Synthesis of 1-(4-substituted)benzyl-6-hydroxyisoquinolines with potential activity on Na+,K+-ATPase

Article abstract of DOI:10.1002/jhet.5570300622

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 Piclet-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 Heck reaction on 1-(4- bromobenzyl)-6-hydroxyisoquinoline (8) with acrylic acid derivatives was not successful in all cases.