CHEMOENZYMATIC SYNTHESIS OF CHIRAL BIOLOGICALLY-ACTIVE HETEROCYCLES

The chemoenzymatic approach to the preparation of some chiral biologic ally active heterocycles is discussed. Synthetic strategies took advan tage of enantioselective bioconversion processes carried out on suitab le reaction intermediates. Reductions of carbonyl compounds catalyzed by different alcohol dehydogenases (TBADH from Thermoanaerobium brocki i, 20 beta-HSDH from Streptomyces hydrogenans, beta-HSDH from Pseudomo nas testosteroni) allowed the preparation with high enantiomeric purit y of the eutomer of broxaterol (a selective beta(2)-adrenergic agonist ) and six out of the eight muscarine stereoisomers. On the other hand, hydrolyses, catalyzed by lipase PS (from Pseudomonas cepacia), of rac emic butyrates were the key step in the synthesis of both the enantiom ers of two muscarinic antagonists. Finally, the preparation of acetyl cycloserine antipodes was attained by means of a higly enantioselectiv e hydrolysis catalyzed by lipase from Chromobacterium viscosum.