In the present study, a practical method to prepare piperazinyl amides of 18β-glycyrrhetinic acid was developed. Two main procedures for the construction of important intermediate 8 are discussed. One procedure involves the amidation of 1-Boc-piperazine with 3-acetyl-18β-glycyrrhetinic acid, prepared by the reaction of 18β-glycyrrhetinic acid with acetic anhydride without any solvent at 130 °C. The other procedure to prepare compound 8 involves the amidation of 18β-glycyrrhetinic acid followed by the esterification with acetic anhydride. Finally, compound 8 underwent N-Boc deprotection to prepare product 4. To ascertain the scope of the reaction, another C-3 ester derivative 17 was tested under the optimized reaction conditions. Furthermore, the reasons for the appearance of byproducts were elucidated. Crystallographic data of a selected piperazinyl amide is reported.

To identify potential drug candidates, secondary metabolites of Dendrobium nobile were performed. As a result, two previously undescribed phenanthrene derivatives with a spirolactone ring (1 and 2), along with four known compounds, N-trans-cinnamoyltyramine (3), N-trans-p-coumaroyltyramine (4), N-trans-feruloyltyramine (5), and moscatilin (6), were isolated from Dendrobium nobile. The structures of the undescribed compounds were elucidated using NMR spectroscopy, electronic circular dichroism (ECD) calculations, and extensive spectroscopic data analysis. The cytotoxic effects of compounds on human tongue squamous cells OSC-19 were determined using MTT at concentrations of 2.5 μM, 5 μM, 10 μM, and 20 μM. Compound 6 exhibited potent inhibitory activity against OSC-19 cells with an IC₅₀ of 1.32 μM. Migration assays and western blot assays demonstrated that compound 6 effectively inhibited migration by down-regulating MMP2 and MMP9 at concentrations of 0.5 μM and 1 μM. To investigate its effect on apoptosis, we performed AO/PI staining, flow cytometry, and WB experiments. The results showed that increasing concentrations led to increased red fluorescence, decreased green fluorescence, increased apoptosis rate, decreased expression of bcl-2, caspase 3, caspase 9, and parp proteins, and increased bax expression. Furthermore, the phosphorylation of JNK and P38 was activated, suggesting that compound 6 may induce apoptosis via the MAPK pathway.