TOTAL SYNTHESIS OF VERTICILLIN A

提出了一种聚硫代二酮哌嗪类抗肿瘤抗生素的研究方法。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到细胞复制G1期进展的必要事件。研究这些天然产物在细胞环境中的作用，可能会发现对抗癌症的新治疗靶点。详细介绍了附硫代二酮哌嗪双吡咯啉噻西林A的合成路线。Verticillin A是由两个吡咯啉通过双（四）键连接而成的二聚体结构。吡咯啉类含有由l -色氨酸和l -丙氨酸衍生而来的二硫代酮哌嗪环，并且每个吡咯啉类进一步修饰有一个羟基。提出的verticillin A合成引入了一种新的二聚化反应，其中使用硅氧烷系链使反应在分子内进行，从而提供熵优势并引入区域和立体控制元素以进行否则非常困难的转化。

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.