Structural Elucidation and Total Synthesis for the Pair of Unprecedented Polypyridines with Anti-AChE and HIV-1 Protease Activities from

Unlike reported pyridine hybrids, 2 () and 2-alanginenmine A () from featuring an unprecedented piperidine-bridged polypyridine skeleton represented a pair of alkaloid subtypes with a unique multiple pyridine scaffold. Enlightened by the rare structural characteristics and possible biosynthetic pathway, (±)-alanginenmine A () have been achieved in ideal yield by gram-class total synthesis with four steps. In addition, both compounds and exhibited anti-acetylcholinesterase (AChE) and HIV-1 protease activities in the biological activity evaluation. Further, molecular docking was investigated for the mechanism of action between the isolated compounds and HIV-1 protease. The stronger Coulomb interactions and van der Waals interaction, as well as the hydrogen bond interactions of , might be the main cause for its better anti-HIV-1 protease activity than . This work provided a comprehensive research including natural product discovery, bioactivity evaluation, and total synthesis for the new type of leading anti-HIV-1 protease.