| Research Abstract |
Nowadays, lipase-catalyzed asymmetric transesterification of alcohols has been widely employed as one of the most efficient asymmetric synthetic methods. For this kind of reactions, we have recently developed a novel class of acyl donor, 1-ethoxyvinyl esters (EVEs), which are superior to the currently-best acyl donors, vinyl esters (VEs). Their advantages involve solution of the deactivation of lipases by the side-product derived from VEs, high reactivity and enantioselectivity, and easy preparation of EVEs having various acyl moieties. By the use of EVEs, this project aims at developing novel asymmetric synthetic methods that could hardly be attained by the previous methods using VEs. The followings are summary of the results :
1. 1-Ethoxyvinyl 2-furoate 1 was developed as a highly effective acyl donor for the lipase-catalyzed desymmetrization of prochiral 2,2-disubstituted 1,3-propanediols. The method using 1 features high reactivity and enantiotopic selectivity, applicability for wid
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e range of the substrates, increase of the optical purity of the products through kinetic amplification, and stability of the products under various conditions. 1 was also found to be effective for the desymmetrization of meso-1,2-cycloalkanediols. This protocol was successfully applied for the construction of the pivotal optically active spiro quaternary carbon center of the antitumor antibiotic, fredericamycin A, and thereby a divergent asymmetric synthesis of both enantiomers of its ABCDE-analog was established.
2. A novel lipase-catalyzed tandem asymmetric synthesis has been developed, which involves in situ preparation of a 1-ethoxyvinyl acrylate having an electron-withdrawing substituent at the β-position, lipase-catalyzed kinetic resolution of (2-furyl)carbinols, and intramolecular Diels-Alder reaction of thus introduced acyl moiety. This one-pot procedure provides 7-oxabicyclo[2.2.1]heptenes with up to 99% ee. Unprecedented phenomena of the lipase ; viz., catalysis of the Diels-Alder reaction to amplify the enantioselectivity through kinetic resolution was discovered. Less
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