Asymmetric Total Synthesis of a Beer-Aroma Constituent Based on Enantioconvergent Biocatalytic Hydrolysis of Trisubstituted Epoxides

Abstract

A short asymmetric total synthesis of the plant constituent myrcenediol [(R)-1], and (S)-7,7-dimethyl-6,8-dioxabicyclo[3.2.1]octane (2), which is a volatile constituent of the aroma of beer was accomplished via a chemoenzymatic protocol. The key step consisted of a biocatalytic hydrolysis of trisubstituted epoxides bearing olefinic side chains which proceeded in an enantioconvergent fashion, i.e., a single enantiomeric vic-diol was obtained from the racemate in up to 91% ee and 92% isolated yield.

Key words

epoxide hydrolase - enantioconvergent hydrolysis - trisubstituted epoxide - beer-aroma

References and Notes

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15

Since the biocatalytic hydrolysis of trisubstituted epoxides could proceed in an enantioconvergent fashion (not via kinetic resolution), the general use of E-values for the description of enantioselectivities is inapplicable.

20

In contrast, mesylation proceeded very slowly.