Download PDF
Synlett 2010(19): 2923-2927  
DOI: 10.1055/s-0030-1259015
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

A Concise Synthesis of Bengamide E and Analogues via E-Selective Cross-Metathesis Olefination

Safiul Alam, Hamid Dhimane*
Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, UMR 8601 CNRS/Université Paris Descartes, UFR Biomédicale, 45, Rue des Saints-Pères, 75270 Paris cedex 06, France
Fax: +33(1)42864050; e-Mail: hamid.dhimane@parisdescartes.fr;
Further Information

Publication History

Received 2 September 2010
Publication Date:
03 November 2010 (online)

    Permissions and Reprints All articles of this category

Abstract

A modular, eight-step synthesis of bengamide E and six analogues from a common chiral pool has been developed. The key step in this approach is a cross-metathesis coupling of various commercial terminal olefins and a common alkene bearing the required stereogenic centers of bengamides lateral chain, which was easily derived from α-d-glucoheptonic-γ-lactone. Complete E-selectivity, and up to 92% yield were achieved for this crucial cross-metathesis step.

Key words

bengamide - analogues - cross-metathesis - stereoselective olefination - isomerization

    References and Notes

  • 1a Quiñoà E. Adamczeski M. Crews P. Bakus G.
    J. Org. Chem.  1986,  51:  4494 
    Google Scholar
  • 1b Adamczeski M. Quiñoà E. Crews P. J. Am. Chem. Soc.  1989,  111:  647 
    Google Scholar
  • 1c Adamczeski M. Quiñoà E. Crews P. J. Org. Chem.  1990,  55:  240 
    Google Scholar
  • 1d D’Auria MV. Giannini C. Minale L. Zampella A. Debitus C. Frostin M. J. Nat. Prod.  1997,  60:  814 
    Google Scholar
  • 2 Thale Z. Kinder FR. Bair KW. Bontempo J. Czuchta AM. Versace RW. Phillips PE. Sanders ML. Wattanasin S. Crews P. J. Org. Chem.  2001,  66:  1733 
    CrossrefGoogle Scholar
  • 3a For recent review (up to early 2001), see: Kinder FR. Org. Prep. Proced. Int.  2002,  34:  559 
    Google Scholar
  • 3b Banwell MG. McRae KJ. J. Org. Chem.  2001,  66:  6768 
    Google Scholar
  • 3c Liu W. Szewczyk JM. Waykole L. Repic O. Blacklock TJ. Tetrahedron Lett.  2002,  43:  1373 
    Google Scholar
  • 3d Boeckman RK. Clark TJ. Shook BC. Org. Lett.  2002,  4:  2109 
    Google Scholar
  • 3e Sarabia F. Sánchez-Ruiz A. J. Org. Chem.  2005,  70:  9514 ; and references cited therein
    Google Scholar
  • 3f Liu G. Ma Y.-M. Tai W.-Y. Xie C.-M. Li Y.-L. li J. Nan F.-J. ChemMedChem  2008,  3:  74 
    Google Scholar
  • 4 Kinder FR. Versace RW. Bair KW. Bontempo JM. Cesarz D. Chen S. Crews P. Czuchta AM. Jagoe CT. Mou Y. Nemzek R. Phillips PE. Tran LD. Wang R. Weltchek S. Zabludoff S. J. Med. Chem.  2001,  44:  3692 
    CrossrefGoogle Scholar
  • 5 Towbin H. Bair KW. DeCaprio JA. Eck MJ. Kim S. Kinder FK. Morollo A. Mueller DR. Schindler P. Song HK. van Oostrum J. Versace RW. Voshol H. Wood J. Zabludoff S. Phillips PE. J. Biol. Chem.  2003,  278:  52964 
    CrossrefGoogle Scholar
  • For recent reviews, see:
  • 6a Bernier SG. Taghizadeh N. Thompson CD. Westlin WF. Hannig G. J. Cell. Biochem.  2005,  95:  1191 
    Google Scholar
  • 6b Selvakumar P. Lakshmikuttyamma A. Dimmock J. Sharma RK. Biochim. Biophys.  2006,  1765:  148 
    Google Scholar
  • 6c Frottin F. Martinez A. Peynot P. Mitra S. Holz RC. Giglione C. Meinel T. Mol. Cell. Proteomics  2006,  5:  2336 
    Google Scholar
  • 6d Wiltschi B. Merkel L. Budisa N. ChemBioChem  2009,  10:  217 
    Google Scholar
  • 7 Hu X. Dang Y. Tenney K. Crews P. Tsai CW. Sixt KM. Cole PA. Liu JO. Chem. Biol.  2007,  14:  764 
    CrossrefGoogle Scholar
  • 8a Levraud C. Calvet-Vitale S. Bertho G. Dhimane H. Eur. J. Org. Chem.  2008,  1901 
    Google Scholar
  • 8b David M. Dhimane H. Synlett  2004,  1029 
    Google Scholar
  • 9 Xu DD. Waykole L. Calienni JV. Ciszewski L. Lee GT. Liu W. Szewczyk J. Vargas K. Prasad K. Repic O. Blacklock TJ. Org. Process Res. Dev.  2003,  7:  856 
    CrossrefGoogle Scholar
  • 12a Grank G. Eastwood FW. Aust. J. Chem.  1964,  17:  1392 
    Google Scholar
  • 12b Ando M. Ohhara H. Takase K. Chem. Lett.  1986,  879 
    Google Scholar
  • 14 Chatterjee AK. Choi R.-L. Sanders DP. Grubbs RH. J. Am. Chem. Soc.  2003,  125:  11360 
    Google Scholar
  • 16a Maynard HD. Grubbs RH. Tetrahedron Lett.  1999,  40:  4137 
    Google Scholar
  • 16b Edwards SD. Lewis T. Raylor RJK. Tetrahedron Lett.  1999,  40:  4267 
    Google Scholar
  • 16c Bourgeois D. Pancrazi A. Ricard L. Prunet J. Angew. Chem. Int. Ed.  2000,  39:  725 
    Google Scholar
  • 17 Fürstner A. Thiel OR. Ackermann L. Schanz H.-J. Nolan SP. J. Org. Chem.  2000,  65:  2204 
    Google Scholar
  • For review, see:
  • 18a Schmidt B. Eur. J. Org. Chem.  2004,  1865 
    Google Scholar
  • 18b Alcaide B. Almendros P. Chem. Eur. J.  2003,  9:  1259 
    Google Scholar
  • 19a Cadot C. Dalko PI. Cossy J. Tetrahedron Lett.  2002,  43:  1839 
    Google Scholar
  • 19b Maishal TK. Sinha-Mahapatra DK. Paranjape K. Sarkar A. Tetrahedron Lett.  2002,  43:  2263 
    Google Scholar
  • 20 Courchay FC. Sworen JC. Ghiviriga I. Aboud KA. Wagener KB. Organometallics  2006,  25:  6074 ; and references cited therein
    CrossrefGoogle Scholar
  • 21 Hong SH. Sanders DP. Lee CW. Grubbs RH. J. Am. Chem. Soc.  2005,  127:  17160 
    Google Scholar
  • 23 Boyle WJ. Sifniades S. van Peppen JF. J. Org. Chem.  1979,  44:  4841 
    CrossrefGoogle Scholar
  • 24 Liu W. Xu DD. Repic O. Blacklock TJ. Tetrahedron Lett.  2001,  42:  2439 
    CrossrefGoogle Scholar
10

Aldehyde 3 is highly hygroscopic and sensitive to both acid and base; it should be freshly prepared and dehydrated by azeotropic evaporations with i-PrOAc prior to its use.

11

Our initial attempt to carry out the Julia-Kocienski methylenation of aldehyde 3 led to the required olefin 4 in poor yields (<10%).

13

Use of PTSA as catalyst in toluene at 80 ˚C gave similar yields; however, in large-scale batches, we observed transprotection of the acetonide, thus leading to the corresponding bisorthoester. Orthoester 6 was found to be stable at r.t. in the solid state; however, it undergoes gradual hydrolysis (into methyl formiate and diol 2) on standing in CDCl3.

15

The CM adducts 5 could not be quantitatively recovered from the reaction mixtures; aromatic compounds 5e-g could not be fully separated from substrate 4, while the aliphatic ones 5a-d were always contaminated with the substrate isomer 4′.

22

No CM reaction was observed with: H2C=CHTMS, H2C=CHO-t-Bu, H2C=CHOAc, H2C=CHSO2Me, N-vinylimidazole.