’re gathering, comparing, and evaluating sources in this way. For example, imagine this scenario: You and a group of friends want to attend a movie together but cannot decide which one. Each of you makes a recommendation, summarizing key details about your choices (genre, good reviews, compelling plots, and so forth). Together, you and your friends compare the films, discuss each other’s assessments of the options available, and reach a conclusion: you’ll go see the sci-fi flick! That’s synthesis (or “analysis across sources”). In this case, your friends’ individual analyses are your sources; your discussion and conclusion is the synthesis.

For a more academic project, imagine that you need to gather sources, annotate them, then report what connections, differences, gaps, and other relationships you found. That’s one approach to writing a literature review, a common academic genre that synthesizes available research to position the writer to come to a conclusion or a recommendation on a topic. Here’s synthesis in action—in an academic literature review written in APA style:

The emergence of [open educational resources or OER] goes back to 1985, when the Free Software Foundation was founded by Richard Stallman to support the free software movement and to grant a certain freedom to software users (Caswell et al., 2008). In 1994, the term learning objects was introduced by Wayne Hodgins to refer to digital educational resources that could be shared via the World Wide Web (Wiley, 2006). In 1998, the term open content was coined by David Wiley and introduced to the educational community, specifically to the creators of learning objects. (Wiley, 2006)

Did you notice how the authors summarize each source and relate the sources  to one another? Richard Stallman “supported the free software movement.” Wayne Hodgins “introduced” a key concept that was widely shared and evolved into “open content” — the foundational idea for OER. The authors of this paragraph quickly summarize OER history but also show the relationship from one stage to another, and from one person to the next. By the way, analysis lies in the background here; to arrive at this synthesis, the authors had to gather sources, study them, summarize them, then analyze them before arriving at this brief synthesis.

Here’s a less academic example of synthesis that also begins to make an argument:

“While both Jones and Smith question the use of popular music in key scenes, I argue that the background tunes in Movie Z enhance suspense by using the dark sounds of a minor key and a fast, heart-like rhythmic beat.”

In this example, the writer refers briefly to the findings of other critics, demonstrates how or where they depart from those critics, identifies key elements of music in the film (a minor key, a fast beat), and offers an insight or interpretation (“the background tunes … enhances the suspense”). These moves represent a short synthesis. The writer packs a lot of information into this statement. Did you also notice how different it is from the academic synthesis? Like other genres, synthesis varies depending on purpose, audience, and other aspects of the situation.

Here’s another real-world example. Let’s say your chosen topic is “Background Music in the Horror Films Directed by Jordan Peele.” You gather reviews and scholarly articles on Peele, on music in films, on horror films, and so forth. Your goal as a researcher-writer is to summarize those sources for readers, study or analyze them so that you understand them, but primarily to put those sources in relation to each other. That is, you will compare sources, state where you disagree or agree (and why), and possibly point out gaps in the arguments or information supplied by these other sources. Individually, you analyze each source; but cumulatively, you’re using them to move toward your own conclusions.

What are some examples of this genre? 

Attributions

“Synthesis,” Lumen Learning, CC BY: Attribution , https://courses.lumenlearning.com/englishcomp1/chapter/synthesis/

“Synthesizing What You Read,” Excelsior Online Reading Lab, CC BY: Attribution, https://owl.excelsior.edu/orc/what-to-do-after-reading/synthesizing/ .

“Synthesizing Your Research Findings,” Christine Photinos, CC BY: Attribution, https://composingourselvesandourworld.pressbooks.com/chapter/20-2-synthesis/#syn .

Reading and Writing in College Copyright © 2021 by Jackie Hoermann-Elliott and TWU FYC Team is licensed under a Creative Commons Attribution 4.0 International License , except where otherwise noted.

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How to Write a Synthesis Essay

it requires researching several sources to come up with your idea, but it isn’t very different than a research essay or other academic writing assignments that students will be familiar with. This article will guide you through all the elements of a synthesis essay, including the various types, formats, citation styles, outlines, topics, guides, and tips. 

At Studyfy, we understand that writing a synthesis essay can be a challenging task. That's why we offer a custom essay writing service to assist students with their assignments. Our team of expert writers has experience in writing various types of essays, including synthesis essays, and can help you with your assignment. With our online paper writing service , you can be sure that your paper will be well-researched, properly formatted, and tailored to your specific needs. Contact us today and let us help you write a top-quality synthesis essay that meets all your requirements.

What is a Synthesis Essay?

At its core, a synthesis essay asks the writer to analyze several sources and come up with their own opinion on a subject. Think of it as creating your thesis statement based on the information you have collected from several places. It’s actually not unlike any other essay. Synthesis means combining elements of separate materials or abstract entities into a single or unified entity, and that’s what a synthesis essay does. 

Types of Synthesis Essay

There are three main types of synthesis essays:

A Review Essay

A review essay collects available information about a topic to suggest what further research needs to be done. It focuses on analyzing available sources rather than making a point of its own. 

An Argument Essay

These types of essays use multiple sources to back up a claim or argument. Like a typical argumentative essay, the goal is to convince the reader that your viewpoint on an issue is correct providing evidence from research.

An Explanatory Essay

The goal of this type of essay is to present information about a specific topic from various perspectives. Do not make an argument, just explain the topic with every point of information backed by research. 

Synthesis Essay Structure 

A synthesis essay follows the traditional structure of a 5 paragraph essay but with a few modifications. An outline is always helpful to plan any form of writing, but it is especially useful when writing this type of essay because of the many sources and various arguments to keep track of. An outline helps plan an essay and ensures that all the major points are covered as well as helps develop a flow to the paper. 

The basic synthesis essay structure follows the 5 paragraph essay format. 

Introduction - Briefly describe what the paper will be about. Start with a hook to engage the reader from the very beginning, followed by a brief description, and make sure to include your thesis statement. 

Body Paragraphs - The first body paragraph typically contains a counterargument to your thesis. Comprehensive research and proper analysis of a subject requires understanding the issue from the opposing viewpoint as well. By presenting the most popular counterargument and debunking it, you make your overall case stronger. The next body paragraphs should present information supporting your thesis.

Conclusion - The conclusion wraps up your paper by summarizing the main points and stating how you proved your thesis with facts. 

Synthesis Essay Outline

Here’s an outline template for you to use. As you do your research and come up with arguments, fill this template with information. 

Introduction

• Background information
• The importance of the issue
• Thesis statement

Body Paragraph 1

• Topic sentence with a counterargument
• Evidence for the counterargument
• Invalidate the counterargument
• Evidence and facts backing your claim

Conclusion 

• Transition to body paragraph 2

Body Paragraph 2

• Topic sentence supporting your thesis
• Quote a source
• Evidence for your claim
• Analysis of your claim
• How it connects to and supports your claim
• One sentence summary
• Transition to body paragraph 3

Body Paragraph 3

• Quote a different source 
• How it connects to and supports your claim 
• One sentence summary 
• Connect all research backing your claim
• Transition to the conclusion
• Summary of the main points made in the essay
• Restate your thesis
• Your main argument and the most important evidence
• One sentence about why our view is important

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How to Write a Synthesis Paper

Now that you know what a synthesis essay is, what the structure should be, and have an outline to fill, let’s get to how to write a synthesis essay!

How to Start a Synthesis Essay

The first thing you need to do is come up with an appropriate topic. If you’ve been given a prompt, make sure to read it carefully and follow all the instructions.

If you have to choose your own topic make sure that the issue you choose has opposing views so that you can find research backing both sides. 

Find the sweet spot between a topic that’s too broad, which can be difficult to address fully, and a topic that’s too marrow, which might not have enough available information. 

Explore our lists of possible essay topics to get an idea of what you may want to write about and read some example essays to become familiar with the structure and style. 

Once you have a topic in mind, find at least 3 sources and read them thoroughly while taking notes on specific facts to help build your thesis statement.

Writing a Synthesis Essay Thesis

After you’ve found a topic you find interesting and that complies with the prompt, your research should guide your thesis statement. What does your research say about the topic you’ve chosen? Your thesis is the main claim you are making in the essay. This doesn’t have to mean that you follow what a majority of the research says, just make sure you have enough evidence to back up your perspective as well as evidence to refute the main counter-arguments. 

Your thesis statement should be written as a complete sentence, identifying the subject and stating your viewpoint on it. This will be the guiding idea and the main point you will try and prove through the body paragraphs. 

Body Paragraphs

Body paragraphs are the main text of your essay. This is where you will present your research, support your thesis, and build your case. 

The first body paragraph usually describes a major argument against your thesis to show why the argument is wrong, or why your argument is better. There are several different approaches you can take to achieve this.

The straw man technique involves presenting the main counterargument and then destroying it with evidence showing its flaws. It can be a powerful way to strengthen your claim and it shows that you have researched opposing views. End a body paragraph using this technique with a transition sentence that introduces your main statement supporting your thesis.

The concession technique can be thought of as a softer version of the straw man. You present evidence that goes against your thesis and acknowledges that it makes sense, but show that your argument is stronger. This technique is useful for convincing people that hold the opposing view to what you believe. By agreeing with and accepting that the opposing viewpoints have some merits, it put the reader in a less hostile frame of mind.

The comparison and contrast technique presents a nuanced analysis of both sides. This is the most difficult technique because it requires a deep understanding of the issue as well as careful analysis of the strengths and weaknesses of both sides of the argument. When pulled off successfully though, it is incredibly powerful and shows an in-depth understanding of the issue. 

The body paragraphs after the first should provide evidence supporting your thesis. These can contain direct quotes from your sources. Your analysis should be clear and flow logically from the research. Towards the end of each paragraph connect the evidence directly to the thesis statement to build a strong case for your claim.

Your conclusion should state all the main points of the essay as well as the main takeaways. Summarize the evidence that backs your claim and reiterate your thesis statement. Make sure to acknowledge the opposing viewpoint and state why your perspective is either correct or stronger.

Synthesis Essay Format

Citation is important for any paper, but especially for one that is research-driven. The three main citation styles are MLA, APA, and Chicago. Each one has its own synthesis essay format and conventions described below. 

MLA stands for Modern Language Association and is a citation style used for papers in the Humanities like art, literature, and philology. These are the key formatting rules for MLA:

• Font should be Times New Roman
• Font size should be 12
• The entire paper should be double-spaced
• Margins should be 1 inch
• Titles should be centered
• Include your last name and the page number on each page
• The header should contain your name, your professor’s name, the date, and the course code
• The research page at the end should be titled “Works Cited”
• Journal Citation Format: Last, First M. “Publication Title.” Journal Title Series Volume. Issue (Year Published): Page(s). Database Name. Web. Date Month Year Accessed.
• Newspaper (Print) Citation Format: Author's Last Name, First Name. "Title of Article: Subtitle if Any." Name of Newspaper, Date of Publication, p. Page Number.
• Newspaper (Online) Citation Format: Author's Last Name, First Name. "Title of Article: Subtitle if Any." Title of Website, Date of Publication, URL. Accessed Day Month Year site was visited.
• Website Citation Format: Author's Last Name, First Name. Title of Website, Name of Organization Affiliated with the Website, Date of copyright or date last modified/updated, URL. Accessed Day Month Year site was visited.

APA stands for American Psychological Association and is a citation style used for science, education, and psychology. These are the key formatting rules for APA:

• Include a Title Page
• Include an Abstract
• Include the page number on each page
• The header should contain the page number and the paper’s title
• The research page at the end should be titled “References”
• Journal Citation Format: Author’s last name, Author’s first initial. Author’s middle initial. (Year, Month Date Published). Article title. Journal Name, Volume (Issue), page number(s).
• Newspaper Print Citation Format: Author, A. (Year, Month Date of Publication). Article title. Newspaper Title, pp. Xx-xx.
• Newspaper Online Citation Format: Author, A. (Year, Month Date of Publication). Article title. Newspaper Title, Retrieved from newspaper homepage URL
• Website Citation Format: Author’s last name, Initial(s). (Year, Month Day of publication). Title of work. Website. https://URL

The Chicago style is used for history, business, and the fine arts. These are the key formatting rules for the Chicago style:

• The space between lines should be double-spaced
• Use half-inch indents for the beginning of every paragraph
• Use the full names of people and organizations
• The research page at the end should be titled “Bibliography”
• There are 2 main ways of citing sources, Author-Dates and Notes-Bibliography
• Author-Dates uses parenthetical citations in the text referencing the source's author's last name and the year of publication.
• Notes-Bibliography uses numbered footnotes in the text to direct readers to a short citation at the bottom of the page.
• Both styles have a full bibliography as well
• Full source citations are in alphabetical order

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Synthesis Essay Topics

Here are 30 topics to inspire you. You can think of these as brief synthesis essay thesis examples.

What is the impact of culture on academic success?

How does social media influence feelings of loneliness?

How does human crated sound pollution impact urban wildlife?

What will the impact of self-driving cars be on the trucking industry?

Were superheroes better role models in the past as compared to now?

How can private drones be policed?

Will machine learning ever be able to make human artists obsolete?

Does privatization of infrastructure make sense for developing countries?

What would be the best way to communicate with aliens?

Are there negative aspects of meditation?

What is the biggest potential reason for a potential World War III?

Do tall people make better leaders?

Self-fulfilling prophecies and confirmation bias explain why some predictions come true.

What can we learn from interactions with indigenous tribes?

What are the key steps developed countries must take to manage future pandemics?

How have volcanos shaped the Earth’s climate?

What is the impact of snow on overall mood?

Is it possible to reduce the wage gap fairly?

Does having pets enhance the quality of life?

Has the rise of visual media killed imagination?

Which societies in the past have been matriarchal?

How can video games help those with mental disorders?

Which is the worst seven deadly sin?

Why Anime is better than western animation

Is honor beneficial or detrimental in sports?

What are the problems with social Darwinism?

Can anyone become a model now?

What does it take to be considered an expert?

