Applications of Electron Transfer Initiated Cyclizations

描述(由申请人提供)：有机合成可以对公众健康产生巨大影响，因为可以设计出有效和大量地制备具有有用生物特性的分子的策略。为了实现这一目标，设计允许选择性键构建的新反应是必不可少的。这项提案概述了扩大我的研究小组在利用氧化裂解反应创造新的选择性转化方面的研究的计划，并强调了电子转移过程在合成具有生物意义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兼容性，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：利用氧化生成的氧卡宾离子作为悬垂的Lewis酸，以独特的方式启动涉及环氧化物的级联反应，从而获得天然产物乳酸脱氢百里香酚的很大一部分。开发一种利用碳氢键活化形成亲电体的氧化方法。这种方法将用于C-芳基糖苷的合成，并将应用于Morinol A的全合成。该方法还将用于引发环化反应，这些反应由大环碳正离子的亲核加成产生，导致细胞毒素Aspergillide C的全合成。设计一种手性电助剂，促进氧化碳氢键活化，导致形成参与非对映选择性加成反应的亲电体。广泛的亲核基团应该与这种方法兼容，提供了许多以前不能通过这种方法获得的立体化学方法。与公共健康相关：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，如摧毁癌细胞和改变细胞信号序列。这些反应将允许高效地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，使这项研究与超出提案中定义的领域相关。

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.