Cholanic acid conjugation

Recently, Lee et al. showed highly efficient PDT with an in vivo tumor model using chitosan-based nanoparticles (Fig. 6) [78]. They prepared self-assembled amphiphilic glycol chitosan-5p-cholanic acid conjugates and encapsulated the hydrophobic photosensitizer, PpIX, with a high dmg-loading efficiency of over... 

The taurine residue can also be found as an amide derivative of the 26-carboxylic acid function in the 3p,5a,6p,15a-polyhydroxylated steroids 328 and 329, which were obtained from the starfish Myxoderma platyacanthum [245]. The structures of both compounds were determined from spectral data and chemical correlations. The bile of the sunfish Mola mola has been shown to contain a new bile acid conjugated with taurine (330) together with sodium taurocholate. Compound 330 was identified as sodium 2-[3a,7a, 11 a-trihydroxy-24-oxo-5P-cholan-24-yl]amino]ethane-sulfonate on the basis of its physicochemical data and chemical transformations [246]. 

Some bile salts are quite toxic in the liver, leading to cholestasis and morphologic changes in bile canalicular membranes associated with this toxicity. Some of these toxic bile salts, such as lithocholate and 3 hydroxy-5a-cholanic acid are not detoxified by sulfation, but the sulfate conjugates retain their toxic effects almost completely. Although strictly speaking this is no toxlficatlon by sulfation, yet sulfation does not alleviate toxicity of these compounds (42-45). 

The lactone (31), obtainable in three steps from cholanic acid, served as the starting point in a different approach. Phosphorus oxychloride-pyridine dehydration of the corresponding hydroxy-methyl ester afforded a complex mixture of unsaturated esters in which the cis and trans non-conjugated esters (32) predominated Hydrolysis of the entire mixture and treatment of the mixture of free acids with iV-bromosuccinimide gave the new buf-20(22)-enolide (33). DDQ dehydrogenation of (33) could be controlled to yield either the desired bufa-... 

Chemically, the bile acids are hydroxylated derivatives of cholanic acid, a tetracyclic steroid acid of 24 carbon atoms. The acids occur in nature largely as the water-soluble sodium salts of peptide conjugates of glycine and taurine. The free acids are liberated by saponification or specific enzyme hydrolysis. The chemistry of the bile acids has been reviewed in Chapter 1 of this volume (1). In view of their highly polar nature, special attention is called to the recent discovery of the cholic acid conjugates of ornithine (2, 3) and the 3a-sulfate esters of glycolithocholic and taurolithocholic acids (4). 

All alkali metal salts of cholanic acid are extremely insoluble in water from temperatures of 0°C to 100 °C. The sodium and potassium salts of its glycine and taurine conjugates are also very insoluble. 

Since free and conjugated dihydroxy cholanic acids cannot be separated completely by paper and thin-layer chromatography they must be differentiated by specific reactions. The following procedures are suitable for quantitative determination of free bile acids reaction with concentrated sulfuric acid for determination of cholic acid (Hammarsten 1925), reaction with salicylic aldehyde and sulfuric acid for determination of deoxycholic acid (Szalkowski and Mader 1952), reaction with ethyl acetate, concentrated sulfuric acid and acetic acid anhydride for chenodeoxycholic acid (Isaksson 1954). 

The use of thiocyanic acid for thiirane synthesis is usually compatible with many functional groups found in natural steroids. The method has found application in androstanes, pregnanes, cholestanes, cholanates and cardeno-lides. However, the presence of a,j5-unsaturated carbonyl groups may decrease the yield of the thiocyanatohydrin due to conjugate addition of thiocyanic acid. Indeed, the 1,4-addition of thiocyanic acid has been carried... 

Nearly all bile acids are choleretic agents that is, they increase bile flow when infused intravenously into various animal species. In all vertebrtae species examined, there is a close relationship between bile flow and the hepatic excretion rate of bile acids (B24). Acute interruption of the enterohepatic circulation of bile acids in man by diversion of bile flow causes the rate of bile secretion to decrease by about 50% (TIO). Thus, the excretion of bile acids from the liver is the major determinant of bile water and solute excretion, predominantly because of the osmotic activity of bile acids in bile. Some interesting studies in dogs have been performed with the bile salt taurodehydrocholate (taurine conjugate of 3,7,12-triketo-5fl-cholan-24-oic acid), which, for stereochemical reasons, cannot form micelles and should therefore have greater osmotic activity than other bile acids. At the same... 

Hydroxylation. Common to the reports of 3 papers [164,194,198] was identification of the urinary acid 3a,7a,12a,23-tetrahydroxy-5j8-cholanate, present as the taurine and glycine conjugates. Whether this is a precursor of norcholate (23-nor-3a,7 ,12a-trihydroxy-5/S-cholanate) remains to be determined. 

Lithocholic acid 3a-hydroxy-5P-cholanoic add, or 3a-hydroxy-5p-cholan-24 c acid, M, 376.58, m.p. 185 C, [a]D + 32 ° (ethanol). L. a. is a monohydroxyla-ted steroid carboxylic add, and one of the bile acids. It has been isolated from the bile of man, cow, rabbit, sheep and goat, and is normally prepared from bovine bile. L.a. is formed from chenodeoxycholate by intestinal bacteria. It is absorbed and returned to the liver for secretion. It is not readily conjugated, and it is relatively toxic to the liver. L.a. may be important in the pathogenesis of liver damage following biliary sta-... 

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