Stereochemistry of reduction of folic acid using dihydrofolate reductase

Abstract

The dihydrofolate reductase catalysed reduction of the vitamin folic acid (5) to the coenzyme 5,6,7,8-tetrahydrofolic acid (2) involves transfer of the 4-pro-R-hydrogen of NADPH to the si-face at C-7 of folic acid (5); the absolute stereochemistry at C-6 of 5,6,7,8-tetrahydrofolic acid (2) from the enzymic reduction has been correlated with that of biologically active folinic acid (3), and the reduction at both C-6 and C-7 therefore involves the same side of NADPH and the same face of folic acid.