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Moving Past Quinone-Methides: Recent Advances toward Minimizing Electrophilic Byproducts from COS/H2S Donors.

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Hydrogen sulfide (H2S) is an important biomolecule that plays key signaling and protective roles in different physiological processes. With the goals of advancing both the available research tools and the… Click to show full abstract

Hydrogen sulfide (H2S) is an important biomolecule that plays key signaling and protective roles in different physiological processes. With the goals of advancing both the available research tools and the associated therapeutic potential of H2S, researchers have developed different methods to deliver H2S on-demand in different biological contexts. A recent approach to develop such donors has been to design compounds that release carbonyl sulfide (COS), which is quickly converted to H2S in biological systems by the ubiquitous enzyme carbonic anhydrase (CA). Although highly diversifiable, many approaches using this general platform release quinone methides or related electrophiles after donor activation. Many such electrophiles are likely scavenged by water, but recent efforts have also expanded alternative approaches that minimize the formation of electrophilic byproducts generated after COS release. This mini-review focuses specifically on recent examples of COS-based H2S donors that do not generate quinone methide byproducts after donor activation.

Keywords: quinone methides; quinone; past quinone; moving past; h2s donors; electrophilic byproducts

Journal Title: Current topics in medicinal chemistry
Year Published: 2021

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