PREPARATION AND CHARACTERIZATION OF 3-MONOHYDROXYLATED BILE-ACIDS OF DIFFERENT SIDE-CHAIN LENGTH AND CONFIGURATION AT C-3 - NOVEL-APPROACH TO THE SYNTHESIS OF 24-NORLITHOCHOLIC ACID

• Published in: Journal of lipid research Vol. 27; no. 1; pp. 102 - 113
• Main Authors: RADOMINSKAPYREK, A, HUYNH, T, LESTER, R, STPYREK, J
• Format: Journal Article
• Language: English
• Published: AMSTERDAM Elsevier 01.01.1986
• Subjects: Bile Acids and Salts - chemical synthesis; Biochemistry & Molecular Biology; Carbon Radioisotopes; Chromatography, Gas; Chromatography, Thin Layer; Gas Chromatography-Mass Spectrometry; Indicators and Reagents; Isotope Labeling - methods; Life Sciences & Biomedicine; Lithocholic Acid - analogs & derivatives; Lithocholic Acid - chemical synthesis; Science & Technology; Structure-Activity Relationship; Tritium
• ISSN: 0022-2275; 1539-7262
• DOI: 10.1016/S0022-2275(20)38859-3

A series of 3-monohydroxylated bile acids, in unlabeled and radioactive form, of varying side chain length and configuration at C-3 has been synthesized and rigorously characterized. They include: 3.alpha.- and 3.beta.-hydroxy-5.beta.-androstane-17.beta.-carboxylic acids (C20); 3.alpha.- and 3.beta.-hydroxy-5.beta.-pregnan-21-oic acids (C21); 3.alpha.- and 3.beta.-hydroxy-23,24-bisnor-5.beta.-cholan-22-oic acids (C22); 3.alpha.- and 3.beta.-hydroxy-24-nor-5.beta.-cholan-23-oic acids (C23, norlithocholic and isonorlithocholic acids); and 3.beta.-hydroxy-5.beta.-cholan-24-oic acid (C24, isolithocholic acid). A novel approach to the degradation of lithocholic acid acetate to 24-norlithocholic acid is described. This degradation involves the photochemical modification of a Hunsdiecker reaction and Kornblum oxidation of the intermediate 23-bromide. The availability of these compounds makes it possible to study the metabolism and biological effects of short chain bile acids.