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Solid- and Solution-Phase Synthesis of Vancomycin and Vancomycin Analogues with Activity against Vancomycin-Resistant Bacteria |
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Published in | Chemistry. 2001, vol. 7, no. 17, p. 3798-3823 | |
Abstract | Vancomycin, the prototypical member of the glycopeptide family of antibiotics, is a clinically used antibiotic employed against a variety of drug-resistant bacterial strains including methicillin-resistant Staphylococcus aureus (MRSA). The recent emergence of vancomycin resistance, viewed as a growing threat to public health, prompted us to initiate a program aimed at restoring the potency of this important antibiotic through chemical manipulation of the vancomycin structure. Herein, we describe the development of synthetic technology based on the design of a novel selenium safety catch linker, application of this technology to a solid-phase semisynthesis of vancomycin, and the solid- and solution-phase synthesis of vancomycin libraries. Biological evaluation of these compound libraries led to the identification of 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 power of combinatorial chemistry and facilitate chemical biology and medicinal chemistry studies. | |
Keywords | Antibiotics — Biological evaluation — Combinatorial synthesis — Synthesis design — Vancomycin | |
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Citation (ISO format) | NICOLAOU, K. C. et al. Solid- and Solution-Phase Synthesis of Vancomycin and Vancomycin Analogues with Activity against Vancomycin-Resistant Bacteria. In: Chemistry - A European Journal, 2001, vol. 7, n° 17, p. 3798-3823. doi: 10.1002/1521-3765(20010903)7:17<3798::AID-CHEM3798>3.0.CO;2-6 https://archive-ouverte.unige.ch/unige:24520 |