Bile alcohols

These are neutral compounds, based on 3a,7a,12a-trihydroxy- or 3,7,12-triketocholane, the terminal C24-methyl group of which has been substituted by hydroxyl or hydroxyalkyl groups. They occur chiefly as C22 Compounds along with the bile acids and have been classified here for that reason. According to the systematic work of Kazuno and Hoshita [100], they can be subjected to TLC on silica gel, using normal solvents as befits their structure these include benzene-ethyl acetate (60 + 40 40 + 60), ethyl acetate-acetone (80 + 20) (70 + 30), chloroform-ethanol (90 + 10) (80 + 20) or chloroform-acetone-ethanol (70 + 15 + 15). 

The analogous compounds with side chains one methylene group shorter and also those with the same number of carbon atoms but variously positioned hydroxyl group in the side chain, can be satisfactorily separated this had been impossible by the column chromatography hitherto available. As far as other structural elements are concerned, the bile alcohols behave just like other steroids (see section IV). Strongly acid reagents like sulphuric acid are employed for visualisation. 

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Scynmol, a polyhydroxylated cholestane sterol of the bile alcohol class, isolated from the Arctic shark, Scymnus borealis, is one of the few new metabolites described from Arctic species. It is quite similar to ciprinol, however, isolated from the freshwater carp, Cyprinus carpio (Scheuer 1973). 

The bile alcohol Boymnol, a characteristic constituent of the bik of certain sharks, was at one time believed to contain an epoxide function, as in (XXIX)189 Experimental evidence recently published by Cross 8M 1971 however, has confirmed a suspicion already expressed earlier by Fieser and Fieser8 1 that this alignment was in error. The correct structure of scymnol ia probably (XXX). 

Unsaturated sterols such as cholesterol, campesterol, sitosterol and bile alcohols with unsaturated side chains can be transfer hydrogenated efficiently and with high yields under microwave irradiation, using ammonium formate and a Pd/C catalyst in methylene chloride/propylene glycol solvents (Scheme 4.3)17. 

Dayal, B., Ertel, N.H., Rapole, K.R., Asgaonkar, A. and Salen, G., Rapid hydrogenation of unsaturated sterols and bile alcohols using microwaves, Steroids, 1997, 62, 451-454. 

Bile alcohols and Allocholic acid trans alp trans Pla trans Pla... 

Structure and Biosynthesis of Bile Alcohols Disorders of Cholesterol Side-Chain Oxidation in Cerebrotendinous Xanthomatosis... 

Bile alcohols are polyhydroxy C27 sterols that serve as intermediates in the biosjmthesis of cholic acid and chenodeoxycholic acid from cholesterol (1, 2). Recently several studies have shown that increased amounts of bile alcohols namely 27-nor-5p-cholestane-3a,7a,12a,24, 25-pentol and 5P-cholestane-3a, 7a,12a,25,26-pentol are excreted (as glucuronides in urine of patients with liver diseases such as primary biliary cirrhosis (3), liver cirrhosis (4, 5) and a-antitrypsin deficiency (6). Ichimiya et. al., described the occurrence of 5P-cholestane-3a,7a,12a,26,27-pentol (5P-cyprinol) and 5P-cholestane-3a,7a,... 

Isolation and Characterization of Bile Alcohols in Cerebrotendinous Xanthomatosis ( CTX1... 

Chromatographic analysis of the polar sterol fractions of the bile and feces, in conjunction with gas-liquid chromatography (GLC)-mass spectrometry indicated two major components, 5P-cholestane-3a,7a,12a,25-tetrol and 5P-cholestane-3a,7a,12a,23,25-pentol, and a minor component, 5P-cholestane-3a, 7a,12a,24,25-pentol(18-21). Only minute amounts of 5P-cholestane-3a, 7a,12a,23R-tetrol, 5P-cholestane-3a,7a,12a,24R-tetrol, 5P-cholestane-3a,7a, I2a,24S-tetrol and 5P-cholestane-3a,7a,12a,25S,26-pentol have been detected (20-24). The presence of 5P-cholestane-3a,7a,12a,25-tetrol was positively identified by comparison with the synthesized sample prepared in our laboratory (20-22,24-27) (Fig.l). The predominent bile alcohol of the pentol fraction was 5P-cholestane-3a,7a,12a,23,25-pentol, amounting to approximately 80% by weight, while 5P-cholestane-3a,7a,12a,24,25-pentol accounted for approximately 20% of this fraction. The less abundant pentol was shown to be identical with 5P-cholestane-3a,7a,12a,24a,25-pentol, which had been prepared from 5P-cholestane-3a,7a,12a,25-tetrol (20,21). 

The occurrence of bile alcohols hydroxylated at position 25 in CTX patients indicated the presence of an alternate pathway of bile acid synthesis from cholesterol (via 25-hydroxylated intermediates ). In particular, the identification of 5P-cholestane-3a,7a,12a,24a,25-pentol indicated that cholic acid arised from the cleavage of a 24,25- glycol. 

Absolute Configuration of Pentahvdroxv Bile Alcohols bv Lanthanide-Induced Circular Dichroism (CD) Studies. 

