Download PDF
Synlett 2006(7): 0993-1003  
DOI: 10.1055/s-2006-939688
ACCOUNT
© Georg Thieme Verlag Stuttgart · New York

Systematic Synthesis of Diastereomeric THF Ring Cores and Total Synthesis of Anti-Tumor Annonaceous Acetogenins

Naoyoshi Maezaki, Naoto Kojima, Tetsuaki Tanaka*
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan
Fax: +81(6)68798214; e-Mail: t-tanaka@phs.osaka-u.ac.jp;
Further Information

Publication History

Received 16 November 2005
Publication Date:
24 April 2006 (online)

    Permissions and Reprints All articles of this category

Abstract

We have developed a systematic synthesis of the poly-THF ring cores of anti-tumor Annonaceous acetogenins by utilizing asymmetric alkynylation and subsequent stereodivergent THF ring formation as key steps. The asymmetric alkynylation of α-oxyaldehyde and α-tetrahydrofuranic aldehyde with an (S)-3-butyne-1,2-diol derivative proceeded in good yield with very high diastereo­selectivity. These adducts were converted into mono- and bis-THF cores by two different methods involving one-pot THF ring formation. The total syntheses of murisolin, 16,19-cis-murisolin, and longimicin D, which show cytotoxic activity against the human ­tumor cell, were accomplished by applying this methodology.

  • 1 Introduction

  • 2 Synthetic Strategy

  • 3 Asymmetric Alkynylation of α-Oxyaldehyde with a C4-Unit

  • 4 Systematic Synthesis of Mono-THF Segments by Stereo­divergent THF Ring Formation

  • 5 Systematic Synthesis of Bis-THF Segments by an Iterative Process

  • 6 Total Synthesis of Murisolins and Longimicin D

  • 7 Conclusion

Key words

total synthesis - natural products - asymmetric synthesis - diastereoselectivity

3

Other classifications excluding these THF acetogenins are non-adjacent bis-THF acetogenins, non-classical (THP) acetogenins, and non-THF ring acetogenins.

33

Curran also accomplished the first total synthesis of murisolin almost at the same time as us; see ref. 9.