Synthesis, stereochemistry and antimicrobial evaluation of some N-morpholinoacetyl-2,6-diarylpiperidin-4-ones

In a search for new leads towards potent antimicrobial agents, an array of novel N-morpholinoacetyl-2,6-diarylpiperidin-4-ones has been synthesized and their in vitro antibacterial activity against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Salmonella typhi and antifungal activity against Candida albicans, Rhizopus sp., Aspergillus niger and Aspergillusflavus were evaluated. Structure and stereochemistry of all the N-morpholinoacetyl-2,6-diarylpiperidin-4-ones have been analyzed using H-1 and C-13 NMR spectroscopic techniques. In all the cases, amide N-C=O group is preferentially in coplanar orientation with respect to the dynamically averaged plane of the piperidone ring. Further, all the symmetrically substituted compounds 19, 23, 24, 26 and 27 are expected to adopt half boat conformations while other compounds 20-22 and 25 adopt twist-boat conformations. Structure-activity relationship results for these nine compounds have shown that compounds 26 and 27 exerted excellent antibacterial activity against all the bacterial strains used except 27 against S. aureus. Against C. albicans and A. flavus, compound 24 recorded excellent antifungal activities while against Rhizopus sp., compound 25 showed potent activities. The obtained results may be used as key step for the building of novel chemical compounds with interesting antimicrobial profiles comparable to that of the standard drugs. (c) 2007 Elsevier Masson SAS. All rights reserved.