Synthesis And Antibacterial Activity Of Yanglingmycin Analogues

Since the discovery of penicillin in 1928,antibiotics has become the most widely used drugs in clinical,which experienced 80 years of rapid development.Due to the abuse of antibiotics,the drug resistance of bacteria has become a major obstacle in the development of antibiotics at the same time.The discovery Andrimid which is the first inhibitor for fatty acid synthesis,opens a new generation of antibiotics development process for inhibiting fatty acid synthesis.In 2012,Pesticide Institute of Northwest Agriculture and Forestry University has discovered a new efficient and broad-spectrum fungicide inhibiting fatty acid synthesis,namely yanglingmycin,(S)-2-(o-hydroxyphenyl)-4-hydroxymethyl-4,5-dihydrooxazol.We investigate the structure dependence of biological activities.Aromatic nitrile was used as starting material to synthesize the yanglingmycin analogues.The biological activities of these compounds towards a wide variety of bacteria were evaluated,with the following results:(1)Synthetic route:The structure of 4-methoxycarbonyl-4,5-dihydroazol,was synthesized from aromatic nitrile starting material,through a product of pinner reaction with amino acid methyl ester.And the 4-hydroxymethyl-1,3-dihydroazol was synthesized by reduction of NaBH4.20 yanglingmycin analogues were synthesized,which were characterized by 1H-NMR,13C-NMR,DEPT135.(2)Disk diffusion antibiotic testing was utilized,with penicillin as a positive control,to evaluate the biological activities of all 20 synthesized yanglingmycin analogues against Bacillus cereus,Staphylococcus aureus,Bacillus subtilis,Pseudomonas aeruginosa,Escherichia coli,Pseudomonassyringaepv.actinidiae,Ralstonia solanacearum.Of the compounds tested,D1-2,L1-2,D2-2,L2-2 exhibited a high degree of activity towards all the tested bacteria;D1-1,L1-1,D2-1,L2-1 exhibited a medium degree of activity towards Gram positive Bacillus cereus and Bacillus subtilis.(3)Microdilution antibiotic testing was utilized,with penicillin as a positive control to evaluate the the minimum inhibitory concentration against all the 7 tested bacteria.The MIC of compounds D1-2,L1-2,D2-2,L2-2 were at 62.50～1.96μg/ml,wherein D2-2,L2-2 were the strongest inhibition of of Staphylococcus aureus with MIC of 1.96μg/ml...