Alkynyliodonium Salts and Derived Diyls in Synthesis

炔基碘鎓盐和衍生二基化合物的合成

• 批准号: 7046950
• 负责人: KEN S. FELDMAN
• 金额: $ 23.69万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-01-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7046950
• 关键词: alkaloids; alkynes; antileukemic agent; antineoplastics; carbene; carbopolycyclic compound; chemical addition; cyclization; drug design /synthesis /production; drug screening /evaluation; free radicals; immunosuppressive; iodine; stereochemistry

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.

描述（由申请人提供）：基于炔基碘鎓盐及其衍生的亚烷基卡宾的化学性质的合成策略的持续开发将占据大部分拟议工作。基于炔基碘鎓盐的化学将在针对抗生素的卡那霉素家族的成员（如卡那霉素F）以及设计的类似物的全合成努力中找到购买，所述设计的类似物将用于探测与文献中发现的那些不同的新的作用机制假设。深入了解这些有效抗癌药物的作用机制可以进一步设计和开发新型小分子癌症化疗药物。此外，使用炔基碘鎓盐化学来获得带状二氢吡咯，从而获得用于大环灵菌红素metacycloprodigiosin和链脲菌素B的对映选择性合成的统一策略，这将展示将高价碘化学与下游烯烃复分解转化相联系以有效合成高度官能化的吡咯的价值。这项工作的成功执行将导致分配的绝对立体化学的两个物种，令人惊讶的是，（目前未知的）相对立体化学的链脲菌素B。这些有前途的免疫抑制化合物的完整的立体化学定义将作为一个基础的作用机制和结构活性研究，旨在开发新的移植排斥治疗，具有最小的细胞毒性。