Applications of Electron Transfer Initiated Cyclizations

电子转移引发环化的应用

• 批准号: 7692246
• 负责人: Paul E Floreancig
• 金额: $ 28.16万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7692246
• 关键词: Acids; Area; Biological; Biological Factors; Carbon; Cations; Chemicals; Complex; Cyclization; Cytotoxic agent; Cytotoxin; Development; Electron Transport; Electrons; Epoxy Compounds; Evolution; Excision; Exercise; Exhibits; Funding; Glycosides; Goals; Health; Human; Hydrogen Bonding; Ions; Methods; Molecular; Operative Surgical Procedures; Organic Synthesis; Oxidants; Peptide Signal Sequences; Play; Preparation; Process; Property; Protein phosphatase; Protocols documentation; Public Health; Reaction; Reagent; Research; Research Proposals; Role; Signal Transduction; Stereoisomer; Structure; Theoretical model; Transcend; Work; base; cancer cell; cytokine; design; functional group; improved; inhibitor/antagonist; interest; meetings; nucleophilic addition; oxidation; programs; public health relevance

DESCRIPTION (provided by applicant): Organic synthesis can have a dramatic impact on public health when strategies can be devised to prepare molecules with useful biological properties efficiently and in large quantity. Designing new reactions that allow for selective bond construction is essential to meet this objective. This proposal outlines plans for expanding upon my research group's studies in utilizing oxidative fragmentation reactions in creating new selective transformations, and highlights the unique role that electron transfer processes can play in the synthesis of complex molecules of biological interest. The projects have been selected to show the unique chemoselectivity and functional group compatibility of the reaction conditions and to demonstrate the manner in which oxidative cleavage reactions create opportunities for new synthetic strategies. Specific goals for this project include: Utilizing oxidatively-generated oxocarbenium ions as pendent Lewis acids to initiate cascade reactions involving epoxides in unique ways that will provide access to a significant portion of the natural product lactodehydrothyrsiferol. Developing an oxidative method to use carbon-hydrogen bond activation to form electrophiles. This approach will be useful in the synthesis of C-aryl glycosides and will be applied to the total synthesis of morinol A. The method will also be used to initiate cyclization reactions that result from nucleophilic additions into macrocyclic carbocations, leading to a total synthesis of the cytotoxin aspergillide C. Devising a chiral electroauxiliary that promotes oxidative carbon-hydrogen bond activation, resulting in the formation of an electrophile that engages in diastereoselective addition reactions. A wide range of nucleophilic groups should be compatible with this method, providing access to numerous stereochemically that could not previously be accessed through this protocol. PUBLIC HEALTH RELEVANCE: The projects that are described in this proposal involve the use of electron transfer to prepare molecules that have important biological activities, such as destroying cancer cells and altering cell signalling sequences. These reactions will allow for efficient preparations of agents that optimize these activities and for the design of unique processes that can be used to prepare compounds that exhibit a wide range activities, making this research relevant to areas that transcend those that are defined in the proposal.

描述（由申请人提供）：当可以设计策略以有效地和大量的生物学特性制备分子时，有机合成可能会对公共卫生产生巨大影响。设计允许选择性债券构建的新反应对于满足这一目标至关重要。该建议概述了扩大我的研究小组在创造新的选择性转化中利用氧化碎片反应的研究的计划，并强调了电子传递过程在合成生物学兴趣的复杂分子中可以发挥的独特作用。已选择这些项目以显示反应条件的独特化学选择性和功能组兼容性，并证明氧化裂解反应为新的合成策略创造了机会。该项目的具体目标包括：利用氧化产生的氧化核离子作为垂直刘易斯酸来启动涉及环氧化物的级联反应，以独特的方式，将提供访问大部分天然产物乳dode饮硫胆酚的大部分。开发一种使用碳 - 氢键活化的氧化方法形成电力物。这种方法将在C-芳基糖苷的合成中有用，并将应用于Morinol A的总合成A。该方法还将使用该方法来引发来自亲核细胞碳纤维中的环化反应引起的环化反应。激活，导致形成从事非对映选择性添加反应的亲电体。多种亲核基团应与该方法兼容，从而提供了以前无法通过该协议访问的几个立体化学访问。公共卫生相关性：该提案中描述的项目涉及使用电子转移来制备具有重要生物学活性的分子，例如破坏癌细胞和改变细胞信号序列。这些反应将允许对优化这些活动的代理进行有效的制备，并设计可用于制备展示广泛活动的化合物的独特过程，从而使这项研究与超越提案中定义的领域相关。