Download PDF
Synthesis 2005(2): 301-305  
DOI: 10.1055/s-2004-834936
PAPER
© Georg Thieme Verlag Stuttgart · New York

Efficient Chiral Pool Synthesis of the C1-C6 Fragment of Epothilones

Ulrich Klar*, Bodo Röhr, Frank Kuczynski, Wolfgang Schwede, Markus Berger, Werner Skuballa, Bernd Buchmann
Research Laboratories of Schering AG, Müllerstrasse 170, 13342 Berlin, Germany
Fax: +49(30)46892635; e-Mail: ulrich.klar@schering.de;
Further Information

Publication History

Received 7 September 2004
Publication Date:
01 December 2004 (online)

    Permissions and Reprints All articles of this category

Abstract

An efficient chiral pool synthesis of the C1-C6 fragment of epothilones starting from readily available
(-)-pantolactone is described.

Key words

epothilone - pantolactone - chiral pool synthesis

    References

  • 1 Gerth K. Bedorf N. Höfle G. Irschik H. Reichenbach H. J. Antibiotics  1996,  49:  560 
    CrossrefGoogle Scholar
  • 2 Bollag DM. McQueeney PA. Zhu J. Hensens O. Koupal L. Liesch J. Goetz M. Lazarides E. Woods CM. Cancer Res.  1995,  55:  2325 
    Google Scholar
  • 3 Chou T.-C. Zhang X.-G. Balog A. Su D.-S. Meng D. Savin K. Bertino JR. Danishefsky SJ. Proc. Natl. Acad. Sci. U.S.A.  1998,  95:  9642 
    CrossrefGoogle Scholar
  • 4 Chou T.-C. Zhang X.-G. Harris CR. Kuduk SD. Balog A. Savin K. Bertino JR. Danishefsky SJ. Proc. Natl. Acad. Sci. U.S.A.  1998,  95:  15798 
    CrossrefGoogle Scholar
  • 5 Sepp-Lorenzino L. Balog A. Su D.-S. Meng D. Timaul N. Scher HI. Danishefsky SJ. Rosen N. Prostate Cancer Prostatic Dis.  1999,  2:  41 
    CrossrefGoogle Scholar
  • 6 Christina R. Harris CR. Danishefsky SJ. J. Org. Chem.  1999,  64:  8434 
    CrossrefGoogle Scholar
  • For reviews on the total syntheses of epothilones see:
  • 7a Altmann K.-H. Org. Biomol. Chem.  2004,  2137 
    CrossrefPubMedGoogle Scholar
  • 7b Zhang R. Liu Z. Curr. Org. Chem.  2004,  8:  267 
    CrossrefPubMedGoogle Scholar
  • 7c Wartmann M. Altmann K.-H. Curr. Med. Chem.: Anti-Cancer Agents  2002,  2:  123 
    CrossrefPubMedGoogle Scholar
  • 7d Flörsheimer A. Altmann K.-H. Expert Opin. Ther. Pat.  2001,  11:  951 
    CrossrefPubMedGoogle Scholar
  • 7e Nicolaou KC. Ritzén A. Namoto K. Chem. Commun.  2001,  1523 
    CrossrefPubMedGoogle Scholar
  • 7f Mulzer J. Monatsh. Chem.  2000,  131:  205 
    CrossrefPubMedGoogle Scholar
  • 7g Nicolaou KC. Roschangar F. Vourloumis D. Angew. Chem. Int. Ed.  1998,  37:  2014 
    CrossrefPubMedGoogle Scholar
  • For another protecting group strategy see:
  • 8a Klar U, Schwede W, Skuballa W, Buchmann B, and Schirner M. inventors; PCT Int. Appl., WO  9907692. 
    Google Scholar
  • 8b Klar U. Skuballa W. Buchmann B. Schwede W. Bunte T. Hoffmann J. Lichtner RB. In New Prospects in Anticancer Agents for the 21st Century, ACS Symposium Series 796   Ojima I. Vite GD. Altmann K.-H. American Chemical Society; Washington DC: 2001.  p.131 
    Google Scholar
  • For alternative approaches to the C1-C6 fragment of epothilones see:
  • 9a Zheng Y. Avery MA. Tetrahedron  2004,  60:  2091 
    Google Scholar
  • 9b Ramachandran PV. Prabhudas B. Chandra JS. Reddy M. Venkat R. Brown HC. Tetrahedron Lett.  2004,  45:  1011 
    Google Scholar
  • 9c Chandrasekhar S. Raji Reddy C. Tetrahedron: Asymmetry  2002,  13:  261 
    Google Scholar
  • 9d Shioji K. Kawaoka H. Miura A. Okuma K. Synth. Commun.  2001,  31:  3569 
    Google Scholar
  • 9e Panicker B. Karle JM. Avery MA. Tetrahedron  2000,  56:  7859 
    Google Scholar
  • 9f Taylor RE. Galvin GM. Hilfiker KA. Chen Y. J. Org. Chem.  1998,  63:  9580 
    Google Scholar
  • 9g Gabriel T. Wessjohann L. Tetrahedron Lett.  1997,  38:  1363 
    Google Scholar
  • 9h De Brabander J. Rosset S. Bernardinelli G. Synlett  1997,  824 
    Google Scholar
  • 9i Erratum 1: De Brabander J. Rosset S. Bernardinelli G. Synlett  1998,  328 
    Google Scholar
  • 9j Erratum 2: De Brabander J. Rosset S. Bernardinelli G. Synlett  1998,  692 
    Google Scholar
  • 9k Schinzer D. Limberg A. Böhm OM. Chem.-Eur. J.  1996,  2:  1477 
    Google Scholar
  • 10 A similar observation has been described for 3,4-dialkoxy-1-alkenes by: Jung ME. Karama U. Tetrahedron Lett.  1999,  40:  7907 
    CrossrefGoogle Scholar