New Aromatic Abietane Diterpenoids from Lycopus europaeus L. Fruits: 1H NMR Simulation-Aided Structure Elucidation and Enzyme Inhibition Screening

The fruits of Lycopus europaeus L. represent an unusual source of highly oxygenated aromatic abietane diterpenoids. Following our previous identification of euroabienol (1) from this plant material, a phytochemical reinvestigation of the dichloromethane fruit extract was undertaken to characterize related minor constituents. Three new aromatic abietane diterpenoids, 4-epileonubiastrin (2), 3α-acetoxyeuroabienol (3), and 11-deoxyeuroabienol (4), were isolated together with euroabienol (1). Their structures and relative configurations were established by MS, HRMS, IR, and extensive 1D and 2D NMR analyses. Manual iterative full spin analysis of selected 1H NMR spin systems enabled refined determination of chemical shifts and coupling constants and provided additional support for conformational and configurational assignments, particularly in structurally congested parts of the molecules. To obtain a preliminary indication of biological relevance, compounds 1–4 and the semisynthetic O-methylated euroabienol derivative 5 were evaluated for acetylcholinesterase and urease inhibition. The observed effects were modest: compound 2 showed the highest AChE inhibition, reaching 31% at 50 μM, whereas compound 4 was the most active against jack bean urease, producing 40% inhibition at 100 μM. The study expands current knowledge of L. europaeus fruit diterpenoids and illustrates the value of 1H NMR simulation as a complementary tool in the elucidation of closely related abietane natural products.