Biosynthesis. Part XXII. The origin of chelidonine and of other alkaloids derived from the tetrahydroprotoberberine skeleton

Abstract

The major benzophenanthridine alkaloid chelidonine (14) is shown to be biosynthesised in Chelidonium majus plants from (S)-reticuline (2)via(S)-scoulerine (4) and (S)-stylopine (7), and evidence consistent with a dihydroisoquinoline intermediate [e.g.(11)] is presented. Similar though less extensive evidence is provided for the same pathway to the aromatic systems, e.g. sanguinarine (13). Protopine (10) is shown to be formed in vivo from (S)-scoulerine (4) and (S)-stylopine (7). Studies have been made of the late biosynthetic stages beyond scoulerine and stylopine and the role of isocorypalmine (6) and canadine (21) in the biosynthesis of narcotine (3) and berberine in the opium poppy has been investigated.The results from 3H labelling at four different sites in the various precursors limit the possible mechanisms which can be considered for the enzymic transformations revealed by this research. Unexpected increases in 3H : 14C ratio (up to 20%) are discussed.Extensive degradations of the labelled alkaloids have been carried out to establish quantitatively the level of radioactivity at the multiple sites. The syntheses for the many specifically labelled substances used in this study are described.