Hyocholic acid isolation

Hyocholic acid was isolated from pig bile by Haslewood in 1954 (123, 124). It has not been detected in the bile of other species. Hyocholic acid was characterized by Haslewood (125), Ziegler (126,127) and by Hsia et al. (89) as 3a,6a,7a-trihydroxycholanic acid. The acid may be synthesized by NaBH4 reduction of 3a,6a-dihydroxy-7-ketocholanic acid, which in turn is prepared from chenodeoxycholic acid (89). 

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. 

Hyocholic acid is a major acid in pig bile and isolation of hyocholic acid from this natural source is feasible. Partial synthesis of hyocholic acid from cholic acid is therefore of interest in verifying its structure rather than for the purpose of obtaining the material. On the other hand, the muricholic acids are minor constituents of rat bile. Isolation of these acids in large amounts would not be practical, and partial syntheses remain the necessary means to provide pure muricholic acids in useful quantities. 

The main bile acids present in man, rat, rabbit, and pig are illustrated in Fig. 4. All occur as taurine or glycine conjugates. Hydroxyl functions are found at one or more of the following positions 3a. 6a. 7a, and I2a. The 6a-hydroxylated structures appear thus far to be exclusive for the pig whose bile acids consist in major of chenodeoxycholic and hyocholic acids. 6j3-Hydroxylated acids are only formed to a minor extent. The 7/5-hydroxylated derivative isolated after the administration of chenodeoxycholic acid to the rat (Hsia et al., 1958) has been shown through experiments with a C-7j8 tritiated structure to arise through the inversion of the 7a-hydroxy isomer via the keto structure (Bergstrom et al., 1960b). 16a-Hydroxylated acids have been isolated from boas and pythons but not from a variety of other species of snakes examined (Hazlewood, 1959). The most recent references to pertinent studies are listed in Table I. 

Medici and co-workers [22] isolated and classified several microorganisms from 50 environmental samples withdrawn from ICE industry [23], which extracts and purifies bile acids from raw materials (ox and pig bile). These microorganisms (mostly bacteria) have been screened in oxidation reactions of cholic 1, chenodeoxycholic 34, deoxychdlic 40, and hyocholic 31 acids. The most significant results are summarized in Table 7. 

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