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

René Martin; Arndt W. Schmidt; Gabriele Theumer; Teymuras V. Kurzchalia; Hans-Joachim Knölker

doi:10.1055/s-2008-1077958

LETTER

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

René Martin^a, Arndt W. Schmidt^a, Gabriele Theumer^a, Teymuras V. Kurzchalia^b, 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

Abstract

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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

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References

References and Notes

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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.

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