J. Luo et al., EFFICIENT SYNTHESES OF PYROFOLIC ACID AND PTEROYL AZIDE, REAGENTS FORTHE PRODUCTION OF CARBOXYL-DIFFERENTIATED DERIVATIVES OF FOLIC-ACID, Journal of the American Chemical Society, 119(42), 1997, pp. 10004-10013
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.