TOTAL SYNTHESIS OF VERTICILLIN A

提出了一种合成表硫代二酮基哌嗪双(吡咯吲哚)类抗肿瘤抗生素的方法。这些天然产物已被发现抑制c-fos原癌基因转录，这是细胞从G0发展到G1期细胞复制所必需的事件。研究这些天然产物在细胞环境中的作用可能会导致发现抗癌的新治疗靶点。详细介绍了一种合成二硫代二酮并哌嗪双(吡咯吲哚)轮枝菌素A的合成路线。轮枝菌素A是由两个吡咯吲哚通过双(四)键连接而成的二聚体结构。吡咯吲哚类化合物含有由L-色氨酸和L-丙氨酸衍生的二硫代酮并哌嗪环，并且每个吡咯烷吲哚类化合物还带有羟基装饰。所提出的轮枝菌素A合成引入了一种新的二聚化反应，通过使用硅氧烷链条将反应呈现在分子内，从而提供了熵优势，并引入了区域和立体控制元件来进行原本非常困难的转化。

An approach to the epipolythiodiketopiperazine bis(pyrroloindoline) class of antitumor antibiotics is proposed. These natural products have been found to inhibit c-fos proto-oncogene transcription, an event necessary for the cell's progression from the G0 yields G1 phase of cellular replication. Study of the role of these natural products in the cellular environment could lead to the discovery of a new therapeutic target for the fight against cancer. A synthetic route to the epidithiodiketopiperazine bis(pyrroloindoline) verticillin A is described in detail. Verticillin A is a dimeric structure composed of two pyrroloindolines connected through a bis(quaternary) linkage. The pyrroloindolines contain dithioketopiperazine rings that are derived from L-tryptophan and L-alanine, and each pyrroloindoline is further adorned with an hydroxyl group. The proposed verticillin A synthesis introduces a novel dimerization reaction whereby a siloxane tether is used to render the reaction intramolecular, thus affording an entropic advantage and introducing a regio- and stereocontroling element to an otherwise very difficult transformation.