CONVERSION OF BERBERINE INTO PHTHALIDEISOQUINOLINES

Ferricyanide oxidation of berberine (1) yields the dimer oxybis (berberine) whose breakdown with methanolic hydrogen chloride gives 8-methoxyberberinephenolbetaine (12). Hydration of 12 in wet ether furnishes enaminol 14 which can be N-methylated to dehydrohydrastine methyl ester (15). NaBH4 reduction of 15 leads to a 1:2 mixture of (±)-a-hydrastine (9) and (±)-d-hydrastine (6), thus achieving the first conversion of 1 to the hydrastines. Whereas NaBH4 reduction of 14-HC1 gives mostly d-norhydrastine (5) together with a little a-norhydrastine (8), similar reduction of. V-n-propyldehydronorhydrastine methyl ester (17) hydroiodide provides only. V-n-propyl-a-norhydrastine (11). Diisobutylaluminum hydride reduction of 5 leads to (±)-epiophiocarpine (22), and the diastereoisomeric (i)-ophiocarpine (23) is formed by NaBH4 reduction of betaine 12. Hydration of 12 in wetTHF generates methyl isoanhydroberberilate (26), while methyl anhydroberberilate (32) is obtained through acetic anhydride treatment of betaine 12 to furnish 13-acetoxyoxoberberine (30), followed by reaction with methanolic KOH. © 1979, American Chemical Society. All rights reserved.