Three methods were developed for the transformation of naturally occurring 9, 10-oxygenated protoberberines into non-naturally occurring 11, 12-oxygenated protoberberines through ring D inversion via spirobenzylisoquinolines. Berberine (14) was converted to the spirobenzylisoquinoline (18) through regioselective cleavage of the 8, 14-cycloberbine (17). Alkaline hydrolysis of the oxazolidinone (20) derived from 18 efficiently afforded the 11, 12-oxygenated protoberberine (23), which was also obtained from 8-methoxyberberinephenolbetaine (24) through treatment of the keto-hydroxy-spirobenzylisoquinoline (25) with alkali. The spirobenzylisoquinoline (26) derived from the 8, 14-cycloberbine (16) was subjected to hydrogenolysis and subsequent hydrolysis to give the amino-ketone (28), photolysis of which furnished the 11, 12-oxygenated protoberberine (29).