Natural occurrence and chemical synthesis of bile alcohols, higher bile acids, and short side chain bile acids.

Abstract

Both bile acids and bile alcohols, a subclass of steroids, are made from cholesterol as its major end metabolites by the liver of vertebrates. Their conjugates are the major constituents of the bile and possess a special function as an aid to intestinal lipid digestion and absorption. The most common naturally occurring bile acids in mammals, birds, most snakes, and various teleostean fishes, are cholic acid, chenodeoxycholic acid, deoxycholic acid, and lithocholic acid. In addition to these 3a-, 7a-, or 12a-hydroxy derivatives of 5~-cholan-24-oic acid, a number of 5~-cholan-24-oic acids carrying a hydroxyl group at C-1, C-2, C-4, C-6, C-16, C-22, or C-23 position, a ~-oriented hydroxyl group, or a keto group have been found in the bile, serum, urine and feces of these vertebrates. 5a-Cholan-24-oic acid derivatives occur as a high proportion of the bile acids in some lizards and in lesser amounts in various vertebrates. Biles of evolutionarily primitive vertebrates such as some lizards, crocodiles, alligators, turtles, tortoises, all amphibians, certain bony fishes, sharks, and rays contain, in place of the C24 bile acid conjugates, other types of bile salts, sulfate esters of bile alcohols and unconjugated or taurine-conjugated bile acids with more than 24 carbon atoms (higher bile acids). Bile alcohols and higher bile acids have the C24 bile acid type of nuclear structure and all or part of the cholesterol type side chain in their carbon skeleton. Although the distribution of bile alcohols and higher bile acids in nature was long considered to be confined to the primitive vertebrates, it is now recognized that these compounds are accummulated in patients with inherited diseases related to abnormal cholesterol metabolism. They are present in trace amounts even in healthy humans. Furthermore, a few 4or 5-cholen-24-oic acid derivatives and a few C22 and C23 bile acids with the shortened side chain have been found in biological fluids of healthy and diseased humans. Several excellent reviews about the naturally occurring bile acids and bile alcohols have appeared61 ' 74, 75, lOl, 105, 183>. It should be mentioned, however, that there is no review covering all the known bile acids and bile alcohols including chemically synthetic derivatives. The present review is a detailed tabulation of bile alcohols, higher bile acids, and short side chain bile acids. Derivatives of 5aand 5~-cholan-24-oic acids and of 4and 5-cholen-24-oic acids are not included in this review. Natural occurrence and chemical synthesis of these C24 bile acids are the subject of our forthcoming review.