Synthesis of 1‐(4‐substituted)benzyl‐6‐hydroxyisoquinolines with potential activity on NA+,K+‐atpase

Abstract
The synthesis of 1‐(4‐substituted)benzyl‐6‐hydroxyisoquinolines, to be evaluated in the displacement of the specific 3H‐ouabain binding to Na+,K+‐ATPase, is described. The key step involved a cyclization to the isoquinoline ring under Pictet‐Gams conditions which was best performed with the 6‐hydroxy group protected as the benzyl ether. When an unsaturated ester group was present in position 4 of the 1‐benzyl group, this was best introduced before the cyclization step, since the IIeck reaction on 1‐(4‐bromobenzyl)‐6‐hydroxyisoquinoline (8) with acrylic acid derivatives was not successful in all cases.