Chemoenzymatic approach to enantiomerically pure (R)-3-Hydroxy-3-methyl-4-pentenoic acid ester and its application to a formal total synthesis of taurospongin A

(R)-3-Hydroxy-3-methyl-5-hexanoic acid p-methoxybenzyl ester 1b was prepared by carbonchain elongation on both termini of the starting material, (R)-3-benzyloxy-2-methylpropane-1,2-diol 2a, which was prepared by an over-expressed Bacillus subtilis epoxide hydrolase-catalyzed enantioselective hydrolysis of the racemic 1-benzyloxymethyl-1-methyloxirane 3. One of the key steps of the requisite transformation was the Rhodococcus rhodochrous NBRC 15564-mediated hydrolysis of a cyano group to a carboxyl group under neutral conditions, to exclude any racemization of the intermediate and/or product. The enantiomerically pure form of (R)-1b was applied to a new formal total synthesis of taurospongin A.