Open AccessDevelopment of an Effective Scalable Enantioselective Synthesis of the HIV-1 Entry Inhibitor BNM-III-170 as the Bis-trifluoroacetate Salt
Author(s) -
Junhua Chen,
Jun Park,
Sharon Kirk,
Hung-Ching Chen,
Xiangqin Li,
Daniel J. Lippincott,
Bruno Melillo,
Amos B. Smith
Publication year - 2019
Publication title -
organic process research and development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 109
eISSN - 1520-586X
pISSN - 1083-6160
DOI - 10.1021/acs.oprd.9b00353
Subject(s) - enantioselective synthesis , human immunodeficiency virus (hiv) , salt (chemistry) , chemistry , combinatorial chemistry , stereochemistry , organic chemistry , virology , medicine , catalysis
We report here the development and optimization of a process synthesis for the HIV-1 entry inhibitor BNM-III-170 bis-TFA salt ( 1 ). The synthesis features a dynamic-kinetic resolution (DKR) to establish the initial stereogenicity. By taking advantage of significant sequence modifications of our first generation synthesis, inconjunction with the low solubility of late-stage intermediates, the overall efficiency of the synthesis has been significantly improved, now to proceed in an overall yield of 9.64% for the 16-steps, requiring only a single chromatographic separation.