1.N-Alkylated galanthamine derivatives: Potent acetylcholinesterase inhibitors from Leucojum aestivum.
Berkov S1, Codina C, Viladomat F, Bastida J. Bioorg Med Chem Lett. 2008 Apr 1;18(7):2263-6. doi: 10.1016/j.bmcl.2008.03.008. Epub 2008 Mar 7.
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 (1)H and (13)C NMR spectroscopy and two-dimensional experiments. N-allylnorgalanthamine (IC(50)=0.18microM) and N-(14-methylallyl)norgalanthamine (IC(50)=0.16microM) inhibit AChE considerably more than the approved drug galanthamine (IC(50)=1.82microM).
2.Alkaloids of Lycoris guangxiensis1.
Li HY1, Ma GE, Xu Y, Hong SH. Planta Med. 1987 Jun;53(3):259-61.
A new alkaloid, N-allylnorgalanthamine ( 1), was isolated from the bulbs of LYCORIS GUANGXIENSIS Y. Hsu et Q. J. Fan (Amaryllidaceae). Additionally, seven known alkaloids, lycorine, narwedine, galanthamine, lycoramine, crinine, norgalanthamine, and pseudolycorine were also obtained. The structure of 1 was established through the interpretation of spectral data.
3.Antioxidant properties of galantamine hydrobromide.
Traykova M1, Traykov T, Hadjimitova V, Krikorian K, Bojadgieva N. Z Naturforsch C. 2003 May-Jun;58(5-6):361-5.
The antioxidant properties of galantamine hydrobromide ((4alpha,6beta)-4a,5,9,10,11,12-hexahydro-3-methoxy-11-methyl-6H-benzofuro[3a,3,2-ef]benzazepin-6-ol hydrobromide) were studied in vitro, using luminol-dependent chemiluminescence and spectrophotometry. It was found that this compound was a scavenger of reactive oxygen species (ROS). By comparing the antioxidant effects of galantamine ((4alpha,6beta)-4a,5,9,10,11,12-hexahydro-3-methoxy-11-methyl-6H-benzofuro[3a,3,2-ef]benzazepin-6-ol), galantamine hydrobromide, narwedine (4a,5,9,10,11,12-hexahydro-3-methoxy-11-methyl-6H-benzofuro[3a,3,2-ef]benzazepin-6-one), and narwedine hydrobromide it was found that the antioxidant activity depended on the enolic OH group in the molecule. The presence of a quaternary nitrogen in the compound increased the strength of the scavenging effect. It is proposed that the antioxidant properties observed in vitro may contribute to the therapeutical effect of galantamine hydrobromide on patients with brain degeneration.
4.Concise syntheses of (-)-galanthamine and (+/-)-codeine via intramolecular alkylation of a phenol derivative.
Magnus P1, Sane N, Fauber BP, Lynch V. J Am Chem Soc. 2009 Nov 11;131(44):16045-7. doi: 10.1021/ja9085534.
Suzuki coupling of 7 to 8 gave the biphenyl derivative 9. Reaction of 9 with ethyl vinyl ether/bromine/base gave 10, which on treatment with CsF/DMF at 130 degrees C resulted in the cross-conjugated 2,5-cyclohexadienone 6. Acid hydrolysis of 6 gave 11, which was reductively aminated to give (+/-)-narwedine 2. Since 2 has been converted into (-)-galanthamine 1 in two steps, this synthesis proceeds in eight steps with an overall yield of 63%. Also treatment of the cross-conjugated cyclohexadienone 6 with nitromethane/base gave 12, which was reduced to provide 13. Reduction of the nitro group in 13 to an amine, followed by reductive amination under acidic conditions, arrives at the codeine skeleton 15. Elaboration of 15 into (+/-)-codeine proceeds via the previously unknown alpha-epoxide derivative 18. This is the shortest synthesis of codeine (13 steps, 20% overall yield) and, for the first time, allows access to codeine without having to reduce codeinone.