Applications of Electron Transfer Initiated Cyclizations

描述（由申请人提供）：有机合成可以对公共卫生产生巨大影响，当策略可以设计有效和大量制备具有有用生物学特性的分子。设计允许选择性键构建的新反应对于实现这一目标至关重要。本提案概述了扩大我的研究小组在利用氧化断裂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生物学感兴趣的复杂分子中可以发挥的独特作用。这些项目被选中是为了展示独特的化学选择性和反应条件的官能团相容性，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：利用氧化生成的氧羰基离子作为悬垂的路易斯酸，以独特的方式引发涉及环氧化物的级联反应，从而获得很大一部分天然产物乳脱氢thysiferol。开发一种利用碳氢键活化形成亲电试剂的氧化方法。该方法将用于c -芳基糖苷的合成，并将应用于森酚a的全合成。该方法还将用于引发由亲核添加到大环碳阳离子引起的环化反应，从而导致细胞毒素曲霉酰烯c的全合成。导致形成亲电试剂，参与非对映选择性加成反应。广泛的亲核基团应该与这种方法兼容，提供了许多以前无法通过这种方法获得的立体化学途径。公共卫生相关性：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地制备优化这些活性的药物，并设计独特的工艺，可用于制备具有广泛活性的化合物，使本研究与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.