Where is the line between advertising and manipulation?

Is there an objective idea of ethical behavior?

Here are some tips to keep in mind when writing your essay.

• Write in the third person
• Make sure your research comes from credible sources
• Cite every fact
• Write multiple drafts of your essay
• Spend time editing and proofreading
• Organize your arguments clearly
• Think about your audience
• Use technical terms
• Use paragraph transitions
• Use a synthesis essay outline template
• Use present tense for MLA
• Use past tense for APA

What Not To Do

• Use informal language
• Rely only on opinion
• Use the passive voice
• Stick to the outline template exactly
• Use fewer than three sources
• Use more than five sources
• Submit the first draft

A synthesis essay might be more technical than the types of writing you’re used to, but don’t stress too much. If you think about it as any other essay, but just a little more research-intensive, it’ll be easy to write. Choose a topic that you are interested in to make the research more fun. If you know about the topic, it will guide your research and make the writing flow more smoothly as well. Citations may seem daunting, but using a citation generator will make it a cinch!

If you need assistance with writing a synthesis essay, Studyfy has a team of qualified coursework writers who can provide you with high-quality, custom essays. Whether you need to order an essay online, or require help with essay editing or proofreading, our experts are available to assist you. Don't hesitate to contact us and say " write my essay for me " if you need any kind of academic assistance.

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How to Write a Synthesis Essay Like a Pro

The definition of a synthesis entails a written discourse integrating support from multiple sources, each offering diverse perspectives.

Writing a synthesis essay demands the skill to comprehend information and structure it cohesively. This proficiency cultivated in academic settings also holds value in the realms of business and advertising. In this article, you will learn about the main types of this essay, writing steps, optimal structure, and hands-on writing hints. If you still require any help with any of the material, feel free to consult our essay writing service online .

What is a Synthesis Essay: Types and a Step-by-Step Writing Guide

The essence of how to write synthesis essay lies in forging insightful connections among various elements within a work or across multiple works, all with the overarching objective of formulating and substantiating a claim on a specific topic. Essentially, it's the art of researching a subject and discovering linkages that culminate in a well-supported perspective. It’s possible to name three types of synthesis essays:

Argument Synthesis: Featuring a robust thesis statement, a synthesis argument essay articulates the writer's viewpoint. It systematically arranges relevant research findings to bolster the thesis, commonly seen in business white papers and AP test essays.

Review Synthesis: Often a precursor to an argument synthesis, this essay evaluates previous literature on a topic, offering a critical analysis. Typically, its implicit thesis suggests the need for further research or that the topic's problem remains unaddressed. It's prevalent in social sciences and medicine.

Explanatory/Background Synthesis: Focused on elucidating a topic, an explanatory synthesis essay categorizes facts to enhance the reader's comprehension. It refrains from advocating a particular perspective, and if it features a thesis, it tends to be relatively weak. Some business white papers adopt this approach, occasionally with a subtle viewpoint. Now, let’s find out how to start a synthesis essay.

Brainstorm Good Synthesis Essay Topics

Synthesis essay topics you choose should strike a balance – they must encompass a scope wide enough to unite various interconnected sources, yet not so expansive that they amalgamate vastly unrelated ones. If you are free to select your topic, conducting some initial research can guide your decision-making process. To illustrate, consider the transformation of a broad subject like "Social Media" into a more focused essay topic, such as exploring the impact of texting on the English language. When synthesis paper topics are assigned in a class, be sure to meticulously examine the prompts to ensure a thorough comprehension of their requirements.

Carefully Select and Double-Check Your Sources

For the AP test, your sources will be provided. For the purpose of learning what is synthesis essay, you should aim to choose a minimum of three sources for your essay. If time permits, study one or two additional sources, especially those directly relevant to your essay's purpose or argument.

Remember, it's more advantageous to analyze three sources than to superficially cover five thoroughly. While working on synthesis essay writing regarding sources, annotate them by jotting down notes in the margins. This practice will help you maintain a clear line of thought and develop your ideas effectively.

Write a Thesis Statement 

After reviewing the assigned sources or conducting independent research, it's time to formulate a synthesis essay thesis on the topic. Your thesis serves as the central concept in your essay, encompassing the subject and articulating your perspective. It should be expressed as a complete sentence. In your essay, the thesis statement can function as either the opening sentence or the concluding sentence of the first paragraph, depending on the essay's structure. For instance, consider the following example: " Climate change is an urgent global crisis, and its mitigation requires a coordinated effort involving government policies, renewable energy adoption, and public awareness campaigns to combat its detrimental effects on our planet. ”

Revisit Your Source Material to Identify Supporting Elements for Your Thesis

When learning how to write a synthesis thesis, thoroughly review your sources and identify key quotes, statistics, ideas, and facts that align with and support your thesis. As you encounter these elements, document them for use throughout your essay.

If you intend to address opposing claims and challenge them, seek out ideas or quotes that contradict your thesis statement and devise strategies to refute them. This practice, known as a concession, refutation, or rebuttal, can significantly bolster your argument when executed effectively.

For example, with the provided thesis statement of an argumentative synthesis essay, valuable sources may encompass quotes from linguists discussing the emergence of new words in 'text-speak,' statistics showcasing the continuous evolution of the English language with each generation, and factual evidence demonstrating that students maintain the ability to write with proper grammar and spelling. These elements can serve to counter the arguments against the positive impact of texting on the English language.

Optimal Synthesis Essay Structure

You can choose to organize your approach formally with a synthesis paper outline or plan the structure in your head. But it's crucial to determine the most effective way to present your material. If you're composing this paper for the AP test, be aware that graders expect a specific structure of a synthesis essay thesis outline.

Synthesis Essay Introduction:

• An attention-grabbing opening sentence to engage the reader.
• Clear identification of the issue under discussion.
• Presentation of your thesis statement.

Body Paragraphs:

• Start with a topic sentence that supports one aspect of your thesis.
• Provide your interpretation and viewpoint on the topic.
• Cite evidence from your sources to support your assertion.
• Explain the significance of the source(s) in the context of your argument.

Conclusion Paragraph:

• Reiterate the broader significance of your topic based on the evidence and reasons explored in the essay.
• Conclude with a profound insight or thoughtful ending for your paper.

Explore a More Imaginative Structure for Your Synthesis Essay

If you are learning how to write a synthesis essay AP lang, consider adopting a structure that was outlined earlier. In another case, approach a synthesis essay structure more creatively. You have the flexibility to employ one or more of the following creative approaches:

1. Example/Illustration: This approach involves providing detailed anecdotes, summaries, or direct quotes from your source material to offer substantial backing for your perspective. You can employ multiple examples or illustrations, but avoid making your essay solely a series of examples at the expense of supporting your thesis.

2. Straw Man: With this method, you mean to present an argument opposing the thesis in your argumentative synthesis essay, subsequently highlighting its weaknesses and flaws. By showcasing your understanding of the opposing viewpoint and your ability to counter it, you enhance the strength of your argument. In the beginning, present the counter-argument immediately after your thesis, follow with evidence to disprove it, and conclude with a compelling argument supporting your thesis.

3. Concession: Essays structured with concessions resemble those using the straw man technique. However, they acknowledge the validity of the counter-argument while demonstrating that the original argument holds more weight. This structure effectively presents your paper to readers who maintain opposing viewpoints.

4. Comparison and Contrast: This structure involves examining similarities and differences between two subjects or sources to showcase their various aspects. Crafting an essay using this structure necessitates a meticulous analysis of your source material to identify both subtle and significant points of similarity and contrast. You can present your arguments either source-by-source or by highlighting points of similarity or difference. We know that this information might sound tricky, so we would like to offer you to order essay writing from expert writers to save you the trouble.

Generate an Outline Tailored for a Background and Review Essays

While a synthesis paper primarily focuses on articulating and substantiating a thesis, background and review essays delve into the concepts and ideas contained within the sources rather than centering on the author's perspective. There are two fundamental approaches to structuring such essays:

1. Summary: This framework provides summaries of each relevant source, gradually constructing a more robust argument for your thesis. It offers specific evidence to bolster your viewpoint but typically refrains from expressing your personal opinions. This method is most commonly employed in background and review essays.

2. List of Reasons: This approach consists of a series of sub-points derived from the central thesis of your synthesis in English. Each reason is fortified with supporting evidence. Similar to the summary method, the reasons should progress in importance, with the most significant reason appearing last.

Writing Tips That Will Help You Score Better 

One of the cornerstones of how to write a synthesis paragraph is to be ready to adjust your plan as needed, especially if you synthesize ideas and information in your source material that strengthens your thesis. If you're composing the synthesis for the AP test, remember that you won't have the luxury of multiple drafts, so manage your time wisely to ensure it reaches its utmost potential.

Synthesis essay writing should commence with an introductory paragraph that features your thesis, followed by a body that provides compelling evidence in support of your thesis. Conclude your essay with a summary of your perspective. Is everything clear so far? If not, simply say, ‘ Help me write my essay ,’ and our experts will get back to you with more practical assistance.

Write in the Third Person 

If you are wondering how to write a synthesis paper correctly, remember that writing in the third person is recommended. It involves the use of pronouns like "he," "she," and "it," alongside crafting clear and comprehensive sentences. It's essential to provide sufficient information that demonstrates your expertise in the subject matter of your essay. Writing a synthesis essay, strive to maintain an active voice in your writing. However, passive voice can be employed when necessary, particularly when avoiding the use of first-person ("I") or second-person ("you").

Use Transitions

Transitions serve as effective tools for illustrating the intersections where your sources reinforce each other. For instance, you can highlight this synergy as follows: " Hallstrom's insights into market dynamics receive further validation from Anderson's comprehensive study, 'Market Trends Unveiled,' where he argues… "

For extensive quotations spanning three lines or more, it's advisable to set them apart as block quotes to emphasize their significance.

Self-Check List Before Handing Your Work In

Now is the moment to fortify your argumentative synthesis essay and enhance the flow between points and paragraphs. Strive for clarity and conciseness in your argumentation, making it easily comprehensible. Reading your essay aloud can be beneficial, as it reveals awkward sentences and incoherent arguments.

Consider enlisting a second set of eyes for proofreading; the phrase "two heads are better than one" remains relevant. Request feedback from a friend or colleague regarding potential additions or removals from your synthesis in English writing. Crucially, ascertain whether your argument is logically sound and well-supported by your sources.

Proofread Carefully

In the framework of how to write an academic essay , proofreading is absolutely key. Thoroughly review your paper to identify and rectify any grammar, punctuation, or spelling mistakes. Pay special attention to the accurate spelling of names and proper nouns. Check for run-on sentences or sentence fragments and make necessary corrections as you proceed.

To ensure accuracy, read your paper aloud, as this can help prevent accidental insertions or omissions that might occur when reading silently. Whenever possible, seek the assistance of a friend or classmate for additional proofreading to enhance the overall quality of your essay.

Acknowledge and Cite Your Source Material

The process of how to cite in a synthesis essay includes Incorporating footnotes to cite material within the body of your essay and compiling a bibliography of the cited works at the conclusion is the preferred method. Ensure that footnotes and in-text citations are employed whenever you quote, paraphrase, or reference any material. If you're composing this essay for the AP test, a specific citation style may not be required, but it is essential to identify the source after citing it.

For instance, in an AP essay, you might mention: “ Johnson posits, ‘The advent of texting has revolutionized the English language, offering a distinct mode of communication for the younger generation. ’"

In college essays, you'll typically adhere to MLA format, although you may be asked to use APA or Chicago style. Regardless of the format, maintain consistency in its application throughout your essay. To help you with this, we’ve prepared a guide on how to format an essay .

What Should Not Be Said in a Synthesis Essay?

In an argumentative synthesis essay, it's crucial to avoid expressing personal opinions or introducing new informative insights not supported by your cited sources. Steer clear of making sweeping generalizations or assumptions without proper evidence, and do not rely solely on personal anecdotes or anecdotes that aren't reinforced by reputable sources. Additionally, avoid simply summarizing sources without analyzing and documenting the information to build a cohesive argument. Your essay should focus on presenting a well-supported thesis derived from the integrated ideas of your sources rather than introducing personal viewpoints or extraneous information.

Should a Synthesis Paper Have a Title?

Yes, you can certainly have a title for a synthesis paper. A well-chosen title can provide readers with an initial understanding of the essay's topic or theme and can make your paper more engaging. The title should be relevant to the content and give readers a sense of what to expect from your essay. Make sure the title is concise, descriptive, and reflective of the main idea or argument in your paper.

What Is the Length of a Synthesis Paper?

When writing a synthesis paper, the length can vary significantly depending on the specific assignment or guidelines provided by your instructor. Typically, synthesis papers range from 2-5 pages for shorter assignments to longer papers of 10 or more pages for more extensive projects. The exact page count may also depend on the complexity of the topic and the number of sources you are required to integrate into your synthesis. It's essential to adhere to your instructor's instructions regarding the required length for your synthesis paper.

Is There a Difference Between Synthesis and Argument Essay?

A synthesis essay combines information from multiple sources to develop a balanced viewpoint on a topic, emphasizing objectivity. In contrast, an argument essay focuses on presenting and defending a particular perspective on a subject, often using reasons and evidence to persuade the audience. The use of sources and the tone differs, with synthesizing essays adopting a more objective tone and incorporating various perspectives. In contrast, argument essays take a persuasive approach with a clear thesis. In summary, the key distinction lies in their purpose, use of sources, and the tone and voice employed.

