Mollecarbamates, Molleureas, and Molledihydroisoquinolone, o -Carboxyphenethylamide Metabolites of the Ascidian Didemnum molle Collected in Madagascar

Abstract : The extract of a sample of the tunicate Didemnum molle (MAY13-117) collected in Mayotte afforded eight new metabolites, mollecarbamates A−D (1−4) and molleureas B−E (5−8), along with the two known natural products, N,N′-diphenylethyl urea (10) and molleurea A (11). Another sample of D. molle (MAD11-BA065) collected in Baie des Assassins, Madagascar, afforded molledihydroisoquinolone (9). Mollecarbamates 1−4 are a family of compounds that possess repeating o-carboxyphenethylamide units and a carbamate moiety, while the molleureas 5−8 contain tetra-and penta-repeating carboxyphenethylamide units and a urea bridge in different positions. Molledihydroisoquinolone (9) is a cyclic form of o-carboxyphenethylamide. We propose that these unique natural products are most probably produced by an unprecedented biosynthetic pathway that contains a yet unknown chorismate mutase variant. The structures of the compounds were elucidated by interpretation of the data from 1D and 2D NMR, HRESIMS, and MS/MS analyses of the positive ESIMS experiments. Compounds 1−8 were tested against pathogenic bacteria and in a cytoprotective HIV cell based assay but did not show any significant effects in these assays.