Dual site reactivity of indole-3-Schiff bases with S/Se/Cl substituted ketenes for stereoselective C-4 substituted indole-ß-lactams, biological evaluations, magic chloro effect and molecular docking studies.

ABSTRACT

A convenient methodology for C-4 indole-ß-lactam hybrids with chloro, sulphur and seleno substitutions through dual site reactivity of indole-3-Schiff bases towards ketenes has been developed. The reaction proceeded in a stereospecific manner with the exclusive formation of trans-ß-lactams assigned with respect to C3-H and C4-H. The synthesized novel ß-lactams have been characterized with the help of elemental analysis (CHNS) and spectroscopic techniques viz.1H NMR, 13C NMR, DEPT 135, HSQC and IR. The trans configuration was further estabilished based on X-ray crystallographic data. Examination of antibacterial properties unveiled that only derivatives 5a and 5b, featuring chloro substitution, exhibited potent activities, underscoring the emergence of the recently coined term "magic chloro effect". Molecular docking analysis provided additional support for the observed in vitro antibacterial activities of compounds 5a-b.