Development of an Enzymatic Process for the Production of (R)-2-Butyl-2-ethyloxirane

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.