Novel side chain modified Delta 8(14)-15-ketosterols

Synthesis of five novel Delta 8(14)-15-ketosterols comprising modified side chains starting from ergosterol is described. Ergosteryl acetate was converted into (22E)-3 beta-acetoxy-5 alpha-ergosta-8(14),22-dien-15-one through three stages in 32% overall yield; further transformations of the product...

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Bibliographic Details
Published inSteroids Vol. 72; no. 3; pp. 305 - 312
Main Authors Misharin, Alexander Yu, Ivanov, Vitali S., Mehtiev, Arif R., Morozevich, Galina E., Tkachev, Yaroslav V., Timofeev, Vladimir P.
Format Journal Article
LanguageEnglish
Published NEW YORK Elsevier 01.03.2007
Subjects
Biochemistry & Molecular Biology
Endocrinology & Metabolism
Life Sciences & Biomedicine
Science & Technology
STEROL SYNTHESIS
oxysterols
sterol biosynthesis inhibitors
3-BETA-HYDROXY-25,26,26,26,27,27,27-HEPTAFLUORO-5-ALPHA-CHOLEST-8-EN-15-ONE
SPECTRAL PROPERTIES
5-ALPHA-CHOLEST-8-EN-3-BETA-OL-15-ONE
ergosterol
CHOLESTEROL-METABOLISM
A REDUCTASE-ACTIVITY
CHEMICAL-SYNTHESIS
CULTURED-MAMMALIAN-CELLS
INHIBITORS
3-BETA-HYDROXY-5-ALPHA-CHOLEST-8-EN-15-ONE
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Summary:Synthesis of five novel Delta 8(14)-15-ketosterols comprising modified side chains starting from ergosterol is described. Ergosteryl acetate was converted into (22E)-3 beta-acetoxy-5 alpha-ergosta-8(14),22-dien-15-one through three stages in 32% overall yield; further transformations of the product obtained led to (22E)-3 beta-hydroxy-5 alpha-ergosta-8(14),22- dien-15-one, (22S,23S)-3 beta-hydroxy-22,23-oxido-5 alpha-ergost-8(14)-en-15-one, (22R,23R)-3 beta-hydroxy-22,23-oxido-5 alpha-ergost-8(14)-en-15-one, (22R,23R)-5 alpha-ergost-8(14)-en-15-on-3 beta,22,23-triol and (22R,23R)-3 beta-hydroxy- 22,23-isopropylidenedioxy-5 alpha-ergost-8(14)-en-15-one. New Delta 8(14)-15-ketosterols were evaluated for their cytotoxicity and effects on sterol biosynthesis in human hepatoma Hep G2 cells in comparison with known 3 beta-hydroxy-5 alpha-cholest-8(14)-en-15-one. Among the compounds tested, (22R,23R)-3 beta-hydroxy-22,23-oxido-5 alpha-ergost-8(14)-en-15-one was found to be the most potent inhibitor of sterol biosynthesis (IC50 = 0.6 +/- 0.2 mu M), whereas (22R,23R)5 alpha-ergost-8(14)-en-15-on-3 beta,22,23-triol exhibited the highest cytotoxicity (TC50 = 12 +/- 3 mu M at a 24 h incubation). (c) 2006 Elsevier Inc. All rights reserved.
ISSN:0039-128X
1878-5867
DOI:10.1016/j.steroids.2006.12.002