Total synthesis of vancomycin - Part 4: Attachment of the sugar moieties and completion of the synthesis

The total synthesis of vancomycin (1, Figure 1) is described. The successfu l plan for this synthesis involves sequential and stereoselective coupling of vancomycin aglycon acceptor 6 and glycosyl donors, trichloroacetimidate 50 and glycosyl fluoride 27 (Scheme 8). Acceptor 6 was synthesized from van comycin aglycon (2) (Scheme 1), which was derived both by total synthesis a nd by semisynthesis from vancomycin itself (1) (Scheme 2). The vancosamine derivative 27 was obtained by total synthesis (Scheme 3) while the glycosyl derivative 50 was prepared from glucal (46) (Scheme 6). A number of glycos idation model studies, carried out in older to establish the final route to vancomycin (1), are also described and so are a number of failed attempts to secure the target molecule (1).