Synthesis And Activity Of Erythromycin Derivatives

Macrolide antibiotics have been widely used for the treatment of bacterial infections for nearly sixty years since the early 1950s and have played an important role in the clinic. In addition to the anti-microbial effect, there are many other effects such as prokinetic activity, anti-inflammatory activity and luteinizing hormone-releasing hormone antagonistic activity. Moreover, they had been discovered helpful effect on the treatment of tumor.In our efforts to modify erythromycin derivatives, dimmer of erythromycin derivative, a novel class of erythromycin derivative was discovered with antitumor activity. Therefore we picked it up as a lead compound and through structural modification at the C-3, C-6 and C-9 position,15 novel compounds were designed.Following the reported methodologies, intermediates of erythromycin derivatives were synthetized. The cladinose moieties of erythromycin derivatives were selectively removed upon the treatment of dilute hydrochloric acid in an aqueous solution which gave the target products (BXJ-1-BXJ-6). The target products of ketolides (BXJ-7-BXJ-10) were prepared by utilizing DCC as dehydrolyzing agent, DMSO as oxydizing agent and pyridine-trifluoroacetic acid as catalyst in dichloromethane. The products (BXJ-11-BXJ-15) were acylides which were prepared by utilizing DCC as condensing agent and DMAP as catalyst.All of 15 compounds’chemical structures were characterized by the applications of ’H-NMR,13C-NMR and MS. The data of 13C-NMR spectra were discussed briefly.Seven of the target compounds were evaluated for their in vitro antitumor activities against human SGC-7901, KB and HT-1080 cell lines by MTT assay. The results of pharmacological test demonstrated that most of the target compounds were active in the assay.