Smiles rearrangements in a series of berberine analogues containing a secondary acetamide fragment

Smiles rearrangements occurring in the derivatives of the isoquinoline alkaloid, berberine, containing an oxyacetic acid fragment at C-9 are described. Methyl-2-(9-demethoxyberberinebromide-9-yl)oxyacetate reacts with an excess of propylamine followed by sequential aminolysis and Smiles rearrangement leading to 2-hydroxy-N-(berbero-9-yl)-N-propylacetamide in 80% yield. Reactions of berberrubine with secondary amides of bromoacetic acid via Smiles rearrangement give N-substituted 2-hydroxy-N-(berbero-9-yl)acetamides (yields 20–36%). In some cases, the intermediate secondary amides were isolated.