The Development Of A New Entry Point Into Enantiomerically Enriched Sulfinyl Derivatives

Optical probes may be used as reliable tools for detecting and imagining the inside of cells for medical diagnostics. Among available options, the use of thiol probes is of interest as thiols are present in nearly all cells and their levels are tightly regulated, thus any variation is associated with disease. A proper thiol bioimaging probe must have a thiol cleavage group/reactive group and a fluorophore. It is found that novel sulfinate aryl ester (phenoxysulfinate esters) probes selectively cleave thiols at physiological pH and show much promise as effective tools for bioimaging. In this context, the synthesis of the related sulfinate alkyl esters has been extensively reported in the chemical literature. In contrast, the synthesis and application of sulfinate aryl esters has been much less explored. Recently, Menezes, Oliveira, and coworkers reported the attempted synthesis of sulfinate aryl esters but failed to accomplish this goal due to the reactive nature of these compounds. Our interest in the synthesis of the sulfinate aryl esters is two-fold: (1) the development of a facile methodology for the synthesis of sulfinate aryl esters for bioimaging, and (2) the development of sulfinate aryl esters as activated sulfinate esters that would be able to serve as cost-effective, shelf stable reagents allowing for the direct synthesis of sulfinate alkyl esters. This presentation will discuss the development of a new synthetic method for sulfinate aryl esters (phenoxysulfinate esters), their relative stabilities, and their application in the synthesis of sulfinate alkyl esters as stand-alone reagents. Finally, this work will also evaluate other processes that involve the rapid and efficient synthesis of sulfinate alkyl and aryl esters