Computationally-Guided Structure Revision of the Chartellamides

Abstract Chartellamides A and B are heavily oxidized marine alkaloids that were isolated by Christophersen and co-workers from the marine bryozoan Chartella papyracea in 1987. The structures 1 and 2 were derived from MS and NMR-based structure elucidation and comparison of spectroscopic data to related isolates known as the chartellines. Shenvi later suggested alternative structures for chartellamides A and B (10 and 11, respectively). All four structures contain a strained heptacyclic skeleton, a brominated enamide, a bromopyrrolidine ring, and an acylimidazole. Based on our recent experimental studies of the chartellines and the computational modelling presented herein, we suggest that the chartellamides are better represented by structures 18 and 19. The theoretical carbon-13 shifts for 18 and 19 are in agreement with those of the natural isolates (RMSD = 2.07 and 2.12 ppm, respectively), while the theoretical shifts of structures 1, 2, 10, and 11 are in poor agreement (RMSD = 4.88−7.73 ppm). The structures of 18 and 19 are fully consistent with Christophersen’s spectroscopic data, save for two unusual NOE interactions, which cannot be independently accounted for.