Download PDF
Synlett 2010(17): 2561-2564  
DOI: 10.1055/s-0030-1258769
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Improved Synthetic Route to C-Ring Ester-Functionalized Prodigiosenes

Md. Imam Uddin, Srinath Thirumalairajan, Sarah M. Crawford*, T. Stanley Cameron, Alison Thompson*
Department of Chemistry, Dalhousie University, Halifax, NS, B3H 4J3, Canada
Fax: +1(902)4941310; e-Mail: Sarah.Crawford@dal.ca; e-Mail: Alison.Thompson@dal.ca;
Further Information

Publication History

Received 18 August 2010
Publication Date:
30 September 2010 (online)

    Permissions and Reprints All articles of this category

Abstract

An efficient, optimized, and scalable process for the synthesis of C-ring ester-functionalized prodigiosenes has been developed by (i) exploiting a silylative Mukaiyama aldol strategy for the condensation of alkyl 5-formyl-2,4-dimethylpyrrole-3-carboxylate and 4-methoxy-3-pyrrolin-2-one to form the corresponding ester-functionalized dipyrrinone analogues, and (ii) developing a facile synthesis of stable bromodipyrrin analogues for the use in formal Suzuki coupling reactions. The process was applied to the synthesis of three C-ring ester-functionalized prodigiosenes in multigram scales (up to 6.5 g prodigiosene free-base) with useful yields (35-56% overall yields over three steps starting from the 2-formyl pyrroles).

Key words

prodigiosin - prodigiosene - bromodipyrrin - dipyrri­none - bromination

    References

  • 1a Baldino CM. Parr J. Wilson CJ. Ng S. Yohannes D. Wasserman HH. Bioorg. Med. Chem. Lett.  2006,  16:  701 
    Google Scholar
  • 1b D’Alessio R. Bargiotti A. Carlini O. Colotta F. Ferrari M. Gnocchi P. Isetta A. Mongelli N. Motta P. Rossi A. Rossi M. Tibolla M. Vanotti E. J. Med. Chem.  2000,  43:  2557 
    Google Scholar
  • 1c Davis JT. Gale PA. Okunola OA. Prados P. Iglesias-Sánchez JC. Torroba T. Quesada R. Nature Chem.  2009,  1:  138 
    Google Scholar
  • 1d Diaz RIS. Regourd J. Santacroce PV. Davis JT. Jakeman DL. Thompson A. Chem. Commun.  2007,  2701 
    Google Scholar
  • 1e Gerber NN. J. Antibiot.  1975,  28:  194 
    Google Scholar
  • 1f Isaka M. Jaturapat A. Kramyu J. Tanticharoen M. Thebtaranonth Y. Antimicrob. Agents Chemother.  2002,  46:  1112 
    Google Scholar
  • 1g Melvin MS. Calcutt MW. Noftle RE. Manderville RA. Chem. Res. Toxicol.  2002,  15:  742 
    Google Scholar
  • 1h Melvin MS. Tomlinson JT. Park G. Day CS. Saluta GR. Kucera GL. Manderville RA. Chem. Res. Toxicol.  2002,  15:  734 
    Google Scholar
  • 1i Melvin MS. Tomlinson JT. Saluta GR. Kucera GL. Lindquist N. Manderville RA. J. Am. Chem. Soc.  2000,  122:  6333 
    Google Scholar
  • 1j Mortellaro A. Songia S. Gnocchi P. Ferrari P. Fornasiero C. D’Alessio R. Isetta A. Colotta F. Golay J. J. Immunol.  1999,  162:  7102 
    Google Scholar
  • 1k Seganish JL. Davis JT. Chem. Commun.  2005,  5781 
    Google Scholar
  • 2 Fürstner A. Angew. Chem. Int. Ed.  2003,  42:  3582 
    CrossrefPubMedGoogle Scholar
  • 3 Regourd J. Al-Sheikh Ali A. Thompson A. J. Med. Chem.  2007,  50:  1528 
    CrossrefGoogle Scholar
  • 4 Sáez Díaz RI. Bennett SM. Thompson A. ChemMedChem  2009,  4:  742 
    CrossrefGoogle Scholar
  • 5 Rapoport H. Holden KG. J. Am. Chem. Soc.  1962,  84:  635 
    CrossrefGoogle Scholar
  • 6a Boger DL. Patel M. J. Org. Chem.  1988,  53:  1405 
    Google Scholar
  • 6b Wasserman HH. Lombardo L. Tetrahedron Lett.  1989,  30:  1725 
    Google Scholar
  • 6c Wasserman HH. Petersen AK. Xia M. Wang J. Tetrahedron Lett.  1999,  40:  7587 
    Google Scholar
  • 7 D’Alessio R. Rossi A. Synlett  1996,  513 
    Article in Thieme ConnectGoogle Scholar
  • 8 Dairi K. Tripathy S. Attardo G. Lavallee J. Tetrahedron Lett.  2006,  47:  2605 
    CrossrefGoogle Scholar
  • 9a Dairi K. Yao Y. Faley M. Tripathy S. Rioux E. Billot X. Rabouin D. Gonzalez G. Lavallee J. Attardo G. Org. Proc. Res. Dev.  2007,  11:  1051 
    Google Scholar
  • 9b Pinkerton DM. Banwell MG. Willis AC. Org. Lett.  2007,  9:  5127 
    Google Scholar
  • 10 Clift MD. Thomson RJ. J. Am. Chem. Soc.  2009,  131:  14579 
    CrossrefGoogle Scholar
  • 11 Sun LLC. Shirazian S. Zhou Y. Miller T. Cui J. Fukuda JY. Chu J.-Y. Nematalla A. Wang X. Chen H. Sistla A. Luu TC. Tang F. Wei J. Tang C. J. Med. Chem.  2003,  46:  1116 
    CrossrefGoogle Scholar
  • 12a Curti C. Sartori A. Battistini L. Rassu G. Burreddu P. Zanardi F. Casiraghi G. J. Org. Chem.  2008,  73:  5446 
    Google Scholar
  • 12b Downey CW. Johnson MW. Tetrahedron Lett.  2007,  48:  3559 
    Google Scholar
  • 13 Brunings KJ. Corwin AH. J. Am. Chem. Soc.  1944,  66:  337 
    CrossrefGoogle Scholar
  • 14 Rapoport H. Castagnoli N. J. Am. Chem. Soc.  1962,  84:  2178 
    CrossrefGoogle Scholar
  • 15 Regourd J. Al-Sheikh Ali A. Thompson A. J. Med. Chem.  2007,  50:  1528 
    CrossrefGoogle Scholar
  • 16 Wood TE. Ross AC. Dalgleish ND. Power ED. Thompson A. Chen X. Okamoto Y. J. Org. Chem.  2005,  70:  9967 
    CrossrefGoogle Scholar