Synthesis And Activity Of Erythromycin Derivatives

Erythromycin had been extensively used in the treatment of bacterial infections. In addition to its anti-microbial and prokinetic effects, some novel activities of the erythromycin derivatives had attracted much attention as new therapeutic potentials, especially the anti-inflammatory activity. 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.We picked 12-membered ring erythromycin derivative LY267108, erythromycin, roxithromycin and clarithromycin as the lead compounds and through structural modification of the side chain and 3' amino group, 23 compounds were designed.Through the modification at the C-12 position and 3' amino group of LY267108, 12-membered ring erythromycin derivatives WH101 - WH112 were got.The synthesis of WH201 to WH211 was accomplished through 3'-N-alkylation. Treatment of N-demethyl derivatives (3-1 to 3-4) and 6-membered heterocyclic ring in DMF or CH₂Cl₂ with N, N-diisopropylethylamine and l-bromo-3-chloropropane or 1, 4-dibromo-2-butene effected the formation of the target products.During our experiment, the N-monodemethylated 12-membered-ring erythromycin derivative 3-3 was obtained straightforward from 3-1 in 66% yield.Erythromycin and the intermediate 3-2, 3-6 were evaluated for their in vitro anti-inflammatory activities against T lymphocyte.All of the chemical structures of the 23 compounds were characterized by the applications of ¹H-NMR,¹³C-NMR and MS. The data of ¹³C-NMR spectra were discussed briefly.