STUDIES ON THE HEMORRHAGIC SWEET CLOVER DISEASE

Abstract

Shortly after it was established that 3,3'-methylenebis(li-hydroxycoumarin) is the causative agent of the hemorrhagic sweet clover disease of cattle (April, 1940), it was found that the hypoprothrombinemia that characterizes this disease could also be induced by analogous compounds (l-3).In a preliminary announcement made in February, 1942 ((3) p. 953), we outlined the scope of e&eriments under way designed to show the relationship of structure in the 4-hydroxycoumarin group to hypoprothrombinemia-inducing (anticoagulant)l capacity.In the interim work by Jansen and Jensen (4), Lehmann (5), and Fantl (6) has appeared which reports on the activity of twelve of the compounds included in this study.Although the methods of assay and of expressing the results used by them differ from ours, the results are qualitatively in agreement.Practically all of the bis-4-hydroxycoumarins and their derivatives, as well as most of the 4-hydroxycoumarin compounds used in this study, were synthesized by methods described in a recent series of papers (7-12).