Chemoenzymic Synthesis of Chiral Furan Derivatives: Useful Building Blocks for Optically Active Structures

Practical procedures have been developed for the enantioselective reduction of 2-acetylfuran (6a) and 2-(trifluoroacetyl) furan (6b) to the corresponding carbinols (S)-1 and 7b with 88-90% ee using Thermoanaerobium brockii alcohol dehydrogenase coupled with an NADPH regeneration system. Kinetic resolution of racemic (S)-1 via lipase-catalyzed esterification, followed by cholesterol esterase or lipase-catalyzed hydrolysis of the ester gives (R)-1 with 94% ee. Conversion of (S)-1 to the dihydropyranones 4 and 5 without racemization has been illustrated. Enantioselective hydrolysis of N-protected furylglycine methyl esters catalyzed by papain gave the unreacted esters and the free acids (S form) both in 45% yield and 97% ee. The resolved furylglycines are excellent substrates for the synthesis of optically active synthons for alkaloids.