ISSN:
0009-2940
Keywords:
Diastereoselective hydrogenation
;
Folic acid
;
Immobilized optically active rhodium(I)/diphosphane catalysts
;
Leucovorin
;
HPLC analysis of 5-formyltetrahydrofolic acid derivatives
;
Chemistry
;
Inorganic Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
For 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 Al2O3 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 (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 acid (1).
Additional Material:
1 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/cber.19971300109
Permalink