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Literature Review Survival Library Guide: Thesis, antithesis and synthesis

• What is a literature review?
• Thesis, antithesis and synthesis
• 1. Choose your topic
• 2. Collect relevant material
• 3. Read/Skim articles
• 4. Group articles by themes
• 5. Use citation databases
• 6. Find agreement & disagreement
• Review Articles - A new option on Google Scholar
• How To Follow References
• Newspaper archives
• Aditi's Humanities Referencing Style Guide
• Referencing and RefWorks
• New-version RefWorks Demo
• Tracking Your Academic Footprint This link opens in a new window
• Finding Seminal Authors and Mapping the Shape of the Literature
• Types of Literature Review, including "Systematic Reviews in the Social Sciences: A Practical Guide"
• Research Data Management
• Tamzyn Suleiman's guide to Systematic Reviews
• Danielle Abrahamse's Search String Design and Search Template

Thesis, antithesis, synthesis

The classic pattern of academic arguments is:

Thesis, antithesis, synthesis.

An Idea (Thesis) is proposed, an opposing Idea (Antithesis) is proposed, and a revised Idea incorporating (Synthesis) the opposing Idea is arrived at. This revised idea sometimes sparks another opposing idea, another synthesis, and so on…

If you can show this pattern at work in your literature review, and, above all, if you can suggest a new synthesis of two opposing views, or demolish one of the opposing views, then you are almost certainly on the right track.

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• How to Write a Thesis Statement | 4 Steps & Examples

How to Write a Thesis Statement | 4 Steps & Examples

Published on January 11, 2019 by Shona McCombes . Revised on August 15, 2023 by Eoghan Ryan.

A thesis statement is a sentence that sums up the central point of your paper or essay . It usually comes near the end of your introduction .

Your thesis will look a bit different depending on the type of essay you’re writing. But the thesis statement should always clearly state the main idea you want to get across. Everything else in your essay should relate back to this idea.

You can write your thesis statement by following four simple steps:

• Start with a question
• Write your initial answer
• Develop your answer
• Refine your thesis statement

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Table of contents

What is a thesis statement, placement of the thesis statement, step 1: start with a question, step 2: write your initial answer, step 3: develop your answer, step 4: refine your thesis statement, types of thesis statements, other interesting articles, frequently asked questions about thesis statements.

A thesis statement summarizes the central points of your essay. It is a signpost telling the reader what the essay will argue and why.

The best thesis statements are:

• Concise: A good thesis statement is short and sweet—don’t use more words than necessary. State your point clearly and directly in one or two sentences.
• Contentious: Your thesis shouldn’t be a simple statement of fact that everyone already knows. A good thesis statement is a claim that requires further evidence or analysis to back it up.
• Coherent: Everything mentioned in your thesis statement must be supported and explained in the rest of your paper.

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The thesis statement generally appears at the end of your essay introduction or research paper introduction .

The spread of the internet has had a world-changing effect, not least on the world of education. The use of the internet in academic contexts and among young people more generally is hotly debated. For many who did not grow up with this technology, its effects seem alarming and potentially harmful. This concern, while understandable, is misguided. The negatives of internet use are outweighed by its many benefits for education: the internet facilitates easier access to information, exposure to different perspectives, and a flexible learning environment for both students and teachers.

You should come up with an initial thesis, sometimes called a working thesis , early in the writing process . As soon as you’ve decided on your essay topic , you need to work out what you want to say about it—a clear thesis will give your essay direction and structure.

You might already have a question in your assignment, but if not, try to come up with your own. What would you like to find out or decide about your topic?

For example, you might ask:

After some initial research, you can formulate a tentative answer to this question. At this stage it can be simple, and it should guide the research process and writing process .

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Now you need to consider why this is your answer and how you will convince your reader to agree with you. As you read more about your topic and begin writing, your answer should get more detailed.

In your essay about the internet and education, the thesis states your position and sketches out the key arguments you’ll use to support it.

The negatives of internet use are outweighed by its many benefits for education because it facilitates easier access to information.

In your essay about braille, the thesis statement summarizes the key historical development that you’ll explain.

The invention of braille in the 19th century transformed the lives of blind people, allowing them to participate more actively in public life.

A strong thesis statement should tell the reader:

• Why you hold this position
• What they’ll learn from your essay
• The key points of your argument or narrative

The final thesis statement doesn’t just state your position, but summarizes your overall argument or the entire topic you’re going to explain. To strengthen a weak thesis statement, it can help to consider the broader context of your topic.

These examples are more specific and show that you’ll explore your topic in depth.

Your thesis statement should match the goals of your essay, which vary depending on the type of essay you’re writing:

• In an argumentative essay , your thesis statement should take a strong position. Your aim in the essay is to convince your reader of this thesis based on evidence and logical reasoning.
• In an expository essay , you’ll aim to explain the facts of a topic or process. Your thesis statement doesn’t have to include a strong opinion in this case, but it should clearly state the central point you want to make, and mention the key elements you’ll explain.

If you want to know more about AI tools , college essays , or fallacies make sure to check out some of our other articles with explanations and examples or go directly to our tools!

• Ad hominem fallacy
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• Appeal to authority fallacy
• False cause fallacy
• Sunk cost fallacy

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A thesis statement is a sentence that sums up the central point of your paper or essay . Everything else you write should relate to this key idea.

The thesis statement is essential in any academic essay or research paper for two main reasons:

• It gives your writing direction and focus.
• It gives the reader a concise summary of your main point.

Without a clear thesis statement, an essay can end up rambling and unfocused, leaving your reader unsure of exactly what you want to say.

Follow these four steps to come up with a thesis statement :

• Ask a question about your topic .
• Write your initial answer.
• Develop your answer by including reasons.
• Refine your answer, adding more detail and nuance.

The thesis statement should be placed at the end of your essay introduction .

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How to Write a Synthesis Essay: Examples, Topics, & Outline

A synthesis essay requires you to work with multiple sources. You combine the information gathered from them to present a well-rounded argument on a topic. Are you looking for the ultimate guide on synthesis essay writing? You’ve come to the right place!

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In this guide by our custom writing team, you will find:

• a step-by-step writing guide;
• a list of 34 synthesis essay topics;
• a full essay sample in MLA format.
• 📚 Synthesis Essay Definition
• 📝 Essay Types
• ✅ Step-by-Step Guide
• ✍️ Topics & Prompts
• 📑 Example & Formatting Tips

📚 What Is a Synthesis Essay?

A synthesis essay is an assignment that requires a unique interpretation of a particular topic using several reliable sources. To write it, you need to understand, analyze, and synthesize information. That is why this type of essay is used in the AP Lang exam to assess students’ reasoning skills.

The key features of the synthesis essay are:

• Debatable topic . If your goal is to write a good synthesis essay, it’s necessary to choose an arguable topic. It’s best to choose something that people have different opinions about. This will allow you to use many sources with various viewpoints for your synthesis.
• Clear thesis statement. It’s a sentence that briefly describes the main idea of your essay.
• Reliable sources to prove your thesis . For a synthesis essay, your opinion is not enough. You also need to find the evidence. Keep in mind that simply reading an online encyclopedia won’t do; make sure to choose only reliable sources.

What Does It Mean to Synthesize Information?

Synthesis is a process that has huge importance in nature, science, and our everyday life. The word stems from Ancient Greek “synthesis,” which means “putting together.” In general, synthesis is the combination of components to form a connected whole.

In everyday life, we usually resort to it to synthesize information . This means taking the data from different sources and bringing it together. This process is the opposite of analyzing:

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• For an analysis , you break problems into pieces,
• For a synthesis , you combine separate elements into a whole.

We use synthesis for analysis papers, research papers, argument papers, and business reports.

What Does Synthesis Mean in Writing?

Synthesis in writing means summarizing and connecting different sources considering a particular topic. Although synthesis and analysis are two opposite things, they usually go together in synthesis essays. The process consists of 2 stages:

• Conduct the analysis. For that, you break down a problem into parts and analyze the sources. It’s helpful to highlight everything regarding your topic while reading.
• Carry out the synthesis. The next step is to formulate an opinion and combine the highlighted information from the sources.

Synthesis is not only used in writing but also in reading comprehension . It’s useful to do this kind of reading while studying your sources. There are three reading comprehension stages:

• Your previous knowledge about the topic.
• Expansion of your knowledge while you are reading.
• Understanding of the problem when you have finished reading.

So, synthesized reading comprehension means combining three stages in one and formulating one statement.

Synthesis vs Summary: What Is the Difference?

A summary is a paraphrasing of the written source in your own words. For a good summary, it’s necessary to include all of the text’s key elements. Meanwhile, synthesis means combining different ideas from different sources. You don’t have to include all the key points; just choose everything related to your topic.

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Both of these techniques are used for the synthesis essay:

• The summary goes in the conclusion. You briefly sum up your paper’s main ideas.
• Synthesis goes in the body paragraphs. Here, you combine multiple sources to prove a point.

📝 Synthesis Essay Types

There are two main types of a synthesis essay: argument and explanatory synthesis.

Both of them require working with multiple reliable sources and analyzing information. The only difference is that an argument synthesis essay requires your own opinion, while an explanatory synthesis essay does not.

Argument Synthesis Essay: Outline and Definition

As you already know, an argument synthesis essay requires you to state your own opinion about the given topic and back it up with several reliable sources. The purpose of such an essay is to persuade the reader that your point is correct.

Here’s what an argument synthesis essay consists of:

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Explanatory Synthesis Essay: Definition and How to Write

An explanatory informative synthesis essay requires you to stay neutral towards the problem you are discussing. This means you cannot express your own opinion considering the given question or a problem. Your task is just to inform the reader. That’s why this essay type is also called informative synthesis.

Check out this explanatory essay outline:

✅ How to Write a Synthesis Essay Step by Step

When it comes to the synthesis essay outline, it’s not too different from other assignments. Have a look at this template:

How to Synthesize: Working with Sources

After you’ve decided on your topic, it’s time to figure out how to synthesize articles into one text. This is how you do it:

• Choose reliable sources: the ones printed in journals or published on academic websites.
• Become familiar with them and see if they fit into your essay.
• Try to find a few sources for each point. It will increase your essay’s reliability.
• Relate each source to your arguments and see similarities between them.
• Don’t forget to list every source in the references.

When you are done with a comprehensive analysis of related literature, try to step back and imagine a person who has a different opinion on this topic. Think of some arguments that they can provide to prove their opinion. After you have the list of arguments, find the written evidence of why they are wrong and put them in your essay.

Analyzing and organizing sources is the first and very important step for the synthesis essay. So make sure you do understand what the text means before using it as a reference.

Synthesis Essay Outline: How to Write

For structuring your essay, it’s useful to try mapping . This technique means combining the information from different sources and rearranging it to create a new direction. To do it, you need to analyze the authors’ ideas and come up with your own conclusions.

The best way to do that is called synthesis matrix or graphic organizer. It’s a chart that you can make when you start working on your essay. Here you have a horizontal column that states the main ideas and a few vertical columns that present sources. Your task is to take sources you have chosen and write down the main ideas from them.

Here’s an example of a matrix chart:

While doing that, you will see how many sources contain the same ideas. When you analyze them, you will be able to formulate your thesis backed up with evidence. The synthesis matrix also helps to see new arguments you can cover in your synthesis paper.

How to Write an Introduction for a Synthesis Essay

Now it’s time to start writing the paper. In the introductory part of the essay, you can include:

• A short yet catchy sentence or a quotation that would present the topic. The start of your essay should make people interested. It’s best to make the first sentence not only informative but also easy to understand.
• The texts that are used for the essay. Provide the titles and the authors’ names (use the appropriate guidelines depending on the writing style.)
• The background information which is needed to understand your essay. Definitions of terms or unknown words considering the topic can be included in this part. Otherwise, people may find it hard to understand what they are reading about.

How to Write a Thesis for a Synthesis Essay

A thesis statement is a point of view on a certain problem that you will defend in your essay. It should contain the key points that you want to include in your paper. Here’s how to create a perfect thesis statement:

• Find several central ideas in the chart.
• Choose the ones that are repeated the most often and the ones that you feel need to be in your essay.
• Combine them, and you have a thesis statement with all the key points.
• Make a draft of the thesis statement. Try to formulate the main idea you want to present in your essay.
• Elaborate on this idea. Add some details and expand it a bit further.

If the whole picture is coherent, and it conveys exactly what you wanted, then this is your perfect thesis statement. See the example below:

Gender inequality still exists at the workplace: women are less likely to get the most responsible positions, easily lose careers due to maternity leave, and often receive less pay for the same amount of work.

How to Write Synthesis Paragraphs for the Main Body

Your essay’s main body consists of a few paragraphs. Each of them presents a different argument considering the topic. When you start a paragraph, make sure to begin with a topic sentence, which informs the reader about the paragraph’s main idea. Then, include the synthesized sources and elaborate on them.

Here’s what you should and shouldn’t do when writing the main body:

You can use the following words to present the ideas from your sources. They will help you reflect the authors’ tone:

How to Conclude a Synthesis Essay

There are quite a few ways to conclude the synthesis paper. Have a look at some of the options:

• Paraphrase the thesis. As you remember, the thesis is the main idea of your essay. The conclusion is a good place to remind your readers about it. When they are done with the reading, they remember the most important thing from your essay.
• Synthesize the arguments. There is no need to repeat everything you wrote in your essay. Just briefly summarize the most crucial points.
• Answer the “So what” question. Tell the readers why this topic matters, why you’ve chosen it, and why it’s valuable for the reader.
• Provide a closure. It’s an effective strategy when you want to make the reader think. Leave them with a strong statement at the end of your essay.

Synthesis Paper Proofreading Tips

When you have finally written your paper, there is still one important thing left to do. You need to check your paper for any grammatical and contextual mistakes. You certainly can do it yourself, but it would be perfect if you could ask somebody else to read it.

The first thing you need to check grammar-wise is the tense you are using. There is no single tense you need to use for the synthesis essay. It depends on the format:

• If you’re writing in MLA format, use the present tense;
• For APA essays, you use the past tense.

The next step is to check whether your synthesis essay has everything that’s required. For that, we have prepared the checklist of questions you can ask yourself to proofread your essays.

