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The study was aimed to assess the ability of Borassus flabellifer haustorium methanolic extract (BHE) on de novo glutathione biosynthesis in normal and pro-oxidant exposed cells via Nuclear factor ...

Summary tert-(Hetero)cyclobutanols are important synthetic building blocks. However, previous synthesis of these compounds has mainly focused on the nucleophilic addition of organometallic reagents to (hetero)cyclobutanones. Herein, we disclose a single-electron process for preparing allyl tert-(hetero)cyclobutanols with readily available organosilicon reagents. The success of the reaction is attributed to the favored radical 1,2-silyl transfer over β-carbon elimination of the alkoxyl radicals. The mechanism of the generation of carbon radicals from alkoxyl radicals is distinct from previous photoredox-mediated oxidation of hypervalent silicates. Our reaction shows broad substrate scope and wide functional-group tolerance. With the highly functionalized allyl tert-(hetero)cyclobutanols, we have achieved ring-opening reactions to synthesize thiolated 1,4-diketones and ring-expansion reactions to prepare seven-membered ring compounds.

Control of selectivity is