40 (-)-ペスタロチオプシンAの全合成(口頭発表の部)

概要

論文の詳細を見る
(+)-Pestalotiopsin A (1) was isolated from an endophytic fungus of the Pacific yew tree and showed cytotoxicity and immunosuppressive activity. The structure of 1 is comprised of a cyclobutane ring fused with both an (E)-cyclononene ring and a γ-lactol unit. So far three groups, in addition to our group, have reported a number of synthetic studies of 1. Herein, we report the first total synthesis of (-)-pestalotiopsin A (2), thereby establishing the absolute stereochemistry of natural 1. The total synthesis began with the [2+2] cycloaddition of N-propioloyl Oppolzer's camphorsultam 6 and ketene acetal 7. The 1,4-hydride addition to the adduct 8 and subsequent protonation provided the cyclobutane derivative 9 with an excellent level of stereoselection. Removal of the camphorsultam from 9 provided cyclobutanemethanol 10 with >95% ee, which was converted into the bicyclic lactone 4 in 8 steps. The aldol reaction of 4 with the chiral aldehyde 5, prepared from the known epoxy chloride 16, provided the desired anti-aldol product 21 predominantly. The intramolecular NHK reaction of aldehyde/alkenyl iodide 3, which in turn was derived from 21, proceeded smoothly to provide the cyclized product 23 in 92% yield as a single diastereomer. Considering the highly strained nature of the (E)-cyclononene moiety, the observed high yield of 23 was remarkable. After some examinations examined for the removal of the hydroxy group introduced in 23, we eventually found that the palladium(0)-catalyzed reduction of the mesylate 27 in the presence of NaBH_4 proceeded well without isomerization of the (E)-olefin moiety into the Z-form, providing 28. Finally, the deoxygenated product 28 was converted into (-)-pestalotiopsin A (2), the antipode of natural (+)-pestalotiopsin A (1), in 3 steps.
天然有機化合物討論会の論文
2008-09-01

40 (-)-ペスタロチオプシンAの全合成(口頭発表の部)

スポンサーリンク

概要

著者

関連論文

スポンサーリンク