Stereoselective Asymmetric Syntheses of Molecules with a 4,5-Dihydro-1<i>H</i>-[1,2,4]-Triazoline Core Possessing an Acetylated Carbohydrate Appendage: Crystal Structure, Spectroscopy, and Pharmacology
Anwaar S. Al Maqbali,
Nawal K. Al Rasbi,
Wajdi M. Zoghaib,
Nallusamy Sivakumar,
Craig C. Robertson,
Musa S. Shongwe,
Norbert Grzegorzek,
Raid J. Abdel-Jalil
Affiliations
Anwaar S. Al Maqbali
Department of Chemistry, College of Science, Sultan Qaboos University, Al-Khod 123, Muscat P.O. Box 36, Oman
Nawal K. Al Rasbi
Department of Chemistry, College of Science, Sultan Qaboos University, Al-Khod 123, Muscat P.O. Box 36, Oman
Wajdi M. Zoghaib
Department of Chemistry, College of Science, Sultan Qaboos University, Al-Khod 123, Muscat P.O. Box 36, Oman
Nallusamy Sivakumar
Department of Biology, College of Science, Sultan Qaboos University, Al-Khod 123, Muscat P.O. Box 36, Oman
Craig C. Robertson
Department of Chemistry, University of Sheffield, Sheffield S3 7HF, UK
Musa S. Shongwe
Department of Chemistry, College of Science, Sultan Qaboos University, Al-Khod 123, Muscat P.O. Box 36, Oman
Norbert Grzegorzek
Institute of Organic Chemistry, University of Tübingen, Auf Der Morgenstelle 18, A-Bau, 72076 Tübingen, Germany
Raid J. Abdel-Jalil
Department of Chemistry, College of Science, Sultan Qaboos University, Al-Khod 123, Muscat P.O. Box 36, Oman
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.
