STUDIES ON BILIARY EXCRETION IN THE RABBIT. II. THE RELATIONSHIP BETWEEN THE CHEMICAL STRUCTURE OF CERTAIN NATURAL OR SYNTHETIC PENTACYCLIC TRITERPENES AND THEIR ICTEROGENIC ACTIVITY. PART 2: THE SUBSTITUENTS ON CARBON ATOMS 17, 19, 20 AND 22.

Abstract

Previously reported work in this series (Brown, Rimington & Sawyer 1963) produced evidence that icterogenic activity (i.a.) of the pentacyclic triterpene acids is based upon the presence of a β-equatorially orientated hydroxyl group at C (3), or a hydroxyl at C (24), and a 22β-angeloyloxy side chain in the molecule of the particular active compound. The second part of this work, dealing with certain structural variations in triterpenes of the oleanane, 24-noroleanane (hedragane) and ursane series, is reported in this paper. These variations involve i.a. esterification of the C (28) carboxyl, saturation of the 22β-angeloyl side chain or replacement of this by simple saturated aliphatic acids. Assays are recorded of a further thirteen of these compounds for icterogenic activity using the modified technique described in the second paper of this series (Brown et al . 1963). It has been concluded from this work that the icterogenicity of 3β- or 24β-hydroxy triterpene acids is undoubtedly associated with the 22β-angeloyloxy side chain. Removal of the esterifying group at C (22) or its replacement by a simple saturated fatty acid residue is followed by complete loss of activity. Esterification of the C (28) carboxyl produces a considerable decrease in icterogenic potency due, probably, to a decrease in solubility of the compound.