Agallolides A-M, including two rearranged ent-atisanes featuring a bicyclo[3.2.1]octane motif, from the Chinese Excoecaria agallocha

Abstract

Thirteen new diterpenoid compounds, named agallolides A-M (1–13), including ten ent-atisanes, were isolated from the stems and twigs of the Chinese semi-mangrove plant, Excoecaria agallocha. Most notably, agallolides A (1) and B (2) are two rearranged ent-atisanes featuring a unique 6/6/5/7 tetracyclic carbon skeleton. Agallolides C-J (3–10) are ent-atisanes, among which agallolide C (3) represents the first example of 3,4-seco-17-nor-ent-atisane. Agallolides K (11) and L (12) are two ent-isopimaranes, whereas agallolide M (13) is a rare 3,4-seco-ent-trachylobane. The structures of these diterpenoid compounds were established by HR-ESIMS and extensive 1D and 2D NMR investigations. The absolute configurations of agallolide A (1) and agallolides I-K (9–11) were further confirmed by single-crystal X-ray diffraction analyses with Cu Kα radiation. The plausible biogenetic pathways for agallolides A (1), B (2), and I (9) were proposed. Agallolides I (9) and J (10) exhibited NF-κB inhibitory activity with inhibition rates of 23.4% and 19.4%, respectively, at the concentration of 100.0 µM.