Emerging Applications of Aryl Trifluoromethyl Diazoalkanes and Diazirines in Synthetic Transformations

Ollevier, Thierry; Carreras, Virginie

doi:10.1021/acsorginorgau.1c00027

Cited by 26 publications

(18 citation statements)

References 86 publications

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“…7 When activated with heat or light, the diazirine group loses an equivalent of nitrogen gas to liberate a reactive carbene that can undergo rapid insertion into nearby C–H, O–H, or N–H bonds. 5,8 Shortly after our report in 2019 of a rationally designed bis-diazirine reagent ( 1 ) for crosslinking polyethylene, polypropylene, and other aliphatic polymers 9,10 the use of bis- and tetrakis-diazirines in materials science experienced an explosion of interest (Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

Electronically optimized diazirine-based polymer crosslinkers

et al. 2022

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Section: Introductionmentioning

confidence: 99%

Electronically optimized diazirine-based polymer crosslinkers

et al. 2022

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“…Diazirines are considered relevant chemical scaffolds usually employed as photo-labeling agents [ 11 ]. Their high stability—mainly the aryl-based diazirines—makes them appropriate for such a purpose, and to date several applications of diazirine-based compounds in organic synthesis and medicinal chemistry have been found [ 12 , 13 ]. West et al described the reactivity of the trifluoromethyl diazirine scaffold with amino acid side chains, in order to evaluate the labeling preferences of diazirines for peptidic biomolecules [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Discovery of a Novel Trifluoromethyl Diazirine Inhibitor of SARS-CoV-2 Mpro

et al. 2023

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SARS-CoV-2 Mpro is a chymotrypsin-like cysteine protease playing a relevant role during the replication and infectivity of SARS-CoV-2, the coronavirus responsible for COVID-19. The binding site of Mpro is characterized by the presence of a catalytic Cys145 which carries out the hydrolytic activity of the enzyme. As a consequence, several Mpro inhibitors have been proposed to date in order to fight the COVID-19 pandemic. In our work, we designed, synthesized and biologically evaluated MPD112, a novel inhibitor of SARS-CoV-2 Mpro bearing a trifluoromethyl diazirine moiety. MPD112 displayed in vitro inhibition activity against SARS-CoV-2 Mpro at a low micromolar level (IC50 = 4.1 μM) in a FRET-based assay. Moreover, an inhibition assay against PLpro revealed lack of inhibition, assuring the selectivity of the compound for the Mpro. Furthermore, the target compound MPD112 was docked within the binding site of the enzyme to predict the established intermolecular interactions in silico. MPD112 was subsequently tested on the HCT-8 cell line to evaluate its effect on human cells’ viability, displaying good tolerability, demonstrating the promising biological compatibility and activity of a trifluoromethyl diazirine moiety in the design and development of SARS-CoV-2 Mpro binders.

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“…Upon exposure to heat or light, the strained diazirine heterocycle loses a molecule of nitrogen gas (N 2 ) to generate a highly reactive carbene, which in turn can insert into neighboring C−H bonds [15] . Thus, the use of bis ‐, tetrakis ‐, or poly ‐diazirines provides a convenient and practical method to rationally install molecular crosslinks into commercial polyolefins without the risk of competing fragmentation reactions, and without any requirement for functional groups to be already present along the polymer chain [13b, 16] . Recent structure‐function studies revealed that trifluoromethyl aryl diazirines bearing electron‐rich aryl groups were much more efficient at undergoing C−H insertion than the corresponding electron‐neutral or electron‐poor systems [17a] .…”

Section: Introductionmentioning

confidence: 99%

A Cleavable Crosslinking Strategy for Commodity Polymer Functionalization and Generation of Reprocessable Thermosets

Godwin

Baran³

et al. 2023

Angewandte Chemie

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Covalently crosslinked polymeric materials, known as thermosets, possess enhanced mechanical strength and thermal stability relative to the corresponding uncrosslinked thermoplastics. However, the presence of covalent inter‐chain crosslinks that makes thermosets so attractive is precisely what makes them so difficult to reprocess and recycle. Here, we demonstrate the introduction of chemically cleavable groups into a bis‐diazirine crosslinker. Application of this cleavable crosslinker reagent to commercial low‐functionality polyolefins (or to a small‐molecule model) results in the rapid, efficient introduction of molecular crosslinks that can be uncoupled by specific chemical inputs. These proof‐of‐concept findings provide one potential strategy for circularization of the thermoplastic/thermoset plastics economy, and may allow crosslinked polyolefins to be manufactured, used, reprocessed, and re‐used without losing value. As an added benefit, the method allows the ready introduction of functionality into non‐functionalized commodity polymers.

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Emerging Applications of Aryl Trifluoromethyl Diazoalkanes and Diazirines in Synthetic Transformations

Cited by 26 publications

References 86 publications

Electronically optimized diazirine-based polymer crosslinkers

Electronically optimized diazirine-based polymer crosslinkers

Discovery of a Novel Trifluoromethyl Diazirine Inhibitor of SARS-CoV-2 Mpro

A Cleavable Crosslinking Strategy for Commodity Polymer Functionalization and Generation of Reprocessable Thermosets

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