Open AccessThe Chiron Approach to (3R,3aS,6aR)-Hexahydrofuro[2,3-b]furan-3-ol, a Key Subunit of HIV-1 Protease Inhibitor Drug, Darunavir
Author(s) -
Arun K. Ghosh,
Shivaji B. Markad,
William L. Robinson
Publication year - 2020
Publication title -
journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.2
H-Index - 228
eISSN - 1520-6904
pISSN - 0022-3263
DOI - 10.1021/acs.joc.0c02396
Subject(s) - darunavir , chemistry , enantioselective synthesis , stereochemistry , furan , hiv 1 protease , stereoselectivity , derivative (finance) , anomer , combinatorial chemistry , human immunodeficiency virus (hiv) , catalysis , organic chemistry , protease , enzyme , medicine , family medicine , viral load , antiretroviral therapy , financial economics , economics
We describe an enantioselective synthesis of (3 R ,3 aS ,6 aR )-hexahydrofuro[2,3- b ]furan-3-ol which is a key subunit of darunavir, a widely used HIV-1 protease inhibitor drug for the treatment of HIV/AIDS patients. The synthesis was achieved in optically pure form utilizing commercially available sugar derivatives as the starting material. The key steps involve a highly stereoselective substrate-controlled hydrogenation, a Lewis acid catalyzed anomeric reduction of a 1,2- O -isopropylidene-protected glycofuranoside, and a Baeyer-Villiger oxidation of a tetrahydrofuranyl-2-aldehyde derivative. This optically active ligand alcohol was converted to darunavir efficiently.