Recent developments with macrolide antibiotics

Macrolide antibiotics have recently experienced a significant renaissance with the introduction of several new semi-synthetic derivatives, and subsequent research has identified many additional opportunities for useful new agents. Modifications at position C-3 of erythromycin have been especially promising, yielding ‘ketolides’ such as HMR 3647, as well as other investigational compounds from Taisho and Abbott. Within 16-membered macrolides, new series of derivatives of the leucomycins and repromicin have been disclosed by Meiji Seika and Pfizer, respectively. Advances in the molecular biology and genetics of macrolide-producing organisms have now made feasible the directed biosynthesis of new hybrid structures by methodologies that it is becoming possible to employ on a combinatorial scale. Finally, non-anti-infective activities associated with the macrolides are being pursued, especially with the gastrointestinal prokinetic macrolides (motilides).