EFFICIENT SYNTHESES OF PYROFOLIC ACID AND PTEROYL AZIDE, REAGENTS FORTHE PRODUCTION OF CARBOXYL-DIFFERENTIATED DERIVATIVES OF FOLIC-ACID

Reaction of folic acid (1) with excess trifluoroacetic anhydride provi des access to both the previously unknown N-10-(trifluoroacetyl)pyrofo lic acid (8) and pyrofolic acid (9). Reaction of either of these mater ials with hydrazine selectively affords pteroyl hydrazide (13), which may be oxidized to pteroyl azide (27) on a large scale (62% overall fr om 1 without the need for chromatography). Treatment of 27 with differ entially protected glutamates provides a convenient and high-yielding synthesis of differentially protected, optically pure folates.