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Synthesis
DOI: 10.1055/a-2603-0471
review

Stereoselectivity Seems To Be the Hardest Word: Tracking the Evolution of Asymmetric API Syntheses from Medicinal Chemistry to Process Development

José María Álvarez-Calero
,
Matthew A. Horwitz∗
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Abstract

While medicinal chemistry campaigns are frequently carried out using non-stereoselective syntheses, the goal of most small molecule drug discovery programs involving chiral drug substances is to nominate and subsequently develop a single, unichiral entity. One of the consequences of this is that fit-for-purpose solutions like chiral SFC and HPLC, which are routinely employed during the discovery phase, must be replaced with more efficient approaches to obtaining the stereoisomer of interest as the program enters development. In this review, we examine twenty case studies from the last two decades of R&D in the pharmaceutical industry where non-stereoselective routes identified during medicinal chemistry campaigns were revised and new solutions for the stereoselective API candidate syntheses were identified during process development.

1 Introduction

2 Case Studies

3 Conclusion and Outlook

Key words

drug discovery - discovery chemistry - process development - route scouting - asymmetric synthesis


Publikationsverlauf

Eingereicht: 14. März 2025

Angenommen nach Revision: 08. Mai 2025

Accepted Manuscript online:
08. Mai 2025

Artikel online veröffentlicht:
11. Juni 2025

© 2025. Thieme. All rights reserved

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

 

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