Work

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

Year: 2019

Type: article

Abstract: 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 .

Source: The Journal of Organic Chemistry

DOI: 10.1021/acs.joc.9b01361

Authors: Arun K. Ghosh, William L. Robinson

Institution: Purdue University West Lafayette

Language: English

Topic: Asymmetric Synthesis and Catalysis

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: green

Funders: National Institutes of Health, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases

Awards: Cancer Center Support Grant, DESIGN AND SYNTHESIS OF NONPEPTIDE PROTEASE INHIBITORS, Design & Synthesis of Nonpeptide Protease Inhibitors, Design & Synthesis of Nonpeptide Protease Inhibitors, G9000252667