Late-Stage Diversification: A Motivating Force in Organic Synthesis

• Published in: Journal of the American Chemical Society Vol. 143; no. 41; pp. 16890 - 16901
• Main Authors: Kim, Kelly E, Kim, Alexia N, McCormick, Carter J, Stoltz, Brian M
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 20.10.2021
• Subjects: Biological Products
• ISSN: 0002-7863; 1520-5126; 1520-5126
• DOI: 10.1021/jacs.1c08920

Interest in therapeutic discovery typically drives the preparation of natural product analogs, but these undertakings contribute significant advances for synthetic chemistry as well. The need for a highly efficient and scalable synthetic route to a complex molecular scaffold for diversification frequently inspires new methodological development or unique application of existing methods on structurally intricate systems. Additionally, synthetic planning with an aim toward late-stage diversification can provide access to otherwise unavailable compounds or facilitate preparation of complex molecules with diverse patterns of substitution around a shared carbon framework. For these reasons among others, programs dedicated to the diversification of natural product frameworks and other complex molecular scaffolds have been increasing in popularity, a trend likely to continue given their fruitfulness and breadth of impact. In this Perspective, we discuss our experience using late-stage diversification as a guiding principle for the synthesis of natural product analogs and reflect on the impact such efforts have on the future of complex molecule synthesis.