METHODOLOGY FOR THE SYNTHESIS OF OXYGEN CONTAINING HETEROCYCLES

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 该项目的总体目标是开发新的方法，从简单易制备的起始材料制备复杂的含氮或含氧多环分子。这项工作的重要性在于，多环杂环化合物是无处不在的药物，是许多生物活性的天然产物的组成部分。不幸的是，这些有益的化合物通常难以制备。我的团队正在开发的方法将为生物医学研究人员提供新的工具，以便从微不足道的起始材料中轻松制备结构复杂的分子，用于药物评估。随着研究的进展，我对该方法的范围和局限性有了更好的理解，我的目标是将这些方法应用于医学相关天然产物的合成。 这项工作是基于我发现的一个前所未有的反应（如下面的方案1所示）之间的腙和二甲硫醚二三氟甲磺酸酯，它提供了一个高度反应性的1-氮杂-2-azoniallene盐作为中间体。它与侧链烯烃发生后续反应，同时形成新的碳-碳键和新的碳-氮键，最终产生二氮鎓盐。这是重要的，因为有有限的方法可用于制造碳-碳键，并且该过程的产物是具有有趣的三维结构的多环产物。我们使用这种方法制造的结构可能为药物发现提供有用的药效团。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The overarching objective of this project is to develop new ways to prepare complex nitrogen or oxygen-containing polycyclic molecules from simple and easy to prepare starting materials. The importance of this work lies in the fact that polycyclic heterocycles are ubiquitous in medicinal agents and are components of many biologically active natural products. Unfortunately, these beneficial compounds are often difficult to prepare. The methods my group is developing will provide biomedical researchers new tools to easily prepare structurally complex molecules for medicinal evaluation from trivial starting materials. As the research progresses and I gain a better understanding of the scope and limitations of the methodology, I will aim to apply these methods to the synthesis of medicinally relevant natural products. This work is based on my discovery of an unprecedented reaction (shown in Scheme 1 below) between a hydrazone and dimethylsulfide ditriflate which provides a highly reactive 1-aza-2-azoniallene salt as an intermediate. This undergoes a subsequent reaction with a pendent alkene to form a new carbon-carbon and a new carbon nitrogen bond at one time ultimately yielding a diazenium salt. This is important because there are limited methods available to make carbon-carbon bonds, and the product of this process is a polycyclic product that has interesting 3-dimentional structure. The structures that we make using this methodology may provide useful pharmacophores for drug discovery.