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Published on: November 9, 2019
One-pot synthesis of enantiopure 3,4-dihydroisocoumarins through dynamic reductive kinetic resolution processes
Juan Mangas-Sánchez1, Eduardo Busto, Vicente Gotor
1Organic and Inorganic Chemistry Department, University of Oviedo, Avenida Julián Clavería s/n. Oviedo 33006, Spain.
Abstract:
A straightforward chemoenzymatic synthesis of enantiopure 4-alkyl-3-methyl-3,4-dihydroisocoumarins through a ketoreductase-catalyzed one-pot dynamic reductive kinetic resolution is reported. E. coli/ADH-A cells have shown outstanding diastereo- and enantioselectivity toward the bioreduction of a series of racemic ketones, with the use of anion exchange resins or triethylamine being compatible in the same aqueous reaction medium. The so-obtained enantiopure alcohols were subsequently cyclized in acid media affording the corresponding lactones in good to excellent conversions (72-96%) and excellent selectivities (dr ≥99:1 and ee >99%).
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