Chemo-enzymatic routes for naturally occurring bioactive products as well as chiral derivatizing reagents were developed in three examples. Firstly, (R)-3-hydroxy-3-methyl-5-hexanoic acid p-methoxybenzyl ester was prepared by carbon-chain elongation on the both termini of the starting material, (R)-3-benzyloxy-2-methylpropane-1,2-diol, which was prepared by an overexpressed Bacillus subtilis epoxide hydrolase-catalyzed enantioselective hydrolysis of the racemic 1-benzyloxymethyl-1-methyloxirane. One of the key steps of the requisite transformation was the Rhodococcus rhodochrous-mediated hydrolysis of cyano to carboxyl group under neutral conditions, to exclude any racemization of the intermediate and/or product. The enantiomerically pure form of (R)-hydroxy ester was applied to a new formal total synthesis of taurospongin A. Secondly, while the first total synthesis of modiolide A, a ten-membered ring lactone with a marine-origin was achieved, an important chiral building block for constructing the chirality at C-4, (S)-6-[(4-methoxybenzyl)oxy]-1-trimethylsilyl-1-hexyn-3-ol was obtained in as high as 96.1% ee. Asymmetric reduction of the corresponding silylated propargyl ketone mediated by whole-cell of Pichia minuta was established. The ee of the resulting alcohol was further enhanced by applying Pseudomonas cepacia lipase-catalyzed resolution. Thirdly, the synthesis of TBMB carboxylic acid, a chiral derivatizing agent with a characteristic quaternary acetal chiral center, based on enzyme-catalyzed asymmetric reduction of an aromatic trifluoromethyl ketone is presented. Among the possible four diastereomers of key intermediate, cultured cells of a fungus, Geotrichum candidum provided only two enantiomers, in the reduction of the substrate. Furthermore, Candida antarctica lipase B discriminated the remote chiral center on the occasion of the hydrolysis of corresponding acetates. The resulted stereochemically pure alcohol was derived to (S)-TBMB carboxylic acid.
