Group-assisted purification (GAP) chemistry for the synthesis of Velcade via asymmetric borylation of N-phosphinylimines
Abstract
A new approach to the anticancer drug Velcade was developed by performing asymmetric borylation of an imine anchored with a chiral N-phosphinyl auxiliary. Throughout the 7-step synthesis, especially in the imine's synthesis and in the asymmetric borylation reactions, operations and work-up were conducted in simple and easy ways without any column chromatographic purification, which defines the GAP (group-assisted purification) chemistry concept. It was found that the optically pure isomer (dr > 99: 1) can be readily obtained by washing the crude mixture of the asymmetric borylation reaction with hexane; the chiral N-phosphinyl auxiliary can be easily recovered after deprotection is finished. Several other N-phosphinylimines were also investigated for the asymmetric borylation reaction. The absolute configuration of the borylation product was confirmed by single crystal X-ray diffraction analysis.
Citation
Xie , J , Luo , J , Winn , T R , Cordes , D B & Li , G 2014 , ' Group-assisted purification (GAP) chemistry for the synthesis of Velcade via asymmetric borylation of N-phosphinylimines ' , Beilstein Journal of Organic Chemistry , vol. 10 , pp. 746-751 . https://doi.org/10.3762/bjoc.10.69
Publication
Beilstein Journal of Organic Chemistry
Status
Peer reviewed
ISSN
1860-5397Type
Journal item
Description
The authors acknowledge the financial support from the NIH (R33DA031860), the Robert A. Welch Foundation (D-1361) and the Jiangsu Innovation Team Program (P. R. China) for their support of this research. They also thank NSF Grant CHE-1048553 and the CRIF program for supporting their NMR facility.Collections
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