Carbon-Heteroatom Bond-Forming Reactions

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，但在药物化学中常规使用的却很少。部分原因是导致这些杂环的实际方法要么完全缺乏，要么缺乏广泛应用所需的通用性。这种方法的发展是当前提案的主要目标。我们从合成唑的环加成法开始。1,2,3-三唑在过去几年中再次引起人们的兴趣。然而，在绝大多数出版物中，它们仍然是反应性的死胡同：永久的，惰性的连接器，将分子片段与期望的功能结合起来。当人们考虑到这些氮杂环的异常稳定性时，这并不奇怪：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，这一普遍真理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，这些转化利用1,2,3-三唑本身作为活性中间体的能量，但相当稳定的前体，从而产生大量不同的杂环化合物。除了开发合成方法外，我们还将开发使用有机叠氮化物研究生物系统的方法。我们将通过有机金属化学和化学生物学的研究，努力开发新的生物正交催化转化。最终，我们希望为合成有机，生物和材料化学社区提供一系列创建功能结构的工具。

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.