TOTAL SYNTHESIS OF VERTICILLIN A

提出了一种epipolithiodiketopiperazine双（吡咯并吲哚啉）类抗肿瘤抗生素的方法。已经发现这些天然产物抑制c-fos原癌基因转录，这是细胞从细胞复制的G 0期进展到G1期所必需的事件。研究这些天然产物在细胞环境中的作用可能会发现一种新的抗癌治疗靶点。详细介绍了环二硫二酮哌嗪双（吡咯并吲哚啉）轮枝青霉素A的合成路线。轮体青霉素A是由通过双（季）键连接的两个吡咯并吲哚啉组成的二聚体结构。吡咯并吲哚啉含有衍生自L-色氨酸和L-丙氨酸的二硫代酮哌嗪环，并且每个吡咯并吲哚啉进一步用羟基修饰。 所提出的轮枝青霉素A合成引入了一种新的二聚反应，其中使用硅氧烷系链使反应分子内，从而提供熵的优势，并引入区域和立体控制元素，否则非常困难的转换。

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.