Structure Elucidation of Calyxoside B, a Bipolar Sphingolipid from a Marine Sponge <i>Cladocroce</i> sp. through the Use of Beckmann Rearrangement
Kenji Sugawara,
Hiroshi Watarai,
Yuji Ise,
Hisayoshi Yokose,
Yasuhiro Morii,
Nobuhiro Yamawaki,
Shigeru Okada,
Shigeki Matsunaga
Affiliations
Kenji Sugawara
Laboratory of Aquatic Natural Products Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan
Hiroshi Watarai
Department of Immunology and Stem Cell Biology, Faculty of Medicine, Kanazawa University, Ishikawa 920-8640, Japan
Yuji Ise
Sesoko Station, Tropical Biosphere Research Center, University of the Ryukyus, 3422 Sesoko, Motobu, Okinawa 905-0227, Japan
Hisayoshi Yokose
Graduate School of Science and Technology, Kumamoto University, 2-39-1 Kurokami, Chuo-ku, Kumamoto 860-8555, Japan
Yasuhiro Morii
Graduate School of Fisheries Science and Environmental Studies, Nagasaki University, Nagasaki 852-8521, Japan
Nobuhiro Yamawaki
Graduate School of Fisheries Science and Environmental Studies, Nagasaki University, Nagasaki 852-8521, Japan
Shigeru Okada
Laboratory of Aquatic Natural Products Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan
Shigeki Matsunaga
Laboratory of Aquatic Natural Products Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan
Marine sponges are an excellent source of biologically active secondary metabolites. We focus on deep-sea sponges for our discovery study. A marine sponge Cladocroce sp. exhibited cytotoxic activity in the bioactivity screening. From this sponge a previously unreported cytotoxic glycosphingolipid, calyxoside B, was isolated and the structure of this compound was elucidated by analyses of MS and NMR spectra and chemical derivatization. We converted the ketone in the middle of a long aliphatic chain into an oxime to which was applied Beckmann rearrangement to afford two positional isomers of amides. The products were subjected to acidic hydrolysis followed by LC-MS analysis, permitting us to assign unequivocally the position of the ketone. Calyxoside B shows cytotoxicity against HeLa cells with an IC50 value of 31 µM and also weakly stimulated the production of cytokines in mice.
