Bile acid derivatives listed

The following discussion is based on spectra of the bile acid derivatives listed in Table I. This is not a complete list of all published spectra but the results are representative of general fragmentation patterns. The molecular weights of bile acid derivatives can be calculated from the group contributions listed in Table II. This table also shows how the molecular weight changes when a hydroxy and/or keto bile acid methyl ester is converted into the derivatives. 

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. 

Similarly prepared were the compounds listed in Table 11 (p. 395) and several derivatives of bile acids and steroids claimed in patents. 

Apart from the classical, well-known hormones listed in Fig. 4.1, other compounds are also used as signaling ligands for the activation of certain nuclear receptors. These ligands may be synthesized intracellularly as normal metabolites such as fatty acids and bile acids and they may be derived from foreign lipophilic substances like drugs. 

Most primitive bile acids found in lower vertebrates possess the carbon skeleton of cholesterol. Differences within these C27 bile acids are associated with number, position, and configuration of hydroxyl groups and with side-chain unsaturation. In addition, some C2g bile acids have been found in bile of a few species of amphibians. Cholenoic acid derivatives have not been found in lower vertebrates. A list of primitive bile acids in lower vertebrates is given in Table 2. 

Primitive bile acids in mammals may be classified by carbon numbers as higher bile acids and as cholenoic acid derivatives. A list of primitive bile acids from mammalian sources is given in Table 4. 

Fales and Pisano (1964) have discussed the gas chromatography of amines, alkaloids, and amino acids. Pollock and Kawauchi (1968) have resolved derivatives of serine, hydroxyproline, tyrosine, and cysteine, as well as racemic aspartic acid and tryptophan. VandenHeuvel and Horning (1964) have listed derivatives of steroids that can be separated. VandenHeuvel et al. (1960) first described the separation of bile acid methyl esters and Sjovall (1964) has extended the methods to bile acids. Gas liquid chromatography (GLC) is useful in the analysis of pesticides, herbicides, and pharmaceuticals (Burchfield and Storrs, 1962). Analysis of alkaloids, steroids, and mixtures of anesthetics and expired air are other examples of the application of this very useful technique. Beroza (1970) has discussed the use of gas chromatography for the determination of the chemical structure of organic compounds at the microgram level. 

With isotopically labeled primary bile salts, cholate and chenodeoxycholate, it is possible to show that in addition to deoxycholate a wide variety of secondary bile salts are derived from cholate, the chief ones being 12a-hydroxy-3-keto-5/ -cholanoic acid, 3), 12a-dihydroxy-5) -cholanoic acid, 3a-hydroxy-12 keto-5/5-cholanoic acid, and 3/ -hydroxy-12-keto-5j -cholanoic acid (30). A smaller number are derived from chenodeoxycholate, mainly lithocholate, 3/ -hydroxy-5i -cholanoic acid, and 3-keto-5i -cholanoic acid (31). The secondary bile acids which have been identified in man are listed in Table III. 

Table I lists the available critical micelle concentrations of bile acids in water and in a salt solution. Accordingly, during chromatography the concentration of the bile acids should be kept below 0.01 M for the trihydroxy salts and below about 0.05 M for the dihydroxy derivatives. Further decreases in the concentration of the external solution at least may be required when working in the presence of salt or buffer and swelling amphipaths (monoglycerides, sterols). When more concentrated solutions are desired, the addition of alcohol to the aqueous solution of bile acids should be considered. The presence of simple and/or mixed micelles in the external solution during chromatography, however, may not necessarily be detrimental to the resolution of the acids, as the micelles would be expected to be in rapid equilibrium with the bile acids in the molecular solution. The actual rates of exchange of various bile acids between micelles and molecular solutions have not been determined.

Christie (1987) noted that a variety of diverse compounds generally soluble in organic solvents are usually classified as lipids, i.e., fatty aeids and their derivatives, steroids, terpenes, carotenoids, and bile acids. He suggested that many of these diverse compounds have little in the way of structure or function to make them related and that many substances regarded as lipids may be more soluble in water, e.g., glycolipids and gangliosides, than in organic solvents. Fried (1991, 1996) provided a list of numerous diverse lipophilic substances that have been examined by TLC and included typical sorbents, solvent systems, and references for these substances. 

The main bile acids present in man, rat, rabbit, and pig are illustrated in Fig. 4. All occur as taurine or glycine conjugates. Hydroxyl functions are found at one or more of the following positions 3a. 6a. 7a, and I2a. The 6a-hydroxylated structures appear thus far to be exclusive for the pig whose bile acids consist in major of chenodeoxycholic and hyocholic acids. 6j3-Hydroxylated acids are only formed to a minor extent. The 7/5-hydroxylated derivative isolated after the administration of chenodeoxycholic acid to the rat (Hsia et al., 1958) has been shown through experiments with a C-7j8 tritiated structure to arise through the inversion of the 7a-hydroxy isomer via the keto structure (Bergstrom et al., 1960b). 16a-Hydroxylated acids have been isolated from boas and pythons but not from a variety of other species of snakes examined (Hazlewood, 1959). The most recent references to pertinent studies are listed in Table I. 

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