Selective Ring-Opening of Di-Substituted Epoxides Catalysed by Halohydrin Dehalogenases

Halohydrin dehalogenases (HHDHs) are valuable biocatalysts for the synthesis of beta-substituted alcohols based on their epoxide ring-opening activity with a number of small anionic nucleophiles. In an attempt to further broaden the scope of substrates accepted by these enzymes, a panel of 22 HHDHs was investigated in the conversion of aliphatic and aromatic vicinally di-substituted trans-epoxides using azide as nucleophile. The majority of these HHDHs was able to convert aliphatic methyl-substituted epoxide substrates to the corresponding azidoalcohols, in some cases even with absolute regioselectivity. HheG from Ilumatobacter coccineus exhibited also high activity towards sterically more demanding di-substituted epoxides. This further expands the range of beta-substituted alcohols that are accessible by HHDH catalysis.