American Chemical Society
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Development of an Enzymatic Process for the Production of (R)‑2-Butyl-2-ethyloxirane

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journal contribution
posted on 2017-06-30, 00:00 authored by Gheorghe-Doru Roiban, Peter W. Sutton, Rebecca Splain, Christopher Morgan, Andrew Fosberry, Katherine Honicker, Paul Homes, Cyril Boudet, Alison Dann, Jiasheng Guo, Kristin K. Brown, Leigh Anne F. Ihnken, Douglas Fuerst
An epoxide resolution process was rapidly developed that allowed access to multigram scale quantities of (R)-2-butyl-2-ethyloxirane 2 at greater than 300 g/L reaction concentration using an easy-to-handle and store lyophilized powder of epoxide hydrolase from Agromyces mediolanus. The enzyme was successfully fermented on a 35 L scale and stability increased by downstream processing. Halohydrin dehalogenases also gave highly enantioselective resolution but were shown to favor hydrolysis of the (R)-2 epoxide, whereas epoxide hydrolase from Aspergillus niger instead provided (R)-7 via an unoptimized, enantioconvergent process.