Open AccessA Photochemical Route to Optically Active Hexahydro-4H-furopyranol, a High-Affinity P2 Ligand for HIV-1 Protease Inhibitors
Author(s) -
Arun K. Ghosh,
William L. Robinson
Publication year - 2019
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.9b01361
Subject(s) - hiv 1 protease , chemistry , enantiomer , ligand (biochemistry) , stereochemistry , optically active , protease , pyran , protease inhibitor (pharmacology) , enzyme , combinatorial chemistry , human immunodeficiency virus (hiv) , organic chemistry , biochemistry , receptor , biology , antiretroviral therapy , viral load , immunology
We describe here the syntheses of optically pure (3a S ,4 S ,7a R )-hexahydro-4 H -furo[2,3- b ]pyran-4-ol and (3a R ,4 R ,7a S )-hexahydro-4 H -furo[2,3- b ]pyran-4-ol. These stereochemically defined heterocycles are important high-affinity P2 ligands for a variety of highly potent HIV-1 protease inhibitors. The key steps involve an efficient Paternò-Büchi [2 + 2] photocycloaddition, catalytic hydrogenation, acid-catalyzed cyclization to form the racemic ligand alcohol, and an enzymatic resolution with immobilized Amano Lipase PS-30. Optically active ligands (-)- 6 and (+)- 6 were obtained with high enantiomeric purity. Enantiomer (-)- 6 has been converted to potent HIV-1 protease inhibitor 3 .