Preparation of a-Muricholic Acid

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%. 

This zl derivative (XX) is obtained by refluxing the above bromohydrin (XIa, 1 g) in acetic acid (20 ml) with zinc dust (1 g) which is added in small portions through 1.5 hr. The excess of zinc is removed by filtration, and the product (XX) is obtained from the filtrate in platelets by the addition of water and is recrystallized from methanol m.p. 123-125 C yield, 66%. 

The above J derivative (700 mg) is added to an ether solution containing excess of monoperphthalic acid prepared according to Bohmn (54). The mixture is allowed to remain at room temperature for 3 days, then the excess of reagent and phthalic acid are removed by extraction with 5% sodium carbonate. The ether solution is evaporated to dryness and a crystalline product (XVI) is obtained which is recrystallized from benzene and hexane m.p. 172-174°C yield, 85%. 

The a-epoxide (XVI, 120 mg) is refluxed in acetic acid (20 ml) for 3.5 hr. The solution is diluted with water and extracted with ether. The product (methyl 3a,6 -diacetoxy-7a-hydroxy-5p-cholanate) is purified on a silica gel column and is eluted by 20 % ether in benzene. After hydrolysis by methanolic KOH (2%, 20 ml) at room temperature overnight, a-muricholic acid is obtained after acidification and extraction with ether. It forms crystals from an acetic acid solution after the addition of water. These crystals contain 

A solution of bromine (384 mg) in acetic acid (1.2 ml) is added slowly with stirring to a suspension of finely pulverized silver acetate (410 mg) in acetic acid (130 ml). The color of the bromine disappears immediately with the precipitation of silver bromide. The supernatant pale yellow solution was obtained by decantation, and to the solution (20 ml), methyl 3a-acetoxy-J -5/3-cholenate (XX, 550 mg) is added. After 30 min at room temperature, the mixture is diluted with water and extracted with ether. The residue from the ether extract (XVIIIa) is crystallized from acetone and water m.p. 153-154°C yield, 88%. 

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