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

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• 作者：Mark McLaughlinJongrock Kong ; Kevin M. Belyk ; Billy Chen ; Andrew W. Gibson ; Stephen P. Keen ; David R. Lieberman ; Erika M. Milczek ; Jeffrey C. MooreDavid Murray ; Feng Peng ; Ji Qi ; Robert A. Reamer ; Zhiguo J. SongLushi Tan ; Lin Wang ; Michael J. Williams
• 刊名：Organic Letters
• 出版年：2017
• 出版时间：February 17, 2017
• 年：2017
• 卷：19
• 期：4
• 页码：926-929
• 全文大小：343K
• ISSN：1523-7052

文摘

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.