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

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.