A Useful Synthesis of 2-Acylamino-1,3,4-oxadiazoles from Acylthiosemicarbazides Using Potassium Iodate and the Discovery of New Antibacterial Compounds
Tianlei Li,
Gang Wen,
Jishun Li,
Wenxuan Zhang,
Song Wu
Affiliations
Tianlei Li
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, China
Gang Wen
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, China
Jishun Li
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, China
Wenxuan Zhang
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, China
Song Wu
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, China
A useful method for the synthesis of 2-acylamino-1,3,4-oxadiazoles was developed. By using potassium iodate as an oxidant in water at 60 °C, a wide range of 2-acylamino-1,3,4-oxadiazoles were afforded in moderate to excellent yields within two hours. This method could provide a facile shortcut to generate a series of 2-acylamino-1,3,4-oxadiazoles in medicinal chemistry. Interestingly, some highly potent antibiotic compounds were found through this synthetic method, and some of them displayed a significant improvement in activity compared with the corresponding 1,4-diacylthiosemicarbazides. Compound 2n was the most active against Staphylococcus aureus with MIC (minimum inhibitory concentration) of 1.56 mg/mL, and compounds 2m and 2q were the most active against Bacillus subtilis with MIC of 0.78 mg/mL. The preliminary cytotoxic activities of the most potent compounds 2m, 2n, and 2q against the androgen-independent (PC-3) prostate cancer cell line were more than 30 μM (IC50 > 30 μM).
