Building Addressable Libraries: Olefin Functionalization Reactions and the Development of a Site-Selective, Cleavable Linker

Abstract

Microelectrode arrays are potentially powerful tools for monitoring molecular interactions between small molecules and biological targets in "real-time". Yet while the potential for the arrays is coming into focus, there are still barriers that prevent us from taking full advantage of the devices. Chief among these is the need to construct and characterize molecules on the arrays so that they are specifically located by individually addressable electrodes or groups of electrodes in the array. Currently, we are working on methods to construct larger molecular libraries directly on the arrays, an effort that seeks to avoid transferring the libraries to the array one member at a time. To do so, we need to expand the synthetic toolbox available on the arrays. In that context, olefin functionalization is one of the most powerful strategies in modern organic chemistry because it converts readily available double bonds into a wide array of functional groups. For this reason, we are initially examining the role of cis-dihydroxylation, epoxidation, and diazidation reactions which can play in a site-selective array-based synthesis. The chemistry is already paying dividends. In one application, we have shown that a site-selective cis-hydroxylation reaction can enable a new “safety-catch" linker strategy that is completely orthogonal to the typical deprotection strategies used for diversity of oriented syntheses. The result provides a foundation for future synthetic efforts because it enables full characterization of molecules synthesized by any electrode in an array. In this poster, we will discuss progress towards additional array-based olefin functionalization reactions as well as detail the safety-catch linker strategy mentioned above. Figure 1