155690-84-9Relevant academic research and scientific papers
Synthesis of (6R)- And (6S)-5,10-dideazatetrahydrofolate oligo-γ-glutamates: Kinetics of multiple glutamate ligations catalyzed by folylpoly-γ-glutamate synthetase
Tomsho, John W.,McGuire, John J.,Coward, James K.
, p. 3388 - 3398 (2007/10/03)
Folylpoly-γ-glutamate synthetase (FPGS, EC 6.3.2.17) catalyzes the ATP-dependent ligation of glutamic acid to reduced folates including (6S)-5,6,7,8-tetrahydrofolate (H4PteGlu), as well as to anticancer drugs such as 5,10-dideaza-5,6,7,8-tetrahydrofolate ((6R)-DDAH 4PteGlu1, (6R)-DDATHF, Lometrexol(tm)). Synthesis of unlabeled mono- and polyglutamates, DDAH4PteGlu n (6R, n = 1-6; 6S, n = 1-2), as well as (6R)-DDAH 4Pte[14C]Glu1, was effected from (6R)- or (6S)-5,10-dideazatetrahydropteroyl azide and glutamic acid, H-Glu-γ- Glun-y-Glu-OH (n = 0-4), or [14C]glutamic acid, respectively. These compounds were evaluated as FPGS substrates to determine steady-state kinetic constants. Michaelis-Menten kinetics were observed for (6-R)-DDAH4PteGlu1, the isomer corresponding to H 4PteGlu, whereas marked substrate inhibition was observed for (6S)-DDAH4PteGlun (n = 1-2) and (6R)-DDAH 4PteGlun (n = 2-5), but not (6.R)-DDAH 4PteGlu6. Multiple ligation of glutamate renders a quantitative analysis of these data difficult. However, approximate values of KM = 0.65-1.6 μM and K1, = 144-417 μM for DDAH 4PteGln were obtained using a simple kinetic model. The Royal Society of Chemistry 2005.
Selective reduction of the 7-oxo group in pyrido[2,3d]pyrimidine-4,7- diones: A new synthetic approach to 5,10-dideazatetrahydrofolic acid (DDATHF)
Borrell, José I.,Teixidó, Jordi,Matallana, Josep Lluís,Martínez-Teipel, Blanca,Couceiro, Esther
, p. 1207 - 1214 (2007/10/03)
A selective reduction of the carbonyl group at C7 with borane in THF is accomplished for 2,4-diamino-7-oxo and 2-amino-4,7-dioxo substituted pyridopyrimidines (7a-c) and (13a-c) respectively, the ester group remaining unaltered in both cases. The synthesi
