Synthesis of potential C27-intermediates in bile acid biosynthesis and their deuterium-labeled analogs.
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 3 beta-hydroxy-5-cholestenoic acid. Clemmensen reduction of kryptogenin in unlabeled and deuterated solvents yielded 27-hydroxy-cholesterol and 16-oxo-5-cholestene-3 beta,27-diol, which were separated by adsorption chromatography on Unisil. The labeled 27-hydroxycholesterol and 3 beta-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 3 beta-hydroxy-5-cholestenoate were 7 alpha-hydroxylated in a copper-catalyzed reaction with tert-butylperbenzoate, and the products were purified by chromatography on Unisil. The 7 beta-epimers were obtained as side products. Labeled 3 beta,7 alpha-dihydroxy-5-cholenoic acid was prepared in the same way from 3 beta-hydroxy-5-[2,2,4,4,23-2H5]-cholenoic acid. The 3-oxo-delta 4 analogs of the 3 beta-hydroxy-delta 5 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.
Shoda
J
J
Department of Physiological Chemistry, Karolinska Institutet, Stockholm, Sweden.
Axelson
M
M
Sjövall
J
J
D001647:Bile Acids and Salts / Q000096:biosynthesis* / Q000138:chemical synthesis*; D002635:Chenodeoxycholic Acid / Q000031:analogs & derivatives / Q000138:chemical synthesis; D002782:Cholestenes / Q000138:chemical synthesis; D002784:Cholesterol / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry; D002845:Chromatography; D002853:Chromatography, Liquid; D003903:Deuterium; D008401:Gas Chromatography-Mass Spectrometry; D006888:Hydroxycholesterols / Q000138:chemical synthesis; D006900:Hydroxylation; D007553:Isotope Labeling
D001647:Bile Acids and Salts; D002782:Cholestenes; D006888:Hydroxycholesterols; D002635:Chenodeoxycholic Acid; C063075:3,7-dihydroxy-5-cholestenoic acid; C002287:3,7-dihydroxychol-5-enoic acid; C080734:cholest-5-ene-3,7,27-triol; C029435:3-hydroxy-5-cholestenoic acid; C076996:27-hydroxycholesterol; D002784:Cholesterol; D003903:Deuterium