A Muricholic acid

There is a wide variety in the types of bile acids found in different animal species. Some species have unique bile acids, such as a-muricholic acid (3a,6p,7a-trihydroxy-5p-cholan-24-oic add) and -muridiolic add (3a,6, 7 -trihydroxy- -cholan 24-oic acid) in rats and mice, and hyodeoxycholic acid (3a,6a-dihydroxy-Sp-cholan>24-oic acid) in pigs. Haslewood (H9) has studied the distribution of bile acids in the animal kingdom and has suggested that the C-24 adds, which are common to most advanced animal forms, can be regarded as the present endpoints in the evolution of the chemical structure of bile adds. 

TThe following systematic names are given to steroids and bile acids referred to by trivial names cholestanol, 5a-cholestan-3/5-ol cholic acid, 3a,7a,12a-trihydroxy-5j3-cholanoic acid hyocholic acid, 3a,6a,7a-trihydroxy-5/S-cholanoic acid a-muricholic acid, 3a,6/S,7a-trihydroxy-5/S-cholanoic acid /5-muricholic acid, 3a,6/S,7/S-trihydroxy-5/S-cholanoic acid allocholic acid, 3a,7a,12a-trihydroxy-5a-cholanoic acid chenodeoxycholic acid, 3a,7a-dihydroxy-5/5-cholanoic acid deoxycholic acid, 3a,12a-dihydroxy-5iS-cholanoic acid allochenodeoxycholic acid, 3a,7a-dihydroxy-5a-cholanoic acid allodeoxycholic acid, 3a,12a-dihydroxy-5a-cholanoic acid lithocholic acid, 3a-hydroxy-5/5-cholanoic acid. 

Chenodeoxycholic acid is converted into a-muricholic acid (3a,6i8,7a-trihydroxy-5jS-cholanoic acid) and j8-muricholic acid (3a,6)J,7/J-trihydroxy-5j8-cholanoic acid) in the mouse and the rat and probably also in man (68, 102, Chapter 11 in this volume). a-Muricholic acid is a precursor of jS-muri-cholic acid in a reaction involving the intermediary formation of the 7-oxo compound (Chapter 11 in this volume). In the rat, /8-muricholic acid has been shown to be formed also from 3a,7j8-dihydroxy-5i8-cholanoic acid, which is a minor metabolite of chenodeoxycholic acid, and from 3a,6)9-dihydroxy-5)5-cholanoic acid, which is a metabolite of lithocholic acid (Chapter 11 in this volume). The microsomal 6i8-hydroxylase system in rat liver catalyzing the conversion of (tauro)chenodeoxycholic ac d into (tauro)a-muricholic acid has been studied by Hsia and collaborators (103-105), who... 

This acid was isolated from rat bile by Matschiner et al. (46). It has not been isolated from the bile of other species. It was characterized by Hsia et al. (128). a-Muricholic acid may be synthesized from methyl 3a-acetoxy-J -cholenate either through epoxidation (128) or through the bromohydrin acetate (129). 

This chapter brings together the information concerning the isolation, the elucidation of structures, and the methods of chemical synthesis of the four 3a,6,7-trihydroxy-5/3-cholanic acids. Recent findings of taurochenode-oxycholate 6/3-hydroxylase are also discussed since the enzyme system directly concerns the formation of a-muricholic acid. 

The diaxial trans-g yco structure in a-muricholic acid was substantiated by partial synthesis. a-Muricholic acid could be derived from either the 6a, 7a-epoxide XVI [Hsia et al. (39)] or the 6,9,7/9-epoxide XV [Hsia et al. (41)] (Fig. 4) by scission of the epoxide rings and hydrolysis of the acetates thus formed. In accordance to the Fiirst and Plattner rule [Fiirst and Plattner (42)], ionic opening of an ethylene oxide results in the diaxial trans-g yco. The structure of a-muricholic acid therefore should be 3a,6,9,7a-tri-hydroxy-5/9-cholanic acid (XVII). The orientation of the epoxide ring in XV and that... 

The a-epoxide (XVI, 120 mg) is refluxed in acetic acid (20 ml) for 3.5 hr. The solution is diluted with water and extracted with ether. The product (methyl 3a,6 -diacetoxy-7a-hydroxy-5p-cholanate) is purified on a silica gel column and is eluted by 20 % ether in benzene. After hydrolysis by methanolic KOH (2%, 20 ml) at room temperature overnight, a-muricholic acid is obtained after acidification and extraction with ether. It forms crystals from an acetic acid solution after the addition of water. These crystals contain... 

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