Bile acid derivatives

A number of steroids have been regioselectively acylated ia a similar manner (99,104). Chromobactenum viscosum hpase esterifies 5a-androstane-3P,17P-diol [571-20-0] (75) with 2,2,2-triduoroethyl butyrate ia acetone with high selectivity. The hpase acylates exclusively the hydroxy group ia the 3-position giving the 3P-(monobutyryl ester) of (75) ia 83% yield. In contrast, bacillus subtilis protease (subtihsia) displays a marked preference for the C-17 hydroxyl. Candida iylindracea]i 2Lse (CCL) suspended ia anhydrous benzene regioselectively acylates the 3a-hydroxyl group of several bile acid derivatives (104). 

Wess, G., Kramer, W., Han, X. B., Bock, K., Enhsen, A., Glombik, H., Baringhaus, K. H., Boger, G., Urmann, M., Hoffmann, A. et al., Synthesis and biological activity of bile acid-derived HMG-CoA reductase inhibitors. The role of 21-methyl in recognition of HMG-CoA reductase and the ileal bile add transport system, /. Med. Chem. 1994, 37, 3240-3246. 

Racemase deficiency. The biological role of 2-methyl-acyl-CoA racemase has only recently been clarified. This peroxisomal enzyme is essential for certain steps of the oxidation of phytol and bile acid derivatives, which are stereospecific. Biochemically there is accumulation of pristanic acid and C27 bile acid intermediates. Clinical symptoms may include adult-onset peripheral neuropathy, pigmentary degeneration of the retina and liver disease [ 13]. 

A pharmacophore model for FXR agonists based on 14 bile acid derivatives was reported by Ekins et al. The hypothesis consisted of three H features and one H BA - a common functionality pattern among steroidal compounds [42],... 

Pellicciari, R., Costantino, G., Camaioni, E., Sadeghpour, B.M., Entrena, A., Willson, T.M., Fiorucci, S., Clerici, C. and Gioielli, A. (2004) Bile acid derivatives as ligands of the farnesoid X receptor. Synthesis, evaluation, and structure-activity relationship of a series of body and... 

Bile acids derivatives of cholesterol that facilitate the digestion of fats and oils. 

Intestinal bile-acid-binding protein (IBABP) is a small 14-15-kDa protein found in the cytoplasm of cells in the ileum that binds bile acids as they enter the cell. By using photolabile bile-acid derivative and immunoprecipitation, expression was primarily found in the soluble protein fraction of ileal enter-ocytes, although cholangiocytes do show a low level of expression. One molecule of IBABP binds two bile-acid molecules as shown in Figure 2.4. 

The development of lipophillic bile acid-drug conjugates and other bile acid derivatives is an important advance with exciting therapeutic possibilities. 

M. R. Ballestero, M. J. Monte, O. Briz, F. Jimenez, F. Gonzalez-San Martin and J. J. G. Marin, Expression of transporters potentially involved in the targeting of cytostatic bile-acid derivatives to colon cancer and polyps, Biochem. Pharmacol., 2006, 72, 729. 

Separation of Isomers and Enantiomers by Bile Acid Derivatives... 

Extensive systematic work over the past decade has established that bile acid derivatives have the ability to form crystalline inclusion compounds with various organic substances [1], The accumulated data tell us two notable things. One is that their inclusion behavior varies from one case to another. The other is that their crystals consist of host-inherent or guest-dependent assemblies with different molecular arrangements and hydrogen-bonding networks. These facts force us to direct our attention to separation engineering accompanied by crystallization and... 

It is well known that bile acids are produced in the liver of vertebrates for digestion and absorption of fats and fat-soluble vitamins. Starting from isoprene, a series of biochemical reactions yield a key compound, cholesterol, which is converted to primary bile acids, such as cholic acid (CA), deoxycholic acid (DCA), chenodeoxycholic acid (CDCA) and lithocholic acid (LCA). Hereafter the abbreviations of bile acid derivatives can be seen by consulting Table 1 and Figure 1. 

Table 1 Bile acid derivatives and their abbreviations, as used in this article (see also Figure 1).

In contrast to DCA, there were no detailed reports on the inclusion abilities of its related compounds. There are only a few descriptions of apocholic acid [5] (ACA, see later, in Figure 5) with a very similar bilayer structure to DCA. In 1986, Miyata and Miki et al. discovered lots of inclusion compounds of CA with the similar bilayer structures [6], On the other hand, it took a long time to determine the hexagonal crystal structures of CDCA inclusion compounds, and LCA exhibits no inclusion abilities as yet. In this way, it was confirmed that an increase or decrease of only one atom brings about completely different inclusion behaviors and crystal structures. This fascinating fact has given us adequate and continuous motivation to investigate the inclusion compounds of bile acid derivatives. 

CHARACTERISTIC STRUCTURES OF BILE ACID DERIVATIVES 2.1 Unique Molecular Structures... 

We have researched the inclusion abilities of bile acid derivatives by using more than one hundred organic compounds as guest candidates. The inclusion phenomena vary from one case to another, indicating that subtle changes in molecular structures induce alteration in their molecular assemblies. In fact, X-ray diffraction studies prove that the steroidal hosts form various assemblies such as monolayers, bilayers, helical tubes, and so on, as shown in Figure 2. Therefore, systematic investigation of inclusion crystals of bile acid derivatives is expected to reveal a relationship between their molecular structures, assemblies and inclusion behavior. 

Table 3 Formation of the inclusion compounds of bile acid derivatives with their host-guest ratios. 

Most of the bile acid derivatives exhibit guest-dependent polymorphism. The typical host is CA, which forms at least 12 host frameworks, depending on guest sizes and shapes, as shown in Figure 8. Most organic guests form bilayer structures, which can be further classified into several subtypes on the... 

Inclusion crystals of bile acid derivatives can be obtained by direct recrystallization of host and liquid guests. When the guests do not have enough solubility for a host, the third component or the solvent were used. In the case of solid guests, solvents were used as well. The solvent should not form inclusion compounds with the host, and should not interact with host and guest compounds. 

The ability of bile acid derivatives to include various alcohols differs greatly, as is partly shown in Table 3. It can be seen that DCA does not include any... 

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