Development of novel asymmetric reactions oriented to next-generation enzymatic organic syntheses

Abstract

Enzyme-catalyzed organic syntheses have enormous potential in the development of environmentally benign processes. In the last two decades, increased efforts have been devoted to making this a reality. However, the utility of the enzymes is generally limited. For example, although the lipases are extensively used for the kinetic resolution or the desymmetrization of alcohols and carboxylic acid derivatives, little is known about their ability to catalyze carbon-carbon bond-forming reactions. In the past several years, we have been engaged in exploiting a next-generation enzymatic synthesis by using the lipases for the construction of carbon skeletons. This review article describes the results. First, the development of a new type of acyl donor, 1-ethoxyvinyl esters (EVEs), that have significant advantages over common acyl donors (e.g., vinyl esters) for lipase-catalyzed esterification reactions. Second, the highly enantioselective desymmetrization of prochiral 1,3-propanediols and meso 1,2-diols using 1-ethoxyvinyl 2-furoate. The application of this technology for the asymmetric syntheses of fredericamycin A analogues and the oxindoles with a chiral, nonracemic quaternary carbon center has been demonstrated. Third, the first lipase-catalyzed domino reaction using EVEs possessing a suitably functionalized acyl moiety is described. The acyl moiety installed during the enzymatic kinetic resolution was used as a part of the constituent structure for the subsequent Diels--Alder reaction to product optically pure tricyclic compounds with five chiral carbon centers via a one-pot operation. The potential influence of the lipase on the Diets--Alder reaction and the domino process accompanied by the dynamic kinetic resolution are also described.