Phenylahistin, a Small Dipeptidic Colchicine-Like Anti-Microtubule Agent: Total Synthesis and SAR Study of the Derivatives

  • Yoshio Hayashi
  • Sumie Orikasa
  • Koji Tanaka
  • Kaneo Kanoh
  • Yoshiaki Kiso
Part of the American Peptide Symposia book series (APSY, volume 7)

Abstract

Phenylahistin (1), a fungal metabolite from Aspergillus ustus NSC-F038, belongs to a new class of peptidic colchicine-like microtubule-binding agents that exhibits cytotoxic activity against a wide variety of tumor cell lines [1]. (-)-Phenylahistin (-)-1, a diketopiperazine derivative, consists of L-phenylalanine and a unique isoprenylated dehydrohistidine residue with a quaternary carbon at the 5-position of the imidazole ring. To develop more potent anti-tumor agents based on this diketopiperazine derivative, it is important to elucidate the structural components necessary for the anti-microtubule activity of (-)-1. The total synthesis of 1 will establish the synthetic route for its derivatives.

Keywords

Ethyl Dimethyl Aspergillus Benzyl Colchicine 

References

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    Kanoh, K., Kohno, S., Katada, J., Takahashi, J., Uno, I., Hayashi, Y. Bioorg. Med. Chem. 7, 1451–1457 (1999).PubMedCrossRefGoogle Scholar
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    Hayashi, Y., Orikasa, S., Tanaka, K., Kanoh, K., Kiso, Y. J. Org. Chem. 65, 8402–8405 (2000).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2001

Authors and Affiliations

  • Yoshio Hayashi
    • 1
  • Sumie Orikasa
    • 1
  • Koji Tanaka
    • 1
  • Kaneo Kanoh
    • 2
  • Yoshiaki Kiso
    • 1
  1. 1.Department of Medicinal Chemistry, Center for Frontier Research in Medicinal ScienceKyoto Pharmaceutical UniversityKyotoJapan
  2. 2.Shimizu LaboratoriesMarine Biotechnology InstituteShizuokaJapan

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