Synthetic investigations in the field of the curare alkaloids

Abstract

It has been shown that the compounds obtained previously corresponding in comparison to the β-[4′-(5″-carboxymethyl-2″-hydroxyphenoxy)3′-methoxyphenyl]ethylamide of 4-benzyloxyphenylacetic acid have practically the same spectra and on further condensation with 3-bromo-4-hydroxy-5-methoxyphenylethylamine give an equilibrium mixture of diamide compounds. The difference in the physicochemical properties of the diphenyl esters and the diamides can be explained by steric differences. On cyclization, the diamides are converted into bis-dihydroisoquinoline compounds of the same elementary composition. The hydrochloride of 7-[2′-acetoxy-5′-(7″-acetoxy-8″-bromo-6″methoxy-3″, 4″dihydroisoquinol-1″-ylmethyl)phenoxyl)-1-(4″-benzyloxybenzyl)-6-methoxy-3,4-dihydroisoquinoline, with mp 180−181° C, after saponification, intramolecular Ullman condensation, reduction, and stepwise methylation, was converted into isomeric tubocurarin iodides with mp 189–190.5° C, 164–166.5° C, 257–260.5° C, and 210–212° C, which were separated on the basis of their different solubilities in organic solvents and water.