Tausalarin C: A New Bioactive Marine Sponge-Derived Nitrogenous Bismacrolide Ashgan Bishara, † Amira Rudi, † Israel Goldberg, † Maurice Aknin, ‡ Drorit Neumann, § Nathalie Ben-Califa, § and Yoel Kashman* ,† School of Chemistry and Department of Cell and DeVelopmental Biology, Sackler Faculty of Medicine, Tel AViV UniVersity, Ramat AViV 69978, Israel, and Laboratorie de Chimie des Substances Naturelles et des Aliments, Faculte ´ des Sciences et Techniques, UniVersite ´ de la Re ´union, 15 AVenue René Cassin, B.P. 7151, 97715 Saint Denis, Cedex 9, France kashman@post.tau.ac.il Received May 19, 2009 ABSTRACT A novel nitrogenous bismacrolide, designated tausalarin C (1), was isolated from the Madagascar sponge Fascaplysinopsis sp. The structure of the compound was elucidated by interpretation of MS and 1D and 2D NMR spectra. It is suggested that tausalarin C is assembled from salarin A (2) and pretaumycin A. The relative configuration of the chiral centers of salarin A was determined by X-ray diffraction. Tausalarin C was found to inhibit proliferation of K562 leukemia cells. A possible biogenesis is discussed. Marine sponges have proven to be a rich source of secondary metabolites possessing novel structures and biological activities. 1 We recently reported the isolation and structure elucidation of three unprecedented groups of compounds: the salarins, tulear- ins, and taumycins, from the Madagascan sponge Fascaplysi- nopsis sp. 2-5 Changes in chemical composition and relative amounts of compounds, from the three groups, in over two dozen collections of the sponge and mainly structural similari- ties to microorganism and fungal metabolites (e.g., the cyanobac- teria Lyngbia bouillonii metabolites madangolide and laingolide A) 6,7 suggest that these compounds may originate from guest microorganisms rather than from the host sponge. 8-10 † School of Chemistry, Tel Aviv University. ‡ Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University. § IUFM, University of La Re ´union. (1) Munro, M. H. G.; Blunt, J. W. Marine Literature Database; Department of Chemistry, University of Canterbury: New Zealand, 2007. (2) Bishara, A.; Rudi, A.; Aknin, M.; Neumann, D.; Ben-Califa, N.; Kashman, Y. Org. Lett. 2008, 10, 153–456. (3) Bishara, A.; Rudi, A.; Aknin, M.; Neumann, D.; Ben-Califa, N.; Kashman, Y. Tetrahedron Lett. 2008, 49, 4355–4358. (4) Bishara, A.; Rudi, A.; Aknin, M.; Neumann, D.; Ben-Califa, N.; Kashman, Y. Org. Lett. 2008, 10, 4307–4309. (5) Bishara, A.; Rudi, A.; Aknin, M.; Goldberg, I.; Kashman, Y. Tetrahedron Lett. 2009, 50, 3820–3822. ORGANIC LETTERS 2009 Vol. 11, No. 16 3538-3541 10.1021/ol9011019 CCC: $40.75  2009 American Chemical Society Published on Web 07/23/2009