95(P12) 新規抗インフルエンザAウイルス活性物質(±)-スタキフリンの全合成(ポスター発表の部)

概要

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Stachyflin (1) is a new natural product isolated in our laboratories from the culture of Stachybotrys sp. RF 7260. It exhibits potent anti-influenza A virus activity and has a novel skeleton which is made of cis-decalin with oxygenation at the ring junction. Its characteristic structure and biological activity made it an interesting synthetic target. We report the total synthesis of (±)-stachyflin including the two key steps, the construction of cis-decalin and the formation of an etheral bond at its bridgehead. Acid catalyzed aldol condensation of the dimethylacetal (16) with the TMS enolether (13) afforded 17. Formation of the etheral bond at the bridgehead of AB ring junction succeeded via iodoetherification of 21. In this reaction, we used propylene oxide as an effective HI scavenger. Construction of A ring was achieved via intramolecular aldol condensation of the diketone (26). Cis-decalin (AB ring) was constructed with catalytic hydrogenation of the α,β-unsaturated ketone (27). After regioselective methylation of 28, construction of the lactam ring was achieved in 4 steps (bromination, cyanide exchange, hydrogenation of nitrile, and base catalyzed cyclisation). Finally we completed the total synthesis of (±)-stachyflin in 29 steps. Its anti-influenza A virus activity was about half of that of natural (+)-stachyflin.
天然有機化合物討論会の論文
1998-08-31