Enzymes and catalysts. I. Pig liver esterase-catalyzed hydrolysis of heterocyclic diesters.

Recently, we have reported convenient methods for the synthesis of five-membered heterocycles by the use of 1,3-dipolar cycloaddition reactions.1,2) The introduction of chirality into the resulting cycloadducts was required for further application of these methods. Asymmetric synthesis or optical resolution by the use of enzymes is an effective method for obtaining chiral synthons, and pig liver esterase (PLE) has often been used for such enzymatic synthesis3) because it is easy to handle. We wish to describe herein the PLE-catalyzed hydrolysis of five-membered heterocyclic diesters aiming to produce chiral building blocks which are expected to be useful for the synthesis of natural products. Eight diesters with five-membered ring systems were employed for the purposes of the present work: dimethyl pyrrolidine-3,4-dicarboxylate (la), dimethyl N-benzylpyrrolidine-3,4dicarboxylate (lb), and dimethyl tetrahydrothiophene-3,4-dicarboxylate (lc) were synthesized by 1,3-cycloadditions via azomethine or thiocarbonyl ylides. Dimethyl cyclopentane-1,2dicarboxylate (1d), dimethyl pyrrolidine-2,5-dicarboxylate (2a), dimethyl N-benzylpyrrolidine-2,5-dicarboxylate (2b), and dimethyl cyclopentan-1,3-dicarboxylate (2d) were synthesized by the reported methods.4-6) Dimethyl tetrahydrothiophene-2,5-dicarboxylate (2c) was synthesized from dimethyl 2,5-dibromoadipinate and sodium sulfide. The stereo-, chemistry of ester groups in these compounds was restricted to trans from, in which the enzymatic action has not been established.