46 Eudistoma種のホヤの生物活性物質(口頭発表の部)  [in Japanese] 46 Bioactive Compounds from Tunicates of Eudistoma Species  [in Japanese]

During our studies on bioactive metabolites from Okinawan marine organisms, we have isolated iejimalides A(1) and B(2), two novel 24-membered macrolides with powerful antileukemic activity, from the Okinawan tunicate Eudistoma cf. rigida. The structures were elucidated from spectral data including 2D NMR. Compounds 1 and 2 also inhibited Na^+, K^+-ATPase. Eudistomidins B(3), C(4) and D(5), novel β-carbolines with potent cytotoxicity, have been isolated from the Okinawan tunicate Eudistoma glaucus. The stereostructure of 3 was elucidated from the NMR and CD data, while that of 4 was determined through synthesis of 6-O-methyl-10(R)-eudistomidin C. Compound 3 inhibited Na^+,K^+-ATPase but activated actomyosin ATPase, while compound 4 showed calmodulin-antagonistic activity. Eudistomidin D(5) induced Ca^<2+> release from sarcoplasmic reticulum (SR). 9-Methyl-7-bromoeudistomin D(6) synthesized based on structure-activity relationship between caffeine and eudistomin D was ca. 1000 times more potent than caffeine in SR Ca^<2+>-releasing assay. Therefore, compound 6 is used as a valuable tool for elucidating molecular mechanism of Ca^<2+> release from SR.