SYNTHESIS AND BIOLOGICAL EVALUATION OF 14-BETA-METHOXY DIGITALIS DERIVATIVES

The synthesis and biological evaluation of 14 beta-methoxy derivatives of digitoxigenin and of other digitalis-like compounds are reported. These compounds have a 14 beta-oxygen, which can be a hydrogen bonding acceptor, as is the case of 14 beta,15 beta-epoxide derivatives, but not a hydrogen bonding donor as is the case of 14 beta-hydroxy derivat ives. All the new 14 beta-methoxy derivatives show a considerable redu ced binding affinity on Na+,K+-ATPase when compared with the 14 beta-h ydroxy analogues and also with the 14 beta,15 beta-epoxy derivatives. These results could mean that the digitalis receptor does not permit t he presence of a bulky substituent in the 14 beta region, even of rela tively small volume like the methyl group.