METHODOLOGY FOR THE SYNTHESIS OF OXYGEN CONTAINING HETEROCYCLES

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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.