Desoxycholic acid

Desoxyadenosine oligonucleotides la 76 Desoxycholic acid la 334 11-Desoxycorticosterone la 221 lb 346 Detection, group-specific la 4,7 -, substance specific la 4,7 Detection of lipqjhilic substances la 43 -, biological-physiologically la4,6,7, 9,109... 

This procedure, coupled with the procedure described on p. 41, illustrates the Barbier-Wieland method for systematically degrading carboxylic acids. foxwor-Desoxycholic acid may be prepared from wor-desoxycholic acid by repetition of this procedure. If the chromic acid oxidation product is not sufficiently solid to filter after dilution with water, the mixture must be extracted with ether and washed with dilute hydrochloric acid before the alkaline extraction. Wxwor-Desoxycholic acid may be crystallized from ethyl alcohol. It melts at 239-241°. 

The crude carbinol is acetylated and dehydrated by refluxing its solution in 1 1. of glacial acetic acid and 500 ml. of acetic anhydride for 1 hour. The solution is then concentrated to about 500 ml. by distillation. After cooling overnight, the crystalline 3,12-diacetoxy-5A or-cholanyldiphenylethylene is collected on a filter and washed with acetic acid. The yield is 95-105 g. (63.5-70.0%) of material melting at 154-157° (Note 5). This product is sufficiently pure to be used for the preparation of Mor-desoxycholic acid (p. 38) one crystallization from acetone gives white crystals which melt at 156-157.5° fully purified material melts at 159.5-160.5°. 

A good grade of desoxycholic acid should be used. The product from Wilson Laboratories has been found to be satisfactory. 

The crude diacetate is hydrolyzed by dissolving it in 350 ml. of 10% aqueous potassium hydroxide and refluxing the solution for 2 hours. The alkaline solution is diluted to about 700 ml., cooled, and filtered. The filtrate is poured into 300 ml. of 10% hydrochloric acid, and the wor-desoxycholic acid is separated by filtration and dried. The crude product is dissolved in about 600 ml. of acetone and filtered, while hot, to remove small amounts of salt. On cooling, 25-30 g. (57-68%) of white crystals which melt at 209-211° is obtained in two crops (Note 5). This... 

A. Methyl desoxycholate. To a cooled solution of 100 g. (0.255 mole) of desoxycholic acid (Note 1) in 11. of methanol is added carefully 50 ml. of acetyl chloride. The solution is allowed to stand overnight at room temperature (Note 2) and is then diluted with cold water until just turbid. Crystallization is induced by scratching and seeding, if necessary. When much of the ester has crystallized, the mixture is further diluted to about 2.5 1. and allowed to stand for 30 minutes until crystallization is complete. The ester is collected on a filter, washed with water, and dried. The yield is 100-103 g. (97-100%) of material which melts at 95-100° (Note 3). 

The literature on methods of preparation is the same as that given for wor-desoxycholic acid (p. 40). 

Methylcholanthrene (3-MC) is a potent carcinogen, intermediate in activity between DMBA and BP (27,77). It was first prepared in 1925 by Wieland from desoxycholic acid (89). Biological studies have tentatively identified the 9,10-dihydrodiol (24a) and/or its 1- or 2-hydroxy derivatives (24b and 24c) and the corresponding diol and triol epoxides (25 -c) as the proximate and ultimate carcinogenic forms, respectively, of 3-MC (90-93). 

Desoxycholic Acid, Fatty Acids, Cholesterol.—The first alcoholic filtrate obtained during the crystallisation of the cholic acid (see above) is made strongly alkaline to phenolphthalein paper with 2 N-sodium hydroxide solution and concentrated to a syrupy consistency in a porcelain basin on the water bath. The syrup is taken up in 250 c.c. of water, transferred to a separating funnel, cooled, covered... 

The two most important bile acids, cholic acid C24H40Os and desoxy-cholic acid C24H40O4, occur in ox bile in combination, partly with glycine and partly with taurine as glyco- and taurocholic and glyco- and tauro-desoxycholic acids. The linkage between the amino acids and the bile acids is of an amide nature. On hydrolysis the nitrogenous constituents are split off. 

Experiment.—Dissolve 0-4 g. of the acetic acid-desoxycholic acid compound, prepared as above, in 4 c.c. of 2A-sodium hydroxide. Prepare also from about 100 mg. of the fatty acids isolated, by boiling with a few cubic centimetres of dilute sodium hydroxide solution, a soap solution and cool it till it sets to a jelly. Add part of the solution of desoxycholic-acetic acid. The soap dissolves. 

The first synthesis of cortisone (8), for instance,was a partial synthesis from desoxycholic acid (9), performed in 1948 by a group of chemists at Merck and Co under the leadership of Kendall [19], three years before Woodward [20] and Robinson [21], independently, accomplished the first total synthesis of steroids. 

The structure proof for cholesterol paralleled that for two other important steroids, the so-called bile acids, cholic and desoxycholic acid, which function to help solubilize fats in the intestinal tract. Proof that cholesterol and the bile acids have the same general ring system was achieved by dehydration and reduction of cholesterol to two different hydrocarbons, 5a-cholestane and 5/3-cholestane (coprostane), which differ only in the stereochemistry of the junction between rings A and B ... 

Once the connection between cholesterol and the bile acids was established, further work on the structure proof was directed towards degradation experiments on the bile acids which, with their hydroxyl groups on rings B and C, offered more possible degradation reactions than cholesterol. Outstanding contributions toward the structure proof were made by the German chemists H. Wieland and A. Windaus, both of whom were honored by the award of the Nobel Prize in chemistry. Wieland received the award in 1927 and Windaus in 1928. Despite their many years of effort, the structure proposed by Windaus in 1928 for desoxycholic acid was only tentative and was unspecific as to the location of two carbons. 

Methylation of hydrocortisone/prednisolone in positions C-4, C-7, C-12, and C-21 failed to give useful products. Methylation at C-16, in contrast, led to 16a- and 16p-methyl-9a-fluoroprednisolones which were exceptionally useful. Both series were prepared using 3a-acetoxy-5a-pregn-16-ene-ll,20-dione derived from desoxycholic acid (80). A much shorter route was subsequently developed from... 

Sobotka and Goldberg 86 have resolved < -4-phenyl-2-butanol by fractional crystallization of the solid coordination complex formed with desoxycholic acid. Similar resolutions of dZ-caihphor, dJ-limonene, and dZ-methylethylacetic acid indicate that no specific functional group is necessary for the coordination process. The method deserves further study as a possible means of resolving various types of compounds, including alcohols that are not readily esterified. 

Desoxycholic acid, 24, 41, 42 iixwor-Desoxycholic acid, 24, 40 mot-Desoxycholic acid, 24, 38 Desulfonamidation, of 3,5-dichlorosulf-anilamide, 24, 48... 

Esterification—Continued by azeotropic distillation with benzene, 22, 38 by nitric acid, 22, 65 of desoxycholic acid, 24, 41 of lactic acid, 26, 4 of linoleic acid, 22, 77 of linolenic acid, 22, 83 of pyruvic acid with use of methyl ester column, 24, 72 Ester interchange, 26, 5, 19 between polylactic acid and allyl alcohol, 26, 5... 

Desoxycholic Acid occurs as a white, crystalhne powder. It is practically insoluble in water, slightly soluble in chloroform... 

---