6 アンフィジノライドBの合成研究(口頭発表の部) [in Japanese] 6 Synthetic Study on Amphidinolide B [in Japanese]
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From chemical investigations of marine microorganisms as new source of bioactive substances, amphidinolide B was isolated from the cultured marine dinofragellate Amphidinium. In addition to the interesting 26-membered macrolide structure, powerful antitumor activities were shown against L1210 and KB cell. Because of low isolation yields from the natural origin, detailed bioassay has not been carried out. Accordingly, total synthesis was investigated to supply large quantity of samples to bioassay, and to understand structure-activity relationship of this molecule. According to the convergent synthetic strategy, amphidinolide B (1) was divided to the bottom-half fragment (C1-C13) 2 and top-half fragment (C14-C26) 3. Synthesis of the bottom-half fragment 2 was started from dimethy L-tartrate. After introduction of the oxazolidinone chiral auxiliary by employing our own reagent, introduction of the methyl group of the C-11 position was achieved by the Evans protocol. Continuously, Johnson Claisen rearrangement of the corresponding allyl alcohol, effected the desired chain homologation, and final transformation toward the bottom-half fragment was succeed by the Wittig reaction. On the other hand, the top-half fragment 3 was obtained by coupling of the aldehyde prepared by the Shioiri method with fragment obtained from L-malic acid. Additionally, the diene moiety ascribed to C13-C15 was efficiently synthesized by coupling of the aldehyde with the corresponding acetylide, followed by methylation and the Wittig reaction. The allylic epoxide was also constructed by employing the Sharpless protocol via a halohydrine In conclusion, the syntheses of the two fragments of amphidinolide B, and their suitable coupling were accomplished, and construction of the allylic epoxide was demonstrated.