A’-Pyrroline 1-oxides

Substituted 3-hydroxy-2-pyrrolidinones were synthesised via 1,3-DC reactions of furfuryl nitrones with acrylates and subsequent intramolecular cyclisation after N-0 bond reduction. Addition of iV-acryloyl-(2/()-bomane-10,2-sultam to Z-nitrone 83 gave the endo/exo cycloadducts in 85 15 ratio with complete stereoface discrimination <00JOC1590>. The 1,3-DC of pyrroline A-oxide to chiral pentenoates using (-)-/rans-2-phenylcyclohexanol and (-)-8-phenylmenthol as chiral auxiliaries occurred with moderate stereocontrol (39% de and 57% de, respectively) and opposite sense of diastereoselectivity <00EJO3595>. The... 

Pyrroline-A-oxide (258) is isomerized into y-lactam (259) in the presence of lithium diisopropylamine (LDA) (470) and sodium trityl (471). In these reactions, deprotonation at C3 occurs, leading to carbanion (260). Then oxygen migration from Ni to C2 takes place via intermediate formation of oxaziridine... 

A seven step synthesis of (—)-codonopsinine (312) and a ten step synthesis of (—)-radicamine B (310b) also include nucleophilic addition of (4-methoxybenzyl) magnesium chloride and p-benzyloxyphenylmagnezium bromide derivatives to pyrroline-A-oxides as one of the key steps. 

Addition of the Grignard reagent, generated in situ from (375), to nitrone (373) or to 2,5-dimethyl-l-pyrroline-A-oxide, affords biradical (379) or nitrone containing monoradical (380). Furthermore, (380) can be transformed into biradical (381) and triradical (382) (Scheme 2.165) (620). 

Dipolar cycloadditions of 2-tert-butoxycarbonyl-1 -pyrroline A -oxide (627) with several chiral acrylamides (634a-f) (Scheme 2.276) followed by hydrogenolysis of cycloadducts (635) and (636) has been used in the synthesis of enantiopure tert-butyl (2RJ R)- and (2.S. 7a.S )-2-hydroxy-3-oxo-tetrahydro-l II -pyrrolizine-7a(5// )-carboxylates, useful intermediates for the synthesis of Gly-(s-cis)Pro dipeptide mimetic (790). 

The 3 + 2-cycloaddition of pyrroline A-oxide to 2-chloro-2-cyclopropylidene acetate and its spiropentane analogues (60) yields spiro [cyclopropane-1,5 -isoxazolidinejs (61) which undergo a novel cascade ring enlargement to yield indolizinones (62) in high yield (Scheme 21). ... 

ATP, adenosine 5 -triphosphate BH4, 5,6,7,8-tetrahydrobiopterin BMPO, 5- er -butoxycarbonyl-5-pyrroline A-oxide DBNBS, 3,5-dibromo-4-nitrosoben-zene sulfonate DEPMPO, 5-diethoxyphosphoryl-5-methyl-l-pyrroline A-ox-ide DMPO, 5,5-dimethyl- 1-pyrroline A-oxide EMPO, 5-ethoxycarbonyl-5-methyl-l-pyrroline A-oxide GSH, glutathione (y-L-glutamyl-L-cysteinyl-glycine) HRP, horseradish peroxidase MNP, 2-methyl-2-nitrosopropane MPO, myeloperoxidase NAD(P)H, fl-nicotinamine adenine dinucleotide (3 -phosphate), reduced from NMDA, A-methyl-D-aspartic acid PBN, N-tert-butyl-a-phenylnitrone PMN, polymorphonuclear lymphocyte POBN, a-(4-pyridyl-l-oxide)-A-fer -butylnitrone SOD, superoxide dismutase TEMP,... 

