Total Synthesis of Vancomycin—Part 2: Retrosynthetic Analysis, Synthesis of Amino Acid Building Blocks and Strategy Evaluations

A number of valuable new synthetic strategies, such as the triazene-driven biaryl ether synthesis, have been developed during the total synthesis of vancomycin (1). Modern catalytic asymmetric reactions were employed for the construction of the required amino acid building blocks, which were then assembled to the appropriate peptide fragments, whose cyclization in the order C-O-D→AB/C-O-D→AB/C-O-D-E led to framework of the vancomycin aglycon (2). Sequential attachment of the required sugar moieties onto a suitably protected aglycon derivative, followed by deprotection, allowed the stereoselective total synthesis of the glycopeptide antibiotic vancomycin (1).