Developments of Enzymatic Process for Dorzolamide and Associated Optically Pure Intermediates

In the second-year project, it is aimed to develop a Lipase-PS-D-catalyzed alcoholic resolution process for preparing optically pure (4S,6S)-5,6-dihydro-6-methyl-4H- thieno-[2,3-b]thiopyran-4-ol. At first we employ (R)-β-butyrolactone obtained from the first-year project as the substrate for synthesizing (S)-3-(2-thienylthio)butyric acid, and then (6S)-5,6-dihydro-6-methyl-4H- thieno[2,3-b]-thiopyran-4-one via cyclization, and finally (4R,6S)- and (4S,6S)-5,6-dihydro-6-methyl-4H-thieno[2,3- b]thiopyran-4-ol mixture via LiAlH4 reduction. Lipase-PS-D-catalyzed alcoholytic resolution of the mixture with vinyl acetate as the acyl donor is then carried out to give optically pure (4S,6S)-isomer. At 25oC in MTBE solution, the enantioselectivity of E = 11.7 is estimated from the kinetic analysis.

Project ID:PB10301-0502
External Project ID:NSC102-2221-E182-045-MY2