Thermostable Enzymes in Organic Synthesis, 4. Tbadh-Catalyzed Preparation of Bifunctional Chirons. Total Synthesis of S-(+)-Z-Tetradec-5-En-13-Olide

Abstract

Highly enantioselective reduction of various methyl- and ethylketones bearing different functional groups, such as double and triple carbon-carbon bonds, methyl ester, cyano, ethyl ether, phenyl and chloride, employing Thermoanaerobium brockii alcohol dehydrogenase (TBADH) as a catalyst, affords the corresponding optically active, secondary alcohols. As expected on the basis of our previous studies with monofunctional ketones, reduction of most of the substrates yields, uniformly, alcohols with an S configuration, arising from highly selective hydride attack at the re face of the carbonyl. However, with the smaller-sized ketones, there is a clear reversal in stereoselectivity. The synthetic usefulness of these chiral building blocks has been demonstrated by the total synthesis of (S)-(+)-Z-tetradec-5-en-13-olide, one of several synergistic aggregation pheromones produced by male flat grain beetles, Cryptolestes pusillus (Schonherr). The pheromone was prepared from (S)-(+)-methyl-8-hydroxynonanoate with optical purity greater than 99% in a six-step synthesis.