Carbon-Heteroatom Bond-Forming Reactions

碳-杂原子键形成反应

基本信息

批准号：
8056019
负责人：
VALERY V FOKIN
金额：
$ 37.22万
依托单位：
SCRIPPS RESEARCH INSTITUTE, THE
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-05-05 至 2014-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8056019
关键词：
Accounting Affect Autoimmune Diseases Azides Azoles Biocompatible Materials Biological Biological Factors Biological Phenomena Biology Carbohydrates Carbon Chemicals Chemistry Communities Complex Cyclopropanes Dendrimers Development Diagnostic Neoplasm Staging Environment Event Family Foundations Goals Heterocyclic Compounds Imidazole Imidazole-Pyrazole Inflammation Investigation Isoxazoles Ligands Light Lipids Methodology Methods Modification Molecular Molecular Probes Nitrogen Organism Organometallic Chemistry Pattern Peptides Pharmaceutical Chemistry Pharmacologic Substance Physiological Play Process Proteins Publications Publishing Pyrazoles Pyrroles Reaction Research Resistance Rhodium Role Ruthenium Scientist Structure Surveys System Triazoles biological systems catalyst chemical reaction cycloaddition cyclopropane directed evolution drug candidate drug market in vivo interest man novel progenitor programs research and development scaffold sound tool

项目摘要

DESCRIPTION (provided by applicant): Nitrogen heterocycles are ubiquitously present both in natural products and in the man-made bioactive compounds. Despite of the diversity of known heterocyclic systems, it is remarkable how few of them are routinely used in medicinal chemistry. Part of the reason is that practical methods leading to these heterocycles are either absent altogether or lacking the generality required for their widespread utilization. Development of such methods is the main goal of the current proposal. We begin with cycloaddition processes for the synthesis of azoles. 1,2,3-Triazoles have witnessed a resurgence of interest during the last several years. Nevertheless, in the vast majority of publications they remain reactivity cul-de-sacs: permanent, inert connectors that unite molecular fragments with a desired function. This is not surprising when one takes into account the exceptional stability of these nitrogen heterocycles: they are exceedingly resistant to thermal degradation and are not affected by severe hydrolytic, reductive, and oxidative conditions. However, the few notable exceptions to this general truth provide unique opportunities for exploration of synthetic transformations which utilize 1,2,3-triazoles themselves as energetic, but reasonably stable progenitors of reactive intermediates which give rise to a plethora of different heterocyclic compounds. In addition to developing synthetic methodologies, we will develop methods for studying biological systems using organic azides. We will endeavor to develop new bioorthogonal catalytic transformations through studies in organometallic chemistry and chemical biology. Ultimately, we hope to give the synthetic organic, biological, and materials chemistry communities a range of tools for creating functional structures.

描述（由申请人提供）：氮杂环普遍存在于天然产物和人造生物活性化合物中。尽管已知的杂环系统多种多样，但值得注意的是，在药物化学中常规使用的杂环系统却很少。部分原因是导致这些杂环的实用方法要么完全不存在，要么缺乏广泛利用所需的通用性。开发此类方法是当前提案的主要目标。我们从合成唑类的环加成过程开始。在过去几年中，1,2,3-三唑重新引起了人们的兴趣。然而，在绝大多数出版物中，它们仍然是反应性死胡同：将分子片段与所需功能结合起来的永久、惰性连接器。考虑到这些氮杂环的出色稳定性，这一点并不奇怪：它们对热降解具有极强的抵抗力，并且不受严重的水解、还原和氧化条件的影响。然而，这一普遍事实的少数值得注意的例外为探索合成转化提供了独特的机会，这些合成转化利用 1,2,3-三唑本身作为活性中间体的高能但相当稳定的前体，产生大量不同的杂环化合物。除了开发合成方法之外，我们还将开发使用有机叠氮化物研究生物系统的方法。我们将致力于通过有机金属化学和化学生物学的研究开发新的生物正交催化转化。最终，我们希望为合成有机、生物和材料化学界提供一系列创建功能结构的工具。