Allocholanoic acids

Allocholanoic acids (5a-cholanoic acids) are found mainly in lower animals (68,76), but small amounts of allocholic acid (3a,7a,12a-trihydroxy-5a-cholanoic acid), allodeoxycholic acid (3a,12a-dihydroxy-5a-cholanoic acid), and probably also allochenodeoxycholic acid (3a,7a-dihydroxy-5a-cholanoic acid) may be present in bile and feces of mammals (68,76,102). Karavolas et al. (Ill) and Ziller et al. (112) have shown that cholestanol is converted into allocholic acid and allochenodeoxycholic acid in rats with a biliary fistula. The conversion of cholestanol into allocholic acid has also been shown in the rabbit (113). Allodeoxycholic acid is a secondary bile acid, formed from allocholic acid (113,114) and deoxycholic acid (115,116). The early steps in the sequence of reactions from cholestanol to allocholic acid (Fig. 6) have been the subject of two recent investigations. Shefer et al. (17) have shown that the microsomal fraction of rat liver homogenate fortified with NADPH catalyzes 7a-hydroxylation of cholestanol. Bjorkhem and Gustafsson (117) have compared the rates of 7a-hydroxylation of cholestanol,... 

Fig. 6. Conversion of cholesterol into allocholanoic acids. I, Cholesterol II, 5-cholestene-3/5,7a-diol III, 7a-hydroxy-4-cholesten-3-one XXIV, cholestanol XXV, 5a-choles-tane-3i ,7a-diol XXVI, 7a hydroxy-5a-cholestan-3-one XXVII, 5a-cholestane-3a,7a-diol XXVIII, 5a-cholestane-3a,7a,12a-triol XXIX, allochenodeoxycholic acid XXX, allocholic acid.

Table I lists known allocholanic acids and some of their derivatives. Very few carbon-carbon unsaturated allocholanoic acids have been described (6, 9) several halogenated derivatives of the allo-acids and a number of 4,4,14a-trimethyl allocholanoic acids have been reported (10, 11) but they have not been included in this review. Of the monohydroxy derivatives, the 6-oxy derivative reported by Wieland in 1932 (12) without assignment of configuration was prepared by catalytic reduction of the 6-keto acid, and is probably the axial 6/3 derivative (13). From an inspection of the data in the table it is clear that the subject of this chapter covers a span of 50 years with a renewed interest in the subject evidenced about 38 years after the initial paper of Windaus on allocholanic acid in 1919. Also it is evident that investigations on allo-acids flourished for about 18 years, then lagged, and were revived with new vigor again about 38 years later.

After intraperitoneal administration to the rat, 90% of this acid is recovered unchanged in bile (141) 0.6% was present in monohydroxy acids of which 60% was identified as 3/3-hydroxy allocholanoic acid. About 9% was converted to unidentified trihydroxy acids. In vitro experiments with liver homogenates indicate less extensive metabolism of this dihydroxy allo-acid in this case allolithocholate appears to be formed instead of the 3j9-isomer. 

Partial separations of the substituted methyl allocholanoates have now been achieved by crystallization. Kallner (41, 45) has reported the removal of 82% of the radioactivity after three crystallizations of a mixture of methyl allolithocholate- H and methyl lithocholate 90% of the tritium was removed by several crystallizations of a mixture of methyl lithocholate- H and allolithocholate. Similarly, more than 90% of the radioactivity was removed from a mixture of methyl deoxycholate- H and allodeoxycholate after three crystallizations from aqueous acetic acid or aqueous methanol. Methyl 3/3,12a-dihydroxy-5 -cholanate was separated from methyl deoxy-cholate by crystallization from aqueous methanol. Thomas et al. (46) reported the separation of 3a,6/3-dihydroxy-5 - or 3a,6a-dihydroxy-5 -cholanoic acid from 3a,6/3-dihydroxy-5 -cholanoic acid by crystallization from aqueous acetone or a mixture of methanol, ether, and hexane. 

Mass spectra of the allo-acids and their derivatives generally resemble those of their 5/3-epimers. Thus, allocholanoates (M") with free or protected hydroxyl groups provide fragment ions by ready loss of water (M-18), acetic... 

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