Download PDF
Synlett 2008(13): 1965-1968  
DOI: 10.1055/s-2008-1077958
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Stereoselective Synthesis of (25R)-Dafachronic Acids and (25R)-Cholestenoic Acid as Potential Ligands for the DAF-12 Receptor in Caenorhabditis elegans

René Martina, Arndt W. Schmidta, Gabriele Theumera, Teymuras V. Kurzchaliab, Hans-Joachim Knölker*a
a Department Chemie, Technische Universität Dresden, Bergstraße 66, 01069 Dresden, Germany
Fax: +49(351)46337030; e-Mail: hans-joachim.knoelker@tu-dresden.de;
b Max-Planck Institut für Molekulare Zellbiologie und Genetik, Pfotenhauerstraße 108, 01307 Dresden, Germany
Further Information

Publication History

Received 14 May 2008
Publication Date:
15 July 2008 (online)

    Permissions and Reprints All articles of this category

Abstract

Commercially available diosgenin has been used as starting material for a highly efficient synthesis of (25R)-dafachronic ­acids and (25R)-cholestenoic acid, potential ligands for the receptor DAF-12 in the nematode Caenorhabditis elegans.

Key words

carboxylic acids - oxidations - protecting groups - stereo­selective synthesis - steroids

    References and Notes

  • 1 Matyash V. Entchev EV. Mende F. Wilsch-Bräuninger M. Thiele C. Schmidt AW. Knölker H.-J. Ward S. Kurzchalia TV. PLoS Biol.  2004,  2:  1561 
    Google Scholar
  • 2 Motola DL. Cummins CL. Rottiers V. Sharma KK. Li T. Li Y. Suino-Powell K. Xu HE. Auchus RJ. Antebi A. Mangelsdorf DJ. Cell  2006,  124:  1209 
    CrossrefGoogle Scholar
  • 3 Held JM. White MP. Fisher AL. Gibson BW. Lithgow GJ. Gill MS. Aging Cell  2006,  5:  283 
    CrossrefGoogle Scholar
  • 4 Khripach VA. Zhabinskii VN. Konstantinova OV. Khripach NB. Antonchick AV. Antonchick AP. Schneider B. Steroids  2005,  70:  551 
    CrossrefGoogle Scholar
  • 5 Giroux S. Corey EJ. J. Am. Chem. Soc.  2007,  129:  9866 
    CrossrefGoogle Scholar
  • 6 Giroux S. Corey EJ. Org. Lett.  2008,  10:  801 
    CrossrefGoogle Scholar
  • 7 Schmidt AW. Doert T. Goutal S. Gruner M. Mende F. Kurzchalia TV. Knölker H.-J. Eur. J. Org. Chem.  2006,  3687 
    CrossrefGoogle Scholar
  • 8a Williams JR. Chai D. Wright D. Steroids  2002,  67:  1041 
    Google Scholar
  • 8b Williams JR. Chai D. Bloxton JD. Gong H. Solvibile WR. Tetrahedron  2003,  59:  3183 
    Google Scholar
  • 8c Gong H. Williams JR. Org. Lett.  2006,  8:  2253 
    Google Scholar
  • 9 Chidambaram N. Chandrasekaran S. J. Org. Chem.  1987,  52:  5048 
    CrossrefGoogle Scholar
  • 10 Shing TKM. Yeung Y.-Y. Su PL. Org. Lett.  2006,  8:  3149 
    CrossrefGoogle Scholar
  • 11 Salmond WG. Barta MA. Havens JL. J. Org. Chem.  1978,  43:  2057 
    Google Scholar
  • 12 Knölker H.-J. Ecker A. Struwe P. Steinmeyer A. Müller G. Neef G. Tetrahedron  1997,  53:  91 
    CrossrefGoogle Scholar
  • 14 Corey EJ. Schmidt G. Tetrahedron Lett.  1979,  399 
    CrossrefGoogle Scholar
  • 15a Šolaja BA. Milić DR. Došen-Mićović LI. Steroids  1994,  59:  330 
    Google Scholar
  • 15b Chodounská H. Pouzar V. Buděšínský M. Slavíková B. Kohout L. Steroids  2004,  69:  605 
    Google Scholar
  • 16 Brunel JM. Loncle C. Vidal N. Dherbomez M. Letourneux Y. Steroids  2005,  70:  907 
    CrossrefGoogle Scholar
  • 17a Miranda Moreno MJS. Sá e Melo ML. Campos Neves AS. Tetrahedron Lett.  1991,  32:  3201 
    Google Scholar
  • 17b Acosta CK. Rao PN. Kim HK. Steroids  1993,  58:  205 
    Google Scholar
  • 18a Nagaoka H. Rutsch W. Schmid G. Iio H. Johnson MR. Kishi Y. J. Am. Chem. Soc.  1980,  102:  7962 
    Google Scholar
  • 18b Boschelli D. Takemasa T. Nishitani Y. Masamune S. Tetrahedron Lett.  1985,  26:  5239 
    Google Scholar
  • 18c Nicolaou KC. Webber SE. Synthesis  1986,  453 
    Google Scholar
13

