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Asymmetric Catalysis, 105 . Stereoselective Hydrogenation of Folic Acid with Immobilized Optically Active Rhodium(I)/Diphosphane Catalysts
Author(s) -
Brunner Henri,
Bublak Petra,
Helget Martina
Publication year - 1997
Publication title -
chemische berichte
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.667
H-Index - 136
eISSN - 1099-0682
pISSN - 0009-2940
DOI - 10.1002/cber.19971300109
Subject(s) - chemistry , formic acid , diastereomer , rhodium , pyridine , catalysis , organic chemistry , asymmetric hydrogenation , silica gel , dicarboxylic acid , medicinal chemistry , enantioselective synthesis
For the hydrogenation of the CN 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 Al 2 O 3 were 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 natural L ‐glutamic acid part of the molecule two diastereomers with (6 S,S ) and (6 R,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 acid ( 1 ).