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Synlett 2012(3): 371-374  
DOI: 10.1055/s-0031-1290135
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Total Synthesis of Altenusin and Alterlactone

Judith Cudaj, Joachim Podlech*
Institut für Organische Chemie, Karlsruher Institut für Technologie (KIT), Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany
Fax: +49(721)60847652; e-Mail: joachim.podlech@kit.edu;
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Publikationsverlauf

Received 27 October 2011
Publikationsdatum:
19. Januar 2012 (online)

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Abstract

The resorcylic lactone alterlactone, a mycotoxin produced by alternaria sp., was synthesized for the first time. The total synthesis was achieved in nine steps with 69% yield starting with acetal-protected phloroglucinic acid and 6-bromopiperonal, where the longest linear sequence consists of five steps. Key step is a ­Suzuki coupling used for the construction of the central biaryl bond. When the final deprotection with cleavage of benzyl ethers (yielding unprotected alterlactone) was performed in a less polar solvent the biaryl mycotoxin altenusin was obtained.

Key words

polyketides - fungal metabolites - resorcylic lactones - cross-coupling - Suzuki reaction

    References and Notes

  • 1 Bringmann G. Günther C. Ochse M. Schupp O. Tasler S. In Fortschritte der Chemie organischer Naturstoffe   Herz W. Falk H. Kirby GW. Moore RE. Springer; Vienna: 2001.  p.1-249  
    Google Scholar
  • 2a Handbook of Toxic Fungal Metabolites   Cole RJ. Cox RH. Academic Press; New York: 1981.  p.614-645  
    Google Scholar
  • 2b Stinson EE. J. Food Prot.  1985,  48:  80 
    Google Scholar
  • 2c Harvan DJ. Pero RW. In Mycotoxins and other Fungal Related Food Problems   Rodricks JV. American Chemical Society; Washington D.C.: 1976.  p.344-355  
    Google Scholar
  • 3a Pero RW. Posner H. Blois M. Harvan D. Spalding JW. Environ. Health Perspect.  1973,  4:  87 
    Google Scholar
  • 3b Davis VM. Stack ME. Appl. Environ. Microbiol.  1994,  60:  3901 
    Google Scholar
  • 4a Combina M. Dalcero A. Varsavsky E. Torres A. Etcheverry M. Rodriguez M. Gonzalez Quintana H. Mycotoxin Res.  1999,  15:  33 
    Google Scholar
  • 4b Tournas VH. Stack ME. J. Food Prot.  2001,  64:  528 
    Google Scholar
  • 5a Harris TM. Hay JV. J. Am. Chem. Soc.  1977,  99:  1631 
    Google Scholar
  • 5b Kanakam CC. Mani NS. Subba Rao GSR. J. Chem. Soc., Perkin Trans. 1  1990,  2233 
    Google Scholar
  • 5c Alo BI. Kandil A. Patil PA. Sharp MJ. Siddiqui MA. Snieckus V. Josephy PD. J. Org. Chem.  1991,  56:  3763 
    Google Scholar
  • 5d Koch K. Podlech J. Pfeiffer E. Metzler M. J. Org. Chem.  2005,  70:  3275 
    Google Scholar
  • 6a Altemöller M. Podlech J. Fenske D. Eur. J. Org. Chem.  2006,  1678 
    Google Scholar
  • 6b See also: Altemöller M. Podlech J. J. Nat. Prod.  2009,  72:  1288 
    Google Scholar
  • 7 Altemöller M. Podlech J. Eur. J. Org. Chem.  2009,  2275 
    Google Scholar
  • 8 Thomas R. Biochem. J.  1961,  80:  234 
    Google Scholar
