STRUCTURAL PARALLELS BETWEEN THE CARDIOTONIC STEROIDS AND THE ERYTHROPHLEUM ALKALOIDS .2. SYNTHESIS AND NA+,K+-ATPASE INHIBITORY ACTIVITY OF NOVEL ERYTHROPHLEUM ALKALOID ANALOGS

Erythrophleum alkaloid analogues, which differ in the ester side-chain configuration, in the nature of the 14-axial substituent (H, Me, Et) and in their absolute configuration, have been prepared. A pronounced trend towards increased Na+,K+-ATPase inhibitory activity occurs through the H, Me and Et series, with the E side-chain configuration more active than the Z. This trend is largely confined to the analogues with an absolute configuration matching that of the natural alkaloids. A structural parallel between the 14-axial alkyl substituent of the alkaloids and the D-ring of the cardiotonic steroids is proposed.