Alkaloids of Lycopodiumselago. On the identity of selagine with huperzine A and the structure of a related alkaloid

Abstract

Selagine, an alkaloid of Lycopodiumselago, is shown to be identical with huperzine A (2). A minor alkaloid, C15H18N2O2, isolated from L. selago is found to be 6β-hydroxyhuperzine A (4). Keywords: huperzine A, selagine, Lycopodium alkaloids, Alzheimer's disease, acetylcholine esterase inhibitor.

Complete 1H NMR spectral fingerprint of huperzine A

“…In general, besides the basic challenge to analyze the 1D 1 H NMR spectra of extended spin systems of alicyclic compounds, to understand in-depth the 1 H NMR resonances of one typical compound is typically key for the analysis of a whole corresponding structural class. One such example is huperzine A (syn.…”

“…One such example is huperzine A (syn. selagine, 1 isoselagine 2 ), a selagin-type Lycopodium alkaloid, which in the recent past has received considerable attention owing to its interesting acetylcholinesterase (AChE) inhibitory activity 3 -6 and for being a potential drug lead for Alzheimer's disease. 7,8 Huperzine A is currently being tested in 160 patients in a phase II clinical trial sponsored by the NIH (http://clinicaltrials.gov/show/NCT00083590).…”

“…As expected for an alicyclic small molecule, considering the case ofˇ-pinene which was solved only recently, 9 a large number of long-range couplings are present, whereas only one such connectivity has been reported so far. 10 Furthermore, while the 1 H/ 13 C assignments have been examined by means of selective INEPT 10 and self-aggregation has been studied by 1 H NMR relaxation experiments, 11 the expected diastereotopism of the two methylene groups that are contained in a highly chiral chemical environment remains unsupported, 10,12 and the assignment of the two olefinic lactam protons remains contradictious in the literature. To fill this knowledge gap, but also sparked by our analytical interest in this key alkaloid, we attempted the full spin analysis of this 15-spin 15-carbon molecule.…”

Macleanine, a unique type of dinitrogenous Lycopodium alkaloid

“…Huperzine A (1) is isolated from the Chinese folk medicinal plant Huperzia serrata (= Lycopodium serrata) (1) and has been shown to be identical with the alkaloid selagine, which had previously been isolated from L. selago and incorrectly assigned structure 2 (4,5). Huperzine A is reported to increase efficiency for learning and memory in animals (1) and to show promise in the treatment of Alzheimer's disease and myasthenia gravis ( 6 8 ) .…”

Huperzine A, A Potential Therapeutic Agent for Treatment of Alzheimer's Disease

“…Reinvestigation of these structures has revealed that the earlier structural assignments for selagine and isoselagine are incorrect. In fact, they are identical with HupA [11].…”