The scope and limitation of the regio- and enantioselective hydrolysis of aliphatic epoxides using Bacillus subtilis epoxide hydrolase, and exploration toward chirally differentiated tris(hydroxymethyl)methanol

The substrate specificity of an engineered Bacillus subtilis epoxide hydrolase, which so far had shown high activity and enantioselectivity with 1-benzyloxymethyl-1-methyloxirane, has been studied by altering the methyl substituent into hydrogen, oxygen-containing functionalities, and unsaturated homologs. High enantioselectivity (E = 44) was observed with 1-benzyloxymethyl-1-vinyloxirane with a proper catalytic activity. The elaboration of the reaction conditions and work-up procedures enabled a preparative-scale kinetic resolution, to give (R)-2-benzyloxymethyl-3-butene-1,2-diol and its antipodal (R)-epoxide in high ees.

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(R)-1-Benzyloxymethyl-1-vinyloxiraneC12H14O2Ee = 82.9%[α]D24=+28.9 (c 1.12, MeOH)Source of chirality: Bacillus subtilis epoxide hydrolase-catalysed hydrolysisAbsolute configuration: (R)

(R)-2-Benzyloxymethyl-3-butene-1,2-diolC12H16O3Ee = 97.7%[α]D24=-28.1 (c 0.65, CH2Cl2)Source of chirality: Bacillus subtilis epoxide hydrolase-catalysed hydrolysisAbsolute configuration: (R)