SELECTIVE METHODS FOR SYNTHESIS WITH STRAINED MOLECULES AND CARBENOIDS

应变分子和类胡萝卜素的选择性合成方法

• 批准号: 7736059
• 负责人: JOSEPH M FOX
• 金额: $ 30.6万
• 依托单位: UNIVERSITY OF DELAWARE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-05 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7736059
• 关键词: Address; Alkenes; Biological Sciences; Chemistry; Complex; Cyclization; Cyclopropanes; DNA Sequence Rearrangement; Development; Family; Funding; Glycols; Goals; Grant; Health; Human; Ligands; Methodology; Methods; Organic Synthesis; Outcome; Paper; Pathway interactions; Play; Process; Protocols documentation; Publishing; Pyrrolizidine Alkaloids; Reaction; Research; Rhodium; Ring Compound; Role; Sucrose; Transition Elements; United States National Institutes of Health; carbene; catalyst; computer studies; cycloaddition; cyclopropane; design; diazo compound; drug discovery; flustramine A; insight; interest; public health relevance; small molecule

The goal of the proposed research is to develop selective methods for organic synthesis with strained molecules and rhodium carbenoids. The proposed research involves development of stereoselective transformations of strained three-membered ring compounds. Modes of reactivity that will be explored will include Diels-Alder reactions, and tandem Ring expansion/Claisen rearrangments of allyl cycloprop-2-ene carboxylates. Of particular interest is the unusual ability of strained molecules to control the stereochemical outcome of such reactions. Another goal of the proposed research is to expand the scope of Rh-carbenoid chemistry. Of particular interest is the development of ligands that facilitate reactions of )-alkyldiazo compounds, which are susceptible to (R)- hydride elimination. With insight from computational studies, catalysts will be designed that can navigate away from undesired reaction pathways and provide desired products with maximum selectivity. Because Rh-carbeniods are critical to the synthesis of cyclopropenes and cyclopropanes, addressing the limitations of the chemistry of Rhcarbenes is integral to advancing all aims of this proposal. A final aspect of this program will be to develop general, stereoselective methods for the synthesis of medium ring trans-cycloalkenes. Also developed will be new stereospecific reaction chemistry that transfers the planar chirality of the alkene to newly created stereocenters in products. Reactions to be studied include transannular cyclization reactions, and a stereoselective protocol for synthesizing trans-1,2-diols. Applications will include the development of a unified approach to the synthesis of a family of pyrrolizidine alkaloids.

拟议研究的目的是开发有机合成的选择性方法 分子和hod恒甲苯二甲酸胺。拟议的研究涉及 紧张的三元环的立体选择性转换的发展 化合物。将要探索的反应性模式将包括Diels-Alder反应， 和串联环膨胀/烯丙基环丙醇蛋白酶-2-Ene的Claisen重排 羧酸盐。特别感兴趣的是应变分子控制的异常能力 这种反应的立体化学结果。拟议研究的另一个目标是 扩大Rh-Carbenoid化学的范围。特别感兴趣的是发展 促进） - 碱性化合物的反应的配体，这些化合物容易受到（r） - 氢化物消除。有了计算研究的洞察力，将设计催化剂 可以远离不希望的反应途径并提供所需的产品 具有最大选择性。因为Rh-Carbeniods对于合成至关重要 环丙烯和环丙烷，解决了化学的局限性 Rhcarbenes是推进该提案的所有目标不可或缺的一部分。最后一个方面 程序将是开发一般的立体选择方法来合成培养基 环反环烯烃。还开发的是新的立体特异性反应化学 这将烯烃的平面性手性转移到了新创建的立体中心 产品。要研究的反应包括经隔离环化反应，A 合成反式1,2-二醇的立体选择性方案。申请将包括 开发统一的方法来合成吡咯烷碱性生物碱家族。