Unprecedented stylissazoles A-C from Stylissa carteri: another dimension for marine pyrrole-2-aminoimidazole metabolite diversity.

The pyrrole-2-aminoimidazole (P-2-AI) alkaloids have been exclusively reported to be isolated from marine sponges. The P-2-AIs are well known for their dense structures with a very low carbon/nitrogen (mainly nxC11N5) ratio. [1] Their intriguing dimeric polycyclic ring systems that were isolated during the last years revealed their elaborate structures and molecular diversity which arise from a variety of modes of dimerization and polycyclization. Structurally, it is assumed that these metabolites arise from the crucial intermediates clathrodin, hymenidin, or oroidin through either an interesting intramolecular or intermolecular reaction occurring at ambident centers. Although the biosynthesis of these intermediates is not clear, it is obvious that dipeptides involving proline and another amino acid residue such as ornithine or arginine constitute an interesting route for early biosynthetic precursors. The reactivity of the monomers that give rise to the diversity of P-2-AI dimers isolated thus far is very intriguing. Biomimetic synthesis approaches toward several members of P-2-AIs reported by various groups have led to better understanding of the reactivity and the potential biosynthetic chemical pathways of the dimeric compounds. The lack of biosynthetic studies using labeled precursors, necessitates the exhaustive isolation of the targeted P-2-AI metabolome. Research into the biosynthetic intermediates is crucial for the construction of the chemical pathway. Isolation of new intermediates helps to explore the ability of the corresponding phylogenetically related sponges to create newly targeted metabolomes. Specifically, we are interested in four families of marine sponges (Agelasidae, Axinellidae, Halichondriidae, and Dictyonellidae) that could afford additional P-2-AI metabolites. We have investigated the methanolic extract of a Pacific Stylissa carteri which is known to yield compounds such as cyclopeptides, oroidin, 4,5-dibromopyrrolecarboxamide, 4-dibromopyrrolecarboxamide and hanishin, latonduine A and B, (E)and (Z)-hymenialdisine, (E)and (Z)-debromohymenialdisine, (E)and (Z)-bromohymenialdisine, stevensine, debromostevensine, hymenin and debromohymenin, dibromoisophakellin and ugibohlin, carteramine A, and hanishenol A and B. We report herein the isolation of three unprecedented N C bonded stylissazoles A–C (1—3 ; Figure 1), which fit well with our previous biosynthetic proposal and add another dimension to the diversity of marine P-2-AI metabolites. Consequently, the universal proposal is also updated.