A synthesis of thebaine and northebaine has been developed from codeinone dimethyl ketal and norcodeinone dimethyl ketal. Attempts to prepare the ketal by the action of trimethyl orthoformate on codeinone led only to 8-methoxyd6-dihydrothebaine. However, addition of methyl hypobromite to A6-dihydrothebaine gave 7-bromodihydrocodeinone dimethyl ketal, and dehydrobromination of the latter gave codeinone dimethyl ketal. Acid-catalyzed elimination of methanol resulted in thebaine, but this reaction was erratic and codeinone was an accompanying by-product. Good yields of thebaine from codeinone dimethyl ketal were achieved by using phosphorus oxychloride. Northebaine was obtained in the same way from norcodeinone dimethyl ketal, the latter being prepared by the action of cyanogen bromide on codeinone dimethyl ketal followed by lithium aluminum hydride hydrogenolysis of the N-cyano derivative to the nor compound. A method for separating ketonic, a,/$ unsaturated ketonic, and nonketonic alkaloidal material based on formation of the bisulfite addition compounds is described.hebaine is prodigious among the morphine alka-
The natural occurrence of the diphenolic benzyltetrahydroisoquinoline alkaloid, reticuline, was established in fresh budding plants and seedlings of Papaver somniferum L. Exposure of such plants to I4CO2 for 1-3 hr was followed by determination of the radioactivity incorporated: (a) into reticuline and thebaine (I) and (b) into the N-and 0-methyl groups for both alkaloids. These results confirm those from feeding experiments, and establish beyond question the role of reticuline as the true biosynthetic benzyltetrahydroisoquinoline precursor of the hydrophenanthrene alkaloids. The high rate of incorporation of radioactivity into the total alkaloids as well as into thebaine and reticuline both in seedlings and in mature
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