• Is there a clear thesis statement?
• Did you include all of the key points from the synthesis?
• Are there clear transitions between paragraphs?
• Did you organize a paragraph around a single idea?
• Did you use reliable and up-to-date sources?
• Did you analyze sources rather than just summarize them?
• Did you mention every source you’ve used?

If you’ve answered “yes” to all the questions—congratulations, you are done with the essay! Otherwise, you need to come back and fix everything that you’ve answered “no” to.

✍️ Synthesis Essay Topics and Prompts

Sometimes, when you don’t have a topic , it is tough to come up with a suitable idea. That is why we have prepared two lists of topics that you can use for any synthesis essay type.

Explanatory Synthesis Essay Topics

The topics below are suitable for an explanatory synthesis essay:

• The beginning of Hollywood cinema . Cinema is a huge industry in the USA. Tell the readers about its history. Describe what it was like in the beginning, which movie was the first one, and who started this industry.
• Tactics on dealing with noisy children. Sometimes kids can be very loud, especially in public places. Write about different tactics that can help with this issue.
• The effects of climate change  on the water cycle.  Climate change has affected the water cycle significantly. Your task is to explain how.
• The best American cities to live in. Provide the list of the best cities and explain why you’ve included them.
• The importance of a healthy diet . Keeping a healthy diet is beneficial in many ways. Write about all the advantages it brings.
• Who can become an entrepreneur? Entrepreneurship is not for everybody. In this essay, you can describe the qualities needed for having your own business.
• The correlation between overpopulation and poverty . Describe how overpopulation leads to poverty and vice versa.
• The advantages of taking an active vacation.
• Cultural shock as a part of moving to a different country.
• The consequences of the first wave of feminism .
• Synthesis of Tan and Rodriguez’ essays ideas.
• Difficulties you may encounter during the job interview.
• How does reading prevent Alzheimer’s disease ?
• The effect of the COVID-19 pandemic on businesses .
• The connection between  religion and politics  in ruling the country.
• What can non-verbal signals tell you about a person ?
• The psychology of leadership .
• The origins of the most common  stereotypes  about Americans.
• Role of social media in business communication .
• The synthesis of personal nursing philosophy concept.
• Behavioral components of schizophrenia and psychosis.
• Main components of successful entrepreneurship.
• Critical components of scientific research.
• Change in religion and human beliefs throughout history.
• The effect of global warming on modern life.

Argument Synthesis Paper Topics

The list of topics for the Argument Synthesis Essay:

• Vaping is better than smoking . People are starting to exchange cigarettes for vapes and e-cigarettes. In what ways are they less harmful?
• Rich people should pay higher taxes. The same percentage of money doesn’t equal for rich and poor people. Explain why the ones who can afford more should share with others.
• Depression is a disease . Prove that psychological problems must be recognized as real health issues that should be cured and not ignored.
• Social media affects young people’s lives. Social media has a massive influence on people. In this essay, you can discuss which life spheres are the most affected.
• Beauty pageants should be banned. Provide the reasons why they should be banned and tell the reader about psychological problems they can cause.
• People should cut meat from their diet to stop global warming . Describe how the meat industry influences climate change.
• The voting age should be 25+. Your task is to show the reasons why the votes of people under 25 should not be taken into account during elections.
• A healthy lifestyle requires a lot of money.
• Each healthy man should serve in the military.
• School bullying should be punished by immediate exclusion.
• Does friendship exist between men and women?
• Drinking coffee is a bad habit.
• Working hard is more important than being talented.
• Everybody should visit a therapist at least once.
• Should universities be free ?
• Artificial intelligence will cause huge unemployment rates.
• Gaming should not be allowed to children under 18.
• Components and strategies of social responsibility
• Integration of relevant ethical theory and conceptual principles in health care
• Children under 10 should be banned from gadgets .
• Social media platforms facilitate cyberbullying.
• Issues of distance education .
• Social media addiction is a serious disease.
• Deforestation critically contributes to global warming.
• Healthcare should be free for everyone.

📑 Synthesis Essay Example & Synthesis Essay Format Tips

Now let’s talk about formatting. There are two writing styles you can use for a synthesis essay: APA or MLA. You need to choose the one that is required for your assignment.

We will start with the paper in APA format. It is usually used in science and education.

And these are MLA formatting rules:

Finally, we’ve prepared a synthesis essay sample for you to check out. Feel free to download the PDF file below:

First introduced in the Civil Rights Act of 1964, affirmative action policies aim to mitigate the discrepancy in opportunities available for underrepresented social groups by taking into account one’s minority background. The policies have become a pressing public issue that obstructs previously marginalized individuals, particularly in the educational environment.

Thank you for reading the ultimate guide on synthesis essay writing. We hope you found it helpful. Don’t forget to share it with your friends. Good luck with your assignments!

🔍 References

• Writing a Synthesis Essay: Bowling Green State University
• What Is Synthesis: University of Manitoba
• Synthesis: Biology Online
• Reading Strategies: Difference Summarizing and Synthesizing: WordPress
• Summary, Analysis, Synthesis Definitions: University of Utah
• Argumentative Synthesis: University of Arkansas
• How to Synthesize Written Information: Simply Psychology
• Mapping of Synthesis Essay: University of Nevada, Reno
• Writing a Literature Review and Using a Synthesis Matrix: Florida International University
• Synthesis Essay: Cleveland State University
• Literature Review: Synthesizing Multiple Sources: Louisiana State University
• Writing a Conclusion: Texas Women’s University
• General APA Guidelines: Purdue University
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In philosophy, the triad of thesis, antithesis, synthesis (German: These, Antithese, Synthese; originally: Thesis, Antithesis, Synthesis) is a progression of three ideas or propositions. The first idea, the thesis, is a formal statement illustrating a point; it is followed by the second idea, the antithesis, that contradicts or negates the first; and lastly, the third idea, the synthesis, resolves the conflict between the thesis and antithesis. It is often used to explain the dialectical method of German philosopher Georg Wilhelm Friedrich Hegel, but Hegel never used the terms himself; instead his triad was concrete, abstract, absolute. The thesis, antithesis, synthesis triad actually originated with Johann Fichte.

1. History of the Idea

Thomas McFarland (2002), in his Prolegomena to Coleridge's Opus Maximum , [ 1 ] identifies Immanuel Kant's Critique of Pure Reason (1781) as the genesis of the thesis/antithesis dyad. Kant concretises his ideas into:

• Thesis: "The world has a beginning in time, and is limited with regard to space."
• Antithesis: "The world has no beginning and no limits in space, but is infinite, in respect to both time and space."

Inasmuch as conjectures like these can be said to be resolvable, Fichte's Grundlage der gesamten Wissenschaftslehre ( Foundations of the Science of Knowledge , 1794) resolved Kant's dyad by synthesis, posing the question thus: [ 1 ]

• No synthesis is possible without a preceding antithesis. As little as antithesis without synthesis, or synthesis without antithesis, is possible; just as little possible are both without thesis.

Fichte employed the triadic idea "thesis–antithesis–synthesis" as a formula for the explanation of change. [ 2 ] Fichte was the first to use the trilogy of words together, [ 3 ] in his Grundriss des Eigentümlichen der Wissenschaftslehre, in Rücksicht auf das theoretische Vermögen (1795, Outline of the Distinctive Character of the Wissenschaftslehre with respect to the Theoretical Faculty ): "Die jetzt aufgezeigte Handlung ist thetisch, antithetisch und synthetisch zugleich." ["The action here described is simultaneously thetic, antithetic, and synthetic." [ 4 ] ]

Still according to McFarland, Schelling then, in his Vom Ich als Prinzip der Philosophie (1795), arranged the terms schematically in pyramidal form.

According to Walter Kaufmann (1966), although the triad is often thought to form part of an analysis of historical and philosophical progress called the Hegelian dialectic, the assumption is erroneous: [ 5 ]

Whoever looks for the stereotype of the allegedly Hegelian dialectic in Hegel's Phenomenology will not find it. What one does find on looking at the table of contents is a very decided preference for triadic arrangements. ... But these many triads are not presented or deduced by Hegel as so many theses, antitheses, and syntheses. It is not by means of any dialectic of that sort that his thought moves up the ladder to absolute knowledge.

Gustav E. Mueller (1958) concurs that Hegel was not a proponent of thesis, antithesis, and synthesis, and clarifies what the concept of dialectic might have meant in Hegel's thought. [ 6 ]

"Dialectic" does not for Hegel mean "thesis, antithesis, and synthesis." Dialectic means that any "ism" – which has a polar opposite, or is a special viewpoint leaving "the rest" to itself – must be criticized by the logic of philosophical thought, whose problem is reality as such, the "World-itself".

According to Mueller, the attribution of this tripartite dialectic to Hegel is the result of "inept reading" and simplistic translations which do not take into account the genesis of Hegel's terms:

Hegel's greatness is as indisputable as his obscurity. The matter is due to his peculiar terminology and style; they are undoubtedly involved and complicated, and seem excessively abstract. These linguistic troubles, in turn, have given rise to legends which are like perverse and magic spectacles – once you wear them, the text simply vanishes. Theodor Haering's monumental and standard work has for the first time cleared up the linguistic problem. By carefully analyzing every sentence from his early writings, which were published only in this century, he has shown how Hegel's terminology evolved – though it was complete when he began to publish. Hegel's contemporaries were immediately baffled, because what was clear to him was not clear to his readers, who were not initiated into the genesis of his terms. An example of how a legend can grow on inept reading is this: Translate "Begriff" by "concept," "Vernunft" by "reason" and "Wissenschaft" by "science" – and they are all good dictionary translations – and you have transformed the great critic of rationalism and irrationalism into a ridiculous champion of an absurd pan-logistic rationalism and scientism. The most vexing and devastating Hegel legend is that everything is thought in "thesis, antithesis, and synthesis." [ 7 ]

Karl Marx (1818–1883) and Friedrich Engels (1820–1895) adopted and extended the triad, especially in Marx's The Poverty of Philosophy (1847). Here, in Chapter 2, Marx is obsessed by the word "thesis"; [ 8 ] it forms an important part of the basis for the Marxist theory of history. [ 9 ]

2. Writing Pedagogy

In modern times, the dialectic of thesis, antithesis, and synthesis has been implemented across the world as a strategy for organizing expositional writing. For example, this technique is taught as a basic organizing principle in French schools: [ 10 ]

The French learn to value and practice eloquence from a young age. Almost from day one, students are taught to produce plans for their compositions, and are graded on them. The structures change with fashions. Youngsters were once taught to express a progression of ideas. Now they follow a dialectic model of thesis-antithesis-synthesis. If you listen carefully to the French arguing about any topic they all follow this model closely: they present an idea, explain possible objections to it, and then sum up their conclusions. ... This analytical mode of reasoning is integrated into the entire school corpus.

Thesis, Antithesis, and Synthesis has also been used as a basic scheme to organize writing in the English language. For example, the website WikiPreMed.com advocates the use of this scheme in writing timed essays for the MCAT standardized test: [ 11 ]

For the purposes of writing MCAT essays, the dialectic describes the progression of ideas in a critical thought process that is the force driving your argument. A good dialectical progression propels your arguments in a way that is satisfying to the reader. The thesis is an intellectual proposition. The antithesis is a critical perspective on the thesis. The synthesis solves the conflict between the thesis and antithesis by reconciling their common truths, and forming a new proposition.

• Samuel Taylor Coleridge: Opus Maximum. Princeton University Press, 2002, p. 89.
• Harry Ritter, Dictionary of Concepts in History. Greenwood Publishing Group (1986), p.114
• Williams, Robert R. (1992). Recognition: Fichte and Hegel on the Other. SUNY Press. p. 46, note 37. 
• Fichte, Johann Gottlieb; Breazeale, Daniel (1993). Fichte: Early Philosophical Writings. Cornell University Press. p. 249. 
• Walter Kaufmann (1966). "§ 37". Hegel: A Reinterpretation. Anchor Books. ISBN 978-0-268-01068-3. OCLC 3168016. https://archive.org/details/hegelreinterpret00kauf. 
• Mueller, Gustav (1958). "The Hegel Legend of "Thesis-Antithesis-Synthesis"". Journal of the History of Ideas 19 (4): 411–414. doi:10.2307/2708045.  https://dx.doi.org/10.2307%2F2708045
• Mueller 1958, p. 411.
• marxists.org: Chapter 2 of "The Poverty of Philosophy", by Karl Marx https://www.marxists.org/archive/marx/works/1847/poverty-philosophy/ch02.htm
• Shrimp, Kaleb (2009). "The Validity of Karl Marx's Theory of Historical Materialism". Major Themes in Economics 11 (1): 35–56. https://scholarworks.uni.edu/mtie/vol11/iss1/5/. Retrieved 13 September 2018. 
• Nadeau, Jean-Benoit; Barlow, Julie (2003). Sixty Million Frenchmen Can't Be Wrong: Why We Love France But Not The French. Sourcebooks, Inc.. p. 62. https://archive.org/details/sixtymillionfren00nade_041. 
• "The MCAT writing assignment.". Wisebridge Learning Systems, LLC. http://www.wikipremed.com/mcat_essay.php. Retrieved 1 November 2015. 

