Synthesis and antifungal activities of 5-(3,4,5-trimethoxyphenyl)-2-sulfonyl-1,3,4-thiadiazole and 5-(3,4,5-trimethoxyphenyl)-2-sulfonyl-1,3,4-oxadiazole derivatives

• Published in: Bioorganic & medicinal chemistry 2007-06, Vol.15 (12), p.3981-3989
• Main Authors: Chen, Cai-Jun, Song, Bao-An, Yang, Song, Xu, Guang-Fang, Bhadury, Pinaki S., Jin, Lin-Hong, Hu, De-Yu, Li, Qian-Zhu, Liu, Fang, Xue, Wei, Lu, Ping, Chen, Zhuo
• Format: Article
• Language: English
• Subjects: Antibiotics. Antiinfectious agents. Antiparasitic agents; Antifungal activity; Antifungal agents; Antifungal Agents - chemical synthesis; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; Biological and medical sciences; Catalyst; Crystallography, X-Ray; Fungi - classification; Fungi - drug effects; Ionic liquid; Magnetic Resonance Spectroscopy; Medical sciences; Microbial Sensitivity Tests; Models, Molecular; Oxadiazole moiety; Oxadiazoles - chemical synthesis; Oxadiazoles - chemistry; Oxadiazoles - pharmacology; Pharmacology. Drug treatments; Spectrophotometry, Infrared; Sulfone; Synthesis; Thiadiazole moiety; Thiadiazoles - chemical synthesis; Thiadiazoles - chemistry; Thiadiazoles - pharmacology
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2007.04.014

A new series of sulfone derivatives containing trimethoxyphenyl substituted 1,3,4-thiadiazole and 1,3,4-oxadiazole moieties ( 9a– 9i, 10a– 10q) were synthesized and evaluated for antifungal activities against Gibberella zeae, Botrytis cinerea, and Sclerotinia sclerotiorum. These compounds are shown to be fungicidally active. Title compounds 10i and 10j can inhibit mycelia growth by approximately 50% (EC 50) at 2.87–99.33 μg/mL in vitro against 10 kinds of fungus. Starting from the key intermediate 5-(3,4,5-trimethoxyphenyl)-1,3,4-thiadiazole-2-thiol ( 4) or the oxadiazole analogue ( 5), the title compounds 9 and 10 are synthesized by a two-step process. Thioetherification reaction of 4 or 5 with an organic halide catalyzed by indium or indium tribromide first affords appropriate sulfide 7 or 8, which is then converted into title compounds 9 or 10 by hydrogen peroxide oxidation catalyzed by ammonium molybdate in ionic liquid [bmim]PF 6. The structures are unequivocally confirmed by spectroscopic (IR, 1H and 13C NMR) data and elemental analyses. The structures of 8d and 10q are further established by X-ray crystallographic diffraction analysis. The compounds have been shown to be fungicidally active. Title compounds 10i and 10j can inhibit mycelia growth by approximately 50% (EC 50) at 2.9–93.3 μg/mL in vitro against 10 kinds of fungi.