RECENT DEVELOPMENTS WITH MACROLIDE ANTIBIOTICS

Macrolide antibiotics have recently experienced a significant renaissa nce with the introduction of several new semi-synthetic derivatives, a nd subsequent research has identified many additional opportunities fo r useful new agents. Modifications at position C-3 of erythromycin hav e been especially promising, yielding 'ketolides' such as HMR 3647, as well as other investigational compounds from Taisho and Abbott. Withi n 16-membered macrolides, new series of derivatives of the leucomycins and repromicin have been disclosed by Meiji Seika and Pfizer, respect ively. Advances in the molecular biology and genetics of macrolide-pro ducing organisms have now made feasible the directed biosynthesis of n ew hybrid structures by methodologies that it is becoming possible to employ on a combinatorial scale. Finally, non-anti-infective activitie s associated with the macrolides are being pursued, especially with th e gastrointestinal prokinetic macrolides (motilides).