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• Five tips for developing useful literature summary tables for writing review articles
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• http://orcid.org/0000-0003-0157-5319 Ahtisham Younas 1 , 2 ,
• http://orcid.org/0000-0002-7839-8130 Parveen Ali 3 , 4
• 1 Memorial University of Newfoundland , St John's , Newfoundland , Canada
• 2 Swat College of Nursing , Pakistan
• 3 School of Nursing and Midwifery , University of Sheffield , Sheffield , South Yorkshire , UK
• 4 Sheffield University Interpersonal Violence Research Group , Sheffield University , Sheffield , UK
• Correspondence to Ahtisham Younas, Memorial University of Newfoundland, St John's, NL A1C 5C4, Canada; ay6133{at}mun.ca

https://doi.org/10.1136/ebnurs-2021-103417

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Introduction

Literature reviews offer a critical synthesis of empirical and theoretical literature to assess the strength of evidence, develop guidelines for practice and policymaking, and identify areas for future research. 1 It is often essential and usually the first task in any research endeavour, particularly in masters or doctoral level education. For effective data extraction and rigorous synthesis in reviews, the use of literature summary tables is of utmost importance. A literature summary table provides a synopsis of an included article. It succinctly presents its purpose, methods, findings and other relevant information pertinent to the review. The aim of developing these literature summary tables is to provide the reader with the information at one glance. Since there are multiple types of reviews (eg, systematic, integrative, scoping, critical and mixed methods) with distinct purposes and techniques, 2 there could be various approaches for developing literature summary tables making it a complex task specialty for the novice researchers or reviewers. Here, we offer five tips for authors of the review articles, relevant to all types of reviews, for creating useful and relevant literature summary tables. We also provide examples from our published reviews to illustrate how useful literature summary tables can be developed and what sort of information should be provided.

Tip 1: provide detailed information about frameworks and methods

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Tabular literature summaries from a scoping review. Source: Rasheed et al . 3

The provision of information about conceptual and theoretical frameworks and methods is useful for several reasons. First, in quantitative (reviews synthesising the results of quantitative studies) and mixed reviews (reviews synthesising the results of both qualitative and quantitative studies to address a mixed review question), it allows the readers to assess the congruence of the core findings and methods with the adapted framework and tested assumptions. In qualitative reviews (reviews synthesising results of qualitative studies), this information is beneficial for readers to recognise the underlying philosophical and paradigmatic stance of the authors of the included articles. For example, imagine the authors of an article, included in a review, used phenomenological inquiry for their research. In that case, the review authors and the readers of the review need to know what kind of (transcendental or hermeneutic) philosophical stance guided the inquiry. Review authors should, therefore, include the philosophical stance in their literature summary for the particular article. Second, information about frameworks and methods enables review authors and readers to judge the quality of the research, which allows for discerning the strengths and limitations of the article. For example, if authors of an included article intended to develop a new scale and test its psychometric properties. To achieve this aim, they used a convenience sample of 150 participants and performed exploratory (EFA) and confirmatory factor analysis (CFA) on the same sample. Such an approach would indicate a flawed methodology because EFA and CFA should not be conducted on the same sample. The review authors must include this information in their summary table. Omitting this information from a summary could lead to the inclusion of a flawed article in the review, thereby jeopardising the review’s rigour.

Tip 2: include strengths and limitations for each article

Critical appraisal of individual articles included in a review is crucial for increasing the rigour of the review. Despite using various templates for critical appraisal, authors often do not provide detailed information about each reviewed article’s strengths and limitations. Merely noting the quality score based on standardised critical appraisal templates is not adequate because the readers should be able to identify the reasons for assigning a weak or moderate rating. Many recent critical appraisal checklists (eg, Mixed Methods Appraisal Tool) discourage review authors from assigning a quality score and recommend noting the main strengths and limitations of included studies. It is also vital that methodological and conceptual limitations and strengths of the articles included in the review are provided because not all review articles include empirical research papers. Rather some review synthesises the theoretical aspects of articles. Providing information about conceptual limitations is also important for readers to judge the quality of foundations of the research. For example, if you included a mixed-methods study in the review, reporting the methodological and conceptual limitations about ‘integration’ is critical for evaluating the study’s strength. Suppose the authors only collected qualitative and quantitative data and did not state the intent and timing of integration. In that case, the strength of the study is weak. Integration only occurred at the levels of data collection. However, integration may not have occurred at the analysis, interpretation and reporting levels.

Tip 3: write conceptual contribution of each reviewed article

While reading and evaluating review papers, we have observed that many review authors only provide core results of the article included in a review and do not explain the conceptual contribution offered by the included article. We refer to conceptual contribution as a description of how the article’s key results contribute towards the development of potential codes, themes or subthemes, or emerging patterns that are reported as the review findings. For example, the authors of a review article noted that one of the research articles included in their review demonstrated the usefulness of case studies and reflective logs as strategies for fostering compassion in nursing students. The conceptual contribution of this research article could be that experiential learning is one way to teach compassion to nursing students, as supported by case studies and reflective logs. This conceptual contribution of the article should be mentioned in the literature summary table. Delineating each reviewed article’s conceptual contribution is particularly beneficial in qualitative reviews, mixed-methods reviews, and critical reviews that often focus on developing models and describing or explaining various phenomena. Figure 2 offers an example of a literature summary table. 4

Tabular literature summaries from a critical review. Source: Younas and Maddigan. 4

Tip 4: compose potential themes from each article during summary writing

While developing literature summary tables, many authors use themes or subthemes reported in the given articles as the key results of their own review. Such an approach prevents the review authors from understanding the article’s conceptual contribution, developing rigorous synthesis and drawing reasonable interpretations of results from an individual article. Ultimately, it affects the generation of novel review findings. For example, one of the articles about women’s healthcare-seeking behaviours in developing countries reported a theme ‘social-cultural determinants of health as precursors of delays’. Instead of using this theme as one of the review findings, the reviewers should read and interpret beyond the given description in an article, compare and contrast themes, findings from one article with findings and themes from another article to find similarities and differences and to understand and explain bigger picture for their readers. Therefore, while developing literature summary tables, think twice before using the predeveloped themes. Including your themes in the summary tables (see figure 1 ) demonstrates to the readers that a robust method of data extraction and synthesis has been followed.

Tip 5: create your personalised template for literature summaries

Often templates are available for data extraction and development of literature summary tables. The available templates may be in the form of a table, chart or a structured framework that extracts some essential information about every article. The commonly used information may include authors, purpose, methods, key results and quality scores. While extracting all relevant information is important, such templates should be tailored to meet the needs of the individuals’ review. For example, for a review about the effectiveness of healthcare interventions, a literature summary table must include information about the intervention, its type, content timing, duration, setting, effectiveness, negative consequences, and receivers and implementers’ experiences of its usage. Similarly, literature summary tables for articles included in a meta-synthesis must include information about the participants’ characteristics, research context and conceptual contribution of each reviewed article so as to help the reader make an informed decision about the usefulness or lack of usefulness of the individual article in the review and the whole review.

In conclusion, narrative or systematic reviews are almost always conducted as a part of any educational project (thesis or dissertation) or academic or clinical research. Literature reviews are the foundation of research on a given topic. Robust and high-quality reviews play an instrumental role in guiding research, practice and policymaking. However, the quality of reviews is also contingent on rigorous data extraction and synthesis, which require developing literature summaries. We have outlined five tips that could enhance the quality of the data extraction and synthesis process by developing useful literature summaries.

• Aromataris E ,
• Rasheed SP ,

Twitter @Ahtisham04, @parveenazamali

Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

Competing interests None declared.

Patient consent for publication Not required.

Provenance and peer review Not commissioned; externally peer reviewed.

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Synthesis and clinical application of new drugs approved by FDA in 2022

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• Jing-Yi Zhang 1 ,
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• Sai-Qi Wang 3 &
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The pharmaceutical industry had a glorious year in 2022, with a total of 37 new drugs including 20 new chemical entities (NCEs) and 17 new biological entities (NBEs) approved by the Food and Drug Administration (FDA). These drugs are mainly concentrated in oncology, central nervous system, antiinfection, hematology, cardiomyopathy, dermatology, digestive system, ophthalmology, MRI enhancer and other therapeutic fields. Of the 37 drugs, 25 (68%) were approved through an expedited review pathway, and 19 (51%) were approved to treat rare diseases. These newly listed drugs have unique structures and new mechanisms of action, which can serve as lead compounds for designing new drugs with similar biological targets and enhancing therapeutic efficacy. This review aims to outline the clinical applications and synthetic methods of 19 NCEs newly approved by the FDA in 2022, but excludes contrast agent (Xenon Xe-129). We believe that an in-depth understanding of the synthetic methods of drug molecules will provide innovative and practical inspiration for the development of new, more effective, and practical synthetic techniques. According to the therapeutic areas of these 2022 FDA-approved drugs, we have classified these 19 NCEs into seven categories and will introduce them in the order of their approval for marketing.

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Introduction

The pharmaceutical industry is constantly evolving, with new drugs being developed and approved by the FDA every year. These new drugs offer hope for patients suffering from various diseases and conditions, and they represent a significant advancement in medical science. In 2022, the FDA approved 37 new drugs that have the potential to revolutionize the treatment of various diseases. Of the 37 new drugs, 20 (54%) new drugs belong to new chemical entity (NCE), and 17 (46%) new drugs belong to new biological entity (NBE) [ 1 ]. As shown in Table S 1 , we summarized the drug names, research & development companies, active ingredients, approval dates, indications, and other information of the 37 new drugs [ 2 ]. By analyzing the approved drugs and their indications [ 3 ], it can be found that the main therapeutic field is still oncology, and 10 new oncologic drugs were approved (accounting for 27% of all approved drugs). Seven drugs were approved in the field of the central nervous system (accounting for 19% of the total), five drugs were approved in the field of dermatology (14%), four drugs were approved in the field of anti-infective (accounting for 11% of the total), and three drugs were approved in the fields of hematology (accounting for 8% of the total). Two drugs (5%) were approved in ophthalmology and metabolism respectively, and one drug (3% of the total) was approved in the digestive system and cardiomyopathy respectively. Of these 37 new drugs, up to 25 (68%), new drugs were reviewed and approved through the FDA Center for Drug Evaluation and Research (CDER) accelerated approval process. These accelerated approvals are divided into the following categories: fast track, accelerated approval, priority review, and breakthrough therapy. Among them, 18 new drugs received priority review, 9 new drugs obtained fast track, 4 new Drugs received accelerated approval and 13 new drugs obtained breakthrough therapy, including 6 NCEs and 7 NBEs. It is worth noting that 19 (51%) new drugs were approved to treat rare diseases: For example, Enjaymo is used for the treatment of cold agglutinin disease (CAD), a rare, chronic, serious, autoimmune hemolytic anemia disease [ 4 , 5 ]; Myelofibrosis (MF) is an uncommon condition characterized by abnormalities in the production of blood cells and the presence of fibrosis in the bone marrow [ 6 ], and Vonjo received approval to treat primary and secondary MF in adult patients who have experienced a substantial decrease in their platelet levels [ 7 ]; Amvuttra was approved by FDA to treat polyneuropathy of hereditary transthyretin-mediated amyloidosis (ATTR), a genetic condition resulting from mutations in the TTR gene [ 8 , 9 ]. Compared with the 50 drugs approved by the FDA in 2021 (36 NCEs and 14 NBEs), although the number of drugs approved in 2022 is relatively small, there are still some remarkable achievements. For example, Tirzepatide is the first-in-class glucose-lowering drug approved in recent years with a new mechanism of action. In addition to type 2 diabetes, it has shown good potential for treating obesity. The HIV-1 capsid inhibitor lenacapavir can be taken once every six months. Deucravacitinib, a tyrosine kinase 2 inhibitor used to treat psoriasis, the dual-specificity antibody faricimab-svoa for the treatment of macular degeneration, and the antibody–drug conjugate mirvetuximab soravtansine-gynx targeting folate receptor alpha to treat platinum-resistant ovarian cancer have shown good market value.

As far as we know, the study of the synthetic methods of new chemical molecules and their mechanisms of action in clinical applications will greatly promote the development of new drugs, and the summary of newly introduced drugs will provide innovative and practical inspiration for new drug discovery [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ]. Therefore, the purpose of this review is to provide an overview of 19 NCEs approved by the FDA in 2022 (Fig.  1 ), with a focus on the synthesis of these drugs, their mechanism of action, and their potential benefits and risks. The logical sequence of this review will be to first provide an overview of the new drugs approved by the FDA in 2022 (Table S 1 ), followed by a detailed analysis of the 19 NCEs. Finally, the review will conclude with a summary of the key findings and their implications for healthcare professionals. The review will be of great value to physicians, pharmacists, and other healthcare professionals who are involved in the treatment of patients with the diseases and conditions targeted by these drugs.

Chemical structures of FDA-approved drugs in 2022

Anti-infective drugs

Oteseconazole (vivjoa).

Oteseconazole, developed by Mycovia, was given priority review and approved by the FDA on April 26, 2022, which was sold under the brand name Vivjoa, to prevent recurrent vulvovaginal candidiasis (RVVC) in women with no reproductive potential [ 21 , 22 ]. As an orally active anti-fungal agent, oteseconazole is a highly potent and selective inhibitor of Candida albicans CYP51 with a Ki value of below 39 nM, showing no significant effect on human CYP51 [ 23 , 24 , 25 ]. Thanks to the tetrazole moiety, oteseconazole features high selectivity for fungal CYP51 over human P450s, effectively decreasing off-target interactions, which is obviously distinct from previously discovered azole antifungals [ 26 ]. Compared with oteseconazole, triazole or imidazole-containing fluconazole or ketoconazole causes significant drug-drug interactions due to their effect on human CYPs [ 27 , 28 , 29 ]. By targeting CYP5, oteseconazole blocks the transformation of lanosterol to ergosterol, a sterol necessary for the formation and maintenance of fungal cell membrane integrity, thus exerting antifungal activity toward RVVC-related microorganisms, including Candida dubliniensis, krusei, lusitaniae, albicans, tropicalis, glabrata and parapsilosis [ 30 ]. Oteseconazole carries a risk of embryo-fetal toxicity and is therefore not permitted for use in women with reproductive potential [ 31 , 32 ].

