46147-14-2

Upstream product

• 19805-75-5 2,2,5,5-tetramethyl-3-pyrroline-3-carboxamide 
• 65594-24-3 1-hydroxy-2,2,5,5-tetramethyl-pyrroline-3-carboxamide 
• 2154-69-0 1-oxyl-2,2,5,5-tetramethyl-3-cyano-3-pyrroline 
• 524036-45-1 1-N-acetoxy-3-carbamoyl-2,2,5,5-tetramethylpyrrolidine 

Downstream Products

• 19805-75-5 2,2,5,5-tetramethyl-3-pyrroline-3-carboxamide 
• 2154-67-8 3-carboxy-2,5-dihydro-2,2,5,5-tetramethyl-1H-pyrrol-1-yloxy 
• 71051-83-7 3-formyl-2,2,5,5-tetramethyl-pyrroline-1-oxyl 

Relevant academic research and scientific papers

Room-temperature electron spin relaxation of nitroxides immobilized in trehalose: Effect of substituents adjacent to NO-group

Trehalose has been recently promoted as efficient immobilizer of biomolecules for room-temperature EPR studies, including distance measurements between attached nitroxide spin labels. Generally, the structure of nitroxide influences the electron spin relaxation times, being crucial parameters for room-temperature pulse EPR measurements. Therefore, in this work we investigated a series of nitroxides with different substituents adjacent to NO-moiety including spirocyclohexane, spirocyclopentane, tetraethyl and tetramethyl groups. Electron spin relaxation times (T1, Tm) of these radicals immobilized in trehalose were measured at room temperature at X- and Q-bands (9/34 GHz). In addition, a comparison was made with the corresponding relaxation times in nitroxide-labeled DNA immobilized in trehalose. In all cases phase memory times Tm were close to 700 ns and did not essentially depend on structure of substituents. Comparison of temperature dependences of Tm at T = 80-300 K shows that the benefit of spirocyclohexane substituents well-known at medium temperatures (～100-180 K) becomes negligible at 300 K. Therefore, unless there are specific interactions between spin labels and biomolecules, the room-temperature value of Tm in trehalose is weakly dependent on the structure of substituents adjacent to NO-moiety of nitroxide. The issues of specific interactions and stability of nitroxide labels in biological media might be more important for room temperature pulsed dipolar EPR than differences in intrinsic spin relaxation of radicals.

Synthesis and spectral properties of polymethine-cyanine dye-nitroxide radical hybrid compounds for use as fluorescence probes to monitor reducing species and radicals

Various hybrid compounds comprised of two types of nitroxide radicals and either a pentamethine (Cy5) or trimethine cyanine (Cy3) were synthesized. The nitroxide radicals were linked either via an ester-bond to one or two N-alkyl carboxyl-terminated groups of Cy5, or via two amido-bonds (aminocarbonyl or carbonylamino group) to the 5-position of the indolenine moieties of Cy5 and Cy3. Changes in fluorescence and ESR intensities of the hybrid compounds were measured before and after addition of Na ascorbate in PBS (pH 7.0) to reduce the radicals. Among the hybrid compounds synthesized, those that linked the nitroxide radicals via an aminocarbonyl residue at the 5-position of the indolenine moieties on Cy5 and Cy3 exhibited a 1.8- and 5.1-fold increase in fluorescence intensity with the reduction of the nitroxide segment by the addition of Na ascorbate, respectively. In contrast, fluorescence intensity was not enhanced in the other hybrid compounds. Thus, the hybrid compounds which exhibited an increase in fluorescent intensity with radical reduction can be used in the quantitative measurement of reducing species such as Fe2+ and ascorbic acid, and hydroxyl radicals. Because these hybrid compounds have the advantage of fluorescing at longer wavelengths-661 (Cy5) or 568 (Cy3) nm, respectively, they can be used to measure radical-reducing species or radicals either in solution or in vivo.

Synthesis, resolution and assignment of absolute configuration of trans 3-amino-1-oxyl-2,2,5,5-tetramethylpyrrolidine-4-carboxylic acid (POAC), a cyclic, spin-labelled β-amino acid

