Vancomycin aglycon, total synthesis

Vancomycin (Section 16.1.7) represents a major part of the presentation of Section 16. Vancomycin is a heptapeptide-like structure with interlocking macrocyclic ring systems linked to a disaccharide. Three representative syntheses of vancomycin aglycon are presented. They include a most impressive total synthesis from the Evans Group (Section 16.1.7.1), 37,38 the Nicolaou Group (Section 16.1.7.2), 39 and the Boger Group (Section 16.1.3). 40 Finally, the chapter is concluded with the Nicolaou total synthesis of vancomycin. 41 ... 

Vancomycin Vancomycin (57) is an important antibiotic in the treatment of severe bacterial infections by a variety of pathogens and has been one of the most attractive targets for synthetic chemists over the past decade. In 1998, the completion of the total synthesis of the vancomycin aglycon was almost simultaneously reported by Evans [90] and Nicolaou [91]. 

Vancomycin is well-known as the last line of defense against drug-resistant bacteria. Nic-olaou and his group reported a Suzuki coupling approach to the AB-COD bicyclic system of vancomycin [34]. The total synthesis of the vancomycin aglycon was subsequently reported by the same workers [35]. 

Key reactions of the total synthesis of the vancomycin aglycon presented by Nicolaou and coworkers [4-6] are a Suzuki coupling [15] for the synthesis of the M(5-7) unit (Scheme 5) and the triazene method, described recently for the construction of macrocyclic biaryl ethers (Scheme 6) [16]. 

With the presented total syntheses of the vancomycin aglycon, for the first time comprehensive methods and strategies for the synthesis of vancomycin antibiotics and the construction of modified structures are available. Recently, bacterial strains have been discovered that displayed resistance against vancomycin [2]. Against this background, new biological studies with synthetically modified members of the vancomycin class of natural substances could be promising for the future. 

The total synthesis of the vancomycin aglycon was accomplished by Evans et al. 

The structure of vancosamine was elucidated in 1982 [125] and its total synthesis was finally accomphshed in 1999. By 1998 two groups, had reported independent total syntheses of the vancomycin aglycon [126,127,128,129,130] and by early 1999 the first total synthesis [131,132,133,134,135] of vancomycin itself appeared in the literature followed by another... 

Crowley, B. M., Boger, D. L. Total synthesis and evaluation of [psi[CH2NH]Tpg4]vancomycin aglycon Reengineering vancomycin for Dual D-Ala-D-Ala and D-Ala-D-Lac binding. J. Am. Chem. Soc. 2006,128, 2885-2892. 

Scheme 23. Final stages and completion of Nicolaou s total synthesis of vancomycin aglycon (13).

In 1999, a third total synthesis of the vancomycin aglycon (13) was achieved by Professor Dale Boger and his group at The Scripps Research Institute based on a unique design for determining the order of macrocycle construetion relative to those already presented... 

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