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Scalable Synthesis of the Potent HIV Inhibitor BMS‐986001 by Non‐Enzymatic Dynamic Kinetic Asymmetric Transformation (DYKAT)
Author(s) -
Ortiz Adrian,
Benkovics Tamas,
Beutner Gregory L.,
Shi Zhongping,
Bultman Michael,
Nye Jeffrey,
Sfouggatakis Chris,
Kronenthal David R.
Publication year - 2015
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201502290
Subject(s) - enantiopure drug , kinetic resolution , chemistry , combinatorial chemistry , furanose , pyranose , stereoselectivity , tautomer , transformation (genetics) , stereochemistry , ring (chemistry) , enantioselective synthesis , organic chemistry , catalysis , biochemistry , gene
Described herein is the synthesis of BMS‐986001 by employing two novel organocatalytic transformations: 1) a highly selective pyranose to furanose ring tautomerization to access an advanced intermediate, and 2) an unprecedented small‐molecule‐mediated dynamic kinetic resolution to access a variety of enantiopure pyranones, one of which served as a versatile building block for the multigram, stereoselective, and chromatography‐free synthesis of BMS‐986001. The synthesis required five chemical transformations and resulted in a 44 % overall yield.