Feasible Column Chromatography-Free, Multi-Gram Scale Synthetic Process of VH032 Amine, Which Could Enable Rapid PROTAC Library Construction

PROTACs represent a promising modality that has gained significant attention for the treatment of cancer, Alzheimer’s disease, and so forth. Due to limited structural information of the POI-PROTAC-E3 ligase ternary complex, the discovery of active PROTACs relies on the screening of diversity-oriente...

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Bibliographic Details
Published in:ACS omega 2022-08, Vol.7 (30), p.26015-26021
Main Authors: Yan, Wei, Pan, Bo-Syong, Shao, Jingwei, Lin, Hui-kuan, Li, Hong-yu
Format: Article
Language:English
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Summary:PROTACs represent a promising modality that has gained significant attention for the treatment of cancer, Alzheimer’s disease, and so forth. Due to limited structural information of the POI-PROTAC-E3 ligase ternary complex, the discovery of active PROTACs relies on the screening of diversity-oriented PROTAC libraries. VH032 amine is a key building block for the synthesis of VHL E3 ligase-based PROTACs. To construct VHL PROTAC libraries rapidly, the availability of VH032 amine is crucial. In this paper, we report a column chromatography-free process which enables the production of 42.5 g of VH032 amine hydrochloride in 65% overall yield with 97% purity in a week.
ISSN:2470-1343
2470-1343
DOI:10.1021/acsomega.2c00245