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品的化学和生物学进行详细研究为理解它们的作用模式提供了重要的洞察力，并使开发治疗各种人类疾病的新方法成为可能。这项研究计划致力于通过系统地发现、开发和应用新的合成策略和方法，开发高效、简洁的结构复杂和具有生物活性的天然产物的全化学合成。计划中的合成的一个关键特征是开发了高度化学选择性和立体选择性的转化，从而能够实施新的可推广的合成策略，通常是受到生物遗传学考虑的启发，以快速产生分子复杂性。开发简洁和统一的天然产品系列方法是该计划的一个持续主题，需要同时开发新的方法，以便在复杂的环境中实现高级阶段功能。目标的选择是基于分子结构的新颖性、先前合成研究的匮乏、开发新策略和方法的大量机会、拥有重要的生物活性以及未来化学物质的潜力。 和生物学研究。这项计划将重点研究丰富的环色胺和二酮哌嗪生物碱家族的合成研究。主要的兴趣是定向的、区域选择性的立体选择性和有效的环色胺亚结构的邻接，提供了后期联合以确保具有挑战性的四元立体中心。随着该计划特别关注具有潜在生物活性的二硫代二酮基哌嗪，同时努力开发新的高效方法，使复杂的二酮基哌嗪能够进行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，用于结构验证和详细的化学和生物学研究。正在研究的整个化合物家族公认的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被视为机械工具和新的生物活性化合物，因此它们将通过我们的多学科和合作参与受到持续的评估。

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.