Chemoenzymatic synthesis of chiral biologically active heterocycles

• Published in: Farmaco (Società chimica italiana : 1989) Vol. 52; no. 5; p. 307
• Main Authors: De Amici, M, De Micheli, C, Gianferrara, T, Stefancich, G
• Format: Journal Article
• Language: English
• Published: France 01-05-1997
• Subjects: Alcohol Dehydrogenase - pharmacology; Lipase - pharmacology; Muscarinic Antagonists - chemical synthesis; Muscarinic Antagonists - pharmacology; Stereoisomerism; Structure-Activity Relationship
• ISSN: 0014-827X

The chemoenzymatic approach to the preparation of some chiral biologically active heterocycles is discussed. Synthetic strategies took advantage of enantioselective bioconversion processes carried out on suitable reaction intermediates. Reductions of carbonyl compounds catalyzed by different alcohol dehydogenases (TBADH from Thermoanaerobium brockii, 20 beta-HSDH from Streptomyces hydrogenans, beta-HSDH from Pseudomonas testosteroni) allowed the preparation with high enantiomeric purity 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 racemic butyrates were the key step in the synthesis of both the enantiomers of two muscarinic antagonists. Finally, the preparation of acetyl cycloserine antipodes was attained by means of a highly enantioselective hydrolysis catalyzed by lipase from Chromobacterium viscosum.