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

• 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.

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 1.86 μmol/L.

The present work reports the 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 derived from the 1,3-dipolar cycloaddition of azomethine ylides to 1-methyl-3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones.Figure optionsDownload as PowerPoint slide