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

## TL;DR

This study creates new chiral pyrazoline compounds from lactic acid and tests their antibacterial effects against specific bacteria.

## Contribution

A diastereoselective method for synthesizing (S,R)-pyrazoline derivatives using (S)-lactic hydrazide and chalcones is introduced.

## Key findings

- Compounds 7g and 7j showed strong antibacterial activity against S. aureus.
- Compound 7h exhibited activity against P. aeruginosa and A. baumannii.
- X-ray and DFT analysis confirmed the stereochemistry and stability of the (S,R)-pyrazoline derivatives.

## 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.

The online version contains supplementary material available at 10.1038/s41598-025-32881-3.