Synthetic investigations on the degradation product of bile acids

Abstract

She thesis consists of two parts, Part I After introducing the importance of Wieland’s tricarboxylic acid (obtained by the degradation of bile acids), in the elucidation of their structures, the synthesis of the gross structure of this acid has been described in this part. In section 2 of this part, experiments on the hydrolysis of ethyl 4?(1?carbethoxy?5?oxocyclopentyl)?2?pentenoate and ethyl 4?(1?carbethoxy?5?oxocyclopentyl)?valerate to obtain the normal hydrolysis products are described. It may be mentioned that ethyl 4?(1?carbethoxy?5?oxocyclopentyl)?2?pentenoate serves as a model compound in the projected synthesis of Wieland’s tricarboxylic acid. In section 2 of this part deals with the synthesis of the gross structure of Wieland’s tricarboxylic acid. Methyl 2?methylcyclopentane? 1,2,3,4?tetracarboxylate, prepared from methyl 2?methyl?5?oxocyclo? pentane?1,2,3?tricarboxylate, was condensed with ethyl 4?bromo?2? pentenoate. Hydrolysis and decarboxylation of the tri?acid after esterification was effected by the modified Wolff?Kishner reduction and hydrogenation to yield the tri?methyl ester of Wieland’s acid. Cholic acid is expected to yield the lactone form of 2?methyl? cyclopentane?1,2,3?tricarboxylic acid on degradation. The possibility of using this evidence in providing an additional proof for the ??orientation of the side?chain of bile acids and sterols is discussed. It is highly desirable that the different lactones of 2?methylcyclopentane?1,2,3?tricarboxylic acid should be synthesised for use as reference compounds. With this in view, the syntheses of two isomers of this acid are described in this part. Ethyl 3?acetyl? 2?methylcyclopentane?1,2,3?tricarboxylate, prepared from ethyl 2?methylcyclopentane?2,3?dicarboxylate, on catalytic hydrogenation and hydrolysis yielded two acids. One of these was also prepared by the oxidation of 7?methyl?bicycloheptane?1?one?2,3?dicarboxylic acid obtained from ethyl 2?methylcyclopentane?2,3?dicarboxylate. It has thus been possible to assign configurations for the two acids. Attempts made towards the synthesis of 2?methylcyclopentane?1,2,3? tricarboxylic acid from 2?methyl?5?acetoxyacetylcyclopentanone?carboxylic acid and from the lactone of 2?methyl?1?hydroxyethyl?3? carboxycyclopentanone have also been recorded.