Alkynyliodonium Salts and Derived Diyls in Synthesis

描述(由申请人提供)：基于烷基碘盐及其衍生的烷基亚甲基卡宾的化学合成策略的持续发展将占据提议的大部分工作。基于烷基碘的化学将在所有针对激动素家族成员的合成工作中找到，例如激动素F，以及设计的类似物，这些类似物将用于探索与文献中发现的不同的新的作用机制假说。深入了解这些强效抗癌药物的作用机理，有助于进一步设计和开发新型小分子抗癌化疗药物。此外，在大环灵芝菌素和链霉菌素B的对映选择性合成的统一策略的路线上，利用炔基碘盐化学获得带状二氢吡咯，将展示将高价碘化学与下游烯烃歧化转化联系起来对高效合成高度官能化的吡咯的价值。这项工作的成功实施将导致指定这两个物种的绝对立体化学，令人惊讶的是，链霉菌B的相对立体化学(目前尚不清楚)。这些有希望的免疫抑制化合物的完整立体化学定义将作为旨在开发具有最低细胞毒性的新移植排斥疗法的作用机制和构效研究的基础。

DESCRIPTION (provided by applicant): The continuing development of synthesis strategies based on the chemistry of alkynyliodonium salts and their derived alkylidenecarbenes will occupy the majority of the proposed efforts. The alkynyliodonium salt-based chemistry will find purchase in total synthesis efforts directed toward members of the kinamycin family of antibiotics such kinamycin F, as well as designed analogues that will be used to probe a novel mechanism-of-action hypothesis distinct from those found in the literature. Insight into the mechanism-of-action of these potent anticancer agents can further the design and development of novel small-molecule cancer chemotherapeutics. In addition, use of alkynyliodonium salt chemistry to gain access to belted dihydropyrroles en route to a unified strategy for the enantioselective syntheses of the macrocyclic prodigiosins metacycloprodigiosin and streptorubin B will showcase the value of linking hypervalent iodine chemistry with downstream olefin metathesis transformations for the efficient synthesis of highly functionalized pyrroles. Successful execution of this work will lead to assignment of the absolute stereochemistry of both species, and, surprisingly, the (currently unknown) relative stereochemistry of streptorubin B. The complete stereochemical definition of these promising immunosuppressive compounds will serve as a foundation for mechanism-of-action and structure-activity studies directed toward developing new transplant-rejection therapies that feature minimal cytotoxicity.