BAO-FENG QI. Can. J. Chem. 64, 837 (1986).Huperzine A and B, two new Lycopodium alkaloids isolated from Huperzia serrata (Thunb.) Trev., are shown to possess structures 1 and 3, respectively, on the basis of chemical and spectroscopic data.JIA-SEN LIU, YUAN-LONG ZHU, CHAO-MEI Yu, YOU-ZUO ZHOU, YAN-YI HAN, FENG-WU WU et BAO-FENG QI. Can. J. Chem. 64, 837 (1986).En se basant sur des donnCes chimiques et spectroscopiques, on dkmontre que les deux nouveaux alkaloi'des du Lycopodium, les huperzines A et B, qui ont CtC isolCs du Huperzia serrata (Thunb.) Trev., poss2dent respectivement les structures 1 et 3.[Traduit par la revue]Huperzine A (1) and B (3), two new Lycopodium alkaloids, were isolated from Huperzia serrata (Thunb.) Trev. = Lycopodium serratum Thunb., a Chinese folk medicine. They exhibit strong anticholinesterase activity in pharmacological studies (1) and markedly increase efficiency for learning and memory in animal^.^ Presently, the use of huperzine A in the treatment of myasthenia gravis (2), Alzheimer's dementia, and for the improvement of senile memory loss are under clinical investigation. In this paper we report chemical studies on the structures of huperzine A and B.Hu erzine A (I), C15H18N20 (M+ 242.1426), mp 230°C,[ a ]~. ' -150.4" (c 0.498, MeOH), shows the characteristics of an a-pyridone in its uv spectrum (A, , , (EtOH) nm (log E): 231 (4.01), 313 (3.89)), ir spectrum (3180, 1650, 1615, 1550 cm-'), and 'H nmr spectrum (see Table 1). Dehydrogenation of huperzine A over Pd/C at 300°C affords 6-methyl-2(1H)-pyridone, further attesting to the presence of an a-pyridone ring in the molecule. The presence of an endocyclic double bond and an exocyclic double bond as revealed in the 'H and 13C nmr spectra of huperzine A (Tables 1, 2), as well as the similarity of its mass spectrum with that of selagine (3), indicate that the structure of huperzine A (1) closely resembles that of the known alkaloid selag&e (2) (4). The specific rotation (-99" in MeOH) of selagine (4) is much less than that of huperzine A. The olefinic proton of the endocyclic double bond in the 'H nmr of 1 1,12-dihydroselagine appears as a singlet (4), while in the 'H nrnr of huperzine A (1) or in the 'H nmr of 1 1,12-dihydrohuperzine A the olefinic proton appears as a doublet. This clearly accounts for the structural differences between 2 and 1 and 'presented in part at the International Symposium on Organic Chemistry of Medicinal Natural Products (IUPAC), Shanghai, China, November 1985. After submission of the manuscript to the symposium, we found that an analogous alkaloid named isoselagine had been reported (9). From the published data, we conclude that huperzine A is not identical with isoselagine and that the latter may be the Z isomer of huperzine A.'Author to whom correspondence should be addressed 3X-C. Tang. Personal communication.
