15 The Synthesis of Rhoeadine and Alpinigenine
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Rhoeadine (I), which occurs in a variety of plants of the genus Papaver of the Papaveraceae, is an alkaloid of the group characterized by its 3-benzazepine structure. In connection with our synthtic studies of ochotensine and related alkaloids, we have worked out a route to rhoeadine starting from the intermediate (VII) for the synthesis of ochotensine and applying a Wagner-Meerwein rearrangement which resulted in enlargement of the isiquinoline ring. The spiro-isoquinoline (VII) was treated with ethyl chloroformate and triethylamine to give the urethane (XX). This was methylenated with methylene iodide and potassium carbonate in dimethyl sulphoxide to furnish the dimethylene-dioxy-spiro-isoquinoline (XXI). Treatment of this with lithium aluminium hydride gave the N-methylamino-alcohol (XXII). The alcohol (XXII) was treated with methane sulphonyl chloride and triethylamine in dry tetrahydrofuran to give a mixture of unsaturated amines (XXII) and (XXIV). Oxidation of the allylamine (XXIII) with osmium tetroxide gave the diol (XXV). Treatment of (XXV) with sodium metaperiodate followed by sodium borohydride, gave (±)-rhoeagenine diol (V), m.p. 142-143°whose i.r. (CHCl_3), Mass and n.m.r. spectra were superimposable upon those of rhoeagenine diol from natural sources. The same sequence of reactions starting from dimethoxy-spiro-isoquinoline (XXIX) gave the α-glycol (XXXIII) which was subjected to oxidation with periodate followed by reduction with lithium perhydro-9b-boraphenalylhydride to yield alpinigenine diol (XXXV). The diol (XXXV) was converted to alpinigenine (III) by oxidatione with manganese dioxide.
