STUDIES OF BIOLOGICALLY ACTIVE NATURAL PRODUCTS CONTAINING PYRROLO [2,3-b] INDOLE UTILIZED THE ASYMMETRIC TANDEM REACTIONS

利用不对称串联反应研究含有吡咯并[2,3-b]吲哚的生物活性天然产物

• 批准号: 09672171
• 负责人: KAWASAKI Tomomi
• 金额: $ 1.28万
• 依托单位: MEIJI PHARMACEUTICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09672171/
• 关键词: pyrrolo [2,3-b] indole; flustramine C; Claisen rearrangement; olefination; 2-allyloxyindolin-3-one; asymmetric Claisen rearrangement; optically active ylide; optically active allyl alcohol; ピロロ[2,3-b]インドール; 連続反応

In our studies on total synthesis of alkaloids, aldeemin, amiauromine, flustramine, and peudophynrynaminol, consisting the pyrrolo[2,3-b]indole structure, we have succeeded in synthesis of the desired 3a-allylpyrrolo[2,3-b]indole and in first total synthesis of marine natural product, flustramine C ;1.We found the new methodology for synthesis of 3a-allylpyrrolo[2,3-b]indole ; the tandem reactions, olefination, isomerization, and Claisen rearrangement of 2-(3,3-dimethylallyl)indolin-3-one produced 3,3-disubstituted oxindole, which was reduced to give 3a-(1, 1-dimethylallyl)-pyrrolo[2,3-b]indole. We succeeded in the first total synthesis of marine natural product, flustramine C utilizing our methodology.2.The tandem reactions introduced directly two different substituents to 3-site of indole nucleus, and this procedure is a general method for synthesis of 3,3-disubstituted oxindoles.3.The asymmetric version of the above-mentioned tandem reactions was tried ; olefination, isomerization and Claisen rearrangement of optically active 2-allylindolin-3-one, which was derived from optical active allyl alcohol and 2-bromoindolin-3-one, proceeded stereoselectively to give optically active oxindole in good yield.4.The reaction of a several kind of 2-allylindolin-3-ones with optically active ylides, followed by isomerization to proceed diastereoselective Claisen rearrangement to afford the oxindole, of which diastereomers were easily separated by silica gel column chromatography to give optically active oxindoles.

在我们对由吡咯[2,3-b]吲哚结构组成的生物碱、醛敏、胺嘧啶、氟虫胺和聚phynrynaminol的全合成研究中，我们成功合成了我们期望的3a-烯丙基吡咯[2,3-b]吲哚，并首次全合成了海洋天然产物氟虫胺C；我们发现了合成3a-烯丙基吡咯[2,3-b]吲哚的新方法；2-（3,3-二甲基烯丙基）吲哚-3-酮经串联反应、烯烃化、异构化和Claisen重排生成3,3-二取代吲哚，并还原为3a-（1,1 -二甲基烯丙基）-吡咯[2,3-b]吲哚。我们利用我们的方法首次成功地合成了海洋天然产物氟曲明C。串联反应将两个不同的取代基直接引入到吲哚核的3位上，是合成3,3-二取代吲哚的一般方法。试验了上述串联反应的不对称版本；由光学活性烯丙醇和2-溴吲哚-3- 1合成的光学活性2-烯丙林-3- 1经立体选择性烯烃、异构化和克拉森重排得到光学活性氧吲哚，收率高。几种2-烯丙林-3- 1化合物与旋光性酰化物反应，经异构化，进行非对映选择性clisen重排，得到旋光性氧吲哚，其中非对映体易于用硅胶柱层析分离得到旋光性氧吲哚。

项目成果

T.Kawasaki, R.Terashima, K.Sakaguchi, H.Sekiguchi, and M.Sakamoto: "A Short Route to "Reverse-Prenylated" Pyrrolo [2,3-b] indoles via Tandem Olefination and Claisen Rearrangement of 2-(3,3-Dimethylallyloxy)-indol-3-ones : First Total Synthesis of Flustram

T.Kawasaki、R.Terashima、K.Sakaguchi、H.Sekiguchi 和 M.Sakamoto：“通过 2-( 的串联烯化和克莱森重排实现“反向异戊二烯化”吡咯并 [2,3-b] 吲哚的短途路线

T.Kawasaki 等: "A Short Route to “Reverse-Prenylated"Pyrrolo[2,3-b]indoles via Tandem Olefination and Claisen Rearrangement of 2-(3,3-Dimethylallyloxy)indol-3-ones: First Total Synthesis of Flustramine C" Tetrahedron Lett.37. 7525-7528 (1996)

T. Kawasaki 等人：“通过 2-(3,3-二甲基烯丙氧基)吲哚-3-酮的串联烯化和克莱森重排获得“反向异戊二烯化”吡咯并[2,3-b]吲哚的短途路线：第一个总计Flustramine C" 四面体的合成 Lett.37. 7525-7528 (1996)

T.Kawasaki 等: "A Short Route to “Reverse-Prenylated" Pyrrolo[2, 3-b]indoles via Tandem Olefination and Claisen Rearrangement of 2-(3, 3-Dimethylallyloxy)indol-3-ones : First Total Synthesis of Flustramine C" Tetrahedron Lett.37. 7525-7528 (1996)

T. Kawasaki 等人：“通过 2-(3, 3-二甲基烯丙氧基)吲哚-3-酮的串联烯化和克莱森重排获得“反向异戊二烯化”吡咯并[2, 3-b]吲哚的短途路线：第一个总计Flustramine C" 四面体的合成 Lett.37. 7525-7528 (1996)