Dihydroxy cholanic acid

Hydroxyquinoline, see under Oxine Hyodeoxycholic acid(3a,6 -dihydroxy-cholanic acid),... 

Thin-layer chromatography of bile acids was introduced by Ganshirt et al. (1960) and modifiedfor separation of isomeric dihydroxy cholanic acids (de-oxy- and chenodeoxy cholic acid) by several authors (Hofman 1962, Ene-ROTH 1963, Hamilton 1963, Wagener and Frosch 1963). Gas-liquid chromatography of bile acid methyl esters was described by van den Heuvel (1960) and Sjovall (1961) but is as yet applicable only to free bile acids. 

Since free and conjugated dihydroxy cholanic acids cannot be separated completely by paper and thin-layer chromatography they must be differentiated by specific reactions. The following procedures are suitable for quantitative determination of free bile acids reaction with concentrated sulfuric acid for determination of cholic acid (Hammarsten 1925), reaction with salicylic aldehyde and sulfuric acid for determination of deoxycholic acid (Szalkowski and Mader 1952), reaction with ethyl acetate, concentrated sulfuric acid and acetic acid anhydride for chenodeoxycholic acid (Isaksson 1954). 

Cholanic acid C24H40O2, a monobasic saturated acid containing four hydroaromatic rings, is the parent substance of the two natural acids, which are its trihydroxy- and dihydroxy-derivatives. It is very highly probable that the following structural formula for cholic acid is correct ... 

N.m.r. has been used for the rapid estimation of chenodeoxycholic and ursodeoxycholic acids 3a,7a- and 3a,7/8-dihydroxy-5/3-cholanic acids) in mix-tures. ... 

SYNS DEOXYCHOLATE SODIUM DEOXYCHOLIC ACID SODIUM SALT DIHYDROXY 3-12 CHOLANATE de Na (FRENCH) (3-a,5-3,12-a)-3,12-DIHYDROXY-CHOLAN-24-OIC ACID MONOSODIUM SALT 3-a,12-a-DIHYDROXY-5-3-CHOLAN-24-OIC ACID SODIUM SALT NA-DESOXYCHOLAT (GERMAN) NATRIUM-3-a,12-O-DIHYDROXYCHOLANAT (GERMAN) SODIUM DEOXYCHOLATE SODIUM DEOXYCHOLIC ACID... 

The substances shown in Figure 6 are new compounds synthesized previously (10). The most significant difference in bioassay activities was obtained in the case of 2a,3a-dihydroxy-7-oxa-6-oxo-23,24-dinor-B-homo-5a-cholanic acid (XXVIII) when compared with 24-epiBR. The side chain of this BRst is shorter and terminated at the position 22 with a carboxyl group. This modification makes compound XXVIII 10... 

In a similar study of the metabolism of [24- C]12a-hydroxy-5)8-cholanic acid given intraperitoneally to male rats with bile fistulas [83], the identified biliary metabolites were 7a,12a-dihydroxy-5)8-cholanic acid (26%), deoxycholic acid (18%), cholic acid (15%), 6)8,12a-hydroxy-5)8-cholanic acid (0.8%), and 12% of unchanged 12a-hydroxy-5)8-cholanic acid. Thus, 5)8-cholanic acid and 12a-hydroxy-5)8-cholanic acids are hydroxylated in vivo preferentially in the order 7a, 3a, and 6)8. The preference for 7a-hydroxylation may be related to the concentration and properties of the active enzyme. Although no in vitro studies have been carried out, these studies infer the ability of hepatic tissue to provide characteristic 3a-hydroxy bile acids from derivatives devoid of a C-3 oxygen. How often this activity is required is questionable, because of the abundance of 3-hydroxylated sterol derivatives provided to and by the liver. 

The conversion of lithocholate to 3a,6/8-dihydroxy-5/8-cholanate by the rat [84-86], mouse [87] and chicken [88] confirmed the presence of an active hepatic 6)8-hydrox-ylase. Earlier studies reported the metabolism of chenodeoxycholate [89,90] in the rat and mouse [81,91,92] to a-murocholic acid (3a,6)8,7a-trihydroxy-5)8-cholanic acid) and to )8-muricholic acid [89,90,93,94] (3a,6)8,7)8-trihydroxy-5)8-cholanic acid). 

