The use of the Schmidt reaction in the elaboration of selected alkaloids containing a seven-membered ring
In the past the heterocyclic rings of rnost alkaloirls have been thought to be fiveor six-mernbererl, but rnore recently several exarnples of bases cont:lining a seven-rnernbererl heterocyclic ring have been recognized in nature, e.g. in the inrlole alkaloirl field mavacurine-fluorocurine1 anrl the iboga bases2, anrl arnong the Amaryllidaceae anrl the Stemonaceae alkaloids cornpounrls. The structures of these alkaloirls have been rleriverl rnainly frorn c.egrad.ative sturlies anrl by the application of physico-chernical rnethorls. I t therefore seernerl to us rlesirable to establish these novel structures rnore conclusively by synthetic rnethorls. For this purpose we have exarninerl several synthetic approaches anrl found that the Schrnidt reaction3 is very useful for elaborating a nitrogen-containing seven-rnernbered ring. This paper outlines rnethods by which we have succeeded in synthesizing seven-Jnembered ring heterocyclic cornpounds closely related to selected alkaloids isolated frorn the plants of the Amaryllidaceae and the Stemonacear: growing in the Far East, and ernphasizes the value of the Schrnirlt reaction. In the course of our sturlies on the Amaryllidaceae alkaloirls, it was shown that galantharnirre and its congeners such as lycorarnine, epigalanthamine, and narwerline, represent the first alkaloirls known to contain a sevenrnernhererl nitrogenaus ring4. This conclusion was baserl on the following evirlence. Following Proskurnina and Yakovleva's5 observation, galantharnirre was treated with hyrlrobrornic acid to give apogalantharnine (li), the structure üf which was establisherl by rlegrarlation and synthesis6. From this structure for apogalanthamine, either the forrnula (I) or (III) harl to be assignerl to galantharnirre rlepenrling on whether an acirl-catalysed dienone-phenol rearrangernent had occurred during the above treatrnent.