PDF herunterladen
Synlett 2008(3): 418-422  
DOI: 10.1055/s-2008-1032064
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Chemobiological Synthesis of Eplerenone

Peter G. M. Wuts*, Andrew M. Anderson, Scott W. Ashford, Michael P. Goble, Michael J. White, Doris Beck, Ivan Gilbert, R. E. Hrab
Pfizer Global Research and Development, Groton, CT 06340 and Pfizer, Bioprocess Development Group, Kalamazoo, MI 49001, USA
Fax: +1(860)4410599; e-Mail: peter.g.wuts@pfizer.com;
Weitere Informationen

Publikationsverlauf

Received 12 November 2007
Publikationsdatum:
23. Januar 2008 (online)

   Lizenzen und Reprints Alle Artikel dieser Rubrik

Abstract

This paper will describe an approach to the synthesis of eplerenone, which is being marketed for the treatment of hypertension. The synthesis begins with DHEA available from wild yams and uses a combination of microbiological and chemical transformations to build eplerenone.

Key words

carbonylation - microbial oxidation - hydroformylation - steroids - Ishikawa reagent - microbial deprotection

    References

  • 1 Information update: Drugs Future  2000,  25:  516 
  • 2a Rabasseda X. Silvestre J. Castañer J. Drugs Future  1999,  24:  488 
    CrossrefSuche in Google Scholar
  • 2b Ng JS, Wang PT, Baez JA, Liu C, Anderson DK, Lawson JP, Erb D, Wieczorek J, Mucciariello G, Vanzanella F, Kunda SA, Letendre LJ, Pozzo MJ, and Sing Y.-L. inventors; WO  9721720. 
    Crossref
  • 3 McMahon EG. Curr. Opin. Pharmacol.  2001,  1:  190 
    Suche in Google Scholar
  • 4 White MJ, Wuts PGM, and Beck D. inventors; US 0034215  A1. 
  • 5 Fu X. Tann C.-H. Thiruvengadam TK. Lee J. Colon C. Tetrahedron Lett.  2001,  42:  2639 
    CrossrefSuche in Google Scholar
  • 7a Maeda K. Farrington EJ. Galardon E. John BD. Brown JM. Adv. Synth. Catal.  2002,  344:  104 
    Suche in Google Scholar
  • 7b Takas JM. Lawson EC. Clement F. J. Am. Chem. Soc.  1997,  119:  5956 
    Suche in Google Scholar
  • 7c Andersson PG. Schab S. Organometallics  1995,  14:  1 
    Suche in Google Scholar
  • 8 Wuts PGM. Ritter AR. J. Org. Chem.  1989,  54:  5180 
    CrossrefSuche in Google Scholar
  • 9 Wuts PGM. Ashford SW. Anderson AM. Atkins JR. Org. Lett.  2003,  5:  1483 
    CrossrefSuche in Google Scholar
  • 10 Takahashi Y. Tsukiyama K. Sakai S. Ishii Y. Tetrahedron Lett.  1970,  1913 
    Crossref
  • 11 Murahashi S.-I. Imada Y. Taniguchi Y. Higashiura S. J. Org. Chem.  1993,  58:  1538 
    Suche in Google Scholar
  • 12 Microbial Transformations of Steroids: A Hand-book,Charney W., Herzog H. L.   Academic Press; New York: 1967. 
  • 13 Kieslich K, and Kapp JF. inventors; German Patent DE  2656575. 
  • 14 Kieslich K. inventors; German Patent DE  2746298. 
  • 15 Boeren S. Laane C. Biotech. Bioeng  1987,  29:  305 
    CrossrefSuche in Google Scholar
  • 16 White MJ, Beck DM, Wuts PGM, and Gilbert IG. inventors; US  265948. 
6

Mackey, S. S.; Matison, M. E.; Wu, H. unpublished results.