Mechanismus der basenkatalysierten reaktion von Cardenoliden—I: Abhängigkeit vom Lösungsmittel

Abstract

The mechanism of base-catalysed isomerization of cardenolides, using mainly 17α-digitoxigenin ( 1) and digitoxigenin ( 10) as test compounds, has been studied by means of kinetic analyses. The solvent used is shown to determine decisively reaction course and speed of isomerization. In aqueous potassium hydroxide solution, the attack of the OH ion primarily effects the hydrolysis of the butenolide ring to furnish the α,β-unsaturated γ-hydroxycarbonic acids 2 or 11. In these compounds the double bond is shifted very slowly to β,γ-position, yielding by rearrangement of the aldenols 7 or 12 the γ-aldehyde carbonic acids 3 or 13 as isomerization products, which, on neutralization, are in equilibrium with the cyclic semiacylate 4 or the cyclic semiacetal 16. In absolute methanolic potassium hydroxide solution, the attack of the more basic methoxylate ion effects the formation of the furyl anions 8 or 14. This is shown to be the rate-limiting step of isomerization, accelerated by additional OH groups in 12β-, 16α- or 16β- position of 10. 8 adds methanol to yield methoxy lactone 5. However, 14 by an intramolecular addition of the 14β-OH group to the furyl ring forms 14,21-epoxide 15. In aqueous methanolic potassium hydroxide solution, both initial hydrolysis of the cardenolides 1 or 10 and hydrolysis of the isomerization products 5 or 15 competitively take place, yielding the γ-aldehyde carbonic acids 3 or 13.