21443-49-2Relevant articles and documents
Does electrophilic activation of nitroalkanes in polyphosphoric acid involve formation of nitrile oxides?
Aksenov, Alexander V.,Aksenov, Dmitrii A.,Aksenov, Nicolai A.,Kirilov, Nikita K.,Kurenkov, Igor A.,Nobi, Mezvah A.,Rubin, Michael,Skomorokhov, Anton A.,Sorokina, Elena A.
, p. 35937 - 35945 (2021/12/02)
The mechanistic rationale involving activation of nitroalkanes towards interaction with nucleophilic reagents in the presence of polyphosphoric acid (PPA) was re-evaluated. Could nitrile oxide moieties be formed during this process? This experiment demonstrates that at least in some cases this could happen, as generated nitrile oxides were successfully intercepted as adducts of [3 + 2] cycloadditions. This journal is
Synthesis of Furoxans and Isoxazoles via Divergent [2 + 1 + 1 + 1] Annulations of Sulfoxonium Ylides and tBuONO
Tang, Zhonghe,Zhou, Yao,Song, Qiuling
, p. 5273 - 5276 (2019/09/03)
We have presented a simple and new method for the divergent assembly of furoxans and isoxazoles in which the [2 + 1 + 1 + 1] annulation reaction of sulfoxonium ylides is reported for the first time. When the reaction was performed using tBuONO
Diacylfuroxans Are Masked Nitrile Oxides That Inhibit GPX4 Covalently
Eaton, John K.,Kramm, Anneke,Ruberto, Richard A.,Schreiber, Stuart L.,Viswanathan, Vasanthi S.
supporting information, (2020/01/02)
GPX4 represents a promising yet difficult-to-drug therapeutic target for the treatment of, among others, drug-resistant cancers. Although most GPX4 inhibitors rely on a chloroacetamide moiety to modify covalently the protein's catalytic selenocysteine residue, the discovery and mechanistic elucidation of structurally diverse GPX4-inhibiting molecules have uncovered novel electrophilic warheads that bind and inhibit GPX4. Here, we report our discovery that diacylfuroxans can act as masked nitrile oxide prodrugs that inhibit GPX4 covalently with unique cellular and biochemical reactivity compared to existing classes of GPX4 inhibitors. These observations illuminate a novel molecular mechanism of action for biologically active furoxans and also expand the collection of reactive groups capable of targeting GPX4.
