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）：当可以设计出有效和大量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卫生产生巨大影响。设计允许选择性键结构的新反应对于实现这一目标至关重要。该提案概述了扩大我的研究小组的研究计划，利用氧化断裂反应创造新的选择性转化，并强调了电子转移过程在合成生物学感兴趣的复杂分子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相容性，并展示氧化裂解反应为新的合成策略创造机会的方式。该项目的具体目标包括：利用氧化生成的氧碳正离子作为侧基刘易斯酸，以独特的方式启动涉及环氧化物的级联反应，这将提供获得天然产物乳糖脱氢胸腺素的重要部分。开发一种利用碳氢键活化形成亲电试剂的氧化方法。这一方法将在C-芳基糖苷的合成中得到应用，并将应用于桑酚A的全合成。该方法还将用于引发亲核加成到大环碳阳离子中产生的环化反应，导致细胞毒素曲霉素C的全合成。设计促进氧化碳-氢键活化的手性电助剂，导致形成参与非对映选择性加成反应的亲电试剂。广泛的亲核基团应该与这种方法相容，提供了许多以前无法通过该方案获得的立体化学方法。公共卫生关系：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，并设计可用于制备表现出广泛活性的化合物的独特工艺，使这项研究与超越提案中定义的领域相关。