2-AMINO-4-HYDROXY-6-METHYL-7,8-DIHYDROPTERIDINE AS A MODEL FOR DIHYDROFOLATE

Studies on the structure of dihydrofolic acid are rendered difficult by its lability and because important chemical and physical properties associated with the pteridine nucleus are frequently obscured by groups in the remainder of the molecule. To overcome these difficulties, 2-amino-4-hydroxy-6-methyl-7,8-dihydropteridine was utilized as a model for dihydrofolic acid. The dihydropteridine was synthesized by a modification of the procedure of Boon and Leigh in which the 2 extra hydrogen atoms at positions 7 and 8 were introduced prior to closure of the pyrazine ring; and by reduction of the oxidized pteridine with hydrosulfite or with Zn in basic solution. The 7,8-dihydro structure of the model pteridine was confirmed by measurement of the proton magnetic resonance spectrum. The ultraviolet spectrum of an equimolal mixture of the 7,8-dihydropteridine and N-methyl-p-aminobenzoylglutamic acid was shown to be identical with the spectrum of dihydrofolate at pH 7 and 13 but not at pH 1; reasons for the latter discrepancy are discussed. pK values were determined for prototropic groups in the oxidized, dihydro, and tetrahydro forms of the pteridine.