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烷基二烯碳烯的化学合成策略的持续发展将占据拟议工作的大部分。炔基碘鎓盐基化学将在针对抗生素的kinamycin家族成员的总合成努力中找到购买，例如kinamycin F，以及设计的类似物，将用于探索与文献中发现的不同的新的作用机制假设。深入了解这些强效抗癌药物的作用机制可以进一步设计和开发新的小分子癌症化疗药物。此外，在对映选择性合成大环子红素、元环子红素和链霉素B的统一策略中，利用炔基碘盐化学获得带式二氢吡罗，将展示高价碘化学与下游烯烃复分解转化相结合的价值，以高效合成高功能化的吡罗。这项工作的成功执行将导致这两个物种的绝对立体化学分配，并且令人惊讶的是，（目前未知的）链torubin b的相对立体化学。这些有前途的免疫抑制化合物的完整立体化学定义将作为作用机制和结构活性研究的基础，指导开发具有最小细胞毒性的新移植排斥疗法。