Total Synthesis of Vancomycin Aglycon—Part 1: Synthesis of Amino Acids 4–7 and Construction of the AB-COD Ring Skeleton

Abstract

A triazene-based synthetic strategy for the construction of the complex biaryl ethers and a Suzuki coupling reaction were the key steps in the synthesis of precursor 1 of the aglycon of vancomycin, which already contains the complete skeleton of the target compound. The cleavage of the triazene unit from the D ring and the removal of the other protecting groups led to the aglycon of vancomycin. These strategies should be particularly valuable for the synthesis of other naturally occurring glycopeptide antibiotics and offer opportunities for the synthesis of combinatorial libraries of compounds of the vancomycin family for chemical biology studies.