Synthesis 2016; 48(11): 1637-1646
DOI: 10.1055/s-0035-1561430
special topic
© Georg Thieme Verlag Stuttgart · New York

Suberosanes as Potential Antitumor Agents: First Enantioselective Total Synthesis of (1S)-Suberosanone and Configurational Assignment of Suberosenol A

Mohammad Kousara
a  CNRS-BioCIS UMR 8076, IPSIT and LabEx LERMIT, Université Paris Saclay, Faculté de Pharmacie, Université de Paris Sud, 5 rue J.-B. Clément, 92296 Châtenay-Malabry Cedex, France   Email: francoise.dumas@u-psud.fr
,
Franck Le Bideau
a  CNRS-BioCIS UMR 8076, IPSIT and LabEx LERMIT, Université Paris Saclay, Faculté de Pharmacie, Université de Paris Sud, 5 rue J.-B. Clément, 92296 Châtenay-Malabry Cedex, France   Email: francoise.dumas@u-psud.fr
,
Rama Ibrahim
b  INSERM-UMR749, Institut Gustave Roussy, Université Paris Saclay, Université Paris Sud, Pavillon de recherche, 1114 rue Edouard Vaillant, 94805 Villejuif Cedex, France
,
Angélique Ferry
a  CNRS-BioCIS UMR 8076, IPSIT and LabEx LERMIT, Université Paris Saclay, Faculté de Pharmacie, Université de Paris Sud, 5 rue J.-B. Clément, 92296 Châtenay-Malabry Cedex, France   Email: francoise.dumas@u-psud.fr
,
Pierre-Etienne Venot
a  CNRS-BioCIS UMR 8076, IPSIT and LabEx LERMIT, Université Paris Saclay, Faculté de Pharmacie, Université de Paris Sud, 5 rue J.-B. Clément, 92296 Châtenay-Malabry Cedex, France   Email: francoise.dumas@u-psud.fr
,
Camille Dejean
c  NMR Department, BioCIS UMR CNRS 8076, IPSIT and LabEx LERMIT, Université Paris Saclay, Faculté de Pharmacie, Université de Paris Sud, 5 rue J.-B. Clément, 92296 Châtenay-Malabry Cedex, France
,
Joël Raingeaud
b  INSERM-UMR749, Institut Gustave Roussy, Université Paris Saclay, Université Paris Sud, Pavillon de recherche, 1114 rue Edouard Vaillant, 94805 Villejuif Cedex, France
,
Joëlle Dubois
d  Institut de Chimie des Substances Naturelles, UPR CNRS 2301, Bât. 27, 1 avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France
,
Pascal Retailleau
d  Institut de Chimie des Substances Naturelles, UPR CNRS 2301, Bât. 27, 1 avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France
,
Françoise Dumas*
a  CNRS-BioCIS UMR 8076, IPSIT and LabEx LERMIT, Université Paris Saclay, Faculté de Pharmacie, Université de Paris Sud, 5 rue J.-B. Clément, 92296 Châtenay-Malabry Cedex, France   Email: francoise.dumas@u-psud.fr
› Author Affiliations
Further Information

Publication History

Received: 18 January 2016

Accepted after revision: 17 March 2016

Publication Date:
20 April 2016 (online)

Dedicated to the late Professor Jean d’Angelo

Abstract

The first enantioselective total syntheses of two marine sesquiterpenes, natural (1S)-suberosanone and (1S)-suberosenol A, are achieved leading to the assignment of the absolute configuration of natural suberosenol A. A new access to (1S)-suberosenone from a key tricyclic enone was also developed leading to an overall improvement of the synthesis, allowing an efficient route to suberosenol A. Hyperbaric asymmetric Michael addition and a highly efficient silver trifluoroacetate mediated α-alkylation for the formation of ring A completed the key steps of the synthesis. Regrettably, synthetic (1S)-suberosanone did not retain the reported picomolar cytotoxic activity displayed by the natural product, the reason for which remains to be elucidated.

