Semi-synthetic derivatives of 16-membered macrolide antibiotics

The fermentation-derived 16-membered and 14-membered macrolides have been equally productive sources of semi-synthetic derivatives which have significantly extended the utility of the macrolide class as important antibiotics. New derivatives, prepared by both chemical and biochemical methods, have exhibited a variety of improved features, such as an expanded antimicrobial spectrum, increased potency, greater efficacy, better oral bioavailability, extended chemical and metabolic stability, higher and more prolonged concentrations in tissues and fluids, lower and less frequent dosing, and/or diminished side-effects [302]. However, even more improvements are both achievable and necessary if problems such as resistance to existing antibiotics continue to rise [303, 304]. Newer semi-synthetic macrolides which satisfy these important needs should be anticipated as the contributions from new fields such as genetic engineering of macrolide-producing organisms and more powerful computational chemistry are combined with the more traditional disciplines of chemical synthesis, bioconversions, and screening fermentation broths.