  • 9a Ayer WA. Racok JS. Can. J. Chem.  1990,  68:  2085 
    Google Scholar
  • 9b Singh SB. Jayasuriya H. Dewey R. Polishook JD. Zink DL. Dombrowski AW. Guan Z. Collado J. Platas G. Pelaez F. Felock PJ. Hazuda DJ. J. Ind. Microbiol. Biotechnol.  2003,  30:  721 
    Google Scholar
  • 10 Oyama M. Xu Z. Lee K.-H. Spitzer TD. Kitrinos P. McDonald OB. Jones RRJ. Garvey EP. Lett. Drug Des. Discovery  2004,  1:  24 
    Google Scholar
  • 11 Nakanishi S. Toki S. Saitoh Y. Tsukuda E. Kawahara K. Ando K. Matsuda Y. Biosci. Biotech. Biochem.  1995,  59:  1333 
    Google Scholar
  • 12 Uchida R. Tomoda H. Dong Y. Omura S. J. Antibiotics  1999,  52:  572 
    Google Scholar
  • 13 Cota BB. Rosa LH. Caligiorne RB. Rabello ALT. Alves TMA. Rosa CA. Zani CL. FEMS Microbiol. Lett.  2008,  285:  177 
    Google Scholar
  • 14 Kjer J. Wray V. Edrada-Ebel RA. Ebel R. Pretsch A. Lin W. Proksch P. J. Nat. Prod.  2009,  72:  2053 
    Google Scholar
  • 15a Takahashi S. Kamisuki S. Mizushina Y. Sakaguchi K. Sugawara F. Nakata T. Tetrahedron Lett.  2003,  44:  1875 
    Google Scholar
  • 15b Kamisuki S. Takahashi S. Mizushina Y. Hanashima S. Kuramochi K. Kobayashi S. Sakaguchi K. Nakata T. Sugawara F. Tetrahedron  2004,  60:  5695 
    Google Scholar
  • 15c Kuramochi K. Fukudome K. Kuriyama I. Takeuchi T. Sato Y. Kamisuki S. Tsubaki K. Sugawara F. Yoshida H. Mizushina Y. Bioorg. Med. Chem.  2009,  17:  7227 
    Google Scholar
  • 16a Aly AH. Edrada-Ebel RA. Indriani ID. Wray V. Müller WEG. Totzke F. Zirrgiebel U. Schächtele C. Kubbutat MHG. Lin WH. Proksch P. Ebel R. J. Nat. Prod.  2008,  71:  972 
    Google Scholar
  • 16b Hassan AEHA. PhD Thesis   Heinrich-Heine-Universität Düsseldorf; Germany: 2007. 
    Google Scholar
  • 17a Ishiyama T. Murata M. Miyaura N. J. Org. Chem.  1995,  60:  7508 
    Google Scholar
  • 17b Murata M. Oyama T. Watanabe S. Masuda Y. J. Org. Chem.  2000,  65:  164 
    Google Scholar
  • 18 Altemöller M. Gehring T. Cudaj J. Podlech J. Goesmann H. Feldmann C. Rothenberger A. Eur. J. Org. Chem.  2009,  2130 
    Google Scholar
  • 19a Chandrasekhar S. Reddy NR. Rao YS. Tetrahedron  2006,  62:  12098 
    Google Scholar
  • 19b Kuenburg B. Czollner L. Frohlich J. Jordis U. Org. Process Res. Dev.  1999,  3:  425 
    Google Scholar
  • 20a Reitz A. Avery MA. Verlander MS. Goodman M. J. Org. Chem.  1981,  46:  4859 
    Google Scholar
  • 20b Bhakuni DS. Kumar P. J. Indian Chem. Soc.  1988,  6:  417 
    Google Scholar
  • 20c Vickery EH. Pahler LF. Eisenbraun EJ. J. Org. Chem.  1979,  44:  4444 
    Google Scholar
  • 20d Tatsuta K. Furuyama A. Yano T. Suzuki Y. Ogura T. Hosokawa S. Tetrahedron Lett.  2008,  49:  4036 
    Google Scholar
  • 21 Henry TA. Sharp TM. J. Chem. Soc.  1930,  2279 
    Google Scholar
  • 22a Suzuki A. Proc. Jpn. Acad.  2004,  80:  359 
    Google Scholar
  • 22b Barder TE. Walker SD. Martinelli JR. Buchwald SL. J. Am. Chem. Soc.  2005,  127:  4685 
    Google Scholar
  • 22c Alonso F. Beletskaya IP. Yus M. Tetrahedron  2008,  64:  3047 
    Google Scholar
  • 22d Martin R. Buchwald SL. Acc. Chem. Res.  2008,  41:  1461 
    Google Scholar