An atom economic synthesis and AChE inhibitory activity of novel dispiro 7-aryltetrahydro-1H-pyrrolo[1,2-c][1,3]thiazole and 4-aryloctahydroindolizine N-methylpiperidin-4-one hybrid heterocycles

摘要

The 1,3-dipolar cycloaddition of azomethine ylides generated in situ from acenaphthenequinone and α-amino acids viz. 1,3-thiazolone-4-carboxylic acid and piperidine-2-carboxylic acid to a series of 1-methyl-3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones afforded novel spiro[5.2']acenaphthene-1'-onespiro[6.3']-5'-arylmethylidene-1'-methylpiperidin-4'-one-7-aryltetrahydro-1H-pyrrolo[1,2-c][1,3]thiazoles and spiro[2.2']acenaphthene-1'-onespiro[3.3']-5'-arylmethylidene-1'-methylpiperidin-4'-one-4-aryloctahydroindolizines respectively in quantitative yields. These compounds were evaluated for their AChE inhibitory activity and compound 3c was found to be the most potent with IC50 1.86μmol/L. ?1,3-Dipolar cycloaddition of azomethine ylide to exocyclic dipolarophiles.?Synthesis of 33 new spiro pyrrolo[1,2-c][1,3]thiazole and octahydroindolizine.?Structure of these spiro-heterocycles elucidated with NMR and X-ray.?Compounds evaluated for their acetyl cholinesterase (AChE) inhibitory activity.