Synthetic modification of a novel microbial ionophore: Exploration of anticoccidial structure-activity relationships

Article abstract of DOI:10.1021/jm00088a020

While fermentation-derived polyether ionophores such as salinomycin are the dominant class of anticoccidial feed additives, there is little information concerning the structural features which confer optimal potency/efficacy in this important series. The recently discovered microbial polyether 1a, featuring potent, broad-spectrum anticoccidial activity, was employed as a template to explore structure-activity relationships. A number of single-step synthetic modifications targeted structural changes in both the lipophilic carbon backbone and the ion-binding cavity of 1a. Although previous semisynthetic transformations among the polyether ionophores almost always resulted in a substantial loss of anticoccidial activity, we obtained several analogues, altered on the periphery of the ionophore-ion complex, which retain good potency and efficacy. Monoglycone 7 (semduramicin sodium) has the most impressive anticoccidial profile of this series, and is undergoing further biological testing under field conditions.