AbstractFor the hydrogenation of the CN bonds in the pyrazine ring of the vitamin folic acid (1) optically active rhodium(I)/diphosphane complexes immobilized on supports such as silica gel or Al2O3were used. The reduction was carried out at 50 bar hydrogen pressure in an aqueous solution buffered to pH 7. Thus, 5,6,7,8‐tetrahydrofolic acid (2) was obtained which contains a new asymmetric center at C‐6 of the pterine system. Therefore, in combination with the (S) configuration of the naturalL‐glutamic acid part of the molecule two diastereomers with (6S,S) and (6R,S) configuration arise. The relatively unstable tetrahydrofolic acid (2) was converted into its 5‐formyl derivative folinic acid (4) by treatment with methyl formate/formic acid in a 5:1 mixture of DMSO/pyridine. The Ca salt of folinic acid (4) is the widely used drug leucovorin. The diastereomers were separated by silica gel HPLC. To the column bovine serum albumine (BSA) is covalently bound. With optically active rhodium(I)/diphosphane catalysts, immobilized on silica gel supports, a diastereoselectivity of up to 90% could be achieved in the hydrogenation of folic