Regioselective synthesis of novel 2,3,4,4a-tetrahydro-1H-carbazoles and their cholinesterase inhibitory activities

Abstract

The present study describes the regioselective synthesis of novel 2,3,4,4a-tetrahydro-1H-carbazoles (syn-2(a–q) and anti-3(a–b)) from L-menthone via Fischer indole synthesis. The reaction between L-menthone and different substituted phenyl hydrazines, carried out in acetic acid as catalyst and solvent, yielded a mixture of corresponding 2,3,4,4a-tetrahydro-1H-carbazole diastereomers, instead of the expected indoles. These were characterized by different spectroscopic and single-crystal X-ray diffraction techniques. The isolated single diastereoisomers were further evaluated for inhibitory activities against various enzymes such as cholinesterases, xanthine oxidase, α-chymotrypsin, urease, phosphodiesterase and carbonic anhydrase-II activity, as well as against DPPH radical scavenging and anti-cancer activity against PC-3 cell line. The 2,3,4,4a-tetrahydro-1H-carbazoles show promising inhibitory activities only against acetyl- and butyrylcholinesterase. Moreover, kinetic analyses were carried out for the study of mechanism of inhibition of the active compounds.