Apocholic acid

Deoxycholic acid (DCA), apocholic acid (ACA), and cholic acid (CA) form channel-type inclusion compounds with a wide variety of organic molecules. Of these DCA has been extensively investigated. 

Chiral solid matrices are used for asymmetric synthesis polymerization of 1,3-dienes (inclusion polymerization), although the matrix reaction is not exactly a catalytic synthesis [40,41]. (R)-trans-anti-trans-anti-trans-Perhydrotriphenylene (13) [42,43], deoxyapocholic acid (14) [44,45], and apocholic acid (15) [46,47] are known as effective matrices for the... 

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. 

After much screening it became evident that inclusion complexes would be most suitable for this purpose and so we investigated the inclusion complexes of deoxycho-lic acid (DCA) (13) and apocholic acid (APA) (14), which were known to incorporate a wide variety of guest molecules such as hydrocarbons, alcohols, esters, and acids. ... 

Insight into the photochemical reactions between deoxycholic or apocholic acid ( choleic acids ) and guest molecules in crystalline inclusion complexes has been obtained by X-rzy studies. The choleic acids form channels with wall structures determined by the nature of the guest molecule. Guest ketones of various types react photochemically by addition to the choleic acid at a site determined by the orientation of the ketone molecule in relation to the host (e.g. deoxycholic acid reacts at C-5 or C-6 with linear aliphatic ketones, but at C-16 with cyclohexanone).12... 

An examination of the behaviour in the solid state of guest molecules such as aliphatic ketones ( acetone and ethyl methyl ketone) and suromatic ketones (acetophenone and /7>Cl-acetophenone) in deoxycholic and apocholic acids has identified stereospecific addition of the guest molecules to the host by a hydrogen abstraction radical combination path. A flash photolytic study of fluorenone has shown that the triplet state reacts with electron rich alkenes in an electron transfer process. 

The most common hosts for inclusion polymerization are urea, thiourea, perhydrotriphenylene (PHTP), deoxycholic acid (DCA), apocholic acid (ACA) and tris(o-phenylenedioxy)cyclotriphosphazene (TPP)(Fig. 2). They have the common feature of forming channel-like clathrates, but differ in many specific properties. For instance, urea and thiourea have a rigid structure in which the host molecules are connected by hydrogen bonds and possess a high selectivity towards the guests. In urea channels are rather narrow whereas in thiourea they are wider as a consequence, linear molecules include only in urea and branched or cyclic molecules in thiourea. On the contrary, chainnels existing in PHTP clathrates are very flexible and can accomodate linear, branched and cyclic molecules. 

Apocholic acid ACA Figure 2. Hosts used In Inclusion polymerization. 

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... 

Channel Inclusion Compounds, p. 223 Clathrate Hydrates, p. 274 Deoxycholic, Cholic, and Apocholic Acids, p. 441 Gossypol, p. 606... 

A chiral host could readily be available from a naturally occurring compound. The use of steroidal acid, deoxycholic acid (Fig. 3d), yielded coinprehensive polymers, particularly, optically active polymers from pro-chiral monomers. Many derivatives of deoxy cholic acid have the corresponding characteristic inclusion abilities. For example, use of apocholic acid (Fig. 3e), cholic acid (Fig. 3f), and chenodeoxycholic acid (Fig. 3g) enabled us to perform one-dimensional inclusion polymerization of various diene and vinyl monomers. 

Fig. 3 Organic hosts used for one-dimensional inclusion polymerization (a) urea (b) thiourea (c) perhydrotriphenylene (d) deoxycholic acid (e) apocholic acid (f) cholic acid (g) chenodeoxycholic acid (h) m5 (6>-phenylenedioxy)cyclotriphosphazene and (i) n5(2,3-naphthalenedioxy)cyclotriphosphazene.

