Lycosquarrines A–R, LycopodiumAlkaloids from Phlegmariurus squarrosus

Eighteen new Lycopodiumalkaloids, lycosquarrines A–R (1–18), and eight known alkaloids were isolated from the aerial parts of Phlegmariurus squarrosus. Compounds 1–5and 19, identified from natural sources for the first time, are uncommon lycopodine-type alkaloids with β-oriented H-4. Pentacyclic 4and 5represent the first examples of 5,12- and 5,11-epoxy Lycopodiumalkaloids, respectively, and an epoxide-opening cyclization reaction is suggested to be a key step in their biosynthesis. Compound 18possesses the same carbon skeleton as carinatine A (22), which was previously reported as a unique Lycopodiumalkaloid with a 5/6/6/6 ring system. X-ray crystallographic data analysis was used to determine the absolute configuration of 18, leading to the establishment of the absolute configuration of 22by comparison of the ECD spectra. An anti-acetylcholinesterase activity assay showed that 11and 20exhibited inhibitory activities with IC50values of 4.2 and 2.1 μM, respectively.