106400-18-4Relevant 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.
Asymmetric synthesis of lometrexol ((6R)-5,10-dideaza-5,6,7,8-tetrahydrofolic acid)
Barnett,Wilson,Wendel,Winningham,Deeter
, p. 7038 - 7045 (2007/10/02)
An enantioselective synthesis of lometrexol (1) which utilizes (5R)-2-piperidone 18 as a key intermediate is described. Lipase-catalyzed enantioselective esterification of 1,3-propanediol derivative 5 provided (R)-(+)-6, the absolute configuration of whic
Enantioselective synthesis of antifolates
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, (2008/06/13)
A process and intermediates for the enantioselective synthesis of 5,10-dideaza-5,6,7,8-tetrahydrofolic acid are disclosed.
Asymmetric synthesis and absolute configuration of 5,10-dideaza-5,6,7,8-tetrahydropteroic acid and 5,10-dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF)
Barnett,Wilson
, p. 6291 - 6294 (2007/10/02)
Lipase-catalyzed enantioselective esterification of 2-substituted 1,3-diols has been utilized in the asymmetry synthesis and consequent configurational assignments of the title compounds.
Synthesis and Antifolate Activity of 5-Methyl-5,10-dideaza Analogues of Aminopterin and Folic Acid and an Alternative Synthesis of 5,10-Dideazatetrahydrofolic Acid, a Potent Inhibitor of Glycinamide Ribonucleotide Formyltransferase
Piper, J. R.,McCaleb, G. S.,Montgomery, J. A.,Kisliuk, R. L.,Gaumont, Y.,et al.
, p. 2164 - 2169 (2007/10/02)
The title compounds were prepared in extensions of a general synthetic approach used earlier to prepare 5-alkyl-5-deaza analogues of classical antifolates.Wittig condensation of 2,4-diaminopyridopyrimidine-6-carboxaldehyde (2a) and its 5-methyl ana