It can be seen from Fig. 4 that many diene monomers were polymerized using various hosts. It might be possible to polymerize multiconjugated monomers, such as trienes and tetraenes, in one-dimensional spaces. Diacetylene spontaneously polymerized in channels of three hosts perhydrotriphenylene, deoxycholic acid, and apocholic acid. On the other hand, there are not so many studies of the polymerization of vinyl monomers, because highly stereoregular polymers are not obtained. 

Radical species during inclusion polymerization can readily be detected by ESR spectroscopy, indicating that the radicals are thermally stable in the channels. The reason is that the radicals in the channels do not meet with each other due to the host walls. y-Irradiation produces radicals of the host component as well as the monomers. Monomeric and propagating radicals were observed in the case of urea, while only the propagating radicals were observed in the case of perhydrotriphenylene, deoxycholic acid, and apocholic acid. Simulation of the spectra clarified that the propagating radicals do not rotate freely, indicating that mobilities of the radicals are constrained in the channels. 

There are many possible schemes for addition reactions of diene monomers from electronical and steric viewpoints. Because the monomer molecules arrange along the direction of the channels, a,co-addition may selectively take place in one-dimensional inclusion polymerization. Therefore, conjugated polyenes, such as dienes and trienes, may selectively polymerize by 1,4- and 1,6-addi-tion, respectively. 1,3-Butadiene polymerized via 1,4-addition exclusively in the chaimels of urea and perhydrotriphenylene. while the same monomer polymerized via both 1,2- and 1,4-additions in the channels of deoxycholic acid and apocholic acid. Moreover, we have to evaluate head-to-tail or head-to-head (tail-to-tail) additions in the case of dissymmetric conjugated diene monomers such as isoprene and 1.3-pentadiene. 

It is considered that the motion of guest molecules depends on the space sizes even at the same temperature. That is, the molecules can move more freely in a larger space than in a smaller space. Such a difference would affect polymerization behaviors. Such space effects can be observed on the basis of subtle changes of polymerization behaviors by using a suitable set of hosts. Use of a set of the hosts, deoxycholic acid, apocholic acid, cholic acid, and chenodeoxycholic acid, enables us to observe the effects of one-dimensional polymerization in detail. On the other hand, a pair composed of urea and thiourea is not suitable for such an aim, because the pair does not include identical monomers at the same temperatures. 

Stereoregularities of the resulting polymers depend on the sizes of the host channels. Moreover, the space effect in chirality was observed in asymmetric inclusion polymerization of trans- or cis-2-methy 1-1,3-pentadiene by using a pair of hosts, deoxycholic acid and apocholic acid. We obtained optically active polymers with predominant absolute configurations (R). Optical yields varied with the polymerization conditions and the hosts. A maximum optical yield of the trans monomer was 36% m the channel of apocholic acid. 

Amide- and Urea-Based Anion Receptors, p. 51 Amino Acids Applications, p. 42 Chiral Guest Recognition, p. 236 Deoxycholic, Cholic, and Apocholic Acids, p. 441 Fluorescence Sensing of Anions, p. 566 Guanidinium-Based Anion Receptors, p. 615 Hydrogen Bonding, p. 658 lonophores, p. 760... 

These studies were followed by the asymmetric polymerization of similar trans- and cis-l,3-pentadienes within the channels of two steroids of deoxy-cholic acid (DCA) and apocholic acid (ACA) [12-14]. The packing of the two... 

Asymmetric synthesis polymerization of 1,3-dienes with solid matrices has been reported." This was first attained by using optically active (R)-(-)-trans-anti-trans-flnti-trans-perhydrotriphenylene (256) matrix for y-ray irradiation polymerization of trans-1,3-pentadiene to afford isotactic poly-trans-254. °° Deoxyapocholic ° ° and apocholic acids (257 and 258) are also effective as optically active matrices. Matrix polymerization tended to result in higher optical purity. The highest value of optical purity so far reported is 36% for the polymerization of (Z)-2-methyl-1,3-butadiene with 258 as a matrix. 

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