Racemic trans 3-(9-fluorenylmethyloxycarbonylamino)-1-oxyl-2,2,5,5-tetramethylpyrrolid ine-4-carboxylic acid (Fmoc-POAC-OH), prepared by conventional methods, was resolved upon esterification with (aR)-2,2′-dihydroxy-1,1′-binaphthyl. Separation of the obtained diastereomeric monoesters Fmoc-(±)-trans-POAC-O-(aR)-binaphthol by crystallization/chromatography, and removal of the chiral auxiliary by saponification of the aryl ester function furnished both enantiomers (+)-(3R,4R)-Fmoc-POAC-OH and (-)-(3S,4S)-Fmoc-POAC-OH. The absolute configuration of the asymmetric C3, C4 carbons of POAC were assigned from the induced circular dichroism of a flexible biphenyl probe present in the terminally protected dipeptide derivatives Boc-Bip-(+)-POAC-OMe and Boc-Bip-(-)-POAC-OMe (Bip, 2′,1′:1,2;1″,2″:3,4-dibenzcyclohepta-1,3-diene-6 -amino-6-carboxylic acid). This assignment was confirmed by X-ray diffraction analysis of the diastereomeric monoester Fmoc-(+)-trans-POAC-O-(aR)-binaphthol, shown to be (aR,3R,4R). Solution synthesis of peptides to the hexamer level, based on the (3R,4R)-POAC enantiomer combined with (1S,2S)-2-aminocyclopentane-1-carboxylic acid, was carried out to examine coupling conditions at both C- and N-termini of the POAC residue, in view of further syntheses and 3D-structural investigations.

First synthesis of novel spin-labeled derivatives of camptothecin as potential antineoplastic agents

In an effort to improve the stability of labile lactone ring and water solubility of camptothecin, five novel spin-labeled camptothecin derivatives were synthesized in quantitative yield by a simple modification of the carbodiimide method using the combination of scandium triflate (Sc(OTf)3) and 4-dimethylaminopyridine (DMAP), and the in vitro pharmacokinetic determination of the lactones of representative compound 13a showed that the biological life span of their lactone forms in human and mouse plasma significantly increased when compared with their mother compound camptothecin. Also, the in vitro cytotoxicity of compounds 13a-13e against human bladder cancer T-24 showed either similar or better activity than that of the parent drug, camptothecin, and clinically available drug, irinotecan.

Synthesis and enzyme-catalyzed hydrolysis of a radical-masked glycosylated spin-label reagent

N1-Acetoxy-2,2,6,6-tetramethylpiperidin-4-yl 2,3,4,6-tetra-O-benzyl-α- and -β-d-glucopyranosides (3-α, β) and N1-acetoxy-2,2,5,5-tetramethylpyrrolin-3-oyl 2,3,4,6-tetra-O-benzyl-α- and -β-d-glucopyranosylamines (9-α, β) were synthesized in good yield by Schmidt's glycosylation method. Their subsequent O-debenzylation was proceeded successfully to give the desired products 1-α, and 1-β in good yield, and 2-α in a low yield, without 2-β by only short-timed hydrogenolysis in the presence of palladium-on-carbon (Pd-C) in a CHCl3-MeOH solvent system that included concentrated HCl. Upon enzyme-catalyzed hydrolysis, only 2-α was hydrolyzed by the esterase, while both of 1-α and 1-β were not hydrolyzed by any other enzyme such as lipase. These 2-α can likely be used as a new water-soluble radical-masked glycosylated spin-label reagent.

First access to the spin-labelled β-amino acid POAC in an enantiopure state by resolution through its binaphthyl esters

Resolution of trans 3-(9-fluorenylmethyloxycarbonylamino)-1-oxyl-2,2,5,5- tetramethylpyrrolidine-4-carboxylic acid (Fmoc-POAC-OH) was quickly achieved upon esterification with (aR)-1,1′-binaphthyl-2,2′-diol, chromatographic separation of the obtained diastereomers, and facile saponification of the aryl ester function with removal of the chiral auxiliary.

Oxidation of organonitrogen compounds by the methyltrioxorhenium-hydrogen peroxide system

Methyltrioxorhenium catalyzes the reaction of hydrogen peroxide with organonitrogen compounds. The reactions are facile and high yield at room temperature of below. The observed chemistry is similar to that previously described by us using dimethyldioxirane as the oxidant.

Oxidation of Secondary Amines to Nitroxides with Oxone in Aqueous Buffered Solution

Under biphasic conditions (CH2Cl2/H2O) using acetone, oxone, buffer and phase-transfer catalyst Bu4NHSO4-, some secondary amines without α hydrogens are oxidized to their corresponding nitroxides in rapid and good yields.

Synthesis of nitroxide containing polyenes: two chemically modified retinals and their interaction with bacterioopsin

The synthesis and spectroscopic characterization of two retinal analogues is described, the paramagnetic 3-pyrrolin-1-yloxy analogue 1 and its diamagnetic equivalent, the 3-pyrroline analogue 2.Various aspects of the synthesis of the aminoxy group containing polyenes are discussed.Upon interaction with bacterioopsin, both 1 and 2 are incorporated in the protein and form a system with λmax 459 nm.Neither of the two bacteriorhodopsin analogues is photoactive.ESR spectroscopy data of the system containing 1 show that the ring part of the chromophore in the protein is rigidly fixed in orientation.

A CONVENIENT HIGH YIELD SYNTHESIS OF NITROXIDES

Appropriate secondary amines are readily converted to nitroxides by dimethyldioxirane in a rapid, convenient, and essentially quantitative process.