We describe an enantioselective synthesis of (3,3,6)-hexahydrofuro[2,3-]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--isopropylidene-protected glycofuranoside, and a Baeyer-Villiger oxidation of a tetrahydrofuranyl-2-aldehyde derivative. This optically active ligand alcohol was converted to darunavir efficiently.
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| http://dx.doi.org/10.1021/acs.joc.0c02396 | DOI Listing |
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The Chiron Approach to (3,3,6)-Hexahydrofuro[2,3-]furan-3-ol, a Key Subunit of HIV-1 Protease Inhibitor Drug, Darunavir.
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