Synthesis and antibacterial activity of new 4h-pyrano [3,2-h]quinolines and fused derivatives

Abstract

The starting materials, 2-amino-3-cyano-4-(3,4,5-trimethoxyphenyl)-4H-pyrano[3,2- h]quinoline 1 and ethyl-2-amino-4-(3,4,5-trimethoxyphenyl)-4H-pyrano [3,2-h]quinolin-3-carboxylate 2 were synthesised from 8-hydroxyquinoline and α-cyano-3,4,5-trimethoxycinnamonitrile and/or ethyl-α-cyano-3,4,5-trimethoxy-cinnamate respectively. In order to construct a third heterocyclic ring 1 and 2 were condensed with ethyl bromoacetate, formamide, carbon disulfide to afford pyrrolo-, pyrimido- and thiazinopyranoquinolines 3-6 respectively. The S-alkylated products 7 and 8 were obtained by the effect of chloroacetonitrile and/or ethyl chloroacetate on thiazinopyranoquinoline derivative 6. The attempt of cyanomethylation of the amino functional group of 1 to yield 10 with chloroacetonitrile in AcOH/AcONa failed and instead, pyridopyranoquinoline derivative 9 was obtained which is visualized to occur via cyclization of the initially formed acetylamino derivative by nucleophilic attack on the cyano group. Acetylation of 1 and 2 with acetic anhydride afforded the mono- and di-acetyl derivatives 11a and 11b respectively. A plausible explanation to form the mono-derivative with 1 and the di-derivative with 2 is the higher deactivating effect of the cyano function over that of the carboxyethyl group. Furoylation of 1 and 2 was achieved by furoyl chloride to give 12a and 12b respectively. The structural features of pyranoquinoline 2 were inferred from its microanalysis and spectral data such as IR, 1H-NMR and MS as well as its chemical reactions, as a bifunctional compound with carbon nucleophiles namely, phenyl isothiocyanate and nitrogen nucleophilic species namely, p-toluidine, benzylamine, aniline and hydrazine hydrate to give pyrimidopyranoquinoline derivative 13, carboxamides 14a-c and carboxyhydrazide 15 respectively. When the hydrazide 15 was treated with carbon disulfide in presence of KOH, it afforded the potassium salt 16 which was submitted to react with hydrazine hydrate at room temperature to give 17. The hydrazido group of 15 was utilized to construct heterocyclic moieties attached to postion-3 of the pyranoquinoline structure. Thus, the reaction of the carboxyhydrazide 15 with phenyl isothiocyanate, acetylacetone, and benzoylacetone resulted in the formation of 18, 19a and 19b respectively. Ethyl carbazate as a typical mesophile reacted with 2 to afford a fused tetracyclic product triazepinopyranoquinoline 20 via cyclization of the initially formed hydrazide. Among sixteen compounds screened against E. coli and S. aureus respectively, compounds 2 and 14c show a high order of antibacterial activity against both bacteria. 12b is strongly potent against Staphylococcus aureus.