Synthesis of Novel 4-Pyridone Annelated-Isatin Derivatives as Potential Antitumor Agents
Date
2015-04-21
Authors
Alasad, Randa
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Abstract
A new 6-ethyl-1,1-dihydroxy-2,9-dioxo-2,3,6,9-tetrahydro-1H-pyrrolo[3,2-
f]quinoline-8-carboxylic acid (7) has been synthesized via the interaction of 6-
amino-1-ethyl-4-oxoquinoline-3-carboxylic ester with chloral hydrate and
hydroxylamine hydrochloride that gave the corresponding isonitroso-acetamido
derivative which, upon treatment with concentrated sulfuric acid, was converted
regioselectively into 1,2,9-trioxopyrrolo[3,2-f]quinoline-8-carboxylic acid. This
novel tricyclic system was reacted with selected substituted oxindoles in acidic
medium to deliver the corresponding isoindigo compounds (9a-f).
Newpyrrolidine-2-spiro-3-(2-oxindole) fused to 4-oxopyridine-3-carboxylate
derivatives (10a-o) were also synthesized via 1,3-dipolar cycloaddition reaction of
compound (7) utilizing several (α)-amino acids in a methanol/water medium,
through formation of the azomethineylides, followed by 1,3-dipolar cyclo
addition of the dipolarophile N-methylmaleimide. The newly synthesized
compounds were characterized by spectroscopic techniques (1H-NMR,13C-NMR,
DEPT, 2D-NMR (COSY, HMQC and HMBC)) experiments, IR and High Resolution
Mass Spectrometry (HRMS).