The A pyrroline-A-oxides (SO) undergo violently exothermic reactions with DM AD in the absence of solvent.95 In ether at room temperature, unstable products (51) that rearrange exothermically to the pyrrolines (52) are formed this ring fission recalls that of isoxazolium salts.96 With unsymmetrical acetylenes, two modes of cycloaddition are possible. Propiolic acid adds to 50 (R = H), giving an unstable solid... 

Bicyclic isoxazolines obtained by 1,3-dipolar cycloaddition of 1-pyrroline A-oxides with DMAD undergo ring fission at room temperature to give pyrroline derivatives (equation 2) (66CC607). This ring fission is similar to that of isoxazolium salts but requires no external nucleophile (61JA1007). 

Insoluble polymer-supported dipolarophiles such as 92 were used to mask the nitrone moiety of the chiral pyrroline A-oxide 91 to prevent racemization at the vicinal stereogenic center by temporary formation of the resin linked isoxazolidines 93. A thermally induced 1,3-dipolar cycloreversion was used to cleave the product from the resin and restore the 1,3-dipole functionality which underwent intramolecolar 1,3-DC to afford the enantiomerically pure tricyclic isoxazolidine 95 <03SL1889>. 

Bicyclic A(0-Mti-homonucleoside analogues such as 591 were synthesized through 1,3-dipolar cycloaddition of an enantiopure 3-hydroxy-l-pyrroline A -oxide and protected allyl alcohol and subsequent introduction of thymine by a Mitsunobu reaction <2003T5231>. Furthermore, isoxazole, isoxazoline, and isoxazolidine analogues of (7-nucleo-sides such as 592-594 were synthesized by 1,3-dipolar cycloaddition of nitrile oxides and nitrones derived from uracil-5-carbaldehydes with suitable dipolarophiles <2003T4733, 2006T1494>. 

ESR studies (772, 114-118a) are also consistent with the formation of free radicals upon photolysis of alkylcobalamin and coenzyme B12. For example, Lappert and co-workers (776) demonstrated that homolysis of the cobalt-alkyl bond occurs upon photolysis of coenzyme B12 and ethylcobalamin by trapping the 5 -deoxyadenosyl and ethyl radicals produced with (CH3)3CN0. They were able to detect the spin-trapped (CH3)3CN(0)R radicals by ESR spectroscopy. Homolysis of the cobalt-methyl bond was also shown to occur upon anaerobic photolysis of methylcobalamin (777). However, the presence of traces of oxygen in the methanol solvent was shown to affect signiflcantly the photochemistry of methylcobalamin (775). Indeed, under those conditions, the 5,5-dimethyl-1-pyrroline A -oxide (DMPO) spin adducts of both the methyl and hydrogen radicals, 113 and 114, respectively, were detected by ESR spectro-... 

Due to the quite similar structure of HA and other GAGs, e.g. ChS, clear distinction between both species can hardly be established by H NMR. This is, however, possible by using NMR that is characterized by higher resolution than H NMR [249]. The considerable role of HO radicals in the synovial fluids from patients with RA was recently proven also by electron spin resonance spectroscopy (ESR) using the spin trap 5,5-dimethyl-l-pyrroline-A-oxide to convert the highly reactive HO radical into a more stable compound [250]. 

Two years later (1989), the same authors reported the oxygenation and oxidation chemistry of the Mn-substituted POMs XMnnWn039"- (X = P, Si, Ge, or B) and a2-P2MnnWi706i8-.316 These POMs undergo reversible oxygenation at low temperature in toluene or benzene solution but irreversible oxidation above 22°C. The 02 adduct can be intercepted by the spin trap 5,5-dimethyl-1-pyrroline A-oxide (DMPO). EPR spectra indicate formation of a polyanion-02-DMP0 intermediate that decomposes to the oxidized POM. The nonpolar organic solutions of these POMs catalyze the oxidation of 2,6- and 2,4,6-substituted phenols to benzoquinones or polyphenyl ethers, and a POM-02-phenoxy radical intermediate can be detected by EPR. 

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