Chemical Transformation of Protoberberines. VIII. A Novel Synthesis of (±)-Fumaricine and a Formal Synthesis of (±)-Alpinigenine

Berberine (1) was transformed stereoselectively into either the trans- or cis-hydroxyspiro-benzylisoquinoline (9 or 10) via the 8, 14-cycloberbine (3). This method was applied to a first transformation of the protoberberine (22) into a spirobenzylisoquinoline alkaloid, (±)-fumaricine (6). Irradiation of the phenolbetaine (24) derived from the protoberberine (22) afforded its valence isomer, the 8, 14-cycloberbine (25), treatment of which with ethyl chloroformate gave the spirobenzylisoquinoline (26). Hydrogenolysis of 26 followed by lithium aluminum hydride reduction provided (±)-fumaricine (6). Similarly, palmatine (31) was converted via the 8, 14-cycloberbine (34) and the keto-urethane (35) into the trans-hydroxyspirobenzylisoquinoline (7), the key intermediate in a synthesis of (±)-alpinigenine (8), a rhoeadine alkaloid.