Synthesis and β-Adrenoceptor Activity of the Erythro and Threo Isomers of Substituted α-Hydroxytrimetoquinol

The synthesis and pharmacological activity of erythro and threo isomers of l-(3′,4′,5′-trimethoxy-α-hydroxy-benzyl)-6,7-dihydroxy-l,2,3,4-tetrahydroisoquinoline, 2 and 3, are reported. The structural assignments of 2 and 3 are based upon NMR spectra of the 6,7-dibenzyl precursors, 6 and 10 and of the synthetic derivatives of 13a-and 13β-hydroxy-2,3-(dibenzyloxy)-9,10,11-trimethoxytetrahydroprotoberberine, 8 and 12, respectively. The erythro isomer 2 was a more potent β-adrenoceptor stimulant than the threo isomer 3 in guinea pig atrial, guinea pig tracheal and rat adipocyte preparations. The differential activity of these compounds on lipolysis was favorably correlated to changes in the stimulation of adenylate cyclase activity and cAMP accumulation in rat adipocytes.