HINDERED DIPHENYL ETHERS RELATED TO THE BISBENZYLISOQUINOLINE ALKALOIDS

Sixteen steps from vanillin led to syntheses of (a) dimethyl 3-(4′-carbomethoxyphenoxy)-4,5-dimethoxyphthalate (Ic), a known degradation product of isochondrodendrine, and (b) the more hindered dimethyl 3-(4′-carbomethoxy-2′-methoxyphenoxy)-4,5-dimethoxyphthalate (Ia), which has not been derived from any alkaloid, though the usual concepts of biosynthesis do not rule out the occurrence of alkaloids which could lead to it. Diphenyl ethers related to Ia would be expected to show the effects of steric hindrance, but even with the most hindered member of the group, 7-(4′-carboxy-2′-iodophenoxy)metameconine (VAe), no evidence for an appreciable half-life of rotational isomers could be obtained. Attempts to make diphenyl ethers through the condensation of phenols with dicyclohexylcarbodiimide led to other products.