Characteristic Spectroscopic Data for the(25 R )-Cholesten-26-oic Acids 1, 13, 2, and 3
(25R)-D7-Dafachronic acid (1): colorless solid; mp 174-175 ˚C. ¹³C NMR and DEPT (125 MHz, CDCl3): δ = 11.87 (CH3), 12.44 (CH3), 16.72 (CH3), 18.74 (CH3), 21.66 (CH2), 22.91 (CH2), 23.68 (CH2), 27.90 (CH2), 30.02 (CH2), 33.85 (CH2), 34.35 (C), 35.62 (CH2), 36.01 (CH), 38.09 (CH2), 38.73 (CH2), 39.24 (CH), 39.38 (CH2), 42.82 (CH), 43.33 (C), 44.20 (CH2), 48.78 (CH), 54.87 (CH), 56.01 (CH), 116.99 (CH), 139.46 (C), 182.51 (C=O), 212.19 (C=O). Anal. Calcd (%) for C27H42O3: C, 78.21; H, 10.21. Found: C, 78.42; H, 10.41.
(25R)-3,6-Diketocholest-4-en-26-oic acid (13): colorless solid; mp 105-110 ˚C. ¹³C NMR and DEPT (125 MHz, CDCl3): δ = 11.87 (CH3), 16.76 (CH3), 17.49 (CH3), 18.55 (CH3), 20.84 (CH2), 23.59 (CH2), 23.93 (CH2), 27.97 (CH2), 33.83 (CH2), 33.94 (CH2), 34.16 (CH), 35.50 (CH, CH2), 35.60 (CH2), 39.08 (CH2), 39.21 (CH), 39.78 (C), 42.52 (C), 46.77 (CH2), 50.91 (CH), 55.83 (CH), 56.48 (CH), 125.45 (CH), 161.04 (C), 182.27 (C=O), 199.55 (C=O), 202.34 (C=O). HRMS: m/z calcd for C27H40O4 [M+]: 428.2927; found: 428.2914.
(25R)-D4-Dafachronic acid (2): colorless solid; mp 148-150 ˚C. ¹³C NMR and DEPT (125 MHz, CDCl3): δ = 11.93 (CH3), 16.74 (CH3), 17.35 (CH3), 18.55 (CH3), 20.99 (CH2), 23.60 (CH2), 24.14 (CH2), 28.15 (CH2), 32.00 (CH2), 32.93 (CH2), 33.86 (CH2), 33.94 (CH2), 35.57 (2 CH), 35.64 (2 CH2), 38.58 (C), 39.26 (CH), 39.57 (CH2), 42.37 (C), 53.75 (CH), 55.81 (CH), 55.99 (CH), 123.71 (CH), 171.85 (C), 182.48 (C=O), 199.83 (C=O). Anal. Calcd (%) for C27H42O3: C, 78.21; H, 10.21. Found: C, 78.03; H, 10.46.
(25R)-Cholestenoic acid (3): colorless solid; mp 168-170 ˚C (MeCN). ¹³C NMR and DEPT (125 MHz, CDCl3): δ = 11.85 (CH3), 16.74 (CH3), 18.63 (CH3), 19.38 (CH3), 21.05 (CH2), 23.62 (CH2), 24.27 (CH2), 28.21 (CH2), 31.58 (CH2), 31.87 (CH, CH2), 33.91 (CH2), 35.62 (CH), 35.72 (CH2), 36.47 (C), 37.22 (CH2), 39.27 (CH), 39.73 (CH2), 42.21 (CH2), 42.30 (C), 50.07 (CH), 56.05 (CH), 56.70 (CH), 71.82 (CH), 121.71 (CH), 140.69 (C), 182.46 (C=O). Anal. Calcd (%) for C27H44O3: C, 77.83; H, 10.64. Found: C, 77.26; H, 10.33.