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Synthesis 2010(15): 2567-2570  
DOI: 10.1055/s-0029-1218822
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Total Synthesis of (±)-Batzelladine K: A Biomimetic Approach

Nafees Ahmed, Keyur G. Brahmbhatt, Inder Pal Singh, Kamlesh K. Bhutani*
Department of Natural Products, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S. A. S. Nagar, Mohali, Punjab 160062, India
Fax: +91(172)2232208; e-Mail: kkbhutani@niper.ac.in;
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Publication History

Received 29 March 2010
Publication Date:
17 June 2010 (online)

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Abstract

Total synthesis of batzelladine K was achieved by a biomimetic approach. The key reactions involve two Wittig reactions of phosphoranes and aldehydes leading to an α,β-unsaturated ketone, followed by a condensation with guanidine. The synthesis was accomplished in four steps with an overall yield of 12%. The relative stereochemistry of batzelladine K was established by NOE experiments and comparison with literature values.

Key words

batzelladines - marine natural products - tricyclic guanidine - phosphorane - biomimetic synthesis

    References

  • 1a Berlinck RGS. Nat. Prod. Rep.  1996,  13:  377 
    Google Scholar
  • 1b Berlinck RGS. Nat. Prod. Rep.  1999,  16:  339 
    Google Scholar
  • 1c Berlinck RGS. Nat. Prod. Rep.  2002,  19:  617 
    Google Scholar
  • 1d Berlinck RGS. Kossuga MH. Nat. Prod. Rep.  2005,  22:  516 
    Google Scholar
  • 1e Berlinck RGS. Burtoloso ACB. Kossuga MH. Nat. Prod. Rep.  2008,  25:  919 
    Google Scholar
  • 1f Heys L. Moore CG. Murphy PJ. Chem. Soc. Rev.  2000,  29:  57 
    Google Scholar
  • 2 Patil AD. Kumar NV. Kokke WC. Bean MF. Freyer AJ. Brosse CD. Mai S. Truneh A. Faulkner DJ. Carté B. Breen AL. Hertzberg RP. Johnson RK. Westley JW. Potts BCM. J. Org. Chem.  1995,  60:  1182 
    CrossrefGoogle Scholar
  • 3 Patil AD. Freyer AJ. Taylor PB. Carte B. Zuber G. Johnson RK. Faulkner DJ. J. Org. Chem.  1997,  62:  1814 
    CrossrefGoogle Scholar
  • 4 Gallimore WA. Kelly M. Scheuer PJ. J. Nat. Prod.  2005,  68:  1420 
    CrossrefGoogle Scholar
  • 5 Hua HM. Peng J. Dunbar DC. Schinazi RF. Andrews AGDC. Cuevas C. Garcia-Fernandez LF. Kelly M. Hamann MT. Tetrahedron  2007,  63:  11179 
    CrossrefGoogle Scholar
  • 6a Snider BB. Chen J. Patil AD. Freyer AJ. Tetrahedron Lett.  1996,  37:  6977 
    Google Scholar
  • 6b Rama Rao AV. Gurjar MK. Vasudevan J. J. Chem. Soc., Chem. Commun.  1995,  1369 
    Google Scholar
  • 6c Black GP. Murphy PJ. Walshe NDA. Hibbs DE. Hursthouse MB. Abdul Malik KM. Tetrahedron Lett.  1996,  37:  6943 
    Google Scholar
  • 6d Elliott MC. Long MS. Tetrahedron Lett.  2002,  43:  9191 
    Google Scholar
  • 6e Elliott MC. Long MS. Org. Biomol. Chem.  2004,  2:  2003 
    Google Scholar
  • 6f Black GP. Murphy PJ. Thornhill AJ. Walshe NDA. Zanetti C. Tetrahedron  1999,  55:  6547 
    Google Scholar
  • 6g Davies CD. Elliott MC. Hill-Cousins J. Khan MA. Maqbool T. Wood JL. Synlett  2008,  2028 
    Google Scholar
  • 7 Black GP. Murphy PJ. Walshe NDA. Tetrahedron  1998,  54:  9481 
    CrossrefGoogle Scholar
  • 8a Arnold MA. Day KA. Duron SG. Gin DY.
    J. Am. Chem. Soc.  2006,  128:  13255 
    Google Scholar
  • 8b Shimokawa J. Shirai K. Tanatani A. Hashimoto Y. Nagasawa K. Angew. Chem. Int. Ed.  2004,  43:  1559 
    Google Scholar
  • 9 Shimokawa J. Ishiwata T. Shirai K. Koshino H. Tanatani A. Nakata T. Hashimoto Y. Nagasawa K. Chem. Eur. J.  2005,  11:  6878 
    CrossrefGoogle Scholar
  • 10 Collins SK. McDonald AI. Overman LE. Rhee YH. Org. Lett.  2004,  6:  1253 
    CrossrefGoogle Scholar
  • 11a Cohen F. Overman LE. Sakata SK. Org. Lett.  1999,  1:  2169 
    Google Scholar
  • 11b Evans PA. Qin J. Robinson JE. Bazin B. Angew. Chem. Int. Ed.  2007,  46:  7417 
    Google Scholar
  • 11c Ishiwata T. Hino T. Koshino H. Hashimoto Y. Nakata T. Nagasawa K. Org. Lett.  2002,  4:  2921 
    Google Scholar
  • 12 Snider BB. Chen J. Tetrahedron Lett.  1998,  39:  5697 
    CrossrefGoogle Scholar
  • 13a Cohen F. Overman LE. J. Am. Chem. Soc.  2001,  123:  10782 
    Google Scholar
  • 13b Cohen F. Overman LE. J. Am. Chem. Soc.  2006,  128:  2604 
    Google Scholar
  • 14 Bewley CA. Ray S. Cohen F. Collins SK. Overman LE. J. Nat. Prod.  2004,  67:  1319 
    CrossrefGoogle Scholar
  • 15a Brahmbhatt KG. Ahmed N. Singh IP. Bhutani KK. Tetrahedron Lett.  2009,  50:  5501 
    Google Scholar
  • 15b Ahmed N. Brahmbhatt KG. Singh IP. Bhutani KK.
    J. Heterocycl. Chem.  2010, DOI: 10.1002/jhet.364
    Google Scholar
  • 15c Chauthe SK. Bharate SB. Sabde S. Mitra D. Bhutani KK. Singh IP. Bioorg. Med. Chem.  2010,  18:  2029 
    Google Scholar
  • 15d Singh IP. Bharate SB. Bhutani KK. Curr. Sci.  2005,  89:  269 
    Google Scholar
  • 15e Ahmed N. Brahmbhatt KG. Sabde S. Mitra D. Singh IP. Bhutani KK. Bioorg. Med. Chem.  2010,  18:  2872 
    Google Scholar
  • 16 Yu M. Pochapsky SS. Snider BB. J. Org. Chem.  2008,  73:  9065 
    CrossrefGoogle Scholar
  • 17 Sekine M. Iijima Y. Iwamoto O. Nagasawa K. Heterocycles  2010,  80:  395 
    CrossrefGoogle Scholar
  • 18 House HO. Cronin TH. J. Org. Chem.  1965,  30:  1061 
    CrossrefGoogle Scholar
  • 19 Murphy PJ. Williams HL. Hibbs DE. Hursthouse MB. Abdul Malik KM. Tetrahedron  1996,  52:  8315 
    CrossrefGoogle Scholar