Stereoselective Hydrogenation of Folic Acid Dimethyl Ester Benzenesulfonate:A New Access to Optically Pure L-Tetrahydrofolic Acid

摘要

Folic acid was converted to the corresponding dimethyl ester benzenesulfonate and stereoselectively hydrogenated in organic solvents.An extended screening with rhodium- and iridium-diphosphine catalysts was performed.Under optimized conditions the asymmetric hydrogenation provided a solution of tet-rahydrofolic acid dimethyl ester with up to 44% de.The de could be increased to 98% by fractional crystallization of L-tetrahydrofolic acid dimethyl ester benzenesulfonate from the hydrogenation mixture.Hydrolysis of the ester afforded optically pure L-tetrahydrofolic acid,which can be isolated or converted into its 5- or 10- or 5,10-substituted derivatives.