Other precursors of the muricholates via 6)8-hydroxylation include 5)8-cholanic acid [78], lithocholic acid [84-86], 7-oxolithocholic acid [95,96], and ursodeoxycholic acid (3a,7j6-dihydroxy-5/3-cholanic acid) [97], The rat metabolized 12a-hydroxy-5/S-cholanic acid to 6/S,12a-dihydroxy-5)S-cholanic acid [83] and a small amount of 6)3,7a,12a-trihydroxy-5 -cholanic acid [98]. 3a,6)8,12a-Trihydroxy-5)8-cholanic acid was isolated from urine of surgically jaundiced rats after administration of de-oxycholate [99]. A series of bile acids from rat bile of unconfirmed structures but containing the 6/3,7/3-diol will be reviewed in Section II1.3. 

A study of the reduction of [24- C]3-oxo-5j8-cholanic acid in bile fistula rats given [l- Hjjethanol showed that all metabolites had a 3a-hydroxy group and all radioactive products (lithocholate, 3a,6/8-dihydroxy-5 -cholanate, chenodeoxycho-late and y8-muricholate) contained about 13 atom% excess deuterium in the 3/9 position. Thus, the 3)8-hydroxy-5/9-steroid dehydrogenase isoenzyme of alcohol dehydrogenase [172] has no function in the reductive metabolism of bile acids. Cholic acid was not radioactive but contained deuterium at the 3)8, 5)8 and other positions, probably because of the transfer of deuterium from ethanol via NADH to NADPH, which it utilized in the biosynthesis of cholesterol and bile acids and in oxido reduction of the 3-hydroxyl group of the latter [173]. 

As noted earlier, bile acids were among the first steroids to be obtained in pure crystalline form. These compounds played an important role in the effort devoted to divining the structure of steroids. Bile acids as a result acquired a sizeable number of trivial names, most of which gave little information as to their chemical structure. One approach to systematic names is based on the hypothetical cholanoic acid 8-1 (Scheme 8). Bile acids are then named as derivatives of this structure using the mles used for other classes of steroids. Note the cis A-B ring fusion in this series. The systematic name for 8-2, lithocholic acid, is then simply 3a-hydroxy-5/3-cholanic acid. Chenodeoxycholic acid, 8-3, becomes 3a,7a-dihydroxy-5/3-cholanic acid. The predominant acid in bile, 8-3, is cholic acid itself, or, 3a,7a,12a-trihydroxy-5 )8-cholanic acid. 

Hydroxylation of desoxycholic acid. This perester (1) and desoxycholic acid (2) form a 1 4 molecular complex, which when heated (90°) or irradiated with X>300 nm (25°) decomposes with formation of 3a,50,12o -trihydroxy-cholanic acid (3) and 3-keto-12a-hydroxycholanic acid (4) as the major products. A trace of 3a,12a-dihydroxy-5 -androstane is formed. 

Reaction of steroidal tosylates with KNO2 in DMSO or DMF gave reasonable yields of alcohols with inverted configuration. The previously reported epi-merization at C-3 during Raney nickel-catalysed hydrogenation of methyl 3, 1 a-dihydroxy-12-oxo-5/8-cholanate was incorporated in a report of the synthesis of 3/3,7a,12j8-trihydroxy-5/3-cholanic acid and the 3a,7a,12/3-trihydroxy-analogue. Conversion of mestranol into epimestranol was achieved by treatment of the 17-mesylate with silver nitrate in aqueous THF. ... 

Sodium desoxycholate CAS 302-95-4 EINECS/ELINCS 206-132-7 Synonyms Deoxycholate sodium Deoxycholic acid sodium salt 7-Deoxycholic acid sodium salt (3-a,5-p, 12-a)-3,12-Dihydroxy-cholan-24-oic acid monosodium salt 3-a,12-a-Dihydroxy-5-p-cholan-24-oic acid sodium salt Sodium deoxycholate Sodium deoxycholic acid... 

This acid completes the citation of the four possible 3,12-dihydroxy-5 -cholanic acids as naturally occurring compounds. The 3, 12 acid and the... 

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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