Supporting Information

 
  • References

  • 1 Present address: Faculty of Pharmacy, Tishreen University, Latakia, Syria & Faculty of Pharmacy, Al Andalus University, Tartus, Al Qadmus, P.O.Box 101, Syria.
  • 2 Nobili S, Lippi D, Witort E, Donnini M, Bausi L, Mini E, Capaccioli S. Pharmacol. Res. 2009; 59: 365
  • 3 Bokesch HR, McKee TC, Cardellina JH. II, Boyd MR. Tetrahedron Lett. 1996; 37: 3259
    • 4a Bokesch HR, Blunt JW, Westergaard CK, Cardellina JH. II, Johnson TR, Michael JA, McKee TC, Hollingshead MG, Boyd MR. J. Nat. Prod. 1999; 62: 633
    • 4b Sheu J.-H, Hung K.-C, Wang G.-H, Duh C.-Y. J. Nat. Prod. 2000; 63: 1603
    • 4c Qi S.-H, Zhang S, Li X, Li Q.-X. J. Nat. Prod. 2005; 68: 1288
    • 5a Ranieri RL, Calton GJ. Tetrahedron Lett. 1978; 499
    • 5b Reissig H.-U, Zimmer R In Science of Synthesis . Vol. 33. Molander G.-A. Thieme; Stuttgart: 2006: 371
    • 6a Nakagawa M, Hirota A, Sakai H, Isogai A. J. Antibiot. 1982; 35: 778
    • 6b Turbyville TJ, Wijeratne EM. K, Whitesell L, Gunatilaka AA. L. Mol. Cancer Ther. 2005; 4: 1569
  • 7 Presset M, Coquerel Y, Rodriguez J. Eur. J. Org. Chem. 2010; 2247
  • 8 Lee H.-Y, Kim BG. Org. Lett. 2000; 2: 1951
  • 9 Coates RM, Ho JZ, Klobus M, Zhu L. J. Org. Chem. 1998; 63: 9166
  • 10 Kousara M, Ferry A, Le Bideau F, Serré KL, Chataigner I, Morvan E, Dubois J, Chéron M, Dumas F. Chem. Commun. 2015; 51: 3458
  • 11 Stephens PJ, McCann DM, Devlin FJ, Smith AB. III. J. Nat. Prod. 2006; 69: 1055
    • 12a Torihata M, Kuwahara S. Biosci., Biotechnol., Biochem. 2008; 72: 1628
    • 12b Torihata M, Nakahata T, Kuwahara S. Org. Lett. 2007; 9: 2557
  • 13 Koshiba T, Yokoshima S, Fukuyama T. Org. Lett. 2009; 11: 5354
  • 14 Angers P, Canonne P. Tetrahedron Lett. 1994; 35: 367
  • 15 Majumdar KC, Sinha B. RSC Adv. 2014; 4: 8085
  • 16 d’Angelo J, Desmaële D, Dumas F, Guingant A. Tetrahedron: Asymmetry 1992; 3: 459
  • 17 Miller DG, Wayner DD. J. Org. Chem. 1990; 55: 2924
  • 18 Danishefsky S, Vaughan K, Gadwood R, Tsuzuki K. J. Am. Chem. Soc. 1981; 103: 4136
  • 19 Pecquet F, d’Angelo J. Tetrahedron Lett. 1982; 2777
  • 20 Hirota H, Kakita S, Takahashi T, Hirota A, Nakagawa M, Isogai A. J. Chem. Soc., Perkin Trans. 1 1990; 3345
  • 21 Finefield JM, Sherman DH, Kreitman M, Williams RM. Angew. Chem. Int. Ed. 2012; 51: 4802
  • 22 Qi S.-H, Zhang S, Li X, Li Q.-X. J. Nat. Prod. 2005; 68: 1288
  • 23 Xiao Q, Jackson JJ, Basak A, Bowler JM, Miller BG, Zakarian A. Nature Chem. 2013; 5: 410
  • 24 Still WC, Kahn M, Mitra A. J. Org. Chem. 1978; 43: 2923
  • 25 For comparison with the natural products only (suberosanone, suberosenone, and suberosenol A).
  • 26 Gottlieb HE, Kotlyar V, Nudelman A. J. Org. Chem. 1997; 62: 751
  • 27 The quality of the catalyst (anhydrous) has an important impact on the yield of the reaction.