Stereoselective Asymmetric Syntheses of Molecules with a 4,5-Dihydro-1 H-[1,2,4]-Triazoline Core Possessing an Acetylated Carbohydrate Appendage: Crystal Structure, Spectroscopy, and Pharmacology

Molecules. 2024 Jun 14;29(12):2839. doi: 10.3390/molecules29122839.

Abstract

A new series of chiral 4,5-dihydro-1H-[1,2,4]-triazoline molecules, featuring a β-ᴅ-glucopyranoside appendage, were synthesized via a 1,3-dipolar cycloaddition reaction between various hydrazonyl chlorides and carbohydrate Schiff bases. The isolated enantiopure triazolines (8a-j) were identified through high-resolution mass spectrometry (HRMS) and vibrational spectroscopy. Subsequently, their solution structures were elucidated through NMR spectroscopic techniques. Single-crystal X-ray analysis of derivative 8b provided definitive evidence for the 3-D structure of this compound and revealed important intermolecular forces in the crystal lattice. Moreover, it confirmed the (S)-configuration at the newly generated stereo-center. Selected target compounds were investigated for anti-tumor activity in 60 cancer cell lines, with derivative 8c showing the highest potency, particularly against leukemia. Additionally, substituent-dependent anti-fungal and anti-bacterial behavior was observed.

Keywords: 1,2,4-triazoline; anti-cancer; anti-microbial; asymmetric synthesis; glucopyranoside moiety; single-crystal X-ray analysis; spectroscopic techniques; stereoselectivity.

MeSH terms

  • Acetylation
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Carbohydrates / chemistry
  • Cell Line, Tumor
  • Crystallography, X-Ray
  • Humans
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Stereoisomerism
  • Structure-Activity Relationship
  • Triazoles* / chemical synthesis
  • Triazoles* / chemistry
  • Triazoles* / pharmacology

Substances

  • Triazoles
  • Antineoplastic Agents
  • Carbohydrates

Grants and funding

Sultan Qaboos University is gratefully acknowledged for its financial support (A.S.A.M., PhD; Bench Fees; SQU Internal Grant, IG/SCI/CHEM/24/03).