Utility and Application of Chiral, Unsaturated Acylammoniums

手性不饱和酰胺的效用和应用

• 批准号: 1362949
• 负责人: Daniel Romo
• 金额: $ 45万
• 依托单位: Texas A&M University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1362949&HistoricalAwards=false
• 关键词: Utility; Application; Chiral; Unsaturated; Acylammoniums

Through this award, funded by the Chemical Synthesis Program, Prof. Daniel Romo from Texas A&M University is turning to bioinspired organocascade or domino processes that generate multiple bonds and stereocenters in a single operation, significantly increasing the efficiency of bioactive natural product and pharmaceutical synthesis. Organocatalysis involves the use of small, chiral organic molecules to activate substrates and initiate various bond constructions. Generic substrate activation modes, and their implementation in reaction design, have led to an explosion in covalent organocatalysts over the past decade, using judicious combinations of catalytic activation modes. However, there is a paucity of general substrate activation modes, with only limited types revealing multiple reactive sites in a single catalytic cycle. This research will explore a new activation mode that could prove broadly useful for the development of novel organocascade reactions. Undergraduates, working in the Texas A&M Undergraduate MiniPharma Program, will study certain aspects of the proposed methods gaining teamwork and leadership experience, a taste of various aspects of pharmaceutical research, new research skills, and experience with state-of-the-art equipment ultimately contributing to publishable research.This research pursues a novel and broad design principle based on readily generated chiral unsaturated acylammonium salts, significantly impacting the growing field of scaleable, asymmetric organocatalysis. The organocascade processes focus on cycloadditions, enabling highly practical, enantioselective synthetic routes to carbocycles and heterocycles commonly found in bioactive natural products and pharmaceuticals. In addition, the synthesis of recyclable, supported-isothiourea catalysts and mechanistic studies of unsaturated acylammonium intermediates, given their established and increasing importance for organocascade catalysis, are undertaken in collaboration with Prof. Dean Tantillo (UC Davis). The utility of the developed synthetic methods is demonstrated by targeting the synthesis of natural products with compelling bioactivities enabling further fundamental studies at the chemistry/biology interface with Prof. Stephan Sieber (Tech Univ of Munich, Germany). Hypothesis-driven, novel reaction development and empirical laboratory synthetic methods for reaction discovery are employed to reach these objectives.

通过该奖项，由化学合成计划资助，德克萨斯州农工大学的丹尼尔罗莫教授正在转向生物启发的有机级联或多米诺骨牌过程，在一个操作中产生多个键和立体中心，显着提高生物活性天然产物和药物合成的效率。有机催化涉及使用小的手性有机分子来活化底物并引发各种键结构。通用的底物活化模式，以及它们在反应设计中的实现，在过去的十年中导致了共价有机催化剂的爆炸，使用明智的催化活化模式的组合。然而，有一个缺乏一般的底物活化模式，只有有限的类型揭示多个反应位点在一个单一的催化循环。这项研究将探索一种新的活化模式，可以证明广泛适用于新的有机级联反应的发展。 本科生，在得克萨斯州A& M本科生微型制药项目工作，将学习所提出的方法的某些方面，获得团队合作和领导经验，药物研究的各个方面的味道，新的研究技能，并与国家的最先进的设备，最终有助于可持续的研究经验。这项研究追求一个新的和广泛的设计原则的基础上容易产生的手性不饱和酰基铵盐，显著地影响了可规模化的、不对称的有机催化领域。 有机级联工艺专注于环加成，能够实现高度实用的、对映选择性的合成路线，以合成生物活性天然产物和药物中常见的碳环和杂环。此外，与Dean Tantillo教授（加州大学戴维斯分校）合作进行了可回收的，可回收的异硫氰酸酯催化剂的合成和不饱和酰基铵中间体的机理研究，因为它们对有机级联催化的重要性已经确立并日益增加。 开发的合成方法的实用性通过靶向合成具有引人注目的生物活性的天然产物来证明，从而使Stephan Sieber教授（慕尼黑理工大学，德国）能够在化学/生物学界面进行进一步的基础研究。 假设驱动，新的反应发展和经验的实验室合成方法的反应发现，以达到这些目标。