Arsenicin A: A Unique Natural Product

Chemists in Australia are reporting the synthesis and crystal structure of arsenicin A, the first known natural product to contain multiple arsenic atoms (Organometallics, DOI: 10.1021/om900998q). This tetraarsenic cluster compound has been isolated in trace amounts from a New Caledonian sponge in the southwest Pacific Ocean and shown to possess potent bactericidal and fungicidal activities against human pathogens. In addition, arsenic trioxide (As₂O₃) is already an effective approved drug for treating acute myeloid leukemia. With the prospects for new arsenic drug development at hand, S. Bruce Wild and coworkers of Australian National University, Canberra, took on the challenge of synthesizing arsenicin A. The team started by converting methylenebis(phenylarsinic acid) into a linear tetraarsine derivative. Replacing the phenyl groups with iodine followed by hydrolysis and then dehydration steps sewed up the tetraarsine into the desired adamantane-type structure, which has four arsenic stereocenters. The cage structure is similar to that of As₄O₆, but with three methylene groups replacing three oxygen atoms. The novel structure raises questions about how arsenicin A’s biosynthesis unfolds, Wild and coworkers say. “It is hoped that the synthesis presented here will facilitate further chemical and biological work on this unusual natural product,” they write.