Review of computational studies applied in new macrolide antibiotics

Abstract

Macrolide antibiotics have been the focus of widespread research due to increasing bacterial resistance. Structure elucidation of a large number of macrolides, shows the existence of two parts. The first one is a macrocyclic system from 12 to 40 links with a lactone function; the second part is a sugar. Conformational analysis indicates that each studied macrocycle presents eight families of privileged conformers. They result from the combination of the conformations of the two systems, diene and a,b-unsaturated ester. In presence of tricarbonyliron, the number of the privileged conformations was reduced to four. The study of stereochemical control in macrocycles was carried out using molecular mechanics and molecular dynamics. For complexing macrocycles, a high diastereoselectivity was obtained, this is the result from the combination of local control exerted by the methyl group and stereochemical control with tricarbonyliron.