부산대학교 도서관

Recently, much attention has been paid to several shellfish toxins. Pectenotoxins are a family of cyclic polyether macrolide toxins, in which pectenotoxin 2 was isolated by not only from the digestive glands of poisonous scallop (Patinopecten yessoensis) and also from an identified dinoflagellate (Dinophysis fortii) as the causative organism. Although this compound possesses an unusual and complex molecular structure and shows significant diarrhetic intoxication as well as actin depolymerizing activity, there has been no report on completion of the total synthesis. On the other hand, gymnodimine, isolated from New Zealand oysters (Tiostrea chilensis) and the dinoflagellate (Gymnodinium cf. mikimotoi), is characteristic structurally and toxically. Pinnatoxins have been isolated from the Okinawan bivalve (Pinna muricata). Specially, pinnatoxin A was first isolated as the major toxic compound and the absolute structure was clarified by the first total synthesis of ent-pinnatoxin A by the Kishi group. We have continued studies aiming to the total syntheses of these shellfish toxins, the detail of which will be described. Pectenotoxin 2 was disconnected to the left side (1) and the right side compounds (2), which were planned to construct the main 34-membered lactone system via their Julia-type coupling and the following ring closing metathesis in the 31 and 30 positions. We have succeeded in the efficient synthesis of both the components (1 and 2). Concerning the synthesis of gymnodimine and pinnatoxin A, we have developed the new exo-Diels-Alder reactions by applying Ellman's and Evans' reagents starting from the N-protected α-methylene lactams (19 and 22) as the dienophiles, respectively. When 19 was reacted with the diene (20) in the presence of (-)-siam ligand, CuCl_2, and AgSbF_6, the cyclo-addition occurred to give 21 in 30% isolated yield with 95: 5 diastereo-selectivity. Further reaction using 27 with 19 is now under way in our laboratory. The optically pure methylene lactam 22 was treated with the diene 23 as a model to afford the adduct 24 in 42% isolated yield with 93: 7 diastereo-selectivity. Finally, in order to construct the common B,C,D,E,F ring system of pinnatoxins, the tetra-ketone 28 was prepared and reacted with HF-Py. The extensive solvent effect was observed; when MeCN was used as a solvent, the desired construction proceeded smoothly to provide 29 in high yield. On the basis of these results, we are now investigating toward the total syntheses of these target compounds.