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）：当可以设计有效且大量地制备具有有用生物特性的分子的策略时，有机合成可以对公共健康产生巨大影响。设计允许选择性键合构建的新反应对于实现这一目标至关重要。该提案概述了扩展我的研究小组利用氧化断裂反应创建新的选择性转化的研究的计划，并强调了电子转移过程在具有生物学意义的复杂分子的合成中可以发挥的独特作用。选择这些项目是为了展示反应条件的独特化学选择性和官能团兼容性，并展示氧化裂解反应如何为新的合成策略创造机会。该项目的具体目标包括：利用氧化生成的氧碳鎓离子作为悬垂路易斯酸，以独特的方式引发涉及环氧化物的级联反应，从而获得大部分天然产物乳脱氢甲状腺甾醇。开发一种氧化方法，利用碳-氢键活化形成亲电子试剂。该方法可用于 C-芳基糖苷的合成，并将应用于吗啉醇 A 的全合成。该方法还将用于引发由亲核加成到大环碳阳离子中产生的环化反应，从而导致全合成细胞毒素曲霉内酯 C. 设计一种手性电辅助剂，促进氧化碳氢键活化，从而形成参与非对映选择性加成的亲电子试剂反应。广泛的亲核基团应与该方法兼容，从而提供以前无法通过该方案获得的许多立体化学。公共健康相关性：本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。这些反应将允许有效制备优化这些活性的试剂，并设计独特的工艺，可用于制备表现出广泛活性的化合物，使这项研究与超越提案中定义的领域相关。