Feasible Column Chromatography-Free, Multi-Gram Scale Synthetic Process of VH032 Amine, Which Could Enable Rapid PROTAC Library Construction
Wei Yan, Bo‐Syong Pan, Jingwei Shao, Hui-kuan Lin, Hongyu Li
Abstract
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.
Topics & Concepts
Amine gas treatingComputer scienceReuseCombinatorial chemistryChemistryEngineeringOrganic chemistryWaste managementProtein Degradation and InhibitorsUbiquitin and proteasome pathwaysMultiple Myeloma Research and Treatments