Enantioselective Synthesis of 4′-Ethynyl-2-fluoro-2′-deoxyadenosine (EFdA) via Enzymatic Desymmetrization

• DOI: 10.1021/acs.orglett.7b00091
• Publication Date: 2017-02-06T14:08:27Z
• Authors: Mark McLaughlin; Jongrock Kong; Kevin M. Belyk; Billy Chen; Andrew W. Gibson; Stephen P. Keen; David R. Lieberman; Erika M. Milczek; Jeffrey C. Moore; David Murray; Feng Peng; Ji Qi; Robert A. Reamer; Zhiguo J. Song; Lushi Tan; Lin Wang; Michael J. Williams
• Keywords: Desymmetrization; Deoxyadenosine

An enantioselective synthesis of the potent anti-HIV nucleoside EFdA is presented. Key features stereocontrol include construction fully substituted 4′-carbon via a biocatalytic desymmetrization 2-hydroxy-2-((triisopropylsilyl)ethynyl)propane-1,3-diyl diacetate and Noyori-type asymmetric transfer hydrogenation to control stereochemistry 3′-hydroxyl bearing carbon. The discovery selective crystallization an N-silyl intermediate enabled isolation desired β-anomer from glycosylation step.