Synthesis And Biological Activity Of Erythromycin Derivatives

Erythromycin had been extensively used in the treatment of bacterial infections for over 50 years. In addition to the anti-microbial and prokinetic effects, some novel activities of the erythromycin derivatives had attracted much attention as new therapeutic potentials, especiallythe anti-inflammatory activity. Long-term, low-dose erythromycin therapy is effective in the treatment of diffuse panbronchiolitis （DPB）. It is believed that erythromycin produce this benefit through an anti-inflammatory effect rather than antibacterial effect. Erythromycin and its derivatives could inhibit T lymphocyte proliferation and expression of nuclear factor-kappa B （NF-κB）, which was thought to be the nucleus of the mechanism of anti-inflammatory effect of erythromycin and its derivatives.In this paper, erythromycin, roxithromycin and clarithromycin could be the lead compounds for further modifications of 3’ amino group and 9 hydroxyl group. With the hopes of discovering a novel class of macrolides, we designed dimers of erythromycin derivatives.Following the reported methodologies the N-monodemethyled and oxidative compound could be separated from the lead compounds. The synthesis of QY101～QY105 were straightforward by acylations of amino group in dichloromethane. QY-201 and QY301～QY306 were yielded by employing dibromoalkanes as alkylating agents. QY401～QY403 were prepared by utilizing chloracetyl chloride as acylation agents in the presence of N,Ndiisopropylethylamine in dichloromethane at room temperature.All chemical structures of 15 compounds were characterized by ¹H-NMR, ¹³C-NMR and MS. The data of ¹³C-NMR spectra were discussed briefly.Some compounds were evaluated for their in vitro anti-inflammatory activities against human Jurkat cell lines by MTT assay. The results obtained in test demonstrated that all the compounds were active in this assay.