Abstract: Abstract The pyrrolidine nitroxides with four bulky alkyl substituents adjacent to the N–O∙ group demonstrate very high resistance to reduction with biogenic antioxidants and enzymatic systems. This makes them valuable molecular tools for studying the structure and functions of biomolecules directly in a living cell and for functional EPR and NMR tomography in vivo. The first example of highly strained pyrrolidine nitroxides with both ethyl and tert-butyl groups at each of the α-carbon atoms of the nitroxide moiety with cis-configuration of the tert-butyl groups was prepared using a three-component domino reaction of tert-leucine and 2,2-dimethylpentan-3-one with dimethyl fumarate with subsequent conversion of the resulting strained pyrrolidine into 1-pyrroline-1-oxide and addition of EtLi. The nitroxide has demonstrated unexpectedly fast reduction with ascorbate, the rate constant k2 = (2.0 ± 0.1) × 10−3 M−1s−1. This effect was explained by destabilization of the planar nitroxide moiety due to repulsion with the two neighboring tert-butyl groups cis to each other.

Cite: Zhurko I.F. , Dobrynin S.A. , Glazachev Y.I. , Gatilov Y.V. , Kirilyuk I.A.
2,5-Di-tert-butyl-2,5-diethylpyrrolidine-1-oxyls: Where Is a Reasonable Limit of Sterical Loading for Higher Resistance to Reduction?
Molecules. 2024. V.29. N3. P.599. DOI: 10.3390/molecules29030599 WOS

Dates:

Submitted:	Dec 8, 2023
Accepted:	Dec 26, 2023
Published online:	Jan 25, 2024

Identifiers:

Web of science	WOS:001160269100001
OpenAlex	W4391263349

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