Synthesis of a novel deazaaminopterin analogue

Miller, David O. (1989) Synthesis of a novel deazaaminopterin analogue. Masters thesis, Memorial University of Newfoundland.

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Abstract

This thesis describes the synthesis of a novel deazaaminopterin analogue, which has the glutamate-derived NH group replaced by methylene. This involved the preparation of an aminobenzoyl glutarate by a troublesome decarboxylation of an aroylmalonate, which was studied in some detail. Antibacterial screening revealed activity at 100 μg/mL against Stapliylococcus aureus in the case of the aminopterin analogue, but the aminobenzoylmethylglutarate was inactive against a variety of organisms. -- During synthetic work directed towards the corresponding methotrexate analogue it was found that N-methylation of N-arylbenzenesulfonamides causes enhanced loss of SO₂ in the mass spectrum, as well as interesting shielding effects in the proton and carbon magnetic resonance spectra. This was studied through synthesis and spectroscopic examination of a series of sulfonamides having electron-releasing and/or electron withdrawing substituents.

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