Enzyme-catalyzed resolution of 3,8-dioxatricyclo[3.2.1.0 2,4]octane-6-carboxylic esters and the application to the synthesis of 3-epishikimic acid

Abstract

3,8-Dioxatricyclo[3.2.1.0 2,4]octane-6-carboxylic acid, whose racemic form is readily available on a large scale, is a versatile starting material for the synthesis of carbasugars and carbocyclic biologically active natural products. In this study, the enzyme-catalyzed kinetic resolution was attempted on a variety of corresponding carboxylic esters. The hydrophobic and hydrophilic properties of ester substituents greatly affected the rate of reaction and the enantioselectivity. Hydrolysis of the corresponding 2′-chloroethyl ester with pig liver esterase worked well in a highly enantioselective manner ( E = 116) to give the hydrolyzate (90.6% ee) and unreacted ester recovery (99.4% ee). The hydrolyzate is a precursor for (−)-oseltamivir phosphate, and a route to (3 S,4 S,5 R)-(−)-3-epishikimic acid was developed from the recovered ester.