Novel electrophilic probes have become a point of interest as a means for researching the reactivity of nucleophilic residues in regulatory proteins. Specifically, the modification of cysteine as a target for Michael additions has been a pivotal focus as a treatment for Chagas disease and the modification of the ERK, Nrf2, and NF-kB biological pathways. Here, we report steps toward the synthesis of fluorinated and non-fluorinated exo-vinyl sultams and sulfonamides for the analysis of covalent modification via thiol and cysteine Michael addition. Preliminary studies using 19F NMR as a means to monitor nucleophile–electrophile reactivity patterns lead us to propose a platform for developing new electrophilic fluorinated sulfur containing small molecules as a tool for reactivity studies for Michael additions and other biologically relevant covalent reactions. Comparative studies utilizing 19F NMR analysis for the optimization of different fluorinated thiol additions to previously synthesized five- and six-membered endo- and exo-vinyl sultams and known drugs as modifiers will also be discussed.

Use of 19F NMR to monitor thiol reactions of sultams, sulfonamides, and known drugs

254th National Meeting (2017)

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