Ursodesoxycholic acid

Reduction of ketones. Reduction of ketones with metals in an alcohol is one of the earliest methods for effecting reduction of ketones, and is still useful since it can proceed with stereoselectivity opposite to that obtained with metal hydrides.1 An example is the reduction of the 3a-hydroxy-7-ketocholanic acid 1 to the diols 2 and 3. The former, ursodesoxycholic acid, a rare bile acid found in bear bile, is used in medicine for dissolution of gallstones. The stereochemistry is strongly dependent on the nature of the reducing agent (equation I).2 Sodium dithionite and sodium borohydride reductions result mainly in the 7a-alcohol, whereas reductions with sodium or potassium in an alcohol favor reduction to the 7p-alcohol. More recently3 reduction of 1 to 2 and 3 in the ratio 96 4 has been achieved with K, Rb, and Cs in f-amyl alcohol. Almost the same stereoselectivity can be obtained by addition of potassium, rubidium, or cesium salts to reductions of sodium in t-amyl alcohol. This cation effect has not been observed previously. 

Another problem relates to the use of ursodesoxycholic acid to treat cholestatic diseases, such as primary biliary cirrhosis. The mechanism of its action remains poorly understood. However, it is significant that tauroursodesoxycholic acid,... 

Ketosteroids derived from cheno- and ursodesoxycholic acids have also been prepared (Scheme 13.21) [24]. Let us note that the chemoselectivity of organoman-ganese halides allows protection of the hydroxyl groups as acetates but also as formates in spite of the reactivity of these esters. Moreover, the reaction was performed in the presence of various cosolvents such as dichloromethane or ethyl acetate that are not commonly used in organometallic chemistry. These solvents are necessary to dissolve the starting carboxylic acid chlorides that are practically insoluble in ether. 

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