PDF herunterladen
Synthesis 2009(17): 2927-2934  
DOI: 10.1055/s-0029-1216923
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Second-Generation, Biomimetic Total Synthesis of Chaetominine

Alexis Coste, Ganesan Karthikeyan, François Couty, Gwilherm Evano*
Institut Lavoisier de Versailles, UMR CNRS 8180, Université de Versailles Saint Quentin en Yvelines, 45 Avenue des Etats-Unis,78035 Versailles Cedex, France
Fax: +33(1)39254452; e-Mail: evano@chimie.uvsq.fr;
Weitere Informationen

Publikationsverlauf

Received 1 July 2009
Publikationsdatum:
30. Juli 2009 (online)

   Lizenzen und Reprints Alle Artikel dieser Rubrik
Preview

Abstract

A straightforward total synthesis of the potent anticancer agent (-)-chaetominine is reported. Central to this synthesis was a biomimetic oxidative cyclization of a tryptophanyl-alanine dipeptide, which provided a fully elaborated 1,2,3,4-tetrahydropyrido[2,3-b]indole. Reduction of this intermediate followed by spontaneous cyclization and installation of the side chain provided synthetic chaetominine in a nine-step sequence in 14% overall yield starting from commercially available, inexpensive starting materials.

Key words

alkaloids - total synthesis - oxidative cyclization - anticancer agents - peptides

