PMID: 6410065Aug 1, 1983Paper

Folate analogues. 22. Synthesis and biological evaluation of two analogues of dihydrofolic acid possessing a 7,8-dihydro-8-oxapterin ring system

Journal of Medicinal Chemistry
M G NairG North

Abstract

Two analogues of dihydrofolic acid possessing a 7,8-dihydro-8-oxapterin ring system have been synthesized and evaluated for their antifolate activities. These compounds, N-[(2-amino-4-hydroxy-7,8-dihydro-8-oxa-6-pteridinyl)benzoyl]-L-glutamic acid (3) and N-[[(2-amino-4-hydroxy-7,8-dihydro-8-oxa-6-pteridinyl) methyl]benzoyl]-L-glutamic acid (4), were synthesized by reacting the appropriately substituted alpha-halo ketones with 2,5-diamino-4,6-dihydroxypyrimidine (2). Elaboration of p-carbomethoxybenzaldehyde (5) to p-carbomethoxyphenacyl bromide (7) was accomplished by its oxidation with Jones reagent and the successive treatment of the oxidation product with SOCl2, CH2N2, and HBr. Commercially available p-vinylbenzoic acid (11) was converted to its glutamate conjugate 12 and was further converted to the bromo ketone, diethyl N-[p-(1-bromo-2-oxopropyl)benzoyl]-L-glutamate (17), by a series of reactions involving epoxidation, oxirane ring opening with HBr, Jones oxidation, Zn/HOAc reduction, and successive treatment of the reduction product 16 with SOCl2, CH2N2, and HBr. These bromo ketones, 7 and 17, upon reaction with pyrimidine 2, gave the diethyl esters of the target compounds, which were hydrolyzed to 3 and 4 with NaOH. Com...Continue Reading

Citations

Jul 25, 2015·Journal of Enzyme Inhibition and Medicinal Chemistry·Mert Olgun KarataşOktay Arslan
Feb 24, 2006·Archiv der Pharmazie·Katrin Märschenz, Klaus Rehse
Oct 5, 2019·Chemical Biology & Drug Design·Dhafer S ZinadMohammad Rizki Fadhil Pratama

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