62(P1-10) アプリシアトキシンの合成研究(ポスター発表の部)  [in Japanese] 62(P1-10) SYNTHETIC STUDY ON APLYSIATOXIN  [in Japanese]

Aplysiatoxin (1) isolated from the digestive gland of a sea hare, Stylocheilus longicauda, is an active tumor promoter and is structurally characterized by spiroacetal and hemiacetal structures and stereochemically interesting four consecutive asymmetric centers. Our effort toward the synthesis of 1 is to be presented. 1 was dissected into five fragments, B, C, D, E, and F. Fragments, B, C, and E, were obtained in optically pure forms as 8, 13, and 24, respectively, by using asymmetric epoxidation as a key step. The synthesis of fragment D (18) started with isopropyl (2S,3R,4E)-6-benzyloxy-2-hydroxy-3-methyl-4-hexenoate (15), which was prepared by using the newly developed titanium-mediated [2,3]Wittig rearrangement. 15 was converted into the epoxide 17 stereoelectively by using iodolactonization, and 17 was further converted into the epoxy alcohol 18 in a conventional way. Coupling of C and D was achieved by treatment of 18 with the Grignard reagent 13, giving 26 regioselectively. After the removal of the unnecessary primary hydroxyl group, compound 26 was transformed into the terminal epoxide 28 with the inversion of C_9-configuration (Aplysiatoxin numbering). Thus, the stereochemistry of the part of four consecutive asymmetric centers was established. Coupling of 28 with E was effected by the treatment of 28 with the lithiated 24, giving the C_3-C_<21> fragment 29. The next stage of the synthesis, the introduction of B on the C_9 hydroxyl group was accomplished by using Yamaguchi procedure. Further transformation of 30 to 1 is now in progress.