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Development of carbon-carbon bond forming reaction under environmentally benign conditions and its application to combinatorial synthesis

环境友好条件下碳-碳键形成反应的进展及其在组合合成中的应用

基本信息

批准号：
16390010
负责人：
NAITO Takeaki
金额：
$ 9.93万
依托单位：
Kobe Pharmaceutical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2007
项目状态：
已结题

项目摘要

1. Carbon-carbon bond formation by radical reactionThe use of water as a solvent has generated considerable interest from both economical and environmental points of view. We have developed novel carbon-carbon forming reactions employing radical as a crucial reaction species and aqueous media as solvent. Newly-found radical reactions are proved to be synthetically useful by completing synthesis of several biologically active compounds.We firstly investigated selective and efficient alkyl radical addition to various types of imine derivatives. Structure of an intermediate generated by alkyl radical addition to oxime ethers was firmly established by carbon, hydrogen, and boron NMR analyses. Total synthesis of an abnormal amino acid, penmacric acid was completed for the first time via our radical addition reaction. Domino type of radical addition-cydization-(trapping) reaction was also developed and used for efficient construction of functionalized cyclic compounds. Novel synthetic route for Martinellic acid, isolated as a first pyrroloquinoline alkaloid was developed.Newly-found radical addition-aldol type of reaction is expected to be an efficient and environmentally benign reaction.2. Rearrangement reaction under mild conditionsRearrangement reaction is one of atom-economy reactions. During our systematic investigation on 1,2-Wittig rearrangement of hydroximates, we completed the total synthesis of (+)-cytoxazone. In our continuing study on [3, 3]-sigmatropic rearrangement of hydrazones under the acylating conditions, we developed a short step and efficient method for the synthesis of benzofurans via acylation of O-aryl oxime ethers under very mild reaction conditions, even in the presence of free hydroxyl group.As an environmentally benign synthetic method, one-pot synthesis of N-alkyl arylamines from oxime ethers was also developed.

1.通过自由基反应形成碳-碳键从经济和环境的角度来看，使用水作为溶剂已经引起了相当大的兴趣。我们开发了新型碳-碳形成反应，采用自由基作为关键反应物种，水介质作为溶剂。通过完成几种生物活性化合物的合成，新发现的自由基反应被证明在合成上有用。我们首先研究了各种类型的亚胺衍生物的选择性和高效的烷基自由基加成。通过碳、氢和硼 NMR 分析，确定了烷基自由基加成到肟醚上生成的中间体的结构。通过我们的自由基加成反应，首次完成了异常氨基酸 Penmacric Acid 的全合成。多米诺骨牌型自由基加成-环化-（捕获）反应也被开发出来并用于有效构建官能化环状化合物。开发了第一个吡咯喹啉生物碱马丁内利酸的合成路线。新发现的自由基加成-羟醛型反应有望成为一种高效且环境友好的反应。2．温和条件下的重排反应重排反应是原子经济反应之一。在对羟肟酸盐1,2-Wittig重排的系统研究中，我们完成了(+)-cytoxazone的全合成。在我们对酰化条件下腙的[3, 3]-σ重排的持续研究中，我们开发了一种在非常温和的反应条件下，甚至在游离羟基存在的情况下，通过O-芳基肟醚的酰化合成苯并呋喃的短步骤、高效的方法。作为一种环境友好的合成方法，由肟醚一锅法合成N-烷基芳胺也发达了。