The synthetic method of oteseconazole was reported by Hoekstra, William J. and co-workers (Fig.  2 ) [ 33 ]. The cross-coupling reaction of ethyl bromodifluoroacetate (OTES-002) and 2, 5-dibromopyridine (OTES-001) in the presence of Cu powder in DMSO gives OTES-003. OTES-003 reacts with l-bromo-2,4-difluorobenzene (OTES-004) in methyl tert -butyl ether (MTBE), affording OTES-005, which is then subjected to epoxidation reaction in the presence of trimethyl sulfoxonium iodide (TMSOI) and potassium tert -butoxide to afford epoxide OTES-006. Subsequent addition reaction affords racemic OTES-007. Compound OTES-007 undergoes chiral resolution with di- p -toluoyl-L-tartaric acid (L-DPTTA) in the mix solvents of isopropanol and acetonitrile, followed by the treatment of trimethylsilyl azide, giving tetrazole OTES-009. Finally, OTES-009 undergoes Suzuki–Miyaura reaction with aryl boronic acid OTES-010 to provide coupling compound oteseconazole.

Synthesis of oteseconazole, vonoprazan and lenacapavir

Vonoprazan, amoxicillin, and clarithromycin (Voquezna)

Vonoprazan was first launched in Japan in February 2015 to treat acid-related diseases and as an adjunct to the eradication of Helicobacter pylori [ 34 , 35 , 36 ]. As a potassium-competitive acid blocker (PCAB), vonoprazan blocks the secretion of gastric acid mediated by H + , K + -ATPase, which can be regarded as an alternative to proton-pump inhibitors to treat acid-associated disorders. CYP2C19 genetic polymorphisms show little effect on PCABs, which is obviously different from proton-pump inhibitors [ 37 ]. In addition, vonoprazan exhibits 350 times more active than lansoprazole, a proton pump inhibitor, which is attributed to its ability to accumulation in the gastric corpus mucosa, especially in parietal cells [ 38 ]. In May 2022, Vonoprazan, in combination with clarithromycin and amoxicillin was approved to treat Helicobacter pylori infection [ 39 ]. These approvals are based on the safety and effectiveness data of phalcon-hp phase 3 trial, which is the largest registered trial ever conducted in the United States in Helicobacter pylori , and 1046 patients were randomly assigned [ 40 ]. In the improved intention to treat population, the two vonoprazan treatment regimens showed no worse than lansoprazole triple therapy in patients without clarithromycin or amoxicillin resistant Helicobacter pylori strains at baseline [ 41 ]. The combination of amoxicillin, vonoprazan and clarithromycin has been reported to result in an eradication rate of Helicobacter pylori of about 90% [ 42 , 43 ].

Among the synthetic methods of vonoprazan [ 44 , 45 , 46 ], a relatively simple method starting from pyridine-3-sulfonyl chloride (VONO-001) is exhibited in Fig.  2 [ 47 ]. Nucleophilic substitution of VONO-001 with 5-(2-fluorophenyl)-1 H -pyrrole-3-carbonitrile (VONO-002) gives VONO-003, which then undergoes Raney-Ni promoted reduction reaction to give amine VONO-004. The resulting product VONO-004 is treated with paraformaldehyde and NaBH 4 generating the desired vonoprazan.

Lenacapavir (Sunlenca)

Lenacapavir, a first-in-class picomolar inhibitor of HIV-1 capsid protein, is used as a monotherapy, featuring little cross-resistance with clinically used antiretroviral agents and extended pharmacokinetics [ 48 , 49 ]. The European Commission granted the first worldwide approval of Lenacapavir to treat adults with multidrug-resistant HIV infection on 22 August 2022. On December 22, 2022, it also received FDA approval to treat HIV patients [ 50 , 51 ]. Lenacapavir exhibits its anti-HIV-1 activity through blocking the viral replication of HIV-1 virus, which is closely related to many processes of viral lifecycle: uptake, assembly, and release [ 52 ]. The lenacapavir's difluorobenzyl ring and CPSF6/Nup153 share the same binding pocket, with the benzyl groups of F1417 and F321 overlapping [ 53 ]. The crystal structure reveals that six lenacapavir molecules establishes a wide range of interactions with the protein, including cation-π interactions, hydrophobic interactions, and hydrogen bonds, thereby interrupting capsid interactions with CPSF6 and Nup153. In multiple cell lines, in vitro HIV-1 replication inhibition assays show EC 50 values of ~ 12–314 pM. Lenacapavir exhibits different inhibitory effect at low and high concentrations: it blocks viral nuclear entry at 0.5 nM, while inhibits the reverse transcription and DNA synthesis at 5–50 nM [ 54 ].

The process route of lenacapavir is described below in Fig.  2 [ 55 ]. The sequence begins with acetylation of commercial 2,5-dibromopyridine (LENA-001) with DMF. This is followed by the condensation with diphenylmethanamine (LENA-004) to access the imine LENA-005. Next, LENA-005 is reacted with 1-(bromomethyl)-3,5-difluorobenzene (LENA-006) affording LENA-007, which is converted to the amine LENA-008 through N -deprotection. Racemic LENA-008 undergoes chemical resolution upon treatment with ( R )-2-hydroxy-2-phenylacetic acid (LENA-009) to obtain single enantiomer salt LENA-010. Subjection of LENA-010 and 3-methyl-3-(methylsulfonyl)but-1-yne (LENA-011) to Sonogashira coupling conditions generates the alkyne LENA-012, and this is followed by condensation with the carboxylic acid LENA-013 in base to provide the amide LENA-014. Suzuki reaction of LENA-014 with the borate ester LENA-015 produces the coupling compound LENA-016. This salt is then removed crystalline alcohol through NaOH followed by nucleophilic substitution with methanesulfonyl chloride yielding LENA-018 with two methanesulfonyl groups. Sequential removal of one of methanesulfonyl group and acidification produce lenacapavir.

Central nervous system drugs

Daridorexant (quviviq).

Daridorexant, the second orexin receptor antagonist after suvorexant, was approved by the FDA on January 10, 2022, for clinical use to treat adult insomnia patients with difficulties of sleep maintenance and/or sleep onset [ 56 , 57 ]. It was then approved by the European Commission on 3 May 2022, making it the first dual orexin receptor antagonist to be approved for marketing [ 58 ]. Daridorexant potently inhibits orexins by working on OX1R and OX2R (Ki = 0.47 and 0.93 nM, respectively), which are wake-promoting endogenous ligands and neuropeptides [ 59 ]. Daridorexant is found to decrease overactive wakefulness. Daridorexant has been reported to improve daytime functioning and sleep in insomnia patients [ 60 ]. Before the approval of daridorexant, two orexin receptor antagonists have been marketed, including Mercer's suvorexant (approved in 2014) and Eisai's lemborexant (approved in 2019) [ 61 ]. But neither has fared well in the market so far.

The synthesis of daridorexant is outlined in Fig.  3 [ 62 ]. 2-Methyl-L-proline hydrochloride (DARI-001) is treated with di- tert -butyl pyrocarbonate (Boc 2 O) in 1/1 mixture solvents of MeCN and water, giving N -Boc protection product DARI-002. Treatment of DARI-002 with 6-chloro-2,3-diaminotoluene (DARI-003) under condensation reaction conditions furnishes amide DARI-004. Next, intramolecular condensation of DARI-004 under 100 °C provides DARI-005, which then undergoes N -Boc deprotection and condensation with 5-methoxy-2-(2 H -1,2,3-triazol-2-yl)benzoic acid (DARI-007) to provide daridorexant.

Synthesis of daridorexant, ganaxolone, and taurursodiol

Ganaxolone (Ztalmy)

Developed by Marinus, Ganaxolone was granted FDA approval as the inaugural treatment specifically indicated for seizures in cyclin-dependent kinase-like 5 deficiency disorder (CDD) [ 63 , 64 ]. Ganaxolone is one of the metabolites of progesterone from 3β-methylation of allopregnanolone [ 63 ]. Ganaxolone, a new class of neuroactive steroids, is effective positive allosteric modulators of γ-aminobutyric acid type A (GABAA) receptors [ 65 ], which has specific and potent efficacy, like its endogenous counterparts [ 66 ]. Ganaxolone exerts its effect by binding to one specific allosteric binding site of GABAA, which is different from that of benzodiazepine [ 67 ]. It is characterized by analgesic, sedative, anxiolytic, hypnotic, anticonvulsant, and anesthetic properties [ 68 ]. It is important to note that antiepileptic medications may increase the risk of suicidal ideation and suicidal behavior, and caution should be taken when considering treatment with ganaxolone [ 69 , 70 , 71 ].

To this day, several synthetic methods of ganaxolone have been reported [ 72 , 73 , 74 ], one representative approach is depicted in Fig.  3 [ 72 ]. Starting with pregnenolone (GANA-001), reduction of double bond with hydrogen catalyzed by Pd/C affords compound GANA-002. The subsequent oxidation reaction of GANA-002 with NaOCl and NaBr gives diketone GANA-003, followed by epoxidation reaction to provide epoxide GANA-004. Finally, GANA-004 undergoes NaI promoted ring-opening producing ganaxolone.

Sodium phenylbutyrate/taurursodiol (Relyvrio)

Phenylbutyric acid, a fatty acid derivative of butyric acid produced by natural fermentation of colon bacteria, has many cellular and biological effects, such as easing inflammation, which is used to treat neurological or urea cycle disorders and inherited metabolic syndrome [ 75 ]. Sodium phenylbutyrate is a prodrug of phenylacetic acid that quickly metabolizes to its original style [ 76 ]. Then, phenylacetate binds to phenylacetyl-CoA, which is subjected to acetylation to give phenylacetylglutamine, which is ultimately excreted by the kidneys [ 77 ]. In Europe, taurursodiol, a taurine conjugate of ursodeoxycholic acid, is utilized for the prevention and treatment of gallstones due to its antiapoptotic and inhibitory effects on ER stress response [ 78 ]. Furthermore, taurursodiol has been also investigated in neurodegenerative and inflammatory metabolic diseases due to its array of molecular properties, such as anti-apoptotic effects [ 79 , 80 ]. Taurursodiol effectively decreases the body cholesterol content and intake of dietary cholesterol by reducing intestinal absorption of cholesterol [ 81 ]. Relyvrio, an FDA-approved treatment for amyotrophic lateral sclerosis (ALS), is a blend of sodium phenylbutyrate and taurursodiol [ 82 , 83 ]. ALS is so deadly that most patients have a life expectancy of only 3 to 5 years after onset of symptoms, and they typically die from respiratory failure, a progressive atrophy of the muscles used for respiration [ 84 , 85 , 86 , 87 ]. Relyvrio received early FDA approval due to the highly progressive nature and serious threat of ALS. However, Relyvrio prolong patients’ survival by slowing progression but not cure disease [ 88 , 89 ].

The synthesis of taurursodiol was disclosed by Sandhill One, LLC in 2022 (Fig.  3 ) [ 90 ]. Condensations of 3-ketochol-4-enoic acid (TAUR-001) with 2,2-dimethyl-1,3-propanediol (TAUR-002) and MeOH in the presence of p -toluenesulfonic acid (TsOH), giving TAUR-003. Subsequent hydroxylation and oxidation with NHPI ( N -hydroxyphthalimide) and pyridinium dichromate (PDC) form TAUR-004. Next, TAUR-004 is reduced with H 2 , followed by oxidation with pyridinium chlorochromate (PCC) to provide TAUR-005 over two steps. Treatment of compound TAUR-005 with HCOOH provides TAUR-006, in which the carbonyl is deprotected. One of the carbonyls of TAUR-006 then undergoes reduction, and the ester group is hydrolyzed at the same time, giving TAUR-007. After reduction of the other carbonyl, compound TAUR-008 reacts with taurine sodium salt (TAUR-009), giving taurursodiol.

Dermatologic drugs

Abrocitinib (cibinqo).

On December 10, 2021, abrocitinib was initially approved by the European Commission to treat adult patients with atopic dermatitis (AD) [ 91 , 92 ]. On January 14, 2022, abrocitinib received the FDA approval to treat patients with refractory moderate-to-severe AD who have limited or little response to other systemic drugs [ 93 ]. Abrocitinib potently and selectively inhibits JAK1 with an IC 50 value of 29 nM, which is better than that of JAK2 (IC 50  = 803 nM). Abrocitinib exerts anti-inflammatory effects by blocking pro-inflammatory cytokine signaling associated with atopic dermatitis [ 94 ]. It effectively decreases serum markers of atopic dermatitis inflammation in a dose-dependent manner, including interleukin-31 (IL-31), thymus and activation-regulated chemokine (TARC), and high-sensitivity C-reactive protein (hsCRP) [ 95 ]. Mean absolute lymphocyte counts increased during two weeks of treatment and returned to baseline after 9 months of treatment [ 93 , 96 , 97 ]. According to the Phase 3 results, the experimental group showed significant improvement in disease extent, severity, and skin clarity compared to the placebo group, and patients were able to rapidly relieve itching symptoms after two weeks treatment [ 94 ]. It is one of the first oral JAK inhibitors for AD in the United States, and previously received FDA breakthrough treatment and priority review qualifications [ 98 ].

Several synthetic methods of abrocitinib have been reported [ 95 , 99 , 100 , 101 , 102 , 103 ], one representative synthetic route is described in Fig.  4 [ 104 ]. Curtius rearrangement and addition of 3-oxocyclobutane-1-carboxylic acid (ABRO-001) with phenylmethanol (ABRO-002) give ABRO-003 [ 105 ]. Next, treatment of compound ABRO-003 with monomethylamine in acetic acid, which then undergoes NaBH 4 -catalyzed reduction reaction to provide chiral compound ABRO-004. Treatment of ABRO-004 with pyrimidine ABRO-005 in the presence of K 2 CO 3 provides the corresponding substitution product ABRO-006, followed by dechlorination and hydrolysis, giving salt ABRO-007. Finally, treatment of ABRO-007 with propane-1-sulfonyl chloride (ABRO-008) provides nucleophilic substitution product abrocitinib.

