Efficient Stereoselective Synthesis of Vepdegestrant (ARV‐471) via Ruthenium‐Catalyzed Asymmetric Hydrogenation

Vepdegestrant (ARV‐471) is a novel estrogen receptor (ER) degrader currently under clinical evaluation for the treatment of ER‐positive and HER2‐negative breast cancer. We have developed an efficient catalytic stereoselective synthetic route to produce this important compound. The key step involves...

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Bibliographic Details
Published in:ChemistrySelect (Weinheim) 2025-01, Vol.10 (4), p.n/a
Main Authors: Neerasa, Jayaprakash, Kim, Bongsu, Chung, Hunsuk
Format: Article
Language:English
Subjects:
Diastereoselectivity
PROTAC
Ruthenium‐catalyzed asymmetric hydrogenation
Vepdegestrant
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Summary:Vepdegestrant (ARV‐471) is a novel estrogen receptor (ER) degrader currently under clinical evaluation for the treatment of ER‐positive and HER2‐negative breast cancer. We have developed an efficient catalytic stereoselective synthetic route to produce this important compound. The key step involves a Ruthenium‐catalyzed asymmetric hydrogenation, which establishes the critical stereocenter with exceptional diastereoselectivity(>99% de). This method obviates the need for chiral chromatographic separation, thereby significantly improving the efficiency and scalability of the synthetic sequence compared to previously reported approaches. A highly efficient stereoselective synthesis of Vepdegestrant (ARV‐471), a PROTAC‐based ER degrader in Phase 3 trials for ER+/HER2‐ breast cancer, is achieved through Ruthenium‐catalyzed asymmetric hydrogenation. This catalytic approach delivers exceptional diastereoselectivity (>99% de) while eliminating chromatographic separation, enabling scalable production, and addressing previous manufacturing challenges.
ISSN:2365-6549
2365-6549
DOI:10.1002/slct.202405939