1. Enantioselective Synthesis of 4'-Ethynyl-2-fluoro-2'-deoxyadenosine (EFdA) via Enzymatic Desymmetrization.
- Author
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McLaughlin M, Kong J, Belyk KM, Chen B, Gibson AW, Keen SP, Lieberman DR, Milczek EM, Moore JC, Murray D, Peng F, Qi J, Reamer RA, Song ZJ, Tan L, Wang L, and Williams MJ
- Subjects
- Catalysis, Glycosides chemistry, Glycosylation, Hydrogenation, Molecular Structure, Oxidation-Reduction, Stereoisomerism, Anti-HIV Agents chemical synthesis, Deoxyadenosines chemical synthesis, Reverse Transcriptase Inhibitors chemical synthesis
- Abstract
An enantioselective synthesis of the potent anti-HIV nucleoside EFdA is presented. Key features of stereocontrol include construction of the fully substituted 4'-carbon via a biocatalytic desymmetrization of 2-hydroxy-2-((triisopropylsilyl)ethynyl)propane-1,3-diyl diacetate and a Noyori-type asymmetric transfer hydrogenation to control the stereochemistry of the 3'-hydroxyl bearing carbon. The discovery of a selective crystallization of an N-silyl nucleoside intermediate enabled isolation of the desired β-anomer from the glycosylation step.
- Published
- 2017
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