603. Alkaloid biosynthesis. Part VIII. Use of optically active precursors for investigation on the biosynthesis of morphine alkaloids

Abstract

The quadruply-labelled (+)-, and (-)-forms of reticuline have been synthesised, and their incorporations into thebaine, codeine, and morphine in the opium poppy have been studied. The results prove (-)-reticuline (V; R=H) to be the direct precursor of these alkaloids and that it is in oxidation-reduction equilibrium with 1,2-dehydroreticuline and with (+)-reticuline. Labelled 1,2-dehydroreticuline (IV; R=H) has been synthesised and incorporated in high yield into morphine. It is suggested that 1,2-dehydroreticuline stands at a branching point on the biosynthetic pathway. Incorporation experiments with labelled (+)- and (-)-norlaudanosolines (I; R=H) and (II; R=H) have given unexpected results, which are discussed. The present work illustrates how detailed information can be gained by the use of resolved, multiply labelled precursors. The three diphenolic structural isomers of reticuline have been synthesised in labelled form, and are shown not to act as precursors of morphine.