An Improvement of the Haworth-Pinder Synthesis

A facile route to the methylenedioxy analog 17 of meconine-a-carboxylic acid (18) has been developed and is outlined below.  

The acid 17 was converted to its acid chloride using oxalyl chloride, and further reaction with A-methylhomopiperonylamine provided the amide 19. Bischler-Napieralski cyclization led to the key dehydrophthalideisoquinoline 20, and catalytic hydrogenation supplied the desired adlumidine and bicucul-line.  

7-dimethoxy analogs of adlumidine and bicuculline, namely ad-lumine and corlumine, were prepared by a parallel route.  

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