N-alkylated galanthamine derivatives:: Potent acetylcholinesterase inhibitors from Leucojum aestivum

N-(14-Methylallyl) norgalanthamine, a new natural compound, together with five known alkaloids: N-allylnorgalanthamine, galanthamine, epinorgalanthamine, narwedine, and lycorine were isolated from mother liquors (waste material) obtained after industrial production of galanthamine hydrobromide from Leucojum aestivum leaves. The structures of N-allylnorgalanthamine and N-(14-methylallyl) norgalanthamine were completely determined by H-1 and C-13 NMR spectroscopy and two-dimensional experiments. N-allylnorgalanthamine (IC50 = 0.18 mu M) and N-(14-methylallyl) norgalanthamine (IC50 = 0.16 mu M) inhibit AChE considerably more than the approved drug galanthamine (IC50 = 1.82 mu M). (C) 2008 Elsevier Ltd. All rights reserved.