Vancomycin aglycone

Vancomycin aglycone (VAG) contains the same peptide scaffold as vancomycin, but it lacks the disaccharide unit (C53H52CI2N8O17, molecular mass of 1142). The basic... 

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 ... 

Cyclic amide 100 was iV-Boc deprotected and coupled with the tripeptide 102 (Scheme 20) t47l subsequent diaryl ether formation led to an 8 1 mixture of (P)- and (M)-104 with the natural D-O-E isomer predominating. This stands in contrast to the Nicolaou process (Section 16.7.2), in which the unnatural isomer predominated at this step. Removal of protecting groups led to vancomycin aglycon (105). 

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]. 

Five consecutive papers in Angew. Chem. recently described syntheses of the vancomycin aglycon. D. A. Evans and co-workers developed one route at Harvard [1, 2], while the other comes from K. C. Nicolaou s group at Scripps [3-5]. They represent an amalgamation of synthetic methodologies in schemes that took some of the most skillful bench chemists in academia years to execute. 

The Nicolaou group entered this area relatively recently, hence it is truly remarkable that they were able to develop a synthesis of the vancomycin aglycon so quickly. However, their route stumbles over the sections that involve atropisomeric selectivity or removal of the triazine. Evans group synthesis addresses or avoids these problems. It is a more polished effort that took many years and high levels of financial and human resources to develop. 

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]. 

The biaryl coupling of arylboronic acid furnished a one-pot, two-step procedure for the synthesis of the angiotensin II receptor antagonist losartan 462, which played a critical role in the regulation of blood pressure,827 the AB biaryl ring of vancomycin aglycon 464, S/R= 1/1.3),828 bisporphyrin-based synthetic receptors 463 via a sequential double... 

Crossing the Finishing Line Total Syntheses of the Vancomycin Aglycon... 

With CsF in DMSO at room temperature, the ring closure to the (/f)-configured M(2-4) atropisomer 14a was achieved in a yield of 95 % with a diastereoselectivity of 5 1. Detailed examinations of Evans et al. reveal that the diastereoselectivity of this M(2-4) cyclization is controlled by the natural conformation of the M(5-7) macrocycle [3]. The final functionalization to the chlorine-containing, protected vancomycin aglycon includes a chromatographic separation of the mixture of atropisomers by column chromatography. 

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. 

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