A Comprehensive Overview of Retrosynthetic Analysis

Xikai Zhu

doi:10.54254/2755-2721/2025.29787

Applied and Computational EngineeringOpen access

A Comprehensive Overview of Retrosynthetic Analysis

Research Article

Open Access

A Comprehensive Overview of Retrosynthetic Analysis

Xikai Zhu ^1*

¹ Pioneer Academy

^*Corresponding author: zhuxikai1212@gmail.com

Published on 19 November 2025

ACE Vol.208

ISSN (Print): 2755-273X

ISSN (Online): 2755-2721

ISBN (Print): 978-1-80590-547-9

ISBN (Online): 978-1-80590-548-6

Download Cover

Abstract

Retrosynthetic analysis is a sea change in methodical design of synthesis routes to complex molecules in organic chemistry. The brainchild of Nobel laureate Elias James Corey, this approach-in essence-inverts the convention in synthesis by working one's way backward from the target molecule to simpler, more accessible precursors. Basic concepts like the process of disconnections and synthons, functional group interconversions are basic concepts that form a basis of deconstruction of molecules into manageable pieces. Retrosynthetic analysis has found wide applications in pharmaceuticals, natural product synthesis, and materials chemistry, offering ways of effective solutioning in the manufacturing of active pharmaceutical ingredients, biologically active compounds, and advanced materials. Although some problems concerning molecule complexity and scalability of reactions do arise, this method remains irreplaceable in the process of driving innovation in chemical synthesis. Further evolution of retrosynthesis with state-of-the-art computational tools along with sustainable practices will continue to advance the field of organic chemistry. This article contextualizes retrosynthetic analysis in depth: describing its principles, application, challenges, and prospects of implementation by academic and industrial circles.

Keywords:

Disconnections, Synthons and Synthetic Equivalents, Functional Group Interconversion (FGI), Functional Group Addition, Protecting Groups, Strategic Bond Disconnections

View PDF

References

[1]. Corey, E.J., & Cheng, X.-M. (1989). The Logic of Chemical Synthesis. Wiley. https: //scholar.google.com/scholar?q=Corey, +E.J., +%26+Cheng, +X.-M.+(1989).+The+Logic+of+Chemical+Synthesis.+Wiley.& hl=zh-CN& as_sdt=0& as_vis=1& oi=scholart

[2]. Nicolaou, K.C., & Sorensen, E.J. (1996). Classics in Total Synthesis. VCH. https: //scholar.google.com/scholar?q=Nicolaou, +K.C., +%26+Sorensen, +E.J.+(1996).+Classics+in+Total+Synthesis.+VCH.& hl=zh-CN& as_sdt=0& as_vis=1& oi=scholart

[3]. Warren, S. (1978). Organic Synthesis: The Disconnection Approach. Wiley. https: //scholar.google.com/scholar?q=Warren, +S.+(1978).+Organic+Synthesis: +The+Disconnection+Approach.+Wiley.& hl=zh-CN& as_sdt=0& as_vis=1& oi=scholart

[4]. Smith, M. B. (2011). March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure. Wiley. https: //scholar.google.com/scholar?q=Smith, +M.+B.+(2011).+March%27s+Advanced+Organic+Chemistry: +Reactions, +Mechanisms, +and+Structure.+Wiley.& hl=zh-CN& as_sdt=0& as_vis=1& oi=scholart

[5]. Coley, C.W., Green, W.H., & Jensen, K.F. (2018). Machine Learning in Computer-Aided Synthesis Planning. Accounts of Chemical Research, 51(5), 1281-1289.https: //scholar.google.com/scholar?q=Coley, +C.W., +Green, +W.H., +%26+Jensen, +K.F.+(2018).+Machine+Learning+in+Computer-Aided+Synthesis& hl=zh-CN& as_sdt=0& as_vis=1& oi=scholart

References

Cite this article

Zhu,X. (2025). A Comprehensive Overview of Retrosynthetic Analysis. Applied and Computational Engineering,208,80-85.

Data availability

The datasets used and/or analyzed during the current study will be available from the authors upon reasonable request.

About volume

Volume title: Proceedings of the 5th International Conference on Materials Chemistry and Environmental Engineering

ISBN: 978-1-80590-547-9(Print) / 978-1-80590-548-6(Online)

Editor: Ömer Burak İSTANBULLU

Conference website: https://2025.confmcee.org/

Conference date: 12 January 2026

Series: Applied and Computational Engineering

Volume number: Vol.208

ISSN: 2755-2721(Print) / 2755-273X(Online)

© 2024 by the author(s). Licensee EWA Publishing, Oxford, UK. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. Authors who publish this series agree to the following terms:

1. Authors retain copyright and grant the series right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this series.

2. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the series's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this series.

3. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See Open access policy for details).