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Synlett 2010(5): 729-730  
DOI: 10.1055/s-0029-1219377
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of (+)-Kuraramine

Fabio Frigerio, Claire A. Haseler, Timothy Gallagher*
School of Chemistry, University of Bristol, Bristol, BS8 1TS, UK
Fax: +44(1179)251295; e-Mail: t.gallagher@bristol.ac.uk;
Further Information

Publication History

Received 14 December 2009
Publication Date:
08 February 2010 (online)

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Abstract

The first synthesis of (+)-kuraramine via oxidative cleavage of (-)-N-methylcytisine is reported. An alternative but unsuccessful approach to (+)-kuraramine is also described based on extending an intramolecular enolate addition protocol that had previously been applied successfully to cytisine.

Key words

cytisine - kuraramine - alkaloids

    References and Notes

  • 1 For a review of the lupin alkaloids, see: Leonard NJ. In The Alkaloids: Chemistry and Physiology   Vol. 3:  Manske RHF. Holmes HL. Academic Press; New York: 1953.  p.119-192  
    Google Scholar
  • 2 For a review of the synthetic routes to cytisine, see: Stead D. O’Brien P. Tetrahedron  2007,  63:  1885 
    CrossrefGoogle Scholar
  • For an overview of the pharmacology of cytisine, see:
  • 3a Cassels BK. Bermudez I. Dajas F. Abin-Carriquiry JA. Wonnacott S. Drug Discovery Today  2005,  10:  1657 
    Google Scholar
  • 3b Marks MJ. Whiteaker P. Collins AC. Mol. Pharmacol.  2006,  70:  947 
    Google Scholar
  • 3c Luetje CW. Patrick J. J. Neurosci.  1991,  11:  837 
    Google Scholar
  • 4 Power FB. Salway AH. J. Chem. Soc.  1913,  191 
    Google Scholar
  • 5 Murakoshi I. Kidoguchi E. Haginiwa J. Ohmiya S. Higashiyama K. Otomasu H. Phytochemistry  1981,  20:  1407 
    CrossrefGoogle Scholar
  • 6 Honda T. Takahashi R. Namiki H. J. Org. Chem.  2005,  70:  499 
    CrossrefGoogle Scholar
  • 7 Rouden J. Ragot A. Gouault S. Cahard D. Plaquevent JC. Lasne MC. Tetrahedron: Asymmetry  2002,  13:  1299 
    CrossrefGoogle Scholar
  • 8a Houllier N. Gouault S. Lasne MC. Rouden J. Tetrahedron  2006,  62:  11679 
    Google Scholar
  • 8b Chellappan SK. Xiao YX. Tueckmantel W. Kellar KJ. Kozikowski AP.
    J. Med. Chem.  2006,  49:  2673 
    Google Scholar
  • 10a Fleming I. Henning R. Plaut H. J. Chem. Soc., Chem. Commun.  1984,  29 
    Google Scholar
  • 10b Fleming I. Sanderson PEJ. Tetrahedron Lett.  1987,  28:  4229 
    Google Scholar
  • 10c Tamao K. Ishida N. Kumada M. J. Org. Chem.  1983,  48:  2120 
    Google Scholar
  • 10d Tamao K. Ishida N. Tanaka T. Kumada M. Organometallics  1983,  2:  1694 
    Google Scholar
  • 10e For a review on the oxidation of carbon-silicon bonds, see: Jones GR. Landais Y. Tetrahedron  1996,  52:  7599 
    Google Scholar
  • 12a Gray D. Gallagher T. Angew. Chem. Int. Ed.  2006,  45:  2419 
    Google Scholar
  • 12b Botuha C. Galley CMS. Gallagher T. Org. Biomol. Chem.  2004,  2:  1825 
    Google Scholar
  • 14a Katritzky AR. Arrowsmith J. Binbahari Z. Jayaram C. Siddiqui T. Vassilatos S. J. Chem. Soc., Perkin Trans. 1  1980,  2851 
    Google Scholar
  • 14b Meghani P. Joule J. J. Chem. Soc., Perkin Trans. 1  1988,  1 
    Google Scholar
9

For silane 4, the key NMR signals [¹H NMR (500 MHz, CDCl3): δ = 4.34 (1 H, d, J = 1.0 Hz, H10) and ¹³C NMR (126 MHz, CDCl3): δ = 54.2 (C10)] showed the presence of a single diastereomer. The small coupling constant (J = 1.0 Hz) suggested an equatorial-equatorial coupling between H9 and H10. The equatorial assignment of H10 was further supported by NOE data: irradiation of H10 showed enhancements of H9, H11 and SiCH3, while irradiation of H8ax and H8eq showed no enhancement associated with H10.

11

For carbinol 5, the key NMR signal [¹H NMR (400 MHz, CDCl3): δ = 5.80 (1 H, s, H10)] showed the presence of a single diastereomer and suggested the same (likely thermodynamic) stereochemical preference as silane 4.

13

Key NMR signals for aldehyde 9: ¹H NMR (400 MHz, CDCl3): δ = 9.63 (1 H, s, H10). ¹³C NMR (101 MHz, CDCl3): δ = 200.3 (C10).

15

Supporting Information (as a pdf) is available with this paper and contains full experimental details of all compounds reported and copies of spectra, including NOE experiments.