Synthesis of abrocitinib, tapinarof and deucravacitinib

Tapinarof (Vtama)

Tapinarof was approved by FDA on May 23, 2022, to treat plaque psoriasis [ 106 , 107 ]. Tapiranof was originally identified as a metabolite (3, 5-dihydroxy-4-isopropyl styrenes) generated by Photorhabdus luminescens, a species of gram-negative bacilli living together with allogenic nematodes [ 108 ]. As a first-in-class agonist of aryl hydrocarbon receptor (AhR), Tapinarof exhibits excellent potency toward AhR (EC 50  = 13 nM), which effectively regulates antioxidant activity and skin barrier protein expression, and inhibits inflammatory cytokines [ 109 ]. Tapinarof directly binds to AhR, thereby activating the AhR pathway. Tapinarof induces AhR nuclear translocation in immortalized keratinocytes (HaCaT) in a dose-dependent manner (EC 50  = 0.16 nM). The anti-inflammatory effect of tapinarof may be due to Nrf2, a downstream effector of AhR, but not all AhR agonists can activate the pathway [ 110 ]. Therefore, the dual AhR/Nrf2 action of tapinarof may be responsible for psoriasis therapy [ 111 ].

The total synthesis of tapinarof is depicted in Fig.  4 [ 112 ]. Methylation of commercially available dimethyl sulfate with 3,5-dihydroxybenzoic acid (TAPI-001), followed by reaction with isopropyl alcohol in the presence of 60% ~ 80% concentrated sulfuric acid, giving TAPI-003. Subsequently reduction of carboxyl forms alcohol TAPI-004. Next, chlorination of TAPI-004 with hydrochloric acid provides TAPI-005, which then undergoes Wittig-Horner condensation to generate compound TAPI-006. TAPI-006 reacts with benzaldehyde in the presence of NaH and THF under nitrogen atmosphere, affording TAPI-007, which is subjected to demethylation catalyzed by pyridine hydrochloride to afford the target compound tapinarof.

Deucravacitinib (Sotyktu)

On September 9, 2022, Deucravacitinib was approved by the FDA to treat moderate-to-severe plaque psoriasis [ 113 ]. Deucravacitinib, a member of the Janus kinase (JAK) family, is a highly potent allosteric inhibitor of tyrosine kinase 2 (TYK2) with an IC 50 value of 1.0 nM [ 114 ]. It stabilizes an inhibitory interaction between catalytic and regulatory domains of the enzyme, which blocks the activation of Signal Transducers and Activators of Transcription (STATs) and TYK2in cell-based assays [ 115 , 116 , 117 ]. The precise mechanism by which inhibiting the TYK2 enzyme leads to effective treatment in patients with moderate-to-severe plaque psoriasis is still not fully understood. However, its mechanism is different from other Janus kinase inhibitors targeting the conserved active domain, thereby exerting its high selectivity toward TYK2 [ 118 ], which is expected to avoid various adverse effects caused by non-selective JAK inhibitors, such as kidney and liver dysfunction, and altered triglyceride and cholesterol level.

Preparation of deucravacitinib is outlined in Fig.  4 [ 119 ]. Chlorodehydration of 4,6-dihydroxypyridazine-3-carboxylate (DEUC-001) with phosphorus oxychloride affords the corresponding dichloride DEUC-002, which undergoes hydrolysis in the presence of lithium bromide and Hunig’s base in aqueous acetonitrile to yield the lithium carboxylate DEUC-003. Nucleophilic aromatic substitution with DEUC-004 takes place at C4 position of DEUC-003, in the presence of zinc acetate, leading to the formation of DEUC-005 as a zinc salt. Subsequent coupling with cyclopropanecarboxamide (DEUC-006) is catalyzed by palladium acetate and a Josiphos ligand to generate compound DEUC-007. Finally, DEUC-007 undergoes an amidation with methan-d 3 -amine hydrochloride in the presence of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC), 1-hydroxybenzotriazole (HOBt) and N -methylimidazole (NMI), affording deucravacitinib.

Hematologic drugs

Mitapivat (pyrukynd).

Mitapivat is the first orally active pyruvate kinase allosteric activator, which was approved by FDA on February 17, 2022, to manage hemolytic anemia in individuals with pyruvate kinase (PK) deficiency [ 120 , 121 , 122 ]. Mitapivat activates PK through allosteric regulation, binding to a distinct allosteric site on the PKR tetramer separate from fructose bisphosphate FBP [ 123 ]. The red blood cell (RBC) form of PK is mutated in PK deficiency, resulting in shortened RBC lifespan, reduced adenosine triphosphate (ATP), and chronic hemolysis [ 124 ]. Mitapivat increases its affinity for its substrate and stabilizes phosphoenolpyruvate by binding to pyruvate kinase [ 120 ]. Mitapivat increases ATP production and erythrocyte pyruvate kinase activity (wild-type and mutant forms) but reduces levels of 2,3-DPG [ 123 ]. Mitapivat has also been investigated in other genetic disorders affecting red blood cells and causing hemolytic anemia, such as α-/β-thalassemia and sickle cell disease [ 123 ].

The preparation of mitapivat developed by Agios is shown in Fig.  5 [ 125 , 126 ]. Starting with ethyl 4-aminobenzoate (MITA-001), a nucleophilic substitution reaction with quinoline-8-sulfonyl chloride (MITA-002), followed by NaOH promoted hydrolysis, giving MITA-004. Finally, the condensation of MITA-004 with 1-(cyclopropylmethyl)piperazine (MITA-005) in the presence of 1,1'-carbonyldiimidazole (CDI) gives the desired mitapivat.

Synthesis of mitapivat and pacritinib

Pacritinib (Vonjo)

On February 28, 2022, the FDA granted accelerated approval to Pacritinib, a highly effective inhibitor of JAK2 and FMS-like tyrosine kinase 3 (FLT3), which was used to treat adult patients with low platelets who suffer from intermediate or high-risk primary or secondary myelofibrosis (MF) [ 127 , 128 ]. Pacritinib potently inhibits wild-type JAK2 (IC 50  = 23 nM), JAK2 V617F (IC 50  = 19 nM), FLT3 (IC 50  = 22 nM), and FLT3 D835Y (IC 50  = 6 nM) [ 129 ], which benefits the signaling of many growth factors and cytokines associated with immune and hematopoiesis function. MF is closely related to dysregulated JAK2 signaling. Pacritinib carries significant selectivity for JAK2 over JAK3 and TYK2, and does not inhibit JAK1 at clinically relevant concentrations [ 130 ].

Pacritinib demonstrates a dose-dependent suppression of signal transducer and activator of transcription 5 (STAT5) phosphorylation in expanded erythroid progenitor cells obtained from healthy individuals [ 131 ]. A single 400 mg dose of pacritinib moderately inhibits STAT3 phosphorylation induced by interleukin 6 in the whole blood of healthy subjects [ 132 , 133 ]. Pacritinib is administered orally twice daily and is contraindicated in patients with renal insufficiency and hepatic insufficiency. It offers an alternative for MF patients with severe thrombocytopenia, commonly carrying a pretty poor prognosis [ 134 ].

Although several synthetic routes to pacritinib have been reported [ 135 , 136 ], an efficient approach has been disclosed in Fig.  5 [ 137 ]. Substitution of 3-(2-chloropyrimidin-4-yl)benzaldehyde (PACR-001) with 5-amino-2-(2-chloroethoxy)benzaldehyde (PACR-002), followed by N -Boc protection of compound PACR-003 with di- tert -butyl pyrocarbonate, generating the key intermediate PACR-004. Further NaBH 4 promoted reduction of PACR-004 furnishes PACR-005. Treatment of PACR-005 with ( E )-1,4-dibromobut-2-ene (PACR-006) in basic solution gives the ring-closing product PACR-007, which undergoes nucleophilic substitution reaction with pyrrolidine (PACR-008) to provide the desired pacritinib.

Oncologic drugs

Lutetium ( 177 lu) vipivotide tetraxetan (pluvicto).

As a radioligand therapeutic agent, lutetium ( 177 Lu) vipivotide tetraxetan consists of a radionuclide, lutetium Lu-177, conjugated to a prostate-specific membrane antigen (PSMA)-binding moiety, exercising cytotoxic effect on cancer cells [ 138 , 139 ]. The β-negative emission of lutetium Lu-177 irradiates PSMA-expressing cells and surrounding cells, thereby inducing DNA damage and cell death. In a clinical trial, it was discovered that Lutetium ( 177 Lu) vipivotide tetraxetan exhibited a significant correlation with an 80.4% decrease in serum PSA levels. Additionally, the median progression-free survival for these patients was determined to be 13.7 months [ 140 ]. Following other therapies, it was granted FDA approval on March 23, 2022, to treat metastatic castration-resistant prostate cancer with prostate-specific membrane antigen positivity [ 141 ]. This approval is based on the positive results of phase 3 clinical trial, which showed that the addition of Pluvicto reduced the risk of patient death by 38% compared to standard therapy and that Pluvicto also significantly reduced the risk of patients developing radiographic disease progression or death [ 142 ]. Furthermore, in patients with evaluable disease at baseline, the overall remission rate was 30% in the Pluvicto group, compared to 2% in the standard treatment control group [ 143 ]. In October 2022, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) issued a recommendation for the authorization of marketing for a therapeutic intervention targeting prostate cancer [ 144 ].

Preparation of lutetium ( 177 Lu) vipivotide tetraxetan is depicted in Fig.  6 [ 145 , 146 ]. Starting from 2-chlotrotrityl chloride (2-CT) resin, installation of LUTE-001 is accomplished in the presence of DCM to furnish LUTE-002. From LUTE-002, condensation with isocyanic acid LUTE-003 provides the intermediate LUTE-004. Treatment of LUTE-004 with Pd[P(C 6 H 5 ) 3 ] 4 and morpholine, followed by condensation with Fmoc-L-2-NaI-OH, forming LUTE-006. Following the same procedure, LUTE-007 is synthesized. Further condensation and radiolabelling with 177 Lu give Lutetium ( 177 Lu) vipivotide tetraxetan.

Synthesis of lutetium ( 177 Lu) vipivotide tetraxetan, futibatinib and olutasidenib

Futibatinib (Lytgobi)

On September 30, 2022, the FDA granted approval to Futibatinib, a permanent inhibitor of Fibroblast Growth Factor receptor (FGFR), for the treatment of intrahepatic cholangiocarcinoma that contains FGFR2 gene fusions or other genetic rearrangements [ 147 ]. Futibatinib effectively inhibits FGFR 1–4 (IC 50  = 3.9, 1.3, 1.6, and 8.3 nM), respectively, by forming a covalent bond with cysteine in the ATP-binding pocket of FGFR kinase domain [ 148 , 149 , 150 ]. In addition, Futibatinib exhibits similar inhibitory potency toward wild-type (WT) and mutant FGFR2 with IC 50 values of 0.9 nM, 1–3 nM, 3.6 nM, and 2.4 nM against WT FGFR2, V5651, N550H, and E566G, respectively [ 148 , 149 , 150 ]. FGFR plays a crucial role in cell differentiation, survival, proliferation, and migration, and aberrant signaling pathways and genomic aberrations commonly occur in a variety of cancers since the survival and proliferation of malignant cells can be supported by FGFR signaling [ 148 , 151 ]. Futibatinib efficiently inhibits the phosphorylation of FGFR and subsequent signaling pathways. This inhibition leads to a decrease in the survival of cancer cells harboring FGFR rearrangements, fusions, mutations, and amplifications in xenograft models derived from mice and rats [ 152 ]. In the end, futibatinib effectively decreases the survival of cancer cells with FGFR alterations, such as FGFR fusions or rearrangements, amplifications, and mutations [ 153 ].

Futibatinib is prepared as described in Fig.  6 [ 154 ]. Sonogashira coupling between FUTI-001 and l-ethynyl-3,5-dimethoxybenzene (FUTI-002) gives compound FUTI-003, followed by the treatment of FUTI-003 with 3-chloropropionyl chloride (FUTI-004), affording the product futibatinib.

Olutasidenib (Rezlidhia)

On December 1, 2022, the FDA granted approval to olutasidenib, a highly effective inhibitor of isocitrate dehydrogenase-1 (IDH1), to treat relapsed or refractory acute myeloid leukemia (AML) in adults who possess a susceptible IDH1 mutation [ 155 , 156 ]. Normally, IDH1 catalyzes mediated the conversion of isocitrate to α-ketoglutarate (α-KG) through oxidative decarboxylation reaction [ 157 ]. However, IDH1 mutations are commonly observed in the catalytic sites of arginine in various cancers, such as AML, and stimulate the transfer of α-KG to 2-hydroxyglutarate (2-HG) [ 158 ]. This leads to 2-HG increase, which is closely related to the inhibition of α-KG-dependent mechanisms, such as collagen synthesis, epigenetic regulation, and cell signaling. Olutasidenib effectively decreases 2-HG levels by selectively targeting mutant IDH1, leading to the restoration of normal cell differentiation and offering therapeutic advantages in IDH1 mutant strains. Additionally, olutasidenib is currently investigated to treat myelodysplastic syndromes (MDS), as well as solid tumors and gliomas (NCT03684811) [ 159 , 160 , 161 ].

The synthetic route of olutasidenib as described in the publication is shown in Fig.  6 [ 162 ]. N -oxidation of commercially available 5-fluoropicolinonitrile (OLUT-001) followed by reflux of the N -oxide (OLUT-002) in acetic anhydride give the acetate OLUT-003. Base-mediated hydrolyzation and tautomerism of OLUT-003, followed by N -methylation with methyl iodide provide N -methylated compound OLUT-005. Finally, the condensation of OLUT-005 with the amine OLUT-006 affords olutasidenib.

Of note, the preparation of the amine OLUT-006 arises from commercially available quinoline aldehyde OLUT-007, which is first condensed with ( R )- tert -butanesulfinamide (OLUT-008) to obtain the chiral ( R )- N - tert -butanesulfinimine (OLUT-009) in 81% yield (Fig.  7 ). Next, an addition reaction of OLUT-009 and methylmagnesium bromide in dichloromethane is employed to yield the intermediate OLUT-010 as the major diastereoisomer (98:2 dr). Removal of the sulfonyl group using hydrochloric acid provides the intermediate OLUT-006 in quantitative yield.

