Solid- and solution-phase synthesis of vancomycin and vancomycin analogueswith activity against vancomycin-resistant bacteria

Citation
Kc. Nicolaou et al., Solid- and solution-phase synthesis of vancomycin and vancomycin analogueswith activity against vancomycin-resistant bacteria, CHEM-EUR J, 7(17), 2001, pp. 3798-3823
Citations number
80
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Chemistry
Journal title
CHEMISTRY-A EUROPEAN JOURNAL
ISSN journal
0947-6539 → ACNP
Volume
7
Issue
17
Year of publication
2001
Pages
3798 - 3823
Database
ISI
SICI code
0947-6539(20010903)7:17<3798:SASSOV>2.0.ZU;2-7
Abstract
Vancomycin, the prototypical member of the glycopeptide family of antibioti cs, is a clinically used antibiotic employed against a variety of drug-resi stant bacterial strains including methicillin-resistant Staphylococcus aure us (MRSA). The recent emergence of vancomycin resistance, viewed as a growi ng threat to public health, prompted us to initiate a program aimed at rest oring the potency of this important antibiotic through chemical manipulatio n of the vancomycin structure. Herein, we describe the development of synth etic technology based on the design of a novel selenium safety catch linker , application of this technology to a solid-phase semisynthesis of vancomyc in, and the solid- and solution-phase synthesis of vancomycin libraries. Bi ological evaluation of these compound libraries led to the identification o f a number of in vitro highly potent antibacterial agents effective against vancomycin-resistant bacteria. In addition to aiding these investigations, the solid-phase chemistry described herein is expected to enhance the powe r of combinatorial chemistry and facilitate chemical biology and medicinal chemistry studies.