Azaberbine, synthesis

As in the azaberbine synthesis described in Section IV,C, Ninomiya el al. (68) prepared the spirodihydropyridine 206 by acylation of harmalane with an excessive amount of isonicotinoyl chloride and then synthesized nauclefine (29) by photorearrangement of the corresponding N- nor derivative 207 (Scheme 81). 

Based on the facile thermal cyclization of the nitro-substituted enamides, Naito and Ninomiya (6 7) have further developed thermal cyclization for the synthesis of azaberbines under acylating conditions. 

The cyclization of l-methylene-2-nicotinoylisoquinolines 27 under three different conditions, photochemical, thermal, and acylating conditions, are compared (73). Starting from the above enamide (27), Ninomiya et al. (73) synthesized 10-azaberbine as the major product by simple heating at 195-200°C, whereas 12-azaberbine was the major product under acylating condition as shown in Table II. Further, total synthesis of alamarine (33), the only alkaloid having an azaberbine structure, was synthesized via the route involving enamide cyclization under both thermal and photochemical conditions (73) as shown in Scheme 71. 

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See also in sourсe #XX -- [ , , ]

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