Chapter 3 - Chemical Modification of Macrolides

Abstract

This chapter deals with progress in the chemical modification and structure-activity relationships of 14 and 15-membered macrolides, mainly erythromycin derivatives, 16-membered macrolides, mainly the leucomycin and tylosin families, and the avermectin family of macrolides, showing nematocidal, insecticidal, and arachnidicidal activities. The unique structures and physicochemical properties of macrolides exhibits diversity in biological activity, such as antibacterial, antifungal, antiprotozoal, and immunomodulating activities. Naturally occurring macrolides does not always have the most desirable chemical characteristics and biological properties. Therefore, improvements to their chemical and biological properties by chemical modification and microbial transformation of the lactone ring or sugar moiety is usually done. Coupled with these efforts, rapid advances in technology, such as nuclear magnetic resonance (NMR) analysis, mass spectroscopy, X-ray analysis, computational analysis, chemical synthesis, and biotechnology also helps in chemical modification of macrolides. Macrolides with 14 and 16-membered rings are productive sources of semisynthetic derivatives that have significantly extended the utility of the macrolide class as important antibiotics. New semisynthetic derivatives have exhibited a variety of improved features, such as an expanded antimicrobial spectrum, increased potency, greater efficacy, better oral bioavailability, and antimicrobial activity against resistant strains.