Convenient synthesis of 10-deazaaminopterin via a pteridine ylide.

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Piper JR, Montgomery JA

Convenient synthesis of 10-deazaaminopterin via a pteridine ylide.

J Med Chem. 1980 Mar;23(3):320-1.

PubMed ID

7365749 [ View in PubMed

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Abstract

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.

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Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Methotrexate	Dihydrofolate reductase	IC 50 (nM)	26	N/A	N/A	Details