Abstract
A synthesis of rac-dihydrorotundine (I) was described. Methylsuccinic anhydride was condensed with ethyl 3, 4-dimethoxyphenethylaminoacetate to yield a single methyl-succinamic acid (XI), having the methyl substituent β to the amido group. This was esterified, cyclized, and reduced, and thus the tetrahydroisoquinoline base (XIII) was obtained. Dieckmann cyclization of the latter by means of sodium hydride in boiling toluene gave a fair yield of the keto-ester (XV), but its ketonic fission proceeded with difficulty and thus the ketone (XVI) was produced only in a low yield. When dimethyl ketal (XVII) of (XVI) was submitted to distillation in vacuo a loss of one molecule of methanol took place and rac-dihydrorotundine (I) was collected as a viscous distillate, which was characterized as its crystalline methiodide. rac-Dihydro-norrotundine (X) was also prepared as a model substance and its behavior towards catalytic hydrogenation was studied.
