Catalytic Stereoselective Olefin Metathesis Reactions

催化立体选择性烯烃复分解反应

• 批准号: 9029019
• 负责人: AMIR H HOVEYDA
• 金额: $ 54.53万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-03-01 至 2020-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9029019
• 关键词: Acids; Alkenes; Amides; Anti-Inflammatory Agents; Antifungal Agents; Biology; Bromides; CASP3 gene; Carbon; Chemistry; Chloride Ion; Chlorides; Complex; Coupling; Development; Dopamine Antagonists; Esters; Fluorides; Future; Goals; Healthcare; Human; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Investigation; Iodides; Isomerism; Laboratories; Lead; Ligands; Medicine; Methods; Molybdenum; Oxidoreductase; PAC1 phosphatase; Preparation; Procedures; Process; Protocols documentation; Reaction; Reagent; Research; Site; Structure; Tungsten; antiproliferative agents; base; cabergoline; carbonyl compound; catalyst; chemical synthesis; cost; cost effective; design; diene; drug development; drug discovery; public health relevance

 DESCRIPTION (provided by applicant): Alkenes are found in a great number of naturally occurring molecules and are employed in some of the most widely used transformations. Processes that allow access to Z or E isomeric forms of olefins efficiently, reliably, with high selectivity and cost- effectively are therefore of great importance to chemistry, biology and medicine. Especially valuable are the catalytic procedures that form alkenes stereoselectively. The proposed studies focus on the design, synthesis and development of molybdenum- and tungsten-based catalysts that can be utilized to facilitate one of the most powerful methods in chemical synthesis: olefin metathesis. A variety of concepts, originally conceived in these laboratories, will be used to introduce the needed new catalysts. The goal is to achieve furnish reactivity and/or selectivity levels that remain entirely out of reach and will have a lasting impat on drug discovery and development. Catalytic methods will be put forth that allow access to a wide range of linear Z- a,b-unsaturated esters and amides, as well as various dienoates. Such entities reside in a myriad of biologically active molecules, and are among the most versatile functional units in chemical synthesis. One of the most critical objectives of the proposed investigations will be the development of efficient catalytic processes that will generate Z-alkeny chloride, bromide, and iodide compounds. These are, again, among the most important and widely used entities in chemistry (e.g., substrates for catalytic cross- coupling); moreover, the ability to incorporate F atoms within organic molecules site- and stereoselectively will be crucial to future drug development. The first examples of catalytically E-selective olefin metathesis reactions will be designed; these processes will deliver valuable E-alkenyl halides. Finally, the first cases of stereoslective catalytic cross-metathesis reactions that generate high-energy trisubstituted alkenes will be introduced. The special utility of the new concepts, catalysts and protocols will be underscored through applications to concise syntheses of biologically significant molecules such as anti-inflammatory agent coriolic acid methyl ester, antiproliferative agent hexachlorosulfolipid as well as alkenyl halide derivatives of dopamine receptor antagonist cabergoline, caspase 3 activator PAC-1, and HMG-C0A reductase swertiamarin.

 描述（由申请人提供）：烯烃存在于大量天然存在的分子中，并用于一些最广泛使用的转化中。因此，允许以高选择性和成本效益有效、可靠地获得烯烃的Z或E异构形式的方法对于化学、生物学和医学非常重要。特别有价值的是立体选择性地形成烯烃的催化方法。 拟议的研究集中在钼和钨基催化剂的设计，合成和开发，可用于促进化学合成中最强大的方法之一：烯烃复分解。这些实验室最初设想的各种概念将用于引入所需的新催化剂。目标是实现完全无法达到的反应性和/或选择性水平，并对药物发现和开发产生持久的影响。 将提出允许获得宽范围的线性Z-a，b-不饱和酯和酰胺以及各种二烯酸酯的催化方法。这些实体存在于无数的生物活性分子中，并且是化学合成中最通用的功能单元之一。拟议的调查的最关键的目标之一将是有效的催化过程，将产生Z-烯基氯，溴，碘化合物的发展。这些是化学中最重要和最广泛使用的实体之一（例如，此外，将F原子引入有机分子中的位置和立体选择性将是至关重要的 未来的药物开发。将设计催化E-选择性烯烃复分解反应的第一个例子;这些过程将提供有价值的E-烯基卤化物。最后，将介绍产生高能三取代烯烃的立体选择性催化交叉复分解反应的第一例。新概念、催化剂和方案的特殊用途将通过应用于生物学上重要的分子的简明合成而得到强调，所述生物学上重要的分子例如抗炎剂科里奥利酸甲酯、抗增殖剂、抗肿瘤剂和抗肿瘤剂。 试剂六氯硫脂以及多巴胺受体拮抗剂卡麦角林、半胱天冬酶3激活剂PAC-1和HMG-C 0A还原酶swertiamarin的烯基卤化物衍生物。