Lycophlegmariols A-D: cytotoxic serratene triterpenoids from the club moss Lycopodium phlegmaria L.

Lycopodium serratene triterpenoids, along with an abietane-type diterpene were isolated from the methanol extract of club moss Lycopodium phlegmaria L. The structures of these hitherto unknown lycopodium terpenoids were elucidated on the basis of spectroscopic analysis. Pentacyclic triterpenoids, 21β-hydroxy-serrat-14-en-3α-ol (1) and 21β-hydroxy-serrat-14-en-3α-yl acetate (2) were isolated together with four serratene triterpeneoids established as 21β,29-dihydroxyserrat-14-en-3α-yl dihydrocaffeate (lycophlegmariol A, 5), 21β,24,29-trihydroxyserrat-14-en-3β-yl dihydrocaffeate (lycophlegmariol B, 6), 21α,24-dihydroxyserrat-14-en-3β-yl 4-hydroxycinnamate (lycophlegmariol C, 7), and 14β,21α,29-trihydroxyserratan-3β-yl dihydrocaffeate (lycophlegmariol D, 8) as well as a known lycophlegmarin (9). An abietane-type diterpene, 8,11,13-abietatriene-3β,12-dihydroxy-7-one (margocilin, 10), was isolated for the first time from a Lycopodium plant. Lycophlegmariol B (6), D (8) and compound 1 showed inhibitory effects against MOLT-3 acute lymphoblastic leukemia (T-lymphoblast) with IC(50) of 14.7, 3.0 and 2.9 μM, respectively.