Carbon-Heteroatom Bond-Forming Reactions

碳-杂原子键形成反应

基本信息

批准号：
8244490
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/8244490
关键词：
Accounting Affect Autoimmune Diseases Azides Azoles Beryllium Biocompatible Materials Biological Biological Factors Biological Phenomena Biology Carbohydrates Carbon Chemicals Chemistry Communities Complex Cyclopropanes Dendrimers Development Diagnostic Neoplasm Staging Dyes Environment Event Family Foundations Goals Heterocyclic Compounds Imidazole Imidazole-Pyrazole Inflammation Investigation Isoxazoles Ligands Light Lipids Methodology Methods Modification Molecular Molecular Probes Molecular Structure Nitrogen Organism Organometallic Chemistry Pattern Peptides Pharmaceutical Chemistry Pharmacologic Substance Physiological Planets Plastics Play Process Property Proteins Publications Publishing Pyrazoles Pyrimidine Pyrroles Quinazolines Reaction Research Resistance Rhodium Role Ruthenium Scientist Structure Surveys System Thiazoles Time Triazoles biological systems catalyst chemical reaction cycloaddition cyclopropane directed evolution drug candidate drug market in vivo interest man novel progenitor programs pyridine research and development scaffold small molecule sound tool

项目摘要

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.

氮杂环普遍存在于天然产物和人造生物活性物质中化合物。尽管已知的杂环系统多种多样，但值得注意的是，其中很少有常用于药物化学。部分原因是导致这些的实用方法杂环要么完全不存在，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。我们从环加成开始唑类的合成方法。在过去几年中，1,2,3-三唑重新引起了人们的兴趣。尽管如此，在绝大多数出版物仍然保持反应性死胡同：将永久的、惰性的连接器结合在一起具有所需功能的分子片段。当人们考虑到这一点时，这并不奇怪这些氮杂环具有出色的稳定性：它们具有极强的抗热降解性且不受严重水解、还原和氧化条件的影响。然而，少数值得注意的这一普遍事实的例外情况为探索合成转化提供了独特的机会其利用 1,2,3-三唑本身作为活性物质，但相当稳定的反应祖产生大量不同杂环化合物的中间体。除了开发合成方法之外，我们还将开发研究生物的方法使用有机叠氮化物的系统。我们将努力开发新的生物正交催化转化通过有机金属化学和化学生物学的研究。最终，我们希望能够提供合成有机、生物和材料化学界提供了一系列用于创建功能结构的工具。