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Total Synthesis Confirms Laetirobin as a Formal Diels–Alder Adduct

  1. Oliver Simon1,
  2. Bastien Reux Dr.1,
  3. James J. La Clair Dr.2,
  4. Martin J. Lear Prof.1

Article first published online: 23 DEC 2009

DOI: 10.1002/asia.200900306

Issue

Chemistry – An Asian Journal

Chemistry – An Asian Journal

Volume 5, Issue 2, pages 342–351, February 1, 2010

Additional Information

How to Cite

Simon, O., Reux, B., La Clair, James J. and Lear, Martin J. (2010), Total Synthesis Confirms Laetirobin as a Formal Diels–Alder Adduct. Chem. Asian J., 5: 342–351. doi: 10.1002/asia.200900306

Author Information

  1. 1

    Department of Chemistry, Faculty of Science and Medicinal Chemistry Program of the Life Sciences Institute, National University of Singapore, Singapore 117543 (Singapore), Fax: (+65) 6516-3998

  2. 2

    Xenobe Research Institute, 3371 Adams Avenue, San Diego, California 92116 (USA)

Publication History

  1. Issue published online: 28 JAN 2010
  2. Article first published online: 23 DEC 2009
  3. Manuscript Received: 23 JUL 2009

Funded by

  • Ministry of Education of Singapore. Grant Number: AcRF Tier-2 Grant T206B1112

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Keywords:

  • antitumor agents;
  • biomimetic synthesis;
  • cycloaddition;
  • dimerization;
  • total synthesis

Abstract

Laetirobin, isolated from a parasitic fungus host–plant relationship, was synthesized in six practical steps with an overall yield of 12 % from commercially available 2,4-dihydroxyacetophenone. Because the product is a pseudosymmetric tetramer of benzo[b]furans, each step of the synthesis was designed to involve tandem operations. Highlights include: 1) the double Sonogashira reaction of a bis(alkyne), 2) the practical copper(I)-mediated formation of a bis(benzo[b]furan), and 3) the biomimetic [4+2] dimerization and unexpected cationic [5+2] annulation of gem-diaryl alkene precursors. Preliminary structure–activity relationship data between the isomeric [4+2] and [5+2] tetramers revealed only the natural product to possess promising anticancer potential. Specifically, laetirobin is capable of blocking tumor cell division (mitosis) and invoking programmed cell death (apoptosis).

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