Download PDF
Synlett 2003(5): 0738-0740
DOI: 10.1055/s-2003-38378
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Stereoselective Formation of a β-Lactam Fused Oxathiazepin: A Synthetic Approach to Eudistomins

Tohru Yamashita, Hidetoshi Tokuyama, Tohru Fukuyama*
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
Fax: +81(3)58028694; e-Mail: fukuyama@mol.f.u-tokyo.ac.jp;
Further Information

Publication History

Received 5 February 2003
Publication Date:
28 March 2003 (online)

    Permissions and Reprints All articles of this category

Abstract

A synthetic approach to eudistomin via a β-lactam fused bicyclic oxathiazepin intermediate is described. A β-lactam fused oxathiazepin derivative was synthesized by intramolecular 7-membered oxime ether formation and subsequent face-selective reduction of the C-N double bond. A fully functionalized ortho-alkenylphenylthioanilide bearing oxathiazepin ring was then prepared and construction of the indole skeleton under several radical-mediated conditions was examined.

Key words

eudistomin - bicyclic β-lactam - oxathiazepin - 2,3-di­substituted indole - radical cyclization

    References

  • 1a Rinehart KL. Kobayashi J. Harbour GC. Hughes RG. Mizsak SA. Scahill TA. J. Am. Chem. Soc.  1984,  106:  1524 
    Google Scholar
  • 1b Kobayashi J. Harbour GC. Gilmore J. Rinehart KL. J. Am. Chem. Soc.  1984,  106:  1526 
    Google Scholar
  • 1c Rinehart KL. Kobayashi J. Harbour GC. Gilmore J. Mascal M. Holt TG. Shield LS. Lafargue F. J. Am. Chem. Soc.  1987,  109:  3378 
    Google Scholar
  • 2 Nakagawa M. Liu J.-J. Hino T. J. Synth. Org. Chem., Jpn.  1990,  48:  891 
    Google Scholar
  • 3a van Maarseveen JH. Hermkenes PHH. De Clercq E. Balzarini J. Scheeren HW. Kruse CG. J. Med. Chem.  1992,  35:  3223 
    Google Scholar
  • 3b van Maarseveen JH. Scheeren HW. De Clercq E. Balzarini J. Kruse CG. Bioorg. Med. Chem.  1997,  5:  955 
    Google Scholar
  • 4a Still IWJ. Strautmanis JR. Tetrahedron Lett.  1989,  30:  1041 
    Google Scholar
  • 4b Still IWJ. Strautmanis JR. Can. J. Chem.  1990,  68:  1408 
    Google Scholar
  • 5 Kirkup MP. Shankar BB. McCombie S. Ganguly AK. MacPhail A. Tetrahedron Lett.  1989,  30:  6809 
    Google Scholar
  • 6a Nakagawa M. Liu J.-J. Hino T. J. Am. Chem. Soc.  1989,  111:  2721 
    Google Scholar
  • 6b Nakagawa M. Liu J.-J. Hino T. Tsuruoka A. Harada N. Ariga M. Asada Y. J. Chem. Soc., Perkin Trans. 1  2000,  3477 
    Google Scholar
  • 6c Liu J.-J. Hino T. Tsuruoka A. Harada N. Nakagawa M. J. Chem. Soc., Perkin Trans. 1  2000,  3487 
    Google Scholar
  • 7a Hermkens PHH. van Maarseveen JH. Berens HW. Smits JMM. Kruse CG. Scheeren HW. J. Org. Chem.  1990,  55:  2200 
    Google Scholar
  • 7b Hermkens PHH. van Maarseveen JH. Ottenheijm HC. Kruse CG. Scheeren HW. J. Org. Chem.  1990,  55:  3998 
    Google Scholar
  • 8a Tokuyama H. Yamashita T. Reding MT. Kaburagi Y. Fukuyama T. J. Am. Chem. Soc.  1999,  121:  3791 
    CrossrefGoogle Scholar
  • 8b Reding MT. Fukuyama T. Org. Lett.  1999,  1:  973 
    CrossrefGoogle Scholar
  • 8b Yokoshima S. Ueda T. Kobayashi S. Sato A. Kuboyama T. Tokuyama H. Fukuyama T. Am. Chem. Soc.  2002,  124:  2137 
    CrossrefGoogle Scholar
  • 9a Hubschwerlen C. Specklin J.-L. Org. Synth., Coll. Vol. IX   Wiley; New York: 1998.  p.13 
    CrossrefGoogle Scholar
  • 9b Pearson MJ. Tetrahedron Lett.  1982,  23:  2999 
    CrossrefGoogle Scholar
  • 12a Fukuyama T. Frank RK. Jewell CF. J. Am. Chem. Soc.  1980,  102:  2122 
    CrossrefGoogle Scholar
  • 12b Kronenthal DR. Han CY. Taylor MK. J. Org. Chem.  1982,  47:  2765 
    CrossrefGoogle Scholar
  • 13 Reding MT. Kaburagi Y. Tokuyama H. Fukuyama T. Heterocycles  2002,  56:  313 
    Google Scholar
  • For the hypophosphorous acid mediated radical reaction, see:
  • 14a Barton DHR. Jang DO. Jaszberenyi JC. J. Org. Chem.  1993,  56:  6838 
    Google Scholar
  • 14b Yorimitsu H. Shinokubo H. Oshima K. Bull. Chem. Soc. Jpn.  2001,  74:  225 
    Google Scholar
10

Optically active β-lactam 10 could be prepared using glyceraldehyde as a chiral template. [9a]

11

Choice of solvent (protic or aprotic) was quite important for this reduction. When oxime ether 17 was reduced with NaBH4 in MeOH, an ca. 1:1 mixture of the hemiaminal 25 and the desired product 26 was obtained (Figure [2] ).

Figure 2 Structures of 17, 25, and 26