A divergent route to 9, 10-oxygenated tetrahydroprotoberberine and 8-oxoprotoberberine alkaloids: synthesis of (±)-isocorypalmine and oxypalmatine.

A new route which is germane to the synthesis of 9,10-oxygenated tetrahydroprotoberberines and 8-oxoprotoberberines is described. The route features the use of a diester (14) generated from reaction of dimethylmalonate with an aryl halide in the presence of n-butyllithium. The amide 17 prepared in subsequent steps is a versatile precursor for the synthesis of tetrahydroprotoberberine and 8-oxoprotoberberine scaffolds using standard high-yielding reactions. In this manner, (±)-isocorypalmine and oxypalmatine have been synthesized in 23% and 22 % yields respectively.