Synthetic studies on polycavernosides A and D aiming at the identification of their biological target

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K05450
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 38040:Bioorganic chemistry-related
• Research Institution: Akita University
• Principal Investigator: Fujiwara Kenshu 秋田大学, 理工学研究科, 教授 (20222268)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 全合成研究 / 有機合成化学 / 不斉合成 / 海藻毒 / 細胞毒性 / 神経毒性 / 標的生体分子探索

Outline of Final Research Achievements

Polycavernoside A and D, isolated from a red algae as a lethal toxin and from a cyanobacterium as a cytotoxin, respectively, are structurally similar macrolide glycosides. The mode of toxic action of them is unclear in detail due to difficulty in the supply of them from natural source. Therefore, the synthetic supply of them was planned and examined. Polycavernoside D, which has not been synthesized so far, was planned to be assembled from a sugar chain and a macrolide moiety. The macrolide would be constructed from the upper-half unit and the bottom-half tetrahydropyran (THP) unit. Both the units were successfully synthesized from (R)-pantolactone. For the THP unit, a new synthetic method was developed based on the Hosokawa asymmetric vinylogous Mukaiyama aldol reaction. The late stage of the synthesis would be finished according to the procedure previously developed for polycavernoside A by the author, and, therefore, the completion of the synthesis of polycavernoside D is in sight.

Free Research Field

天然物合成化学

Academic Significance and Societal Importance of the Research Achievements

ポリカバノシドAは食用カタオゴノリの突然毒化の際の致死毒として単離された。毒化は一時的であり、その後カタオゴノリから毒素は検出されなくなったため、ポリカバノシドAの天然供給は絶たれている。最近藍藻から構造の酷似したポリカバノシドDが細胞毒として単離され、ポリカバノシドAとの毒性の特徴の差異が注目された。もし、ポリカバノシド類の毒性の背後に存在する生体分子標的や作用機序を解明できれば、生命維持に重要な新たな生物学的知見が得られると期待される。この毒性に関わる研究の遂行には、ポリカバノシド類の供給が不可欠である。本研究は人工合成でその供給を実現する意義を持ち、簡便供給につながる知見を得た。