Synthetic Efforts Towards
the Synthesis of the Complex Diterpene Providencin

Tanja Gaich; Harald Weinstabl; Johann Mulzer

doi:10.1055/s-0028-1216728

ACCOUNT

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;

Abstract

All articles of this category

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

Full Text

References

<A NAME="RA50908ST-1A">1a</A> Fenical W. Okuda RK. Bandurraga MM. Culver P. Jacobs RS. Science (Washington, D. C.) 1981, 212: 1512

<A NAME="RA50908ST-1B">1b</A> Fenical W. J. Nat. Prod. 1987, 50: 1001

<A NAME="RA50908ST-1C">1c</A> Wright AE. Burres NS. Schulte GK. Tetrahedron Lett. 1989, 30: 3491

<A NAME="RA50908ST-1D">1d</A> Abramson SN. Trischman JA. Tapiolas DM. Harold EE. Fenical W. Taylor P.
J. Med. Chem. 1991, 34: 1798

<A NAME="RA50908ST-1E">1e</A> Gutiérrez M. Capson TL. Guzmán HM. González J. Ortega-Barría E. Quiñoá E. Riguera R. J. Nat. Prod. 2005, 68: 614

For representative syntheses of furanocembranolides, see:

<A NAME="RA50908ST-2A">2a</A> Paquette LA. Doherty AM. Rayner CM. J. Am. Chem. Soc. 1992, 114: 3910

<A NAME="RA50908ST-2B">2b</A> Marshall JA. Van Devender EA. J. Org. Chem. 2001, 66: 8037

<A NAME="RA50908ST-2C">2c</A> Wipf P. Soth MJ. Org. Lett. 2002, 4: 1787

<A NAME="RA50908ST-2D">2d</A> Cases M. Gonzalez-Lopez de Turiso F. Hadjisoteriou MS. Pattenden G. Org. Biomol. Chem. 2005, 3: 2786

<A NAME="RA50908ST-2E">2e</A> Marshall JA. DuBay WJ. J. Org. Chem. 1994, 59: 1703

<A NAME="RA50908ST-2F">2f</A> Roethle PA. Trauner D. Nat. Prod. Rep. 2008, 25: 298

<A NAME="RA50908ST-3">3</A> Marrero J. Rodríguez AD. Baran P. Raptis RG. Org. Lett. 2003, 5: 2551

<A NAME="RA50908ST-4A">4a</A> Bray CD. Pattenden G. Tetrahedron Lett. 2006, 47: 3937

<A NAME="RA50908ST-4B">4b</A> Epifanio R. Maia LF. Fenical W. J. Braz. Chem. Soc. 2000, 11: 584

For preliminary communications, see:

<A NAME="RA50908ST-5A">5a</A> Gaich T. Arion V. Mulzer J. Heterocycles 2007, 74: 855

<A NAME="RA50908ST-5B">5b</A> Schweizer E. Gaich T. Brecker L. Mulzer J. Synthesis 2007, 3807

<A NAME="RA50908ST-6A">6a</A> Rahmann LT. Rector SR. Wipf P. J. Org. Chem. 1998, 63: 7132

<A NAME="RA50908ST-6B">6b</A> Soth MJ. Wipf P. Org. Lett. 2002, 4: 1787

<A NAME="RA50908ST-7">7</A> Vedejs E. Daugulis O. J. Org. Chem. 1996, 61: 5702

For reviews on RCM in natural product synthesis, see:

<A NAME="RA50908ST-8A">8a</A> Roy R. Das SK. Chem. Commun. 2000, 519

<A NAME="RA50908ST-8B">8b</A> Jørgensen M. Hadwiger P. Madsen R. Stütz AE. Wrodnigg TM. Curr. Org. Chem. 2000, 4: 565

<A NAME="RA50908ST-8C">8c</A> Mulzer J. Öhler E. Metal Carbenes in Organic Synthesis, In Topics in Organometallic Chemistry Vol. 13: Dötz KH. Springer; Berlin: 2004. p.271-376

<A NAME="RA50908ST-8D">8d</A> Nicolaou KC. Bulger PG. Sarlah D. Angew. Chem. Int. Ed. 2005, 44: 4490

<A NAME="RA50908ST-8E">8e</A> Gaich T. Mulzer J. Curr. Top. Med. Chem. 2005, 5: 1473

<A NAME="RA50908ST-9A">9a</A> Wittig G. Haag W. Chem. Ber. 1955, 88: 1654

<A NAME="RA50908ST-9B">9b</A> Keough PT. Grayson M. J. Org. Chem. 1962, 27: 1817

<A NAME="RA50908ST-10">10</A> Corey EJ. Carey FA. Winter RAE. J. Am. Chem. Soc. 1965, 87: 934

<A NAME="RA50908ST-11">11</A> Davis FA. Stringer OD. J. Org. Chem. 1982, 47: 1774

<A NAME="RA50908ST-12">12</A> Ohira S. Synth. Commun. 1989, 19: 561