The structures of huperzine A and B, two new alkaloids exhibiting marked anticholinesterase activity

Abstract

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.

Lycopodium clavatum and Lycopodium complanatum subsp. chamaecyparissus ekstrelerinin antiprotozoal aktivitesi ve sitotoksisitesi

“…flowerless and primitive fern plants, rich in so-called "Lycopodium alkaloids" that have quinolizine, pyridine, and alpha-pyridone chemical skeletons [21]. These plants have a long history of use in Chinese folk medicine for the treatment of many ailments [22], but the genus has gained a worldwide reputation after the isolation of huperzine A from Huperzia serrata [23,24]. Huperzine A is a potent, reversible and selective acetylcholinesterase inhibitor [25] and is promising for treatment of symptoms of Alzheimer's disease [23].…”

Synthetic Applications of the Parkins Nitrile Hydration Catalyst [PtH{(PMe2O)2H}(PMe2OH)]: A Review

“…The hydration reaction, performed in aqueous ethanol at 70 °C, with 5 mol% of 1, allowed the quantitative conversion of 3 to the corresponding amide 4. (−)-Huperzine A (9) is a tricyclic alkaloid produced by the Chinese herb Hupercia serrata [26], with intense contemporary interest in clinical application for treating neurodegenerative diseases [27][28][29]. Several total syntheses of 9 have been reported [27][28][29].…”

A review of the use of pteridophytes for treating human ailments

“…cleroda-3,14-diene Raja et al, 1995;Zakaria et al, 2008 26 Psilotum nudum Quercetin, kaempferol, amentoflavone, hinokiflavone, vicenin-2 psilotin, and 3'-hydroxypsilotin Cambie and Ash, 1994 27 Huperzia selago Huperzine A Staerk et al, 2004 28 Huperzia serrata Alkaloids: huperzine A and B Liu et al, 1986 29 Pityrogramma tartarea 2'6'-dihydroxy-4,4'-dimethoxydihydrochalcone, kaempferol 7-methyl ether, and apigenin 7-methyl ether Star and Mabry, 1971 30 Yang et al, 2013 compounds are found only in the genus Dryopteris, which has been used in chemosystematic and phylogenetic studies (Widen, 1971;Britton, 1971a, 1971b). Flavonoids and phenolic compounds are the most general group of bioactive principles in plants, occurring in almost all plant parts, but mainly in photosynthesizing cells.…”