Substituted Quinolinones, Part 10: Synthesis of Angular Tetracyclic Thieno and Thiopyrano[3,2- c ]benzo[ h ]quinolinones Under PTC Conditions as Novel Enzymatic Enhancers

Abstract

4-Chlorobenzo[h]quinolin-2(1H)-one (4) and its 4-sulfanyl derivative 6 were smoothly obtained via chlorination, hydrolysis, and sulfurization starting with 4-hydroxybenzo-[h]quinolin-2(1H)-one (1). Heterocyclization reaction of compound 6 with chloroacetaldehyde diethylacetal, phenacylbromide, chloroacetonitrile, ethyl chloroacetate, and bromomalononitrile under phase transfer catalysis (PTC) conditions was described affording benzo[h]thieno[3,2-c]quinolinones 7–9 , 11, 12, and 14. The PTC-nucleophilic substitution of compound 4 with malononitrile gave quinolinylmalononitrile 15, which subsequently cyclized with sulfur/triethylamine (TEA) to afford benzo[h]thieno[2,3-c]quinolinone 16. The PTC reaction of compound 6 with CS 2 and malononitrile gave benzo[h]thiopyrano[3,2-c]quinolinone 18. Similarly, cyclization of compound 4 with thiosalicylic acid furnished benzo[h]thiochromeno[3,2-c]quinolinedione 20. Thermal condensation of compound 6 with ethyl 2-cyano-3-ethoxyacrylate or ethyl 2-cyano-3,3-di(methylsulfanyl)acrylate afforded benzo[h]thiopyrano[3,2-c]quinolinones 22 and 24, respectively. The effect of new 14 products on α-amylase activity was examined. Thienoquinolinones 9, 11, 14, and 16 were the most potent enhancers in which these compounds multiplicate the activity of the enzyme to produce α-D-glucose up to eightfold.