Selectivity enhancement of enantio- and stereo-complementary epoxide hydrolases and chemo-enzymatic deracemization of (±)-2-methylglycidyl benzyl ether

The kinetic resolution of (±)-2-methylglycidyl benzyl ether was achieved via enantioselective biohydrolysis using microbial and plant epoxide hydrolases. Depending on the type of enzyme, opposite enantiopreference and stereo-complementary mode of action (i.e., retention vs inversion of configuration) led to hetero- and homochiral product mixtures. Optimization of the reaction conditions for Rhodococcus sp. R312 led to significantly enhanced enantioselectivity (E >200), which enabled the deracemization of (±)-2-methylglycidyl benzyl ether via biohydrolysis (proceeding with retention of configuration) followed by inverting acid-catalyzed hydrolysis to furnish (R)-1-benzyloxy-2-methylpropane-2,3-diol in >97% ee and 78% yield from the racemate.

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2-Methylglycidyl benzyl etherC11H14O2Ee >97%[α]D20=+9.2 (c 1.0, CHCl3)Source of chirality: chemo-enzymatic deracemizationAbsolute configuration: (S)

2-Benzyloxymethylpropan-1,2-diolC11H16O3Ee >97%[α]D20=-6.6 (c 1.33, CH2Cl2)Source of chirality: chemo-enzymatic deracemizationAbsolute configuration: (R)