54353-24-1Relevant articles and documents
Synthesis and physicochemical characterization of (6: S)-5-formiminotetrahydrofolate; A reference standard for metabolomics
Lewin,Silinski,Zhong,Gilbert,Mascarella,Seltzman
, p. 5684 - 5690 (2018/08/17)
The one-carbon carrier of the formate oxidation level derived from the interaction of tetrahydrofolate and formiminoglutamate, which has been tentatively identified as 5-formiminoltetrahydrofolate, has been prepared by chemical synthesis. Treatment of a solution of (6S)-tetrahydrofolate in aqueous base with excess ethyl formimidate in the presence of anti-oxidant under anaerobic conditions afforded a gummy solid which, based on mass spectral analysis, conformed to a monoformimino derivative of tetrahydrofolate. Further physicochemical characterization by validated methods strongly suggested that the product of chemical synthesis was identical to the enzymatically produced material and that it was, in fact, (6S)-5-formiminotetrahydrofolate. Conditions and handling methods toward maintaining the integrity of this highly sensitive compound were identified and are described, as is analytical methodology, useful for research studies using it.
Synthesis of Tetrahydropteridine C6-Stereoisomers, Including N5-Formyl-(6S)-tetrahydrofolic Acid
Bailey, Steven W.,Chandrasekaran, Rama Y.,Ayling, June E.
, p. 4470 - 4477 (2007/10/02)
Chiral N1-protected vicinal diamines derived from amino acids were condensed with 2-amino-6-chloro-5-nitro-4(3H)-pyrimidinone, the nitro group reduced, and the amine deprotected.Oxidative cyclization of the resulting triaminopyrimidinone via quinoid pyrimidine intermediates gave a quinoid dihydropteridine, which was then reduced to a tetrahydropteridine C6-stereoisomer.Thus, 6(R)- and 6(S)-propyltetrahydropterin were stereospecifically synthesized (99 percent enantiomeric purity) in good yield from D- and L-norvaline, respectively.Reductive alkylation of (p-aminobenzoyl)-L-glutamate with a niropyrimidine aldehyde derived from D- or L-serine similarly afforded, after cyclization and reduction, (6R)- or (6S)-tetrahydrofolic acid.The latter was then converted to the natural isomer of leucovorin by regioselective N5-formylation with carbonyl diimidazole / formic acid without loss of enantiomeric purity.
Stereochemistry of Reduction of the Vitamin Folic acid by Dihydrofolate Reductase
Charlton, Peter A.,Young, Douglas W.,Birdsall, Berry,Feeney, James,Roberts, Gordon C. K.
, p. 1349 - 1354 (2007/10/02)
Reduction of the vitamin folic acid (6) to the coenzyme 5,6,7,8-tetrahydrofolic acid (1) by the enzyme dihydrofolate reductase is shown to involve transfer of the 4-pro R hydrogen of NADPH to the same face at both C-6 and C-7 of the pteridine system (the re face at C-6 and the si face at C-7).The orientations of the pteridine system of folic acid (6) and of dihydrofolic acid (5) when bound to the enzyme are different from the orientation of the pteridine ring of the anti-cancer drug methotrexate (11) when bound to this enzyme.
