DOI: 10.1021/acs.orglett.6c03027 ISSN: 1523-7060
Stereoselective Synthesis of MK-8527 Enabled by a Dynamic Kinetic Resolution Mitsunobu Glycosylation
Aaron M. Whittaker, Feng Peng, Eric Sirota, Mark McLaughlin, Hongming Li, Charles Orella, Lushi Tan, Wenjun Liu, Thomas P. Vickery, Daniel Bishara, Nicholas J. Rogus, Jongrock Kong, Cyndi Qixin He, Zhiguo J. Song, Kevin M. Maloney, Steven Crossley, Xiao Wang, Chaohui Song, Guangxin Shao, Lianjie Li, Aijie Zhao, Lu ChenAbstract
A practical and asymmetric synthesis of potent anti-HIV nucleoside MK-8527 is described. The key discoveries are a novel stereoselective dynamic kinetic resolution (DKR) Mitsunobu glycosylation and selective amination of the resulting 2,6-dichloro nucleoside. The new route was successfully demonstrated on the kilogram scale and provided isolated MK-8527 with more than 99% HPLC purity through crystallization.