Carbon-Heteroatom Bond-Forming Reactions

碳-杂原子键形成反应

• 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
• 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

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.

氮杂环化合物广泛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的多样性，但值得注意的是它们中的很少 通常用于药物化学。部分原因是导致这些的实际方法 杂环要么完全不存在，要么缺乏其广泛应用所需的通用性。 制定这些方法是本提案的主要目标。我们从环加成反应开始 唑类的合成方法。 1，2，3-三唑在过去几年中再次引起人们的兴趣。但在 绝大多数出版物仍然是反应性死胡同：永久的，惰性的连接器， 具有所需功能的分子片段。这并不奇怪，当一个人考虑到 这些氮杂环的特殊稳定性：它们非常耐热降解 并且不受严重的水解、还原和氧化条件的影响。然而，少数值得注意的 这一普遍真理的例外为探索合成变换提供了独特的机会 其利用1，2，3-三唑本身作为高能但相当稳定的反应性前体， 这些中间体产生过多的不同杂环化合物。 除了开发合成方法，我们还将开发研究生物学的方法。 使用有机叠氮化物的系统。我们将奋进开发新的生物正交催化转化 通过研究有机金属化学和化学生物学。最终，我们希望能给人工合成的 有机，生物和材料化学社区的一系列工具，创造功能结构。