Synthesis and Study of Cyclotryptamine and Diketopiperazine Alkaloids

描述（由申请人提供）：在基础水平上对复杂天然产物的化学和生物学进行详细研究，为理解其作用模式提供了重要见解，并能够开发治疗各种人类疾病的新方法。该研究计划的重点是通过系统地发现，开发和应用新的合成策略和方法来开发结构复杂和生物活性天然产物的高效和简洁的全化学合成。计划合成的一个关键特征是高度化学选择性和立体选择性转化的发展，使得能够实施新的可推广的合成策略，通常受到生物遗传学考虑的启发，用于快速生成分子复杂性。简明和统一的方法来开发天然产品的家庭，这个计划的持续主题，需要同时开发新的方法，允许在复杂的环境中进行高级功能化。目标的选择是基于分子结构的新奇、先前合成研究的缺乏、开发新策略和方法的大量机会、具有显著的生物活性以及未来化学合成的潜力。 和生物学研究。该计划将侧重于环色胺和二酮哌嗪生物碱丰富家族的合成研究。中心的兴趣是定向的，区域选择性的立体选择性，和有效的邻接的环色胺亚结构提供后期工会，以确保具有挑战性的四级立体中心。该计划特别关注具有潜在生物活性的epidithiodiketopiperazine，同时努力开发新的有效方法，以实现复杂二酮哌嗪的区域选择性和立体选择性硫化。该计划将继续提供稀有和珍贵化合物的合成样品，以进行结构验证和详细的化学和生物学检查。研究中的整个化合物家族的公认生物活性确保了通过这些努力获得的许多相关中间体和衍生物也将作为机械工具和新的生物活性化合物具有很大的前景，因此它们将通过我们的多学科和合作参与进行持续评估。

DESCRIPTION (provided by applicant): The detailed study of the chemistry and biology of complex natural products at a fundamental level provides critical insight to understanding their mode of action and enables development of new approaches for treatment of various human ailments. This research program focuses on the development of efficient and concise total chemical syntheses of structurally complex and biologically active natural products through the systematic discovery, development, and application of new synthetic strategies and methodologies. A key feature of the planned syntheses is the development of highly chemoselective and stereoselective transformations that enable the implementation of new generalizable synthetic strategies, often inspired by biogenetic consideration, for the rapid generation of molecular complexity. The development of concise and unified approaches to families of natural products, a continuing theme of this program, requires the concurrent development of new methodologies allowing advanced stage functionalization in complex settings. The targets are selected based on novelty of molecular architecture, paucity of prior synthetic studies, abundance of opportunities for development of new strategies and methodologies, possession of significant biological activity, and the potential for future chemical and biological studies. This program will focus on synthetic studies of the rich family of cyclotryptamine and diketopiperazine alkaloids. Of central interest is the directed, regioselective stereoselective, and efficient adjoining of cyclotryptamine substructures providing late stage unions to secure challenging quaternary stereocenters. With this program's particular focus on the potently bioactive epidithiodiketopiperazine, a concurrent effort is the development of new efficient methodologies to enable regioselective and stereoselective sulfidation of complex diketopiperazines. This program will continue to provide synthetic samples of rare and precious compounds for structure validation and detailed examination of their chemistry and biology. The well recognized biological activity of the entire family of compounds under investigation ensure that the many related intermediates and derivatives accessed through these efforts will also behold great promise both as mechanistic tools and as new bioactive compounds, and thus they will be subject to continuous evaluation through our multidisciplinary and collaborative engagements.