5,10-Dideazatetrahydrofolic acid

Selective reduction of the 7-oxo group in pyrido[23-synthetic approach to 5,10-dideazatetrahydrofolic acid <00H(53)1207>. Cycloaddition of pyrimido[4,5-c][l,2,5]oxadiazine 96 with 2,3-dihydrofuran affords a new synthesis of dimethyllumazine derivative 97 which undergoes a ring-opening reaction to give pyrazine derivative 98 <00JHC419>. 

Furthermore the syntheses of 8,10-dideazatetrahydrofolic acid and its 5-methyl- and 5-formyl derivatives (429) have been reported <93H(35)755>. The 5-/V-methyl derivative turned out to be more potent than 5,10-DDATHF as an inhibitor of growth for L1210 cells in culture but the locus of action is apparently unrelated to inhibition of GAR-Tfase. Unfortunately, 5-methyl-8,10-DDATHF was not active in vivo against an L1210 challenge in mice. 

Typically, the 4-amino group in pyrido[2,3-<7]pyrimidine-2,4-diamines will be replaced by a hydroxy function during a reaction with 5 -10 % aqueous sodium hydroxide at reflux temperature.109, 355 358 This is one of the steps in the synthesis of 8,10-dideazatetrahydrofolic acids. 

Alati T, Worzalla IF, Shih C et al. Augmentation of the therapeutic activity of lometrexol -(6-R)5,10-dideazatetrahydrofolate- by oral folic acid. Cancer Res 1996 56 2331-2335. 

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