240129-43-5Relevant articles and documents
Sterol synthesis. Preparation and characterization of fluorinated and deuterated analogs of oxygenated derivatives of cholesterol
Li, Shengrong,Pang, Jihai,Wilson, William K.,Schroepfer Jr., George J.
, p. 33 - 71 (2007/10/03)
Oxygenated sterols, including both autoxidation products and sterol metabolites, have many important biological activities. Identification and quantitation of oxysterols by chromatographic and spectroscopic methods is greatly facilitated by the availability of authentic standards, and deuterated and fluorinated analogs are valuable as internal standards for quantitation. We describe the preparation, purification and characterization of 43 oxygenated sterols, including the 4β-hydroxy, 7α-hydroxy, 7β-hydroxy, 7-keto, and 19-hydroxy derivatives of cholesterol and their analogs with 25,26,26,26,27,27,27-heptafluoro (F7) and 26,26,26,27,27,27-hexadeuterio (d6) substitution. The 7α-hydroxy, 7β-hydroxy, and 7-keto derivatives of (25R)-cholest-5-ene-3β,26-diol (1d) and their 16,16-dideuterio analogs were also prepared. These d2-26-hydroxysterols and [16,16-2H2]-(25R)-cholest-5-ene-3β,26-diol (1e) were synthesized from [16,16-2H2]-(25R)-cholest-5-ene-3β,26-diol diacetate (2e), which can be prepared from diosgenin. The highly specific deuterium incorporation at C-16 in 1e and 2e should be useful in mass spectral analysis of 26-hydroxycholesterol samples by isotope dilution methods. The Δ5-3β,7α,26- and Δ5-3β,7β,26-triols were regioselectively oxidized/isomerized to the corresponding Δ4-3-ketosteroids with cholesterol oxidase. Also described are 5,6α-epoxy-5α-cholestan-3β-ol, its 5β,6β-isomer, cholestane-3β,5α,6β-triol, their F7 and d6 derivatives, and d3-25-hydroxycholesterol, which was prepared from 3β-acetoxy-27-norcholest-5-en-25-one (30). The 43 oxysterols and most synthetic intermediates were isolated in high purity and characterized by chromatographic and spectroscopic methods, including mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy. Detailed mass spectral assignments are presented, and 1H NMR stereochemical assignments are derived for the C-19 protons of 19-hydroxysterols and for the side chain protons of 30. Copyright (C) 1999 Elsevier Science Ireland Ltd.
Synthesis of potential C27-intermediates in bile acid biosynthesis and their deuterium-labeled analogs
Shoda, Junichi,Axelson, Magnus,Sjoevall, Jan
, p. 119 - 125 (2007/10/02)
In connection with studies of alternative pathways in bile acid biosynthesis, potential intermediates in a pathway starting with 27-hydroxylation of cholesterol have been prepared in natural and deuterated forms. Established methods were used to prepare 27-hydroxycholesterol and 3β-hydroxy-5-cholestenoic acid. Clemmensen reduction of kryptogenin in unlabeled and deuterated solvents yielded 27-hydroxycholesterol and 16-oxo-5-cholestene-3β,27-diol, which were separated by adsorption chromatography on Unisil. The labeled 27-hydroxycholesterol and 3β-hydroxy-5-cholestenoic acid derived from it consisted of molecules with seven (50%), six (20%), and eight (20%) deuterium atoms, and unlabeled molecules were not detected. The acetates of 27-hydroxycholesterol and methyl 3β-hydroxy-5-cholestenoate were 7α-hydroxylated in a copper-catalyzed reaction with ert-butylperbenzoate, and the products were purified by chromatography on Unisil. The 7β-epimers were obtained as side products. Labeled 3β, 7α-dihydroxy-5-cholenic acid was prepared in the same way from 3β-hydroxy-5-[2,2,4,4,23-2H5]-cholenoic acid. The 3-oxo-Δ4 analogs of the 3β-hydroxy-Δ5 compounds were prepared by oxidation with cholesterol oxidase. The labeled products had the same isotopic composition as the starting materials. Gas chromatographic retention indices and mass spectral characteristics of the trimethylsilyl ether derivatives of the neutral steroids and the methylated acids are given for all compounds. (Steroids 58:119-125, 1993).
