权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Asymmetric Synthesis of Nitrogen Heterocycles

氮杂环的不对称合成

基本信息

批准号：
10734529
负责人：
Tomislav Rovis
金额：
$ 33.26万
依托单位：
COLUMBIA UNIV NEW YORK MORNINGSIDE
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-21 至 2027-08-31
项目状态：
未结题

项目摘要

Principal Investigator/Program Director (Last, First, Middle): Rovis, Tomislav Asymmetric Synthesis of Nitrogen Heterocycles Abstract Nitrogen is ubiquitously found in biologically active molecules and pharmaceuticals, the fourth most common element after carbon, hydrogen and oxygen. Its presence impacts interactions with biological targets, pharmacokinetics and pharmacodynamics, as well as myriad physical properties. Given the increased importance of saturation in drug-like molecules, carbon-nitrogen bonds are increasingly stereogenic and thus, methods to incorporate nitrogen should likewise address doing so in stereocontrolled fashion. We have long been interested in constructing saturated nitrogen heterocycles from commonly available feedstocks to address synthetic challenges associates with the most common rings such as piperidines and pyrrolidines. With this competitive renewal, we seek support to address problems associated with acyclic nitrogen containing molecules. Herein we propose a multi-pronged approach to synthesize complex structures containing nitrogen substitution from simple precursors. We focus on using the most commonly available starting materials such as alkenes and dienes, and forge a union to a modestly activated nitrogen coupling partner. Ideal among the latter is the dioxazolone moiety, trivially assembled from carboxylic acids, hydroxylamine and a phosgene equivalent. Importantly, after C-N bond formation, the product is the amide, thereby avoiding subsequent derivatization. We further illustrate that this union can be conducted in an exceedingly complex setting. PHS 398/2590 (Rev. 09/04) Page Continuation Format Page

主要研究者/项目负责人（最后，第一，中间）：Rovis，Tomislav 氮杂环的不对称合成摘要氮在生物活性分子和药物中无处不在，是第四大碳、氢和氧之后的常见元素。它的存在会影响与生物靶标的相互作用，药代动力学和药效学，以及无数的物理性质。鉴于增加饱和的重要性在药物样分子中，碳-氮键越来越立体，因此，引入氮的方法同样应该以立体控制的方式进行。我们早就一直对从通常可获得的原料构建饱和氮杂环感兴趣，解决与最常见的环如哌啶和吡咯烷相关的合成挑战。通过这次竞争性更新，我们寻求支持，以解决与非环氮相关的问题含有分子。在此，我们提出了一种多管齐下的方法来合成含氮的复杂结构从简单的前体取代。我们专注于使用最常用的起始材料，例如烯烃和二烯烃，并与适度活化的氮偶联配偶体结合。后者中的理想是二恶唑酮部分，由羧酸、羟胺和光气简单组装而成相当于重要的是，在C-N键形成后，产物是酰胺，从而避免了随后的反应。衍生化我们进一步说明，这种结合可以在一个非常复杂的环境中进行。 PHS 398/2590（Rev.09/04）