Hyodeoxycholic acid structure

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. 

FIGURE 3.4 Structures of endogenous compounds involved in glucuronidation bile adds, lithocholic add (LA) and hyodeoxycholic acid (HDCA) short chain bile acids, etianic add and isoetianic add, steroid hormones, androsterone, testosterone, estrone, estradiol, estriol. 

Several other atypical acids were eventually isolated from various species. Ursodeoxycholic acid, first isolated in crystalline form from bear bile in 1927 (58), was identified as the 7/S-epimer of chenodeoxycholic acid. The so-called /3-hyodeoxycholic acid (3 3,6a), which Kimura obtained in small amounts from pig bile (59), was structurally identified in the course of a thorough investigation of the four possible 3,6-dihydroxycholanic acids (60). The lagodeoxycholic acids isolated from rabbit bile by Kishi (61) were not characterized until the recent studies of Danielsson et al. (62) identified one of these compounds as allodeoxycholic acid. The contention that one of them may have been the 12 -epimer of deoxycholic acid was placed in doubt by Koechlin and Reichstein (63), who prepared that acid and found that it did not exhibit the physical properties of the natural material. 

During studies of steroid structure, hyodeoxycholic acid became valuable for its ability to be interconverted between the two A/B stereochemical types. It was thus a source of supporting evidence for the C-5-isomers in the steroid family (1). 

The occurrence of a species-specific bile acid in pig bile [Haslewood (1) Haslewood and Sjovall (2)] and of two such acids in rat bile [Bergstrom and Sjovall (3) Hsia et al. (4) Matschiner et al. (5)] was observed almost simultaneously. After their isolation and characterization, these acids were found to be isomeric 3a,6,7-trihydroxy-5/5-cholanic acids. The acid from pig bile was named hyocholic acid [Haslewood (6) Ziegler (7)], and the two acids from rat bile were named a- and /3-muricholic acids [Hsia et al. (8)]. The fourth isomer of these glycols was identified as a metabolite of hyodeoxycholic acid (3rt,6a-dihydroxy-5 9-cholanic acid) in the rat [Matschiner et al. (9, 10)], and was named ry-muricholic acid [Hsia et al. (8)]. The vicinal glycol structures in ring B of these acids are unique features, but even more unique are their species-specific characteristics which are particularly demonstrated in the metabolic pathways that lead to their formation. 

The structure of hyocholic acid was proposed by Haslewood (24) and by Ziegler (7) to be 3a,6a,7 -trihydroxy-5 -cholanic acid (I, Fig. 1). Since it was known that pig bile contains hyodeoxycholic acid (3a,6a-dihydroxy) and chenodeoxycholic acid (3a,7a-dihydroxy) the bile was assumed to contain possibly also an acid with both 6a- and 7a-hydroxyl groups. Chemical evidence for the vicinal glycol structure in hyocholic acid was found after chromic oxidation. The product, 3-keto-6,7-secocholanic acid-6,7-dioic... 

Confirmative evidence of the proposed structure was obtained from partial synthesis of hyocholic acid [Hsia et al. (30)]. An important intermediate in the synthesis was 3a,6a-dihydroxy-7-keto-5 -cholanic acid (VII, Fig. 2), first prepared by Takeda et al. (35). The 3 - and 6a-hydroxyl groups in VII were established by the formation of hyodeoxycholic acid (IX) after hydrogenolysis of the ethylenedithioketal derivative (VIII) with Raney nickel. Hyocholic acid was obtained from VII either by reduction with sodium borohydride or by hydrogenation in the presence of platinum both methods were known to produce the axially oriented 7a-hydroxy from 7-keto bile acids [Mosbach et al. (36) Iwasaki (37)]. More direct evidence for the la-hydroxyl group in hyocholic acid was found in a later study [Hsia et al. (8)], when hyocholic acid was derived from bromohydrin acetate XII (Fig. 3),... 

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