A Photochemical Route to Optically Active Hexahydro-4H-furopyranol, a High-Affinity P2 Ligand for HIV-1 Protease Inhibitors | Zendy

Arun K. Ghosh | Zendy; William L. Robinson | Zendy

Open Access

A 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 -

the 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) - chemistry , hiv 1 protease , enantiomer , ligand (biochemistry) , stereochemistry , protease , pyran , optically active , enzyme , enantioselective synthesis , kinetic resolution , combinatorial chemistry , lipase , catalysis , organic chemistry , biochemistry , receptor

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 .

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