Total synthesis of vancomycin - Part 3: Synthesis of the aglycon

The total synthesis of the vancomycin aglycon (2, Figure 1) is described, C onstruction of the key intermediate, tricyclic triazene 3a (Figure 2), was accomplished in the order C-O-D-->AB/C-O-D -AB/C-O-D/D-O-E, The C-Q-D ring system 18a (Scheme 2) was formed by using the triazene ring-closure methodo logy from a precursor (17) already possessing the AB biaryl fragment 6, syn thesized by a Suzuki coupling reaction. At this point, a macrolactamization reaction furnished the AB ring system. Tripeptide 5 was incorporated in th e main framework and the triazene ring-closure methodology was applied agai n to achieve the formation of D-O-E ring system, providing tricyclic triaze ne 3a (Scheme 6), The latter was converted to the fully protected vancomyci n aglycon 45a by first introducing the phenolic moiety (derivative 43a) and then oxidizing the AA-7 side chain (Scheme 12), Finally, global deprotecti on afforded vancomycin's aglycon (2). Atropisomerization was successfully p erformed for D-O-E ring systems.