Synthesis of bisindole derivatives using immobilized indolylmetal compounds

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。已知双吲哚基马来酰亚胺具有PKC抑制活性，据报道双吲哚基苯醌具有独特的胰岛素样活性。一些双吲哚吡啶对肿瘤细胞也有细胞毒活性。为了建立一种通用的方法来合成这些双吲哚衍生物，我们研究了这些化合物的固相合成和含氟合成。发现固定化吲哚硼是固相合成的有效方法，并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是有效的，而序贯偶联策略则有利于非对称双吲哚结构的构建。氟合成已被证明可用于利用含氟硅胶萃取分离含氟标记的化合物和未标记的化合物，并开发了一种新的磺酰基型标记物用于合成带标记的双吲哚。利用该磺酰氟标记物合成了双吲哚基苯醌。

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.