Hupserrine A, a Caged Lycopodium Alkaloid with a 6/6/5/6/7 Pentacyclic Skeleton from Huperzia serrata

Hupserrine A (1), a Lycopodium alkaloid featuring a novel caged 6/6/5/6/7 pentacyclic skeleton, was isolated from Huperzia serrata. Compound 1 possesses an unprecedented 2-azatetracyclo[6.5.0.03,11.05,10]tridecane unit. Its structure was elucidated by high-resolution electrospray ionization mass spectrometry (HRESIMS), nuclear magnetic resonance (NMR), and X-ray diffraction analyses. A plausible biosynthetic pathway for 1 is proposed. Compound 1 demonstrated significant and highly selective antagonistic activity against the 5-HT3AR with an IC50 value of 10.6 ± 2.58 μM.