Novel fungi-catalyzed reduction of α-alkyl-β-keto esters

A screening of 15 fungi and yeast strains was carried out in fermentation processes to perform the diastereo- and enantioselective reduction of ethyl 2-methyl-3-oxobutanoate, to the corresponding (R∗,S∗)-3-hydroxy-2-methyl esters. Overall, biotransformations led to excellent conversions, as well as good to excellent diastereo- and enantioselectivities. A strain of Aureobasidium pullulans (CCM H1) was found to be the most efficient biocatalyst in terms of conversion (100%), syn:anti ratio (3:97), and enantiomeric excess (94% anti-(2S,3S) isomer). This biotransformation was successfully carried out on a preparative level as well. Other microorganisms, such as Fusarium graminearum (CCM HH 224), Aspergillus terreus (BFQU 121), Geotrichum candidum (CCM H38), Trichoderma koningii (ATCC 76666), and Aspergillus niger (CCM H21) also showed excellent diastereo- and enantioselectivities, combined with high conversions (>95% conversion, ⩾95% ee, and excellent syn:anti ratios). Many of the strains used in this work had scarcely been described as oxido-reducing agents, or had never been used with the substrates reported herein.

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Ethyl 3-hydroxy-2-methylbutanoateC7H14O3Ee = 94%[α]D20=+22.5 (c 1.20, CHCl3)Source of chirality: enzymatic reduction (Aureobasidium pullulans)Absolute configuration: (2S,3S)