    References

  • See:
  • 2a Shu Y.-Z. J. Nat. Prod.  1998,  61:  1053 
    Suche in Google Scholar
  • 2b MacCoss M. Baillie TA. Science  2004,  303:  1810 
    Suche in Google Scholar
  • 2c Lesney MS. Today’s Chemist at Work  2004,  January:  27 
    Suche in Google Scholar
  • 2d Butler MS. Nat. Prod. Rep.  2005,  22:  162 
    Suche in Google Scholar
  • 2e Wilson RM. Danishefsky SJ. J. Org. Chem.  2006,  71:  8329 
    Suche in Google Scholar
  • 3 Newman DJ. Cragg GM. J. Nat. Prod.  2007,  70:  461 
    CrossrefPubMedSuche in Google Scholar
  • 4 Jiao RH. Xu S. Liu JY. Ge HM. Ding H. Xu C. Zhu HL. Tan RX. Org. Lett.  2006,  8:  5709 
    CrossrefPubMedSuche in Google Scholar
  • 5 Snider BB. Wu X. Org. Lett.  2007,  9:  4913 
    CrossrefSuche in Google Scholar
  • 6a For the total synthesis of related natural products, the kapakahines, see: Newhouse T. Lewis CA. Baran PS. J. Am. Chem. Soc.  2009,  131:  6360 
    Suche in Google Scholar
  • 6b During the preparation of this manuscript, a third total synthesis of chaetominine was reported. See: Malgesini B. Forte B. Borghi D. Quartieri F. Gennari C. Papeo G. Chem. Eur. J.  2009,  15:  DOI: 10.1002/chem.200900793 
    Suche in Google Scholar
  • 7a Toumi M. Couty F. Evano G. Angew. Chem. Int. Ed.  2007,  46:  572 
    Suche in Google Scholar
  • 7b Toumi M. Couty F. Evano G. J. Org. Chem.  2007,  72:  9003 
    Suche in Google Scholar
  • 7c Toumi M. Couty F. Evano G. Synlett  2008,  29 
  • 7d Coste A. Toumi M. Wright K. Razafimahaléo V. Couty F. Marrot J. Evano G. Org. Lett.  2008,  10:  3841 
    Suche in Google Scholar
  • 7e Evano G. Blanchard N. Toumi M. Chem. Rev.  2008,  108:  3054 
    Suche in Google Scholar
  • 7f Toumi M. Rincheval V. Young A. Gergeres D. Turos E. Couty F. Mignotte B. Evano G. Eur. J. Org. Chem.  2009,  3368 
  • 7g Evano G. Toumi M. Coste A. Chem. Commun.  2009,  4166 
  • 8 Toumi M. Marrot J. Couty F. Evano G. Org. Lett.  2008,  10:  5027 
    CrossrefPubMedSuche in Google Scholar
  • For examples, see:
  • 9a Ohno M. Spande TF. Witkop B. J. Am. Chem. Soc.  1968,  90:  6521 
    Suche in Google Scholar
  • 9b Savige WE. Aust. J. Chem.  1975,  28:  2275 
    Suche in Google Scholar
  • 9c Kamenecka TM. Danishefsky SJ. Chem. Eur. J.  2001,  7:  41 
    Suche in Google Scholar
  • 9d May JP. Fournier P. Pellicelli J. Partick BO. Perrin DM. J. Org. Chem.  2005,  70:  8424 
    Suche in Google Scholar
  • 9e Depew KM. Marsden SP. Zatorska D. Zatorski A. Bornmann WG. Danishefsky SJ. J. Am. Chem. Soc.  1999,  121:  11953 
    Suche in Google Scholar
  • 9f Hewitt PR. Cleator E. Ley SV. Org. Biomol. Chem.  2004,  2:  2415 
    Suche in Google Scholar
  • 9g Schiavi BM. Richard DJ. Joullié MM. J. Org. Chem.  2002,  67:  620 
    Suche in Google Scholar
  • 9h Movassaghi M. Schmidt MA. Ashenhurst JA. Angew. Chem. Int. Ed.  2008,  47:  1485 
    Suche in Google Scholar
  • 10 Bergman J. Engqvist R. Stålhandske C. Wallberg H. Tetrahedron  2003,  59:  1033 
    CrossrefSuche in Google Scholar
  • 11 He L. Yang L. Castle SL. Org. Lett.  2006,  8:  1165 
    CrossrefPubMedSuche in Google Scholar
  • 12 Davis FA. Towson JC. Vashi DB. ThimmaReddy R. McCauley JP. Harakal ME. Gosciniak DJ. J. Org. Chem.  1990,  55:  1254 
    Suche in Google Scholar
  • For related cleavage of double bonds in indoles with MCPBA, see:
  • 13a Witkop B. Fiedler H. Ann. Chim.  1947,  558:  91 
    Suche in Google Scholar
  • 13b Hino T. Yamaguchi H. Matsuki K. Nakano K. Sodeoka M. Nakagawa M. J. Chem. Soc., Perkin Trans. 2  1983,  141 
  • 13c Astolfi P. Greci L. Rizzoli C. Sgarabotto P. Marrosu G. J. Chem. Soc., Perkin Trans. 2  2001,  1634 
  • For examples of photooxidation of indoles with oxygen, see:
  • 14a Nakagawa M. Watanabe H. Kodato S. Okajima H. Hino T. Flippen JL. Witkop B. Proc. Natl. Acad. Sci. U. S. A.  1977,  74:  4730 
    Suche in Google Scholar
  • 14b Kanji S. Sainsbury M. Phytochemistry  1974,  11:  503 
    Suche in Google Scholar
  • 14c Saito I. Matsugo S. Matsuura T. J. Am. Chem. Soc.  1979,  101:  7332 
    Suche in Google Scholar
  • 14d Ferroud C. Rool P. Heterocycles  2001,  55:  545 
    Suche in Google Scholar
  • 14e Baran PS. Guerrero CA. Corey EJ. J. Am. Chem. Soc.  2003,  125:  5628 
    Suche in Google Scholar
  • 14f Baran PS. Guerrero CA. Hafensteiner BD. Ambhaikar NB. Angew. Chem. Int. Ed.  2005,  44:  3892 
    Suche in Google Scholar
1

See: http://www.who.int/cancer.

15

Electrostatic repulsion between the phthalimide protecting group and the incoming electrophile might also account for the high stereoselectivity observed

16

ArgusLab 4.0; Mark A. Thompson, Planaria Software LLC: Seattle; see: http://www.ArgusLab.com.