90 八丈島産海綿Toxadocia cylindricaから単離したトロンビン阻害物質の構造(ポスター発表の部)

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During the course of our screening program for bioactive metabolites from Japanese marine invertebrates, we found that the marine sponge Toxadocia cylindrica collected off Hachijo-jima Island inhibited thrombin. Bioassay-guided isolation afforded four active compounds named toxadocials A-C and toxadocic acid A. Their structures were elucidated by interpretation of NMR and FAB-MS/MS data. The MeOH extract of the sponge (1.9kg, wet weight) was partitioned between H_2O and Et_2O, the aqueous layer was extracted with n-BuOH. The MeOH soluble portion of the n-BuOH phase was gel-filtered on Sephadex LH-20 with MeOH, and the active fractions were repeatedly purified by reverse phase HPLC with aqueous MeCN containing NaClO_4 to yield toxadocials A-C (1-3) and toxadocic acid A (4)(yield; 2.9×10^<-3>, 4.4×10^<-4>, 1.9×10^<-3> and 5.8×10^<-4>% based on wet weight, respectively). The structures of toxadocials A-C were elucidated by extensive 2D NMR experiments as well as by FAB-MS/MS after removal of sulfate groups followed by derivatization with Girard's reagent P and T. Toxadocic acid A was similarly analyzed to be a tetrasulfated carboxylic acid. Toxadocials A-C and toxadocic acid A inhibited thrombin with IC_<50> of 3.1, 4.6, 3.2, and 2.7μg/mL, respectively.
1993-09-10