Download PDF
Synthesis 2010(1): 67-72  
DOI: 10.1055/s-0029-1217094
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Expedient Access to A-Ring-γ-Dioxygenated Terpenoids: The First Synthesis of (13E)-ent-Labda-8(17),13-diene-3β,15,18-triol

Victoriano Domingoa, Horacio R. Diégueza, Carmen P. Moralesa, Jesús F. Arteagab, José F. Quílez del Moral*a, Alejandro F. Barrero*a
a Department of Organic Chemistry, Institute of Biotechnology, University of Granada, Avda. Fuentenueva, 18071 Granada, Spain
Fax: +34(958)243318; e-Mail: afbarre@ugr.es; e-Mail: jfquilez@ugr.es;
b Department of Chemical Engineering, Physical Chemistry and Organic Chemistry, University of Huelva, Campus el Carmen, 21071 Huelva, Spain
Further Information

Publication History

Received 24 July 2009
Publication Date:
03 November 2009 (online)

    Permissions and Reprints All articles of this category

Abstract

A simple approach to A-ring-γ-dioxygenated terpenoids is described which involves two key steps, namely, selenium-catalyzed selective allylic chlorination of polyprenoids and titanocene-mediated radical cyclization of epoxypolyprenes. We have applied this synthetic route to the first synthesis of the diterpene, (13E)-ent-labda-8(17),13-diene-3β,15,18-triol. A stereoselective approach to this synthesis is also described.

Key words

diterpene - radical cyclizations - oxiranes - stereoselective synthesis - titanocene

    References

  • 2a Tanaka T. Kawamura K. Kitahara T. Kohda H. Tanaka O. Phytochemistry  1984,  23:  615 
    Google Scholar
  • 2b Ohtani K. Yang C. Miyajima C. Zhou J. Tanaka O. Chem. Pharm. Bull.  1991,  39:  2443 
    Google Scholar
  • 3 Cheepracha S. Yodsaoue O. Karalai C. Ponglimanont C. Subhadhirasakul S. Tewtrakul S. Kanjana-opas A. Phytochemistry  2006,  67:  2630 
    CrossrefGoogle Scholar
  • 4a Omura S. Tomoda H. Kim YK. Nishida H. J. Antibiot.  1993,  46:  1168 
    Google Scholar
  • 4b Aggarwal VK. Bethel PA. Giles R. J. Chem. Soc., Perkin Trans. 1  1999,  3315 
    Google Scholar
  • 5a Fujioka T. Iwamoto M. Iwase Y. Hachiyama S. Okabe H. Yamauchi T. Mihashi K. Chem. Pharm. Bull.  1989,  37:  1770 
    Google Scholar
  • 5b Cheng G. Zhang Y. Zhang X. Tang HF. Cao WD. Gao DK. Wang XL. Bioorg. Med. Chem. Lett.  2006,  16:  4575 
    Google Scholar
  • 5c Wang F. Ma R. Yu L. Cancer Chemother. Pharmacol.  2006,  57:  389 
    Google Scholar
  • 6a Jahan N. Ahmed W. Malik A. Phytochemistry  1995,  39:  255 
    Google Scholar
  • 6b Jahan N. Ahmed W. Phytochemistry  1995,  40:  1582 
    Google Scholar
  • 7a Zhu C. Tang P. Yu B. J. Am. Chem. Soc.  2008,  130:  5872 
    Google Scholar
  • 7b García-Granados A. López PE. Melguizo E. Parra A. Simeó Y. J. Org. Chem.  2007,  72:  3500 
    Google Scholar
  • 7c Johnson JA. Li N. Sames D. J. Am. Chem. Soc.  2002,  124:  6900 
    Google Scholar
  • 7d Dangel BD. Godula K. Youn SW. Sezen B. Sames D. J. Am. Chem. Soc.  2002,  124:  11856 
    Google Scholar
  • 7e Bore L. Honda T. Gribble GW. Nat. Prod. Lett.  2002,  16:  273 
    Google Scholar
  • 7f Bore L. Honda T. Gribble GW. J. Org. Chem.  2000,  65:  6278 
    Google Scholar
  • 7g Peakman TM. ten Haven HL. Rullkötter J. Tetrahedron  1991,  47:  3779 
    Google Scholar
  • 7h Carr K. Saxton HM. Sutherland JK. J. Chem. Soc., Perkin Trans. 1  1988,  1599 
    Google Scholar
  • 7i Baldwin JE. Jones RH. Najera C. Yus M. Tetrahedron  1985,  41:  699 
    Google Scholar
  • 8 Justicia J. Oltra JE. Cuerva JM. J. Org. Chem.  2006,  70:  8265 
    Google Scholar
  • 9 Wender PA. Croatt MP. Witulski B. Tetrahedron  2006,  62:  7505 
    CrossrefGoogle Scholar
  • 10a Burns NZ. Baran PS. Hoffmann RW. Angew. Chem. Int. Ed.  2009,  48:  2854 
    Google Scholar
  • 10b Hendrickson JB. J. Am. Chem. Soc.  1975,  97:  5784 
    Google Scholar
  • 11 Barrero AF. Quílez del Moral JF. Herrador MM. Loayza I. Sánchez EM. Arteaga JF. Tetrahedron  2006,  62:  5215 
    CrossrefGoogle Scholar
  • 12 Nakai K. Kamoshita M. Doi T. Yamada H. Takahashi T. Tetrahedron Lett.  2001,  42:  7855 ; these authors reported mixtures of exo-endo olefins and only moderate to acceptable stereoselectivities in the generation of the two stereogenic centres at C-3 and C-4
    Google Scholar
  • 13 Krapcho AP. Glynn GA. Grenon BJ. Tetrahedron Lett.  1967,  215 
    CrossrefGoogle Scholar
  • 14a Barrero AF. Cuerva JM. Herrador MM. Valdivia MV. J. Org. Chem.  2001,  66:  4074 
    Google Scholar
  • 14b Fernandez-Mateos A. Martin de la Nava E. Pascual Coca G. Ramos Silvo A. Rubio Gonzalez R. Org. Lett.  1999,  1:  607 
    Google Scholar
  • 15a Barrero AF. Quílez del Moral JF. Herrador MM. Cortés M. Arteaga P. Catalán JV. Sánchez EM. Arteaga JF. J. Org. Chem.  2006,  71:  5811 
    Google Scholar
  • 15b Tunge JA. Mellegard SR. Org. Lett.  2004,  6:  1205 
    Google Scholar
  • 16 Sharpless KB. Michaelson RC. J. Am. Chem. Soc.  1973,  95:  6136 
    CrossrefGoogle Scholar
  • 17 For a review on the use of this species in radical cyclizations towards the synthesis of natural products, see: Barrero AF. Quílez del Moral JF. Sánchez EM. Arteaga JF. Eur. J. Org. Chem.  2006,  7:  1627 
    CrossrefGoogle Scholar
  • 19 Katsiki T. Sharpless KB. J. Am. Chem. Soc.  1980,  102:  5974 
    CrossrefGoogle Scholar
1

Although the method described herein allows access to dihydroxyterpenes functionalized at C-3 and at the axial methyl at C-4, we use the term γ-dioxygenated terpenoids throughout the text for the sake of simplicity.

18

Since our aim here was to confirm the feasibility of our methodology for asymmetric synthesis, the enantiomeric excess was not measured. Furthermore, epoxy-alcohol 15 was obtained as a mixture of diastereoisomers.

20

No differences were found between the spectroscopic data of 15 and those of 11.