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Synlett 2006(11): 1623-1644  
DOI: 10.1055/s-2006-944213
ACCOUNT
© Georg Thieme Verlag Stuttgart · New York

Progress toward the Total Synthesis of Guanacastepene A

Sarah V. Maifeld, Daesung Lee*
Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI 53706, USA
Fax: +1(608)2654534; e-Mail: dlee@chem.wisc.edu;
Further Information

Publication History

Received 9 December 2005
Publication Date:
04 July 2006 (online)

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Abstract

Guanacastepene A, the leading member of a structurally diverse family of diterpene natural products, was isolated from the extracts of an unidentified fungus. The discovery of its potent antibiotic activity as well as its previously unreported tricyclic architecture render guanacastepene A an attractive and formidable target for total synthesis. Specifically, guanacastepene A’s synthetic challenges include 2 ring-junction quaternary methyl groups and a novel 5-7-6 tricyclic carbon skeleton possessing a dense array of oxygen and unsaturated functionalities. In this account, we will discuss our motivation and efforts toward the total synthesis of guanacastepene A as well as highlight the contributions from the synthetic community toward this pursuit.

  • 1 Introduction

  • 1.1 Biological Activity

  • 1.2 Isolation and Characterization

  • 2 An Overview of Synthetic Strategies

  • 2.1 Hydroazulene Core

  • 2.2 Hydroazulene to Tricycle

  • 2.3 Tricycle Closure by a Formal C10-C11 Connection

  • 2.4 Tricycle Closure between C1-C2

  • 2.5 A-Ring to Tricycle

  • 2.6 C-Ring to Tricycle

  • 3 Our Strategy

  • 3.1 Initial Planning

  • 3.2 Retrosynthesis

  • 3.3 Synthesis of the Guanacastane Tricycle

  • 3.4 Elaboration of the Tricycle

  • 3.5 Investigation of the Aldol Reaction

  • 3.6 A More Convergent Synthetic Approach

  • 4 Current Investigation

  • 5 Conclusion

Key words

guanacastepene - diterpene - total synthesis

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A slight loss of optical purity (13%) was noted in the photorearrangement, presumably due to a process involving fragmentation of the diradical to an intermediate ketene.