Dysiherbaine: A New Neurotoxic Amino Acid from the Micronesian Marine Sponge Dysidea herbacea

详细信息    查看全文

• 作者：Ryuichi Sakai ; Hisao Kamiya ; Michio Murata ; and Keiko Shimamoto
• 刊名：Journal of the American Chemical Society
• 出版年：1997
• 出版时间：May 7, 1997
• 年：1997
• 卷：119
• 期：18
• 页码：4112 - 4116
• 全文大小：162K
• 年卷期：v.119,no.18(May 7, 1997)
• ISSN：1520-5126

文摘

A new amino acid, dysiherbaine (1), was isolated from aMicronesian sponge Dysidea herbacea. Thestructure was determined by using FABMS, ESIMS, FABMS/CID/MS, and one-and two-dimensional NMRexperiments of 1 and its dimethyl derivative 3 tobe a novel diamino dicarboxylic acid, which consisted of acis-fused hexahydrofuro[3,2-b]pyran ring substitutedwith a 3-[2-aminopropanoic acid] side chain. Therelativeconfiguration of the bicyclic portion of 1 was determined by³J_H,H analysis and difference NOEexperiments, andthat of the acyclic side chain was assigned by additional^2,3J_C,H analysis, measured by heterohalf-filtered TOCSY(HETLOC) and phase sensitive HMBC experiments. Systemicadministration of 1 induced neurotoxic symptomsinmice which were reminiscent of neuroexcitatory amino acids such asdomoic acid. Dysiherbaine inhibited bindingsof [³H]-kainic acid (KA) and[³H]-1-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid(AMPA), but not [³H]CGS-19755, an N-methyl-D-asparatic acid (NMDA)receptor antagonist, on rat brain synaptic membranes,suggestingthat 1 is a selective agonist of non-NMDA type glutamatereceptors in the central nervous system.