A structural characteristic of the cardiac poisons.

Abstract

Former investigations 1 have shown that strophanthidin is unsaturated and that the double bond is situated within the lactone ring, between the β and γ carbon atoms, so that strophanthidin may be designated as a Δβ-γ crotonic lactone. Characteristic of strophanthidin and all of its derivatives which still possess this unsaturated lactone ring is their reducing action on Tollens'solution. On the other hand, dihydrostrophanthidin and its derivatives, or isostrophanthidin, in which the double has been either hydrogenated or shifted to another position, no longer react with Tollens'reagent, or at least far more gradually than in the case of strophanthidin and its derivatives. The behavior towards Tollens'solution is thus a very characteristic test for the unsaturated lactone group of these compounds.

Results of a similar and most striking character have been recently obtained by the use of the sodium nitroprusside test. Strophanthidin and all of its derivatives which still possess the unsaturated lactone ring give positive reactions with this reagent. But as soon as this group is hydrogenated or lost by saponification to the acid, the resulting substances no longer give this reaction.

In the course of structural studies with ouabain this substance has been found to be unsaturated since it absorbed two mols. of hydrogen with the formation of a tetrahydro derivative. It contains also a lactone group. Because of our experience with strophanthidin, it was of interest to establish the fact whether the lactone group and an unsaturated linking were associated. Ouabain was found to reduce Tollens' reagent and gave also 3 positive nitroprusside test. On the other hand, tetrahydroouabain failed to react with these reagents. After saponification ouabain likewise no longer reacted with sodium nitroprusside. There appears, therefore, to be a very strong indication that ouabain, like strophanthidin, possesses an unsaturated lactone group.