Conformational analysis in 18-membered macrolide antibiotics based on molecular mechanics

Abstract

Conformational analysis of macrolides with 18-ring membered has been carried out using molecular mechanics calculations and molecular dynamics. A high conformational mobility of no complexed macrocycles has been obtained and an important stereoselectivity has been observed for the complexed macrocycles. For 18d macrolide, which was presented by a privileged conformer with 20.1% without complex, was populated with 50.1% in presence of Fe(CO)3. For the most privileged conformer geometry; the α,β-unsaturated ester group has an s-cis conformation with a torsion angle φ1: O19-C2-C3-C4 = 14.5° for macrocycle 18d macrolide and φ1: O19-C2-C3-C4 = 25.0° for 18s macrolide. The diene group has an s-trans conformation with a torsion angle φ2:C11-C12-C13-C14 = 169.4° for 18d macrolide and φ2:C10-C11-C12-C13 = 179.5° for 18s macrolide