Ascomylactams A-C, Cytotoxic 12- or 13-Membered-Ring Macrocyclic Alkaloids Isolated from the Mangrove Endophytic Fungus sp. CYSK-4, and Structure Revisions of Phomapyrrolidones A and C.

Three new 12- or 13-membered-ring macrocyclic alkaloids, named ascomylactams A-C (-), along with the analogues phomapyrrolidone C () and phomapyrrolidone A () were isolated from the mangrove endophytic fungus sp. CYSK-4. Their structures were elucidated by analysis of extensive spectroscopic data and mass spectrometric data. The structures and absolute configurations of and were determined by single-crystal X-ray diffraction experiments, which represents the first crystal structures described for a (6/5/6/5) tetracyclic skeleton fused with a 12- or 13-membered-ring macrocyclic moiety. The configurations of phomapyrrolidone C () and phomapyrrolidone A () were revised by detailed analysis of the NMR data. In a cytotoxic assay, compounds and showed moderate cytotoxicity against MDA-MB-435, MDA-MB-231, SNB19, HCT116, NCI-H460, and PC-3 human cancer cell lines, with IC values in the range of 4.2-7.8 μM.