Alkynyliodonium Salts and Derived Diyls in Synthesis

炔基碘鎓盐和衍生二基化合物的合成

基本信息

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
项目类别：
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

项目摘要

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）：基于烷基二氮盐及其衍生的烷基肾上腺素的化学反应的合成策略的持续发展将占据拟议的大部分努力。基于炔烃盐的化学将发现针对基诺米霉素家族（例如Kinamycin f）的成员的总合成工作，以及设计的类似物，这些类似物将用于探测与文献中发现的新型效法假设。深入了解这些有效的抗癌药的作用机理可以进一步进一步设计和开发新型的小分子癌化学治疗剂。此外，使用炔烃盐化学能够获得带皮带的二氢吡咯的途径，并途径途径途径，以实现巨大环状蛋白蛋白蛋白质元素蛋白质和链霉菌素的对照组合合成的统一策略，并展示与高额iodine Controncoration与下层的高度合成的价值吡咯。 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.