16 立体選択的中員環エーテル構築法の開発及び海洋産天然物合成への応用(口頭発表の部)

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The wide occurrence of medium-sized ring ethers in a variety of Laurencia species and in the organisms which feed on this alga has become a feature of marine natural products. Much attention has recently been focused on efficient approaches toward these systems. We disclose the efficient method by intramolecular opening of hydroxy epoxides promoted by the (Bu_3Sn)_2O/Lewis acid system, and their application to the synthetic studies on (+)-isolaurepinnacin(2) and (+)-laurencin(4). Regio- and stereoselective cyclization of the hydroxy epoxides would be the most straightforward access to the stereoselective construction of medium-sized ring ethers. The reaction was designed based on the concept that both activation of a hydroxyl group by formation of a tin ether and an epoxy group by coordination of Lewis acid would promote the cyclization reaction. Expected S_N2 process and exo-mode cyclization would stereospecifically afford either α,ω-cis- or α,ω-trans cyclic ethers depending on the stereochemistry of the hydroxyl group and the epoxy group. At first, model compounds 7a, 7b were investigated to explore the general cyclization reaction. After preparation of a tin ether by treatment with (Bu_3Sn)_2O in toluene, several Lewis acids were examined. In the presence of Zn(OTf)_2, Sn(OTf)_2, Yb(OTf)_3, La(OTf)_3, or Eu(OTf)_3, the cyclization reaction proceeded to afford the corresponding 7-membered cyclic ether 8a, 8b as a sole product in high yield regardless of the geometry of the epoxy group. The application to the synthesis of 8-membered cyclic ether 10a, 10b gave unsatisfactory result. The successful result was obtained by using of Eu(fod)_3 as Lewis acid. The extension of this methodology to the stereospecific construction of α,ω-cis- and trans-disubstituted derivatives were also investigated and gave good result. Synthetic study of (+)-isolaurepinnacin(2), a representative marine natural products containing the 7-membered cyclic ether, was examined by using the above methodology as a key step. The key intermediate 19 was prepared from the acetylene fragment 16 and the epoxy fragment 17. Cyclization of 19 promoted by (Bu_3Sn)_2O/Eu(fod)_3 proceeded smoothly to afford the cyclic ether skeleton 22 as a sole product. To the epoxide 23 obtained from 22, a trans-enyne structure was stereoselectively introduced via the Corey's method. After halogenations of the hydroxyl groups at C_6 and C_<13> with inversion of configuration, total synthesis of (+)-2 has been achieved. Synthetic study of (+)-laurencin(4), a representative 8-membered cyclic ether, was next examined. Retrosynthetic analysis showed the analogous key intermediate 30. Cyclization of 30 by using the above methodology was successful to give 31 stereoselectively in high yield. Introduction of a trans-enyne structure to 33 by the similar procedure to the synthesis of (+)-2 and modifications of the hydroxyl groups at C_6 and C_<12> furnished (+)-4.
天然有機化合物討論会の論文
1997-07-20

16 立体選択的中員環エーテル構築法の開発及び海洋産天然物合成への応用(口頭発表の部)

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