Synthesis of adagrasib, mavacamten and terlipressin

Adagrasib (Krazati)

Adagrasib, an orally bioavailable inhibitor of KRAS, was developed by Mirati. On December 12, 2022, Therapeutics obtained accelerated FDA approval to treat KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer in adults who have undergone at least one prior systemic therapy [ 163 , 164 , 165 ]. Normally, activation of KRAS through binding to guanosine triphosphate (GTP) stimulates the activation of intracellular signal transduction and MAP kinase pathway. Hydrolyzation of GTP gives guanosine diphosphate (GDP) and KRAS restores the inactive state [ 166 ]. Cysteine substitution of Gly12 in KRAS (KRASG12C) damages GTP hydrolysis and keeps KRAS in active form, which results in uncontrolled cell growth and proliferation as well as malignant transformation [ 167 ]. Adagrasib covalently and selectively binds to KRASG12C and locks it in the inactive state, thus exerting anti-tumor activity by inhibiting tumor cell viability and growth [ 168 ].

The synthesis of adagrasib begins by condensing ethyl 1-benzyl-3-oxopiperidine-4-carboxylate (ADAG-001) with urea. This reaction forms ADAG-002, which is a bicyclic diol. ADAG-002 is then chlorinated using POCl 3 to produce pyrimidine (ADAG-003) (Fig.  7 ) [ 169 ]. Next, treatment of intermediate ADAG-003 with sodium methoxide in methanol, followed by Buchwald coupling with ( S )-(1-methylpyrrolidin-2-yl)methanol (ADAG-005), gives compound ADAG-006. N -debenzylation of ADAG-006 in the presence of hydrogen catalyzed by Pd(OH)/C affords the amine ADAG-007, which is treated with 1-bromo-8-chloronaphthalene (ADAG-008) under Buchwald-Hartwig amination conditions to give the N -arylated product ADAG-009. Demethylation and subsequent triflate formation provide ADAG-011, which reacts with ( S )-2-(piperazin-2-yl)acetonitrile (ADAG-012) affording the advanced intermediate ADAG-013. It then undergoes ammonolysis with 2-fluoroacrylic acid using T3P as the coupling reagent to obtain adagrasib [ 170 ].

Other drugs

Mavacamten (camzyos).

Mavacamten was approved by US FDA in 2022, which is used to treat adult patients with obstructive hypertrophic cardiomyopathy (oHCM) who are experiencing symptoms and fall into New York Heart Association (NYHA) class II-III [ 171 , 172 ]. Mavacamten is a medication that can be taken by mouth. It acts as an inhibitor of cardiac myosin, which is a protein involved in muscle contraction in the heart. This medication works by regulating the number of myosin heads that can enter the "on actin" states, effectively reducing the likelihood of generating force during systole (contraction) and residual force during diastole (relaxation) across the bridge. Additionally, its inhibitory effects are reversible, meaning that its action can be reversed if necessary [ 173 ]. HCM is characterized by the presence of excessive formation of myosin actin bridges and dysregulation of the hyperrelaxation state [ 174 ]. Mavacamten transforms the total amount of myosin into an energy-saving, absorbable, ultra-relaxed state [ 175 ]. Inhibition of myosin with Mavacamten reduced dynamic left vein obstruction and improved cardiac filling pressure in patients with HCM. It has been reported that the IC 50 values of Mavacamten in the bovine, human, and rabbit system are 490 nM, 711 nM, and 2140 nM, respectively, indicating a 4-fold selectivity for myocardial myosin [ 176 , 177 , 178 ]. Mavakamten is found to reduce contractility through decreasing the activity of adenosine triphosphatase in the heavy chain of myocardial myosin [ 179 ]. Long-term administration results in the inhibition of the development of myocardial cell disorders, myocardial hypertrophy, and myocardial fibrosis, and attenuates the gene expression of profibrotic and hypertrophic in mice featuring heterozygous human mutations in the chain of myosin heavy [ 176 ].

A convenient synthetic method of mavacamten was disclosed in 2014 (Fig.  7 ) [ 180 ]. Addition of commercially available isopropylamine (MAVA-001) with trimethylsilyl isocyanate (MAVA-002), followed by the annulation reaction with dimethyl malonate in the presence of sodium methoxide and methanol, giving MAVA-003. Subsequently, chlorination forms compound MAVA-005. Finally, the coupling of MAVA-005 with ( S )-α-methylbenzylamine (MAVA-006) in dioxane under 90 °C provides desired mavacamten.

Terlipressin (Terlivaz)

Terlipressin, a medication aimed at enhancing kidney function in adult patients with hepatorenal syndrome experiencing a rapid decline in kidney function, obtained FDA approval on September 14, 2022 [ 181 , 182 ]. Terlipressin, an analog of vasopressin, is an endogenous neurohormone that acts as a vasoconstrictor [ 183 , 184 , 185 , 186 , 187 , 188 ]. As a prodrug of lysine-vasopressin, terlipressin itself is pharmacologically active, characterized by a longer half-life and higher selectivity for V1 receptor than vasopressin, which controls acute variceal bleeding, and reduces the splanchnic blood flow and portal pressure [ 189 ]. These favorable pharmacokinetic and molecular properties of terlipressin confer several advantages, such as convenience in patients with limited intravenous access and prevention of rebound hypotension upon discontinuation [ 188 , 190 ].

Preparation of terlipressin is described in Fig.  7 [ 191 ]. Condensation of thioester TERL-001 and N -terminal cysteine TERL-002 furnishes TERL-003 in the presence of 3-( N -morpholino)propanesulfonic (MOPS) and catalytic guanidine. Subsequent condensation of TERL-003 with Boc-Cys(trt)-OH TERL-004 and N -Boc deprotection furnish TERL-005, further guanidine-catalyzed condensation with TERL-006 gives TERL-007. Oxidation of TERL-007 in MeCN/H 2 O gives terlipressin.

Gadopiclenol (Elucirem)

Gadopiclenol, a gadolinium-based contrast agent (GBCA), was developed by Guerbet. On September 21, 2022, after undergoing a priority review, the FDA granted its approval to the product. Its primary objective is to identify and display abnormal vascularity lesions in the body and the central nervous system, in combination with magnetic resonance imaging (MRI). In 2006, linear GBCA use was linked to nephrogenic systemic fibrosis (NSF) [ 192 , 193 , 194 ], a rare disease characterized by hardening and thickening of the subcutaneous and skin tissue, which has not been detected in macrocyclic GBCAs, such as gadopiclenol [ 195 ]. It should be noted that in NSF patients with impaired drug clearance, a black box warning was given to gadopiclenol to remind an increased risk. Gadopiclenol carries two water molecule exchange sites for increased relaxation and contrast [ 195 ]. Compared with other non-specific GBCAs, gadopiclenol dose is only half of the conventional gadolinium dose, alleviating practitioners' concerns about radiation exposure [ 196 ]. Variations in radiofrequency signal strength allow visualization of normal and pathological tissue during MRI, which is characterized by the differences in longitudinal relaxation times (T1) or spin–lattice, proton density, or in transverse relaxation times or spin–spin (T2). The T1 and T2 relaxation times can be shortened by Gadopiclenol, resulting in the visualization of target tissues during MRI [ 197 ]. The extent of a contrast agent affecting the tissue water relaxation rate (1/T1 or 1/T2) is expressed in terms of the relaxation rate (r1 or r2). The high r1 relaxation rate and kinetic stability of gadopiclenol allow it to be used at lower doses than traditional extracellular GBCAs. What deserves special vigilance is that acute kidney injury and hypersensitivity reactions may also occur with gadopiclenol [ 198 ].

The reported synthesis of gadopiclenol was reported by Marc, in 2007 (Fig.  8 ) [ 199 ]. Treatment of compound GADO-001 with 3-aminopropyl-1,2-diol (GADO-002) in the presence of HOBt and EDC gives gadopiclenol.

Synthesis of gadopiclenol and omidenepag isopropyl

Omidenepag isopropyl (Omlonti)

Omidenepag isopropyl, approved in Japan in 2018 as a potent agonist of EP2 receptor to treat ocular hypertension and glaucoma [ 200 ], was then approved by FDA on September 22, 2022, to lower high intraocular pressure in individuals diagnosed with ocular hypertension or open-angle glaucoma. Omidenepag isopropyl is rapidly metabolized to its active metabolite omidenepag, which binds strongly to prostaglandin E2 (EP2) receptor (Ki = 3.6 nM) [ 201 ]. Furthermore, Omidenepag is highly agonistic at the EP2 receptor (EC 50  = 8.3 nM) but has little effect on other receptors such as prostaglandin E1 (EP1) or F receptors (FP) [ 200 , 202 , 203 ]. Unlike omidenepag, omidenepag isopropyl has little or no affinity for prostaglandin receptors [ 200 , 203 ]. EP2 receptor exists in different kinds of ocular tissues related to aqueous humor dynamics, such as ciliary muscle (CM) and trabecular meshwork (TM) [ 204 ]. Stimulation of EP2 receptors may result in increased intracellular cyclic adenosine monophosphate (cAMP), leading to relaxation of CM and TM tissues [ 205 ]. Omidenepag has shown comparable efficacy in lowering IOP to latanoprost, a prostaglandin FP receptor agonist, which is a first-line treatment for primary ocular hypertension and open-angle glaucoma [ 206 ].

Preparation of omidenepag isopropyl is depicted in Fig.  8 [ 202 ]. Treatment of OMID-001 with 1-(4-(bromomethyl)phenyl)-1 H -pyrazole (OMID-002) provides the corresponding coupling product OMID-003, followed by HCl-promoted hydrolysis and N -Boc deprotection, producing omidenepag. Esterification of omidenepag with isopropyl alcohol in dioxane yields omidenepag isopropyl.

Conclusion and prospect

In conclusion, in 2022, FDA approved 37 new drugs, including 20 NCEs, 7 monoclonal antibodies (mAbs), 3 bispecific antibodies (BsAbs), 2 enzymes, 1 fusion protein, 1 synthetic polypeptide, 1 small interfering RNA (siRNA), 1 toxin, 1contrast agent and a colony stimulating factor (CSF). In the context of the COVID-19 pandemic, FDA is still committed to supporting the development of rare disease drugs. The field of anti-tumor is still a hot area for innovative drug development. These approved new drugs will benefit patients suffering from orphans, cancer, nervous system diseases, infectious diseases, and many other diseases.

In this review, we summarized the clinic application and synthetic routes of the 19 NCEs of new drugs approved by the FDA. The pharmacophore library will be enriched and new drug discovery will be benefited by the presence of privileged scaffolds in these drug molecules. For example, me-better drug omidenepag isopropyl is developed based on the molecular structure of CP-533,536, which was reported by previous researchers and optimized through the structural modification of PGE2 [ 202 ]. The AIDS prevention drug lenacapavir is developed based on the structure of PF-3450074. In order to block the unstable metabolic site, researchers focused on introducing electron-withdrawing groups (halogens and sulfonyl groups) and metabolically stable rigid ring systems (cyclopropane and pyrazole) through optimization [ 207 ]. Both deucravacitinib and olutasidenib were first screened through high-throughput screening to obtain lead compounds, and their solubility was improved through SBDD. Adagrasib has increased its in vitro stability in whole blood (WB) by introducing a fluorine atom at the 2-position of acrylamide [ 208 ].

In addition, we discovered that metal-catalyzed coupling reactions were utilized in the synthesis of pharmaceuticals (such as omidenepag, futibatinib, oteseconazole, etc.). Chiral resolution and asymmetric synthesis were employed for obtaining the single enantiomer of the chiral drugs (such as taurursodiol, ganaxolone, and oteseconazole, etc.). Other traditional organic synthetic strategies, such as substitution reaction, hydrolysis reaction, Curtius rearrangement, and addition reaction were still used for the synthesis of these new drug molecules approved by the FDA. The special skeletons in the drug molecules enrich the effective pharmacophores, which will help to design new drugs.

Availability of data and materials

Not applicable.

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Acknowledgements

We extend our sincere appreciation for the generous financial support received from the National Natural Science Foundation of China (No. 82103560).

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College of Chemistry and Chemical Engineering, Zhengzhou Normal University, Zhengzhou, 450044, China

Jing-Yi Zhang

First People’s Hospital of Shangqiu, Henan Province, Shangqiu, 476100, China

Ya-Tao Wang

Henan Engineering Research Center of Precision Therapy of Gastrointestinal Cancer, Zhengzhou Key Laboratory for Precision Therapy of Gastrointestinal Cancer, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China

Ya-Tao Wang, Lu Sun & Sai-Qi Wang

Zhongshan Hospital Affiliated to Dalian University, Dalian, 116001, China

College of Pharmacy and Health Sciences, St. John’s University, Queens, NY, 11439, USA

Zhe-Sheng Chen

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The conceptualization of the project was initiated by Zhe-Sheng Chen, Jing-Yi Zhang, and Sai-Qi Wang, who also assumed the responsibility of curating and categorizing relevant scholarly resources. Furthermore, Jing-Yi Zhang, Ya-Tao Wang and Lu Sun made significant contributions to the generation of graphical illustrations and actively collaborated in the construction of an all-encompassing tabular framework. All authors have read and approved the final manuscript.

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Zhang, JY., Wang, YT., Sun, L. et al. Synthesis and clinical application of new drugs approved by FDA in 2022. Mol Biomed 4 , 26 (2023). https://doi.org/10.1186/s43556-023-00138-y

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Received : 11 March 2023

Accepted : 24 July 2023

Published : 04 September 2023

DOI : https://doi.org/10.1186/s43556-023-00138-y

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