Absolute configuration of 6-methyl-5,6,7,8-tetrahydropterin produced by enzymic reduction (dihydrofolate reductase and NADPH) of 6-methyl-7,8-dihydropterin

Abstract

Dihydrofolate reductase (5,6,7,8-tetrahydrofolate: NADP oxidoreductase, E.C.1.5.1.3.) and NADPH, which catalyse the reduction of 7,8-dihydrofolic acid (1) stereospecifically to give one diastereoisomer of 5,6,7,8-tetrahydrofolic acid (3), also catalyse the reduction of 6-methyl-7,8-dihydropterin (2) stereospecifically to (-)-6-methyl-5,6,7,8-tetrahydropterin (4); the absolute configuration at C-6 of the pterin (4) is shown to be S by correlation with S-alanine using a series of methylations, degradations, and syntheses, and if the most probable assumption is made that the stereospecificities of these two reactions are the same, then the absolute configuration at C-6 of enzymically produced 5,6,7,8-tetrahydrofolic acid should be S.