Axinellasins A–D, Immunosuppressive Cycloheptapeptide Diastereomers, Discovered via a Precursor Ion Scanning–Supercritical Fluid Chromatography Strategy from the Marine Sponge Axinella species

The precursor ion scanning–supercritical fluid chromatography (PI-SFC) method was applied to explore new methionine sulfoxide-containing cycloheptapeptides, axinellasins A–D (1–4), from the marine sponge Axinella sp. Their structures, including absolute configurations, were elucidated by detailed spectroscopic analyses and X-ray crystallography. The total synthesis of 4 was completed via an Fmoc solid/solution-phase synthesis. Compounds 1–4 exhibited immunosuppressive effects via inhibition of T and B cell proliferation, and 1 and 4 showed better inhibitory activities than their corresponding diastereomers.