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Synlett 2009(9): 1357-1366  
DOI: 10.1055/s-0028-1216728
ACCOUNT
© Georg Thieme Verlag Stuttgart ˙ New York

Synthetic Efforts Towards the Synthesis of the Complex Diterpene Providencin

Tanja Gaich, Harald Weinstabl, Johann Mulzer*
Institute of Organic Chemistry, University of Vienna, Währinger Str. 38, 1090 Vienna, Austria
Fax: +43(1)427752189; e-Mail: johann.mulzer@univie.ac.at;
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Publikationsverlauf

Received 6 August 2008
Publikationsdatum:
17. April 2009 (online)

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Abstract

Providencin is a novel, highly oxygenated marine furanocembranolide featuring a cyclobutane ring and a highly strained 7,8-trans-epoxide. Various approaches to the total synthesis of this compound are reported. The cyclobutane moiety is generated via [2+2] cycloaddition and the furan ring is constructed via a Wipf ­palladium-catalyzed alkynone cyclization. The macrocyclic ring is closed via a Horner-Wadsworth-Emmons olefination or ring-­closing metathesis. The latter reaction, however, produces the undesired 7,8-Z-olefin exclusively, and the conversion into the E-isomer has been, thus far, unsuccessful.

1 Introduction

2 Retrosynthetic Analysis

3 First Generation Approach

3.1 Synthesis of the Cyclobutane Moiety

3.2 Synthesis of the Western Fragment

3.3 Combination of Both Fragments and Ring Closure via
Horner-Wadsworth-Emmons Olefination

4 Second Generation Approach via Ring-Closing Metathesis

5 Cyclobutane Model Studies

6 Conclusion

Key words

furanocembranolides - total synthesis - macrocycles, Horner-­Wadsworth-Emmons olefination - ring-closing metathesis

    References

  • 1a Fenical W. Okuda RK. Bandurraga MM. Culver P. Jacobs RS. Science (Washington, D. C.)  1981,  212:  1512 
    Google Scholar
  • 1b Fenical W. J. Nat. Prod.  1987,  50:  1001 
    Google Scholar
  • 1c Wright AE. Burres NS. Schulte GK. Tetrahedron Lett.  1989,  30:  3491 
    Google Scholar
  • 1d Abramson SN. Trischman JA. Tapiolas DM. Harold EE. Fenical W. Taylor P.
    J. Med. Chem.  1991,  34:  1798 
    Google Scholar
  • 1e Gutiérrez M. Capson TL. Guzmán HM. González J. Ortega-Barría E. Quiñoá E. Riguera R. J. Nat. Prod.  2005,  68:  614 
    Google Scholar
  • For representative syntheses of furanocembranolides, see:
  • 2a Paquette LA. Doherty AM. Rayner CM. J. Am. Chem. Soc.  1992,  114:  3910 
    Google Scholar
  • 2b Marshall JA. Van Devender EA. J. Org. Chem.  2001,  66:  8037 
    Google Scholar
  • 2c Wipf P. Soth MJ. Org. Lett.  2002,  4:  1787 
    Google Scholar
  • 2d Cases M. Gonzalez-Lopez de Turiso F. Hadjisoteriou MS. Pattenden G. Org. Biomol. Chem.  2005,  3:  2786 
    Google Scholar
  • 2e Marshall JA. DuBay WJ. J. Org. Chem.  1994,  59:  1703 
    Google Scholar
  • 2f Roethle PA. Trauner D. Nat. Prod. Rep.  2008,  25:  298 
    Google Scholar
  • 3 Marrero J. Rodríguez AD. Baran P. Raptis RG. Org. Lett.  2003,  5:  2551 
    CrossrefGoogle Scholar
  • 4a Bray CD. Pattenden G. Tetrahedron Lett.  2006,  47:  3937 
    Google Scholar
  • 4b Epifanio R. Maia LF. Fenical W. J. Braz. Chem. Soc.  2000,  11:  584 
    Google Scholar
  • For preliminary communications, see:
  • 5a Gaich T. Arion V. Mulzer J. Heterocycles  2007,  74:  855 
    Google Scholar
  • 5b Schweizer E. Gaich T. Brecker L. Mulzer J. Synthesis  2007,  3807 
    Google Scholar
  • 6a Rahmann LT. Rector SR. Wipf P. J. Org. Chem.  1998,  63:  7132 
    Google Scholar
  • 6b Soth MJ. Wipf P. Org. Lett.  2002,  4:  1787 
    Google Scholar
  • 7 Vedejs E. Daugulis O. J. Org. Chem.  1996,  61:  5702 
    CrossrefGoogle Scholar
  • For reviews on RCM in natural product synthesis, see:
  • 8a Roy R. Das SK. Chem. Commun.  2000,  519 
    Google Scholar
  • 8b Jørgensen M. Hadwiger P. Madsen R. Stütz AE. Wrodnigg TM. Curr. Org. Chem.  2000,  4:  565 
    Google Scholar
  • 8c Mulzer J. Öhler E. Metal Carbenes in Organic Synthesis, In Topics in Organometallic Chemistry   Vol. 13:  Dötz KH. Springer; Berlin: 2004.  p.271-376  
    Google Scholar
  • 8d Nicolaou KC. Bulger PG. Sarlah D. Angew. Chem. Int. Ed.  2005,  44:  4490 
    Google Scholar
  • 8e Gaich T. Mulzer J. Curr. Top. Med. Chem.  2005,  5:  1473 
    Google Scholar
  • 9a Wittig G. Haag W. Chem. Ber.  1955,  88:  1654 
    Google Scholar
  • 9b Keough PT. Grayson M. J. Org. Chem.  1962,  27:  1817 
    Google Scholar
  • 10 Corey EJ. Carey FA. Winter RAE. J. Am. Chem. Soc.  1965,  87:  934 
    CrossrefGoogle Scholar
  • 11 Davis FA. Stringer OD. J. Org. Chem.  1982,  47:  1774 
    CrossrefGoogle Scholar
  • 12 Ohira S. Synth. Commun.  1989,  19:  561 
    CrossrefGoogle Scholar