Cholic acid stereochemistry

FIGURE 7.12 Cholic acid. Its 11 chirality centers are those carbons at which stereochemistry is indicated in the structural drawing at the left. The molecular model at the right more clearly shows the overall shape of the molecule. 

In approaches to a synthesis of quassinoids, the ketone (124), derived from cholic acid, has been converted into the lactone (125), with the C-7 stereochemistry of quassinoids. ... 

The stereochemistry of the B/C and C/D ring junctions are as in cholesterol and the cholic acids A/B stereochemistry is indicated where necessary. See p. 1474 for numbering system used for steroids. 

In 1963, Carey and Haslewood isolated trace amounts of (25/ )-3a,7 ,12a-trihy-droxy-5 8-cholestan-26-oic acid from human fistula bile [96]. The stereochemistry at C-25 of this bile acid was recently confirmed by direct comparison with reference compounds of known absolute configuration [97], This trihydroxy-5j8-cholestanoic acid also occurs in baboon bile [98]. Hanson and Williams found the corresponding dihydroxy bile acid, 3 ,7a-dihydroxy-5 S-cholestan-26-oic acid, in human bile [99]. The occurrence of these higher bile acids, quantitatively of minor importance, is of interest because they are biosynthetic precursors of two primary bile acids of mammalian species, cholic acid and chenodeoxycholic acid, respectively (Chapter 9). 

Fig. 12-3 Bile acid and bile salt detergents. (A) Cholic acid drawn showing the stereochemistry of carbon atoms in the system effused rings, (B) glycocholate, and (C) taurocholate.

Bergstrom S, Lindstredt S, Samuelson B, Corey EJ, Gregoriou GA (1958) The stereochemistry of 7a-hydroxylation in the biosynthesis of cholic acid from cholesterol. J Am Chem Soc 80 2337-2338... 

The four isomeric acids can be derived by a series of chemical reactions from cholic acid, which is commercially available (Sigma Chemical). Some of the reactions have already been discussed with regard to structures. This section is intended to provide practical methods by which the four acids can be prepared. Some of the intermediates are by themselves interesting derivatives with regard to the stereochemistry of bile acids. The procedures described here are taken from published works with certain modifications and have been tested in the author s laboratory. 

Most steroids share a common tetracyclic ring system, but are adorned differently in terms of oxidation state at various carbons. The three targets we will consider are only the tip of the iceberg. Fused ring systems with different ring juncture stereochemistry (cis vs trans), different sidechains, and different oxidation patterns are common. A few examples are shown here (see problems for some questions about fiisidic and cholic acids). 

Draw the most stable conformations of cholic acid and fusidic acid (Steroids-1). Describe the stereochemistry at each ring junction and the conformation of each six-membered ring. (Steroids-1)... 

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 ... 

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