Cholanic acid, 3-hydroxy-12-keto

Chlorine monoxide, III, 135 Chlorine water, III, 136, 150 Chlorites, as oxidants, III, 179 Chlorohydrins, of divinylacetylene, II, 109, 110, 113 of divinylglycol, II, 108 Chlorophyll, III, 234 Chlorous acid, as oxidant, III, 179 Cholanic acid, 3-hydroxy-12-keto-, IV, 92... 

From the preceding data it can be seen that reduction studies with NaBH4 have not been as extensive as those with Li AIH4. Reduction at the 4-position of the 5a-H series should give a predominance of the -epimer. Reduction of a 2-keto-3j -acetoxy compound gives 84% of the 2, 3)5-diol. ° In the 5J -H series reduction of 7-ketocholanic acid gives a 75% yield of 7a-hydroxy-cholanic acid with only traces of the 7 -ol, but 7-ketocholesterol gives a mixture of the 7a- and 7j8-epimers. ... 

Metal-alcohol reductions have also been used in the stereoselective reduction of 3a-hydroxy-7-keto-cholanic acid (26) to the commercially important equatorial 7 3-ol (27). These reductions have been carried out with several alkali metals in secondary and tertiary alcohols, where reduction with K in tertiary alcohols is more stereoselective than Na-isopropyl alcohol. These reductions afford the equatorial alcohol as the major product in good yield, in contrast to sodium borohydride reduction, which provides the axial alcohol (28) almost exclusively. 

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),... 

Methyl 12-keto-3a,7a-diacetoxy-5jS-cholanate (XXVII, 20 g) is refluxed in methanol (100 ml) with KOH (6 g/200 ml water) for 45 min till a clear solution is obtained. After the methanol is partially removed by evaporation, the solution is cooled, diluted with water (200 ml) and acidified with acetic acid. The product is 3a-hydroxy-7a-acetoxy-12-keto-5/3-cholanic acid [XXVIII, Wieland and Kapital (52)] m.p. 238-242°C yield, 87%. 

The fecal bile acids are a complex mixture due to the action of the intestinal flora. Among the fecal bile acids which have been identifled are cholic, deoxycholic, chenodeoxycholic, hthocholic, 3 -hydroxy-5/S cholanic, 3 keto-5/S-cholanic acid, 3 a and 3/S-hydroxy-12-keto-5j3 cholanic and 3j8, 12a-dihydroxy-5/5-cholanic acid. 

The steroid nucleus of bile acids can also be modified by intestinal organisms, the reaction generally requiring a 3-keto substituted bile acid as substrate (Figure 2). Under strictly anaerobic conditions some Clostridia can convert 3-oxo-cholanic acid to 3-oxo-4-cholanic acid, 3-oxo-l-cholanic acid or 3-oxo-l, 4-choladienic acid and 3-oxo-7a-hydroxy-choladienic acid to 3-oxo-4, 6-cholanic acid. Although this reaction proceeds readily in vitro unsaturated substrates have yet to be reliably identified in feces. 

Inversion of 3 -hydroxy steroid. Reduction of the dihydroxy keto cholanate 1 with Raney nickel (no. 28) results in partial epimerization of the axial 3 -hydroxy group (but not the axial 7a-group). This inversion step must be fairly slow because it is not observed when reduction of a 12-ketocholanic acid group is effected within 4 hours. This reaction is the mildest method known for inversion of an axial C,-slcroidal alcohol. ... 

Methyl 3a-Acetoxy-6a-bromo-7a-hydroxy-5 -cholanate (XIa, Fig. 9) Methyl 3n -acetoxy-6a-bromo-7-keto-5/3-cholanate (XXXll) (2.4 g) is dissolved in methanol (200 ml) and the solution is chilled in an ice bath. Sodium borohydride (3 g) is added in small portions. The mixture is kept at ice-bath temperature for 15 min and allowed to remain at room temperature for 45 min, then acidified with acetic acid and evaporated at room temperature to a small volume. The crystalline product, methyl 3a-acetoxy-6a-bromo-7a-hydroxy-5,5-cholanate (XIa) is recrystallized from methanol m.p. 149-152°C yield, 85%. 

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