7«-Hydroxycholanic acid

Stereoselective reduction. 12-Ketocholanic acids are reduced by this complex to 12/ - and 12a-hydroxycholanic acids in ratios of 5.0 1.5. 3-Keto- and 7-ketocholanic acids are reduced with some preference to the a-hydroxy acids. 

Inversion of la-hydroxycholanic acids Chenodeoxycholic acid (1, 3a, 7a) has been converted to ursodeoxycholic acid (3, 3a, Iff) by treatment of the 3-cathylate-7-mesylate (2) of 1 with K02-crown ether in DMSO. 

The enzyme 3a-hydroxysteroid dehydrogenase (EC 1.1.1.50), which is isolated from Pseudomonas testosteroni, catalyzes the conversion of all 3a-hydroxycholanic acids to 3-ketochoIanic acids, with the concomitant reduction of NAD to NADH. The NADH formed in the reaction is then determined spectrophotometrically at 340 nm. To ensure complete reaction, hydrazine is usually added to bind the 3-keto products (P2). The optimum conditions for enzymatic assay include a pH of 9.0 to 9.5 and reaction temperature in the range 20 to 40 C (T13). Reaction rates for individual bile acids may not be identical, but the assay is normally carried out as an endpoint determination. Alternatively, the addition of bovine serum albumin appears to overcome the problem of variable aflinity of 3a-hy-droxysteroid dehydrogenase for different bile acids if reaction rates are to be measured (S13). 

Elimination reactions of the 20-hydroxycholanic acid derivative (108) probably illustrate the differing character of the transition state, depending upon the reagent. Thionyl chloride in pyridine gave the 17(20)-enes (109 cis -I- trans, 80% total), as expected from thermodynamic control when a bimolecular elimination has considerable carbonium ion character ( l-like) in the transition state. The 20(22)-enes (110) cis + trans) were major products when phosphoryl... 

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. 

This acid, the 3/3-epimer of lithocholic acid, has been detected as a component of the feces of man and rabbit (32, 62, 73, 74). A compound named isolithocholic acid was isolated from chicken bile in an early study by Hosizima et al. (15). However, the properties of this acid do not coincide with those of 3/3-hydroxycholanic acid. The 3 acid has been prepared from the ketone by hydrogenation under acidic conditions (72). 

This acid was detected by Ali et al. (50) as a trace component of human stool. It has not been detected elsewhere in nature. 7/3-Hydroxycholanic acid may be prepared by reduction of the 7-keto acid with sodium and propanol (76). 

The most important end products in mammalian cholesterol metabolism are the bile acids. The parent C24-acid is cholanic acid with a ring structure identical to that of coprostanol (A/B cis). The bile acids are hydroxylated cholanic acids, all hydroxyl-groups have a-orientation. Consequently, they do not form digi-tonides. The principal acids are cholic acid (3a, 7a, 12a-trihydroxy-cholanic acid), chenodeoxycholic acid (3a, 7a-dihydroxycholanic acid) and deoxy-cholic acid (3a, 12a-dihydroxycholanic acid). Lithocholic acid (3a-hydroxycholanic acid) also occurs in human bile, but only in small amounts. 

Methyl 3-Carbethoxyoxy-7-keto-12a-hydroxycholanate. A solution of 4 g (8.6 mmoles) of crude methyl 3-carbethoxyoxycholate in 50 ml of acetic acid containing 10 g of sodium acetate trihydrate is treated gradually with a solution of 3 g (0.015 mole) of potassium chromate in 8 ml of water with shaking. After 10 hr at 25° the solution is diluted with water and the product collected by filtration to afford 3.9 g (97%) of methyl 3-carbethoxyoxy-7-keto-12a-hy-droxycholanate, mp 150-158°. Crystallization from methanol gives hard, compact needles or rods mp 157-158° 41°. The same substance is... 

C24H40O3 3-hydroxycholan-24-oic acid, (3alpha,5beta) 434-13-9 25.00 0.9629 2 34126 C25H30CIN3 crystal violet 548-62-9 25.00 1.1132 2... 

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