Isolation, structure elucidation, and absolute configuration of 5,6-dioxygenated aaptamine derivatives from the marine sponge Aaptos sp.

A chemical investigation of the Vietnamese marine sponge Aaptos sp. identified eight previously undescribed aaptamines (1-8) and two known analogs (9-10). In particular, derivatives (1-6) feature unusual oxygen-generated stereocenters at C-5 and C-6, rendering them the first examples of optically active aaptamines. The planar structures of 1-8 were elucidated based on interpretation of the 1D and 2D NMR spectra, combined with HRESIMS data. The relative and absolute configurations of 1-6 were determined by 1D NOE and electronic circular dichroism experiments, respectively. In addition, a series of oxidation studies on aaptamine (9) revealed that C-9 and Δ5 can be selectively oxidized under different reagent conditions, providing a potential indication of the biosynthetic pathway of compounds 1-6. Evaluation of the anticancer activities of isolates revealed that compounds 7 and 10 exhibited cytotoxicity against the AGS cell line with EC50 values of 8.95 μM and 5.98 μM, respectively.