Pterins. III. Methylation of 6-Methyl-5,6,7,8-tetrahydropterin, N-5-Demethylation of 1,3,5,6-Tetramethyl-5,6,7,8-tetrahydropterinium chloride hydrochloride and exchange of the 5-Methyl group in 5,6-Dimethyl-5,6,7,8-tetrahydropterin

Abstract

Methylation of 6-methyl-5,6,7,8-tetrahydropterin (1) in the presence of sodium hydroxide furnishes 1,3,6-trimethyl-5,6,7,8-tetrahydropterinium chloride (3) which can be methylated further to yield 1,3,5,6- tetramethyl-5,6,7,8-tetrahydropterinium chloride (4). Demethylation of the latter salt occurred on a Dowex 50W/3 N-aqueous ammonia column with loss of the 5-methyl group to give the salt (3). The structures of these salts were deduced by a study of similar alkylations of authentic 1,6-dimethyl-,3,6-dimethyl- (6), 5,6-dimethyl-(15), 6,8-dimethyl-, 1,5,6-trimethyl-, and 3,5,6-trimethyl-5,6,7,8-tetrahydropterin (7), and of 6-methyl-2-methylamino-5,6,7,8-tetrahydropteridin- 4(3H)-one (10). Methylation of 5,6-dimethyl-5,6,7,8-tetrahydropterin (15), with trideuteromethyl iodide in the presence of alkali, was shown to give the tetramethylpterinium salt (4) in which considerable exchange of the 5-methyl group by a trideuteromethyl group had taken place.    

The pterinium salts (3) and (4) were considerably more stable to aerial oxidation than 6-methyl-, 1,6-, 3,6-, 5,6-, 6,7-, 6,8-dimethyl-, and 1,5,6-trimethyl-5,6,7,8-tetrahydropterin. Loss of the 5-methyl group from the salt (4), and exchange of the 5-methyl group in the 5,6- dimethylpterin (15), allowed a mechanism for the enzymic transfer of the 5-methyl group in 5-methyl-5,6,7,8-tetrahydrofolic acid in biological methylations to be proposed.