Synthesis of bisindole derivatives using immobilized indolylmetal compounds

固定化吲哚基金属化合物合成双吲哚衍生物

• 批准号: 16390002
• 负责人: KONDO Yoshinori
• 金额: $ 4.1万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390002/
• 关键词: indole; organometallics; immobilization; solid-phase synthesis; catalysis; bisindole; compound library; fluorous synthesis; 高分子; 金属錯体; パラジウム触媒; 有機ホウ素; 生理活性; 構造解析; 核磁気共鳴

Many biologically active bisindole derivatives have been isolated from natural products. Bisindolylmaleimides are known to show PKC inhibiting activity and a bisindolylbenzoquinone is reported to have an unique insulin-like activity. Some bisindolylpyridines also have cytotoxic activity toward tumor cells. In order to establish a versatile method to synthesize these bisindole derivatives, we investigated solid phase synthesis and fluorous synthesis for these compounds. The use of immobilized indolylboron was found to be effective for the solid phase synthesis and some bisindole derivatives were synthesized. The pseudo dilution effect of polymer support was also found to be effective for the mono coupling of dihalogeno compounds and the sequential coupling strategy was proved to be convenient for the construction of unsymmetrical bisindole structure. Fluorous synthesis was proved to be useful for the separation of fluorous-tagged compounds from non-tagged compounds using fluorous silica gel extraction and a new sulfonyl type tag was developed for the synthesis of tagged bisindoles. A bisindolylbenzoquinone was synthesized using this sulfonyl fluorous tag.

许多具有生物活性的双吲哚衍生物已从天然产物中分离出来。已知双吲哚马来酰亚胺显示PKC抑制活性，并且据报道双吲哚苯醌具有独特的胰岛素样活性。一些双吲哚基吡啶也对肿瘤细胞具有细胞毒活性。为了建立一种合成此类双吲哚衍生物的通用方法，我们对此类化合物的固相合成和氟代合成进行了研究。利用固定化吲哚硼进行固相合成，合成了一些双吲哚衍生物。聚合物载体的伪稀释效应对二卤代化合物的单偶联反应也是有效的，而顺序偶联策略则有利于不对称双吲哚结构的构建.氟合成被证明是有用的分离的氟标记的化合物从非标记的化合物使用氟硅胶萃取和一种新的磺酰基类型的标签被开发用于合成标记的双吲哚。利用该磺酰基荧光标记物合成了双吲哚基苯醌。

项目成果

Palladium-catalyzed alkylative cyclization of alkynals and alkynones : Remarkable tras-addition of organoboronic reagents

钯催化的炔醛和炔酮的烷基化环化：有机硼试剂的显着反式加成

• 发表时间: 2006
• 期刊: Journal of American Chemical Society 128(5)
• 作者: H.Tsukamoto;T.Ueno;Y.Kondo
• 通讯作者: Y.Kondo

Remarkable ligand effect on the palladium-catalyzed double carbonylation of aryl halides

钯催化芳基卤化物双羰基化反应中显着的配体效应

• 发表时间: 2006
• 期刊: Chemical Communications (in press)
• 作者: M.Iizuka;Y.Kondo
• 通讯作者: Y.Kondo

Organic synthesis using organic superbase

使用有机超强碱进行有机合成

• 发表时间: 2005
• 期刊: Yuki Gosei Kagaku Kyokaishi 63(5)
• 作者: Y.Kondo;M.Ueno;Y.Tanaka
• 通讯作者: Y.Tanaka

Functionalization of Alkynes Catalyzed by t-Bu-P4 Base

• DOI: 10.1002/adsc.200404076
• 发表时间: 2004-08
• 期刊: Advanced Synthesis & Catalysis
• 影响因子: 5.4
• 作者: T. Imahori;C. Hori;Y. Kondo

Immobilized indolylboron as a key intermediate for solid phase synthesis of bisindole analogs

固定化吲哚硼作为固相合成双吲哚类似物的关键中间体

• 发表时间: 2006
• 期刊: Heterocycles 67(1)
• 作者: T.Kasahara;Y.Kondo
• 通讯作者: Y.Kondo