BIOSYNTHESIS OF THE AMARYLLIDACEAE ALKALOID GALANTHAMINE

Application of radioactively as well as C-13-labelled 4'-O-methylnorbe lladine to organs of field grown Leucojum aestivum plants resulted in an optimal incorporation into galanthamine (27%), and N-demethylgalant hamine (31%), respectively. In contrast to expectations based on resul ts from the literature, the N-methylated 4'-O-methylnorbelladine was m etabolized into a minor extent in L. aestivum and was incorporated int o galanthamine as well as into N-demethylgalanthamine to only about 1/ 3 of the rate of 4'-O-methylnorbelladine. Furthermore, it was shown th at N-demethylgalanthamine is N-methylated to galanthamine in the final step of biosynthesis. A revised scheme for the biosynthesis of galant hamine is presented involving the phenol oxidative coupling of 4'-O-me thylnorbelladine to a postulated dienone which undergoes spontaneous c losure of the ether bridge to yield N-demethylnarwedine which upon ste reoselective reduction and N-methylation yields the cholineesterase in hibitor galanthamine. (C) 1998 Elsevier Science Ltd. All right reserve d.