An Efficient Synthesis of the Bicyclic Darunavir Side Chain Using Chemoenzymatic Catalysis
ORGANIC PROCESS RESEARCH & DEVELOPMENT(2022)
摘要
Herein, we describe a chemoenzymatic synthesis of the bicyclic fragment of Darunavir. A ketoreductase was identified using metagenomic mining to catalyze a highly enantio- and diastereoselective dynamic kinetic resolution of a β-ketolactone. Subsequent lactone reduction with diisobutylaluminum hydride and phase transfer cyclization affords the bicyclic acetal fragment in 39% yield over four steps.
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关键词
dynamic kinetic resolution,ketoreductase,biocatalysis,antiviral
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