Diastereoselective synthesis of novel (S)-lactic pyrazoline derivatives and investigation of antibacterial capabilities

Abstract

In this study, a novel series of diastereomerically enriched lactic-derived pyrazoline compounds 7(a-l) were synthesized via cyclocondensation of (S)-lactic Hydrazide with various substituted Chalcones under basic conditions. The methodology benefits from the inherent chirality of (S)-ethyl lactate, serving as a chiral precursor, allowing diastereoselectivity in the formation of (S,R)-pyrazoline derivatives. Structural confirmation was achieved using IR, ¹H NMR, ¹³C NMR, mass spectroscopic data, and elemental analysis. The proposed stereochemistry of compound 7b has been further corroborated by X-ray diffraction study. This selectivity can be related to the stability of (S,R)-pyrazolines versus (S,S)-pyrazoline derivatives, that our DFT calculation method confirmed this idea. The yields of the target compounds ranged from 24 to 63%, with approximately 100% diastereoselectivity giving exclusively the corresponding diastereoisomers that have (R)-configuration of the chiral carbon in their pyrazoline ring moiety. Evaluation of the antibacterial activity revealed that compounds 7g (IZD: 12 mm, MIC: 264 µg/ml) and 7j (IZD: 14 mm, MIC: 264 µg/ ml) exhibited considerable effect against Gram-positive S. aureus. Additionally, compound 7h (IZD: 10 mm, MIC: 512 µg/ml) demonstrated activity against P. aeruginosa and A. baumannii.

Keywords: (S)-lactic hydrazide; (S)-lactic pyrazoline; Antibacterial properties; Chirality induction; Diastereoselective synthesis.