During the course of these studies, the two 5P-cholestane-3a,7a, 12a,24,25-pentols, epimeric at C-24, and 5P-cholestane-3a,7a,12a,23,25-pentol epimeric at C-23 were further resolved by analytical and preparative TLC, and were either synthesized or isolated and characterized. In addition, the absolute stereochemistry at C-23 of 5P-cholestane-3a,7a, 12a,23,25-pentol and at C-24 of 5P-cholestane-3a,7a,12a,24,25-pentol (39,40) was established by circular dichroism (CD) studies employing the method of Nakanishi (41,42). These experiments conclusively defined the chirality of these pentahydroxy bile alcohols having 1,2 and 1,3 glycol systems in the side chain. Using Eu(fod)3... 

In summary, these studies demonstrated that in CTX the impaired synthesis of bile acids is due to a defect in the biosynthetic pathway involving the oxidation of the cholesterol side-chain. As a consequence of the inefficient side-chain oxidation, increased 23, 24 and 25-hydroxylation of bile acid precursors occurs with the consequent marked increase in bile alcohol glucuronides secretions in bile, urine, plasma and feces (free bile alcohols). These compounds were isolated, synthesized and fully characterized by various spectroscopic methods. In addition, their absolute stereochemistiy determined by Lanthanide-Induced Circular Dichroism (CD) and Sharpless Asymmetric Dihydroxylation studies. Further studies demonstrated that (CTX) patients transform cholesterol into bile acids predominantly via the 25-hydroxylation pathway. This pathway involves the 25-hydroxylation of 5P-cholestane-3a,7a, 12a-triol to give 5P-cholestane-5P-cholestane-3a,7a,12a,25- tetrol followed by stereospecific 24S-hydroxylation to yield 5P-cholestane-3a,7a,12a,24S,25-pentol which in turn was converted to cholic acid. 

Finally, treatment of these patients with chenodeoxycholic acid (750 mg per day) decreased cholestanol production and plasma concentrations of bile alcohols and suppressed abnormal bile acid synthesis (70). 

Conjugated bile acids and bile alcohols were analyzed by TLC using silica gel G plates (Brinkmann Instruments, Westbury, NJ 0.25-mm thickness) with the solvent system chloroform/methanol/acetic acid/water 26 8 4 2 (v/v/vA) (5,7,9). Bile salts were made visible with a spray reagent which consisted of 10 % phosphomolybdic acid in ethanol. Detection with naphthoresorcinol (0.2 % in... 

High-performance liquid chromatography (HPLC) of the bile alcohols was carried out on a Waters Associates ALC 201 system employing a Waters model 401 refractive index detector and a Waters 4-mm ID x 30-cm p Bondapak Cjg column (Waters Associates Inc., Milford, MA). The solvent system was 80 % Me0H/H20 (v/v) with a flow rate of 1.5 mL/min. 

Ludwig-Kohn, H., Henning, H. V., Sziedat, A., Mattaei, D., Spitteller, G., Reiner, J. and Egger, H. J. (1983). The identification of urinary bile alcohols by gas chromatography-mass spectrometiy in patients with liver disease and in healthy individuals. Eur. J. Clin. Invest. 13 91-98. 

Karlaganis, G., Nemeth, A., Hammarskjold, B., Strandvik, B. and Sjovall, J. (1982). Urinary excretion of bile alcohols in normal children and patients with a-antitrypsin deficiency during development of liver disease. Eur. J. Clin. Invest. 12 399-405. 

Ichimiya, H., Yanagisawa, J. and Nakayama, F. (1984). Significance of bile alcohols in urine of a patient with cholestasis identification of Sp-cholestane-3a,7a,12a,26,27-pentol (5p-bufoI) and 5P-cholestane-3a,7a, 12a,26-tetrol (27-deoxy-5P-cyprinol). Chem. Pham. Bull. 32 2874-2877. 

Spectrometry of trimethylsilyl ethers of bile alcohols. J. Lipid Res. 19 956-966. 

Dayal, B. and Salen, G. (1990). Fast atom bombardment mass spectrometry (FAB-MS) studies of conjugated bile alcohols. Presented in part at the 17th International Symposium on the Chemistry of Natural... 

Dayal, B., Salen, G., Tint, G. S., Toome, V., Shefer, S., and Mosbach, E.H. (1978). Absolute configuration of pentahydroxy bile alcohols excreted by patients with cerebrotendinous xanthomatosis a circular dichroism study. J. Lipid Res. 19 187-190. 

Shimazu, K., Kuwabara, M., Yoshi, M., Kihira, K., Takeuchi, H., Nakano, I., Ozawa, S., Onuki, M., Hatta, Y., and Hoshita, T. (1986). Bile alcohol profiles in bile, urine, and feces of a patient with cerebrotendinous xanthomatosis. J. Biochem. (Tokyo) 99 477-483. 

Batta, A. K., Shefer, S., Batta, M., and Salen, G. (1985). Effect of chenodeoxycholic acid on biliary and urinary bile acids and bile alcohols in cerebrotendinous xanthomatosis monitoring by high performance liquid chromatography. J. Lipid Res. 26 690-698. 

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