Ningalins A-D: Novel aromatic alkaloids from a Western Australian ascidian of the genus Didemnum

Four aromatic alkaloids, ningalins A-D (1-4), three of which possess new carbon skeletons, were isolated from an undescribed ascidian of the genus Didemnum collected in Western Australia near Ningaloo Reef. The structures of these new alkaloids were elucidated by interpretation of overall spectral data and by 2D NMR correlation methods. Ningalins A-D are composed of C-18, C-25, C-32, and C-40 condensed aromatic systems with the unifying theme that all appear derived via the condensation of the amino acid 3,4-dihydroxyphenylalanine (DOPA). In these highly condensed alkaloids, steric crowding forces several catechol rings into twisted configurations, resulting in unexpected shielding and deshielding of several proton shifts in their NMR spectra. Because the ningalins are related to other metal binding o-catechols, it is conceivable that they too participate in the metal chelation phenomena characteristic of this class of marine invertebrates.