Bile acids inclusion compounds

Sada, K. Sugahara, M. Nakahata. Y. Yasuda. Y. Nishio. A. Miyata, M. First columnar monolayer stracture of bile acids inclusion crystal. Inclusion compounds of 23-nordeoxycholic acid. Chem. Lett. 1998. 31. 

Deoxycholic acid (DCA) (17) and apoeholic acid (ACA) (18) are typical examples of the bile acid family of materials, but with the unique property of forming inclusion compounds with a wide variety of guest molecules 92). Partly due to the cis ring junction between rings A and B, and partly due to the conformation of the steroidal side chain these compounds present a convex hydrophobic P-face and a concave hydrophilic a-face, as shown for DCA (19), a classical aid to the formation of inclusion compounds 93). 

Several prominent types of host molecule, such as the steroidal bile acids and the cyclodextrins, are chiral natural products that are available as pure enantiomers. Chemical modification of these parent compounds provides an easy route to the preparation of large numbers of further homochiral substances. Since all these materials are present as one pure enantiomer, it automatically follows that their crystalline inclusion compounds must have chiral lattice structures. It is not currently possible to investigate racemic versions of these compounds, but the examples discussed previously in this chapter indicate that very different behaviour could result. 

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... 

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... 

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. 

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. 

INCLUSION COMPOUNDS OF BILE ACID DERIVATIVES 3.1 Acid Derivatives... 

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

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. 

K. Miki, A. Masui, N. Kasai, M. Miyata, M. Shibakami, K. Takemoto, New Channel-Type Inclusion Compound of Steroidal Bile Acid Structure of a 1 1 Complex between Cholic Acid and Acetophenone , J. Am. Chem. Soc., 110, 6594 (1988)... 

Miki, K., Masui, A., Kasai, N., Miyata, M., Shibakami, M., and Takemoto, K., New channel-type inclusion compound of steroidal bile acid. Structure of a 1 1 complex between cholic acid and acetophenone, J.Am. Chem. Soc. 110, 6594-6596 (1988). 

Porous host substructures with parallel channels are typical of many inclusion compounds formed by bile acids and their derivatives (see Deoxycholic, Cholic, and Apocholic Acids). In this class of compounds, host molecules are always optically active, and the resulting host networks are chiral. The best known among them are inclusion compounds of deoxycholic acid (DCA) (also known as choleic acidsj. With most guests. DCA molecules assemble via hydrogen bonds into a coiTugated... 

HISTORICAL RESEARCH OF INCLUSION COMPOUNDS OF BILE ACIDS... 

Bile salts are chiral rigid molecules. They serve as important building blocks in the synthesis of both cyclic and acyclic hosts." " Natural bile acids are employed for enantioseparation of racemates of various classes of organic compounds by enantioselective inclusion complex-ation in the solid state." " " Crystals of bile acids contain... 

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