Sordarin, an antifungal agent with a unique mode of action

• Type of Material: Article
• Authors: Huan Liang, Emory University
• Language: English
• Date: 2008-09-05
• Publisher: Beilstein Journal of Organic Chemistry
• Publication Version: Final Published Version
• Copyright Statement: © 2008, Liang
• License: Creative Commons Attribution 2.0 Generic
• Final Published Version (URL): http://dx.doi.org/10.3762/bjoc.4.31
• Title of Journal or Parent Work: Beilstein Journal of Organic Chemistry
• Volume: 4
• Start Page: 31
• End Page: 31
• Grant/Funding Information: Bayer CropScience and the CNRS, the University of British Columbia, NSERC, CIHR, the Canada Research Chair Program, and MerckFrosst Canada are gratefully acknowledged for financial support. H. L. is the recipient of a UBC Graduate Fellowship and Gladys Estella Laird Research Fellowship.
• Keywords: antifungal; sordarin; total synthesis; bioactivity; sordaricin
• Research Categories: Chemistry, Pharmaceutical

Abstract

The sordarin family of compounds, characterized by a unique tetracyclic diterpene core including a norbornene system, inhibits protein synthesis in fungi by stabilizing the ribosome/EF2 complex. This mode of action is in contrast to typical antifungals, which target the cell membrane. This unusual bioactivity makes sordarin a promising candidate for the development of new fungicidal agents, and provided the motivation for extensive research. Three total syntheses (by the Kato, Mander and Narasaka groups), modifications of the glycosyl unit, and changes to the diterpene core (Cuevas and Ciufolini models) will also be discussed in this review. © 2008 Liang; licensee Beilstein-Institut.