Cholic acid derivatives

Selective hydrolysis of the 3a-acetoxy-group of fully acetylated cholic acid derivatives has been achieved with methanolic HCl. The hydrolysis occurs more rapidly than the methylation of the side-chain carboxylic acid. The 3-monosulphates of cholic, chenodeoxycholic, and deoxycholic acids have been prepared using this selective hydrolysis on the fully acetylated methyl esters. The resultant 3a-hydroxy-compounds were then treated with chlorosulphonic acid and the... 

During the past few decades, a number of important studies were published on the effect of cholic acid derivatives on the absorption of macromolecules [81]. Guarini and Ferrari [84—86] compared simultaneous oral dosing of NaDOC and heparin to pretreatment with NaDOC by oral gavage in dogs followed by oral heparin administration at a 0.5-24-h interval. In all pretreatment regimens, NaDOC enhanced heparin absorption, with the maximum effect observed when heparin was administered 1 h after NaDOC. 

MACA is 2/-methacryloylaminoethylene)-3a, 7a, 12a -trihydroxy-5jd-cholano-amide, a cholic acid derivative of natural bioactive amphiphilic compound. The synthetic detail of MACA is not what we would like to discuss here. 

Li, C., Lewis, M.R., Gilbert, A.B., et al. (1999) Antimicrobial activities of amine- and guanidine- functionalized cholic acid derivatives. Antimicrob. Agents Chemother. 43,1347-1349. 

Kobuke Y, Nagatani T (2001) Transmembrane ion channels constructed of cholic acid derivatives. J Org Chem 66 5094-5101... 

Similar principles, depending upon substituents representing potential unsaturation, explain the conversion of the cholic acid derivative (447) into the... 

The 12a-mesyloxy-group is eliminated efficiently (80-85%) from the cholic acid derivative (34) to give the A -compound (35), by heating with sodium or potassium acetate in HMPA. ... 

Lipids with cholesterol moiety 3jS-[iV-(iV , iV -dimethylaminoethane)-carbamoyl] cholesterol (DC-Chol) (121) and other cholesterol derivatives (122), biglycosylated cholic acid derivative (123), and cholesterol with polyamines (124) and spermidines (125,126). 

Dibbelt, L., and Kuss, E., Human placental steroid sulfatase solubilized with a cholic acid derivative Molecular mass, kinetic properties and susceptability to glycosidases. Hoppe-SeylersZ. Physiol. Chem. 365, 1145-1153 (1984). 

A further, convenient variation of this type of reaction, using more readily accessible and inexpensive starting materials, involves the acid-catalyzed condensation of crude g, r-dihydroperoxides 240, derived from cyclohexanone or a cholic acid derivative, with various cycloalkanones (method D, Scheme 45 Table 4) <2002JME3331, 2003JSC291, 2004JSC919>. 

Kobuke, Y. Nagatani, T. A supramolecular ion channel based on amphiphilic cholic acid derivatives. Chcm. Lett. 2000, 4, 298-299. 

It is worth mentioning the use of naturally occmring bile acids, such as cholic acid derivatives, as steroidal building-blocks for the design of supramolecular receptors [10] and organogelators [26,27]. Some of these simple steroid derivatives, such as the dihydroxy bile salt sodium deoxy-... 

Gaica, S.B. Opsenica, D.M. Solaja, B.A. Tesic, Z.Lj. Milojkovic-Opsenica, D.M. The retention behavior of some cholic acid derivatives on different adsorbents. J. Planar Chromatogr.-Mod. TLC 2002, 15 (4),... 

Improved separations of bile acid methyl esters can be observed with increasing amounts of phenyl substituents in the stationary phase (5% in SE-52, 20% in PhSi-20, and 50% in OV-17). Positional and configurational isomers are better resolved than on SE-30 or OV-1 columns. For instance the valuable separation of the trimethylsilyl ethers of 3,6,7-substituted methyl cholanoates from the corresponding cholic acid derivative on OV-17 should be noted. The pronounced effect of a 7/3-hydroxy substituent on retention times on columns of SE-52 and PhSi-20 is noteworthy. The large separation factors between the diacetate derivatives of chenodeoxy- and ursodeo.xycholic acids may be most useful in work with bile acids of biological origin. 

When the separations of the acids within the free and glycine conjugated groups are considered, it is seen that on both columns and thin layers, the cholic acid derivatives are eluted ahead of the derivatives of the deoxycholic and chenodeoxycholic acids, and presumably other dihydroxy bile acids. The derivatives of the lithocholic acid are eluted last. Complete separations of the mono-, di-, and trihydroxy bile acids are not realized even on the thin-layer plates of ion exchangers, and there is no discernible resolution of the various taurine conjugates. This order of elution of the bile acids is opposite to that expected on the basis of their pK values (Table II). Free cholic acid (pK 5.29) would have been expected to be retained longer than the dihydroxy acids (pK 6.18-6.29) which should have been retained... 

Figure 19 Basic structure of cholic acid derivatives.

Steroidal frameworks have been much used in synthetic ion transport designs. Cholate oligomers synthesized from polyamines and cholic acid derivatives represent another class of ion transporters (Figure 12). These compounds, inspired by squalamine antibiotic, are also known as molecular umbrellas because of their amphomorphism. Depending on the polarity of the medium, the hydrophilic cholate faces are exposed or hidden to the surface of the umbrella. These compounds such as 22 are active sodium... 

The cholic acid derived sensors containing two pyrene units 47 (Fig. 14) showed excimer emission. The presence of two thiourea units allowed one to form stable complexes with dicarboxylic acids (with in the range of 10 -10 in acetonitrile), with a decrease of the fluorescence of the excimer band. This interaction was attributed to the enhancement of the PET effect and to a decrease of the n-n stacking interaction of the two pyrene units, which was found to be different for the two tetrabutylammonium salts of d- and L-glutamic acid [108]. Similarly, enantioselective quenching of bands due to both the monomeric fluorophore and the excimer emission was observed for the mandelate anion in a related sensor containing only one thiourea unit [109]. 

Cholesterol is found abundantly in animal plasma membranes, and the specific interaction of cholesterol with lipid bilayers in an important biological topic. It appears that cholesterol derivatives interact specifically with ammonium bilayers as well. In the hydrolysis of phenyl esters, cholest-Im showed an especially high reactivity when bound to the 2C] 2N 2C bilayer(18). Cholic acid-derived nucleophiles showed normal reactivity patterns, as may be expected from the fact that cholic acid tends to disintegrate the phospholipid bilayer. 

Dias, J. R., and R. Ramachandra Studies Directed toward Synthesis of Quassinoids. 2. D-Ring cleavage of Cholic Acid Derivatives. J. Org. Chem. 42, 1613 (1977). 

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