Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Science, 345 Lingling Lu, Shanghai 200032, China.
J Org Chem. 2012 Sep 7;77(17):7538-47. doi: 10.1021/jo3013385. Epub 2012 Aug 21.
A practical and efficient synthesis of C(3)-trifluoromethanesulfanylated hexahydropyrrolo[2,3-b]indoles 5 from tryptamine derivatives was described. The features of this synthesis included electrophilic activation of C(3) of tryptamine derivatives with "CF(3)S(+)" and cascade ring cyclization by carbamate nucleophile attacking at C(2). Surprisingly, when Lewis acid (BF(3)·OEt(2)) was used as activator instead of proton acid (TsOH·H(2)O) for the electrophilic trifluoromethanesulfanylation of tryptamine derivatives, the uncyclized product 6 was formed preferentially. This sequential trifluoromethanesulfanylation-cyclization protocol was used to synthesize several pyrrolidinoindolinic alkaloid analogues. The cytotoxicity activities of these trifluoromethanesulfanylated alkaloid analogues were evaluated against three cancer cell lines (K562, HeLa, L929).
描述了一种从色胺衍生物中实用且高效合成 C(3)-三氟甲硫基六氢吡咯并[2,3-b]吲哚 5 的方法。该合成的特点包括用“CF(3)S(+)”对色胺衍生物的 C(3)进行亲电活化，以及通过氨基甲酸酯亲核试剂在 C(2)处进攻进行级联环环化。令人惊讶的是，当路易斯酸（BF(3)·OEt(2)）用作亲电三氟甲硫基化色胺衍生物的活化剂而不是质子酸（TsOH·H(2)O）时，优先形成未环化的产物 6。该顺序三氟甲硫基化-环化方案用于合成几种吡咯烷吲哚生物碱类似物。对这些三氟甲硫基化生物碱类似物的细胞毒性活性进行了评估，针对三种癌细胞系（K562、HeLa、L929）进行了评估。
