Synthesis of a Model Bicyclic CDE Ring System of Ristocetin A and Observation of a Facile Inversion of Configuration in a 16-Membered DE Ring Model

Abstract

Areneruthenium chemistry was used to effect intramolecular SNAr reactions between phenoxide nucleophiles and chlorophenylalanine residues that are connected by a peptide chain, resulting in the construction of a bicyclic peptido aryl ether system that corresponds to the BCDF system of the glycopeptide antibiotics ristocetin A and teicoplanin. A facile and selective base-catalyzed complete inversion of configuration at the D ring arylglycine residue was observed when this unit is the carboxylate terminus on a 16-membered ring system corresponding to the DEF rings of the target molecules. The inversion appears to result from an overwhelming thermodynamic preference for the inverted system and is supported by molecular mechanics and semiempirical calculations on the minimized conformations of the epimeric molecules.