synthesis, inhibitory effects on nitric oxide and structure-activity relationships of a glycosphingolipid from the marine sponge aplysinella rhax and its analogues一氧化氮合成,抑制作用及构效关系的海洋的鞘糖脂海绵aplysinella rhax及其类似物.pdfVIP

Molecules 2011, 16, 637-651; doi:10.3390/molecule OPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Synthesis, Inhibitory Effects on Nitric Oxide and Structure- Activity Relationships of a Glycosphingolipid from the Marine Sponge Aplysinella rhax and Its Analogues 1 1 1 2 1 Yuzo Fujita , Naohiro Ohshima , Ai Hasegawa , Frank Schweizer , Tadahiro Takeda , Fumiyuki Kiuchi 1 and Noriyasu Hada 1,* 1 Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan 2 Department of Chemistry and Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, R3T 2N2, Canada * Author to whom correspondence should be addressed; E-Mail: hada-nr@pha.keio.ac.jp; Tel.: +81-3-5400-2666; Fax: + 81-3-5400-2556. Received: 9 December 2010; in revised form: 29 December 2010 / Accepted: 14 January 2011 / Published: 17 January 2011 Abstract: The novel glycosphingolipid, β-D-GalNAcp (1→4)[α-D-Fucp (1→3)]-β-D- GlcNAcp (1→)Cer (A), isolated from the marine sponge Aplysinella rhax has a unique structure, with D-fucose and N-acetyl-D-galactosamine moieties attached to a reducing-end N-acetyl-D-glucosamine through an α 1→3 and β1→4 linkage, respectively. We synthesized glycolipid 1 and some non-natural di- and trisaccharide analogues 2-6 containing a D-fucose residue. Among these compounds, the natural type showed the most potent nitric