P-26 オシラトキシンDの合成研究(ポスター発表の部)

抄録

Oscillatoxin D (1) and 30-methyloscillatoxin D (2) are natural products derived from β-polyketides. They occur with aplysiatoxins, potent tumor promoters, in the marine blue-green algae belonging to the Oscillatoriaceae. Oscillatoxin D displays antileukemic activity against the L 1210 cell line. Aplysiatoxins and oscillatoxins have received much attention as attractive synthetic targets and several synthetic studies have recently been reported. In connection with a series of our synthetic studies on aplysiatoxins, we have succeeded to construct the unique spiroether of 1 and 2 which is absent in the structures of aplysiatoxins. Further, the first total synthesis of 2 has been completed. In retrosynthetic analysis, we adopted a possible biomimetic pathway for the cyclization of the spiroether ring and divided 1 and 2 into three main segments (A, B, C). The segment A (C_8-C_<23>) has been synthesized from D-glucose and acetophenon derivative. The segment B (C_1-C_7, C_<24>, C_<25>, C_<26>) has been synthesized from methyl (S)-3-hydroxy-2-methyl- propionate. The segment C1 (C_<27>-C_<30>) and the segment C2 (C_<27>-C_<31>) are known compounds. The acyclic compound (15), obtained by coupling of segment A and segment B, has been converted into the C_1-C_<26> spiroether (19) possessing the same stereogenic centers of oscillatoxin D. The stereochemistry of 19 was elucidated through detailed analysis of their NOE difference spectrum. The construction of the spiroether has been achieved by intramolecular aldol condensation and Michael-type addition as key steps. The cyclohexenone derivative (25) esterified with the segment C2 has been converted into the desired spiroether (26) under the acidic condition. The final deprotection of benzyl ether by hydrogenolysis with Raney-Ni (W-2) provided 30-methyloscillatoxin D (2). The ^1H-NMR spectrum of the synthetic 2 was completely identical with that of natural one.