Design and synthesis via click chemistry of 8,9-anhydroerythromycin A 6,9-hemiketal analogues with anti-MRSA and -VRE activity

Akihiro Sugawara; Toshiaki Sunazuka; Tomoyasu Hirose; Kenichiro Nagai; Yukie Yamaguchi; Hideaki Hanaki; K Barry Sharpless; Satoshi Omura

doi:10.1016/j.bmcl.2007.08.068

Design and synthesis via click chemistry of 8,9-anhydroerythromycin A 6,9-hemiketal analogues with anti-MRSA and -VRE activity

Bioorg Med Chem Lett. 2007 Nov 15;17(22):6340-4. doi: 10.1016/j.bmcl.2007.08.068. Epub 2007 Sep 1.

Authors

Akihiro Sugawara¹, Toshiaki Sunazuka, Tomoyasu Hirose, Kenichiro Nagai, Yukie Yamaguchi, Hideaki Hanaki, K Barry Sharpless, Satoshi Omura

Affiliation

¹ Kitasato Institute for Life Sciences and Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, Japan.

PMID: 17869508
DOI: 10.1016/j.bmcl.2007.08.068

Abstract

An erythromycin analogue, 11,12-di-O-iso-butyryl-8,9-anhydroerythromycin A 6,9-hemiketal (1b), was found to be a potential anti-MRSA and anti-VRE agent. The use of copper catalyzed azide-acetylene cycloaddition, and click chemistry, readily provided 10 types of triazole analogues of 1b in good to nearly quantitative yield. Among the library, 5b exhibited activity against MRSA and VRE bacterial strains, representing more than twice the potency of 1b.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / chemical synthesis*
Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology*
Catalysis
Copper / chemistry
Drug Design*
Enterococcus / drug effects
Erythromycin / analogs & derivatives*
Erythromycin / chemical synthesis
Erythromycin / chemistry
Erythromycin / pharmacology
Methicillin Resistance / drug effects*
Microbial Sensitivity Tests
Molecular Structure
Staphylococcus aureus / drug effects
Vancomycin Resistance / drug effects*

Substances

Anti-Bacterial Agents
8,9-anhydroerythromycin A 6,9-hemiketal
Erythromycin
Copper