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Synthesis 2010(4): 643-650  
DOI: 10.1055/s-0029-1218606
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

First Total Synthesis of (-)-Circumdatin H, a Novel Mitochondrial NADH Oxidase Inhibitor

D. Subhas Bose*, M. Venu Chary
Organic Chemistry Division III, Fine Chemicals Laboratory, Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500607, India
Fax: +91(40)27160387; e-Mail: dsb@iict.res.in; e-Mail: bose_iict@yahoo.co.in;
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Publikationsverlauf

Received 6 October 2009
Publikationsdatum:
16. Dezember 2009 (online)

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Abstract

An efficient and highly convergent synthesis of the mitochondrial NADH oxidase inhibitor (-)-circumdatin H is described. The strategy employs the intramolecular Eguchi aza-Wittig protocol as a key step to install the crucial central core BC ring system, leading to the first total synthesis of the target molecule.

Key words

benzodiazepine alkaloids - circumdatin H - mitochondrial NADH oxidase - intramolecular aza-Wittig reaction - Eguchi protocol - quinazolin-4(3H)-ones

    References

  • 1a Maske SB. Argade NP. Tetrahedron  2006,  62:  9787 ; and references cited therein
    Google Scholar
  • 1b Connolly DJ. Cusack D. O’Sullivan TP. Guiry PJ. Tetrahedron  2005,  61:  10153 
    Google Scholar
  • 1c Michael JP. Nat. Prod. Rep.  2007,  24:  223 
    Google Scholar
  • 1d Michael JP. Nat. Prod. Rep.  2008,  25:  166 
    Google Scholar
  • 2a Joshi BK. Gloer JB. Wicklow DT. J. Nat. Prod.  1999,  62:  650 
    Google Scholar
  • 2b Witt A. Bergman J. J. Heterocycl. Chem.  2002,  39:  351 
    Google Scholar
  • 2c Snider BB. Busuyek MV. Tetrahedron  2001,  57:  3301 
    Google Scholar
  • 2d Zhang W. Williams JP. Lu Y. Nagashima T. Chu Q. Tetrahedron Lett.  2007,  48:  563 
    Google Scholar
  • 3a Goetz MA. Lopez M. Monagham RL. Chang RSL. Lotti VJ. Chen TB. J. Antibiot.  1985,  38:  1633 
    Google Scholar
  • 3b Liesh JM. Hensens OD. Springer JP. Chang RSL. Lotti VJ. J. Antibiot.  1985,  38:  1638 
    Google Scholar
  • 3c He F. Foxman BM. Snider BB. J. Am. Chem. Soc.  1998,  120:  6417 
    Google Scholar
  • 3d Witt A. Bergman J. Curr. Org. Chem.  2003,  7:  659 
    Google Scholar
  • 4a Sun HH. Barrow CJ. Sedlock DM. Gillum AM. Copper R. J. Antibiot.  1994,  47:  515 
    Google Scholar
  • 4b Sugimori T. Okawa T. Eguchi S. Kakehi A. Yashima E. Okamoto Y. Tetrahedron  1998,  54:  7997 
    Google Scholar
  • 5 Rahbaek L. Breinholt J. Frisvad JC. Christophersen C. J. Org. Chem.  1999,  64:  1689 
    CrossrefGoogle Scholar
  • 6 Rahbaek L. Breinholt J. J. Nat. Prod.  1999,  62:  904 
    CrossrefGoogle Scholar
  • 7 Lòpez-Gresa MP. Gonzàlez MC. Primo J. Moya P. Romeo P. Estornell E. J. Antibiot.  2005,  58:  416 
    CrossrefGoogle Scholar
  • 8 Ookura R. Kito K. Ooi T. Namikoshi M. Kusumi T. J. Org. Chem.  2008,  73:  4245 
    Google Scholar
  • 9 Coppola GM. J. Heterocycl. Chem.  1999,  36:  563 ; and references cited therein
    CrossrefGoogle Scholar
  • 10 Bodanszky M. Bodanszky A. The Practice of Peptide Synthesis   Springer-Verlag; Berlin: 1994. 
    Google Scholar
  • 11a Mohapatra DK. Datta A. Bioorg. Med. Chem. Lett.  1997,  7:  2527 
    Google Scholar
  • 11b Witt A. Bergman J. J. Org. Chem.  2001,  66:  2784 
    Google Scholar
  • 12a Ozaki K. Yamada Y. Oine T. Chem. Pharm. Bull.  1984,  32:  2160 
    Google Scholar
  • 12b Zhichkin P. Kesicki E. Treiberg J. Bourdon L. Ronsheim M. Ooi HC. White S. Judkins A. Fairfax D. Org. Lett.  2007,  9:  1415 
    Google Scholar
  • 12c Liu J.-F. Kaselj M. Isome Y. Chapnick J. Zhang B. Bi G. Yohannes D. Yu L. Baldino CM. J. Org. Chem.  2005,  70:  10488 
    Google Scholar
  • 12d Taher D. Ishtaiwi ZN. Al-Said NH. ARKIVOC  2008,  (xvi):  154 
    Google Scholar
  • 13 Garin J. Merino P. Orduna J. Tejero T. Uriel S. Tetrahedron Lett.  1991,  32:  3263 
    CrossrefGoogle Scholar
  • 14 Kamat VP. Kirtany JK. Org. Prep. Proced. Int.  1994,  26:  494 
    CrossrefGoogle Scholar
  • 15 Kshirsagar UA. Mhaske SB. Argade NP. Tetrahedron Lett.  2007,  48:  3243 
    CrossrefGoogle Scholar
  • The intramolecular version of the tandem Staudinger/aza-Wittig reaction is often referred to as the Eguchi aza-Wittig protocol; see:
  • 16a Eguchi S. Matsushita Y. Yamashita K. Org. Prep. Proced. Int.  1992,  24:  209 
    Google Scholar
  • 16b Mollina P. Vilaplaza MJ. Synthesis  1994,  1197 
    Google Scholar
  • 16c Eguchi S. ARKIVOC  2005,  (ii):  98 
    Google Scholar
  • 16d Grieder A. Thomas AW. Synthesis  2003,  1707 
    Google Scholar
  • 17a Thurston DE. Bose DS. Chem. Rev.  1994,  94:  433 
    Google Scholar
  • 17b Bose DS. Srinivas P. Gurjar MK. Tetrahedron Lett.  1997,  38:  5839 
    Google Scholar
  • 17c Kothakonda KK. Bose DS. Bioorg. Med. Chem. Lett.  2004,  14:  4371 
    Google Scholar
  • 18a Coppola GM. Synthesis  1980,  505 
    Google Scholar
  • 18b Scherrer RA. inventors; US Patent  3233201.  ; Chem. Abstr. 1966, 64, 17614
  • 19 Write WB. Brabander HJ. Greenblatt EN. Day IP. Hardy RA. J. Med. Chem.  1978,  21:  1087 
    CrossrefGoogle Scholar