Synthesis, stereochemistry and antimicrobial evaluation of t(3)-benzyl-r(2), c(6)-diarylpiperidin-4-one and its derivatives

Abstract

In a wide research program toward new and efficient antimicrobial agents, a series of t(3)-benzyl-r(2), c(6)-diarylpiperidin-4-ones ( 1– 7) were synthesised and tested for their in vitro antibacterial and antifungal activities. Also, the structures and their stereochemistry of these synthesised compounds 1– 7 were characterized by IR, high resolution 1H NMR, 13C NMR and 1H– 13C COSY spectra. The analysis of coupling constants of compounds 1– 5 reveals that they exist in normal chair conformation with equatorial orientations of all the substituents. The spectra of 6 and 7 reveal the presence of two isomers labeled as E (carbonyl carbon is anti to benzyl group at C-3) and Z (carbonyl carbon is syn to benzyl group at C-3) in solution and the coupling constants ruled out the possibility of normal chair conformation. From the theoretical studies and coupling constant values the favoured conformation for the Z- and E-isomers of 6 and 7 was found to be the boat conformations. Their antibacterial activity against Streptococcus faecalis, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae and antifungal activity against Cryptococcus neoformans, Candida 6, Candida 51, Aspergillus niger and Aspergillus flavus were also evaluated.