Bile alcohols structures

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). 

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

This chapter reviews the natural distribution, the chemical structure, and the metabolism of bile alcohols and primitive bile acids. 

II) Occurrence and structure of bile alcohols in lower vertebrates... 

Noma et al. found 2 keto bile alcohols in unconjugated form in bullfrog bile [42]. Their structures were determined as 24-dehydro-26-deoxy-5a-ranol and its 5 isomer by comparison with synthetic 3a,7a,12a-trihydroxy-27-nor-5a- and 5/8-choles-tan-24-ones, prepared from allocholic acid and chohc acid, respectively [41]. 

The natural distribution and the chemical structure of bile alcohols and primitive bile acids indicate that these compounds found in lower vertebrates are evolutionary precursors of the common bile acids found in mammalian species. Haslewood proposed that the mechanism of conversion of cholesterol to the common bile acids in mammals is a recapitulation of the evolution of bile salts and thus would entail the intermediary formation of bile alcohols and primitive bile adds similar to or the same as those found in lower species [120]. Thus, studies have been carried out to test whether the naturally occurring bile alcohols and primitive bile acids are intermediates in the biosynthetic pathway between cholesterol and the C24 bile acids in mammals. There is no doubt that such studies contributed to the elucidation of the sequence of reactions in the biosynthesis of the mammalian C24 bile acids. 

Bile salts with a steroid structure appear to be confined to vertebrates (76). In some evolutionarily more primitive vertebrates, the major bile salts are sulfate esters of polyhydroxy C27- and C26-steroids and/or taurine-conjugated C27-steroid acids. In other primitive vertebrates, C24 bile acids, usually cholic acid and/or allocholic acid, or mixtures of primitive bile salts (bile alcohols and C27 bile acids) and modern bile salts (C24 bile acids) occur. Most of the work concerning the structure and occurrence of primitive bile salts has been carried out in the laboratories of G. A. D. Haslewood and T. Kazuno, and Haslewood and collaborators have accumu-... 

Bile alcohols polyhydroxylated steroids structurally related to cholestane. They oecur as sulfate esters in the bile of lower vertebrates, e.g. scymmol (3a,7a,12a,24,25,27-hexahydroxy-5p-cholestane) from shark bile. 

Possible structures of bile alcohol (oxysterol) conjugates found in plasma of a child with neonatal hepatitis of unknown etiology. The location of the hydroxyl groups and conjugating groups are not known however, previous studies of children have shown sulfation... 

Myxinol is a unique tetrahydroxy bile alcohol that occurs in the bile of the hagfish, a most primitive marine cyclostome. It has not been detected in the bile of other species. The structure of myxinol recently clarified by Anderson et al. (232) bears resemblance to other bile salts but offers no promise of metabolic relationship with other known structures. It is conjugated with two moles of sulfate. The hydroxyl group at carbon 3 is, 3 the hydroxyl at carbon 16 is reminiscent of pythocholic acid. Unlike pythocholic acid, myxinol has the A/B trawy-conformation and contains other hydroxyl groups at carbons 3 and 7 rather than at carbons 3 and 12. 

Early studies of bile acid mass spectra were made by Bergstrom, Ryhage, and Stenhagen (3-5) and the results were used to determine the structure of Hammarsten s a-phocaecholic acid (6). Other groups applied mass spectrometry to the elucidation of structures of the closely related bile alcohols (7). At about this time combined gas chromatography-mass spectrometry instruments were developed that could be used in studies of compounds with molecular weights as high as those of bile acid derivatives (8-13). The early... 

Therefore, I shall concentrate on only those bile acids that have been reasonably well studied from a physicochemical point of view and which have some relation to physiology and biochemistry of living things. Because the specific physical characteristics of the bile acids and their alkaline metal salts vary considerably with the number of hydroxyl groups present on the steroid nucleus, I will present a fairly detailed description of the physicochemical properties of cholanic acid (no hydroxyl groups), monohydroxy, dihydroxy, and trihydroxy bile acids. Since the triketo bile acid (dehydrocholic acid) has been used widely as a choleretic, its properties will also be discussed. Unfortunately, many interesting bile acids and bile alcohols isolated from a variety of vertebrates (29-32) have not been studied physicochemical ly. However, knowing their molecular structure, many of the properties of these compounds can be deduced by comparison with the known properties of bile acids discussed in this chapter. 

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. 

Ishida, H., Miyamoto, H., Kajino, T, Nakayasu, H., Nukaya, H., and Tsuji, K. (1996) Study of the bile salt from megamouth shark. 1. The structures of a new bile alcohol, 7-deoxyscymnol, and its new sodium salts. Chem. Pharm. Bull., 44,1289-1292. 

Ishida, H., Nakayasu, H Miyamoto, H Nukaya, H and Tsuji, K. (1998b) Study on the bile salts from sunfish, Mola mola L. I. The structures of sodium cyprinol sulfates, the sodium salt of a new bile add conjugated with taurine, and a new bile alcohol and its new sodium sulfates. Chem. Pharm. Butt., 46,12-16. 

Names, structural char acteristics, and func tions of bile acids The primary bile acids, cholic or chenodeoxycholic acids, contain two or three alcohol groups, respectively. Both have a shortened side chain that terminates in a carboxyl group. These structures are amphipathic, and can serve as emulsifying agents. 

Sterols and Cholesterol. Natural sterols are crystalline C76 C1(1 steroid alcohols containing an aliphatic side chain at C17. Sterols were first isolated as lionsaponifiable fractions of lipids from various plant and animal sources and have been identified in almost all types of living organisms. By far, the most common sterol in vertebrates is cholesterol (8). Cholesterol serves two principal functions in mammals. First, cholesterol plays a role in the structure and function of biological membranes.. Secondly, cholesterol serves as a central intermediate in the biosynthesis of many biologically active steroids, including bile acids, corticosteroids, and sex hormones. 

Bile Acids and Alcohols. Bile acids have been detected in all vertebrates that have been examined and are a result of cholesterol metabolism. The C24 acid, 5(8-cholatiie acid (9) is the structural derivative uf the majority of bile acids in vertebrates. Most mammalian bile acids have a cis-fused A-B ring junction resulting in a nonplanar steroid nucleus. Bile acids, like sterols, typically contain a C3a-hydroxyl group (lithocholic acid 3a-hyroxycholanic acid. 

DCA is the first bile acid whose inclusion ability was confirmed in the crystalline state. During the last century many research groups dealt with the inclusion compounds of DCA with various guest molecules, such as aliphatic, aromatic and alicyclic hydrocarbons, alcohols, ketones, fatty acids, esters, ethers, nitriles, peroxides and amines, and so on [2], In 1972, Craven and DeTitta first reported the exact crystal structure of DCA with acetic acid [3], Subsequent crystallographic studies made clear that most of DCA inclusion crystals have bilayer... 

Bile acids can be modified to many derivatives due to their unique molecular structures, as listed in Table 1. First, we can convert the functional groups at the side-chains from carboxylic acid to amide, alcohol, ester, and so on. Second, we can change the length of the side-chains by decreasing or increasing their methylene number. Third, we can regulate the direction of the hydroxyl groups of the skeletons at the axial or equatorial positions. 

Bile acids, which have carboxylic acid groups at their side-chains, form salts with various amines. Salts of DCA and CA with various primary amines [23] show bilayer structures with a one-dimensional ladder hydrogen-bonding network. These salts act as host compounds and will include small alcohols. 

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