Convenient synthesis of 10-deazaaminopterin via a pteridine ylide.
10-Deazaaminopterin, a potential antitumor agent now undergoing clinical trials, has been synthesized by a new approach involving the Wittig reaction. The ylide obtained by reaction of 6-(bromomethyl)-2,4-pteridinediamine with triphenylphosphine in Me2NAc, followed by treatment with NaOMe, underwent smooth reaction with diethyl N-(4-formylbenzoyl)-L-glutamate to give the vinyl precursor of the subject compound. Catalytic hydrogenation (Pt in glacial AcOH) of this product at ambient conditions led to uptake of 3 molar equiv of H2. Exposure to air during saponification of the ester groupings apparently gave the 7,8-dihydro compound according to UV spectral data, and further oxidation with H2O2 led to 10-deazaaminopterin.
D000630:Aminopterin / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D008722:Methods; D011621:Pteridines
D000970:Antineoplastic Agents; D011621:Pteridines; D000630:Aminopterin; C017178:10-deazaaminopterin