9 糖質由来シクロヘキセノンの3成分連結反応を鍵とした天然物合成 : アクチノボリンの全合成(口頭発表の部)

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Actinobolin 1 is reported to show potent antibiotic, antitumor and antileukemic activity as well as therapeutic effect on autoimmune encephalomyelitis. Due to its unique structure involving perhydroisochromane skeleton possessing an amino function with five contiguous asymmetric carbon centers, many reports on the total synthesis and chemical modification of 1 have appeared. We report here the chiral and stereoselective total synthesis of actinobolin starting from D-glucose, using Ferrier's carbocyclization reaction and three components coupling reaction as the key transformations. Reaction of a substituted cyclohexenone 8 derived from D-glucose by way of Ferrier's carbocyclization, with vinyl cuprate followed by treatment with C3 aldehyde 9 afforded the carbon framework 10 of actinobolin in high yield and in highly stereoselective manner. Reduction of 10 with Me_4NBH(OAc)_3 stereoselectively gave diol 12, whose reaction with TsCl followed by protection of the remaining hydroxyl group generated 13. The requisite lactone 18 having proper functionalities with correct stereochemistries was obtained by reduction of methyl ketone 15, followed by lactonization and introduction of an azide group. Deprotection of TBS group in 18 and subsequent oxidation afforded perhydroisochromane skeleton 21. Hydrogenation of 21 followed by condensation with Cbz-D-alanine gave protected (-)-actinobolin 22. Finally, removal of the Cbz group successfully furnished (-)-actinobolin, an antipode of the natural product. Based on this methodology, formal synthesis of (+)-actinobolin starting from D-glucose was also achieved.
天然有機化合物討論会の論文
2002-09-01

9 糖質由来シクロヘキセノンの3成分連結反応を鍵とした天然物合成 : アクチノボリンの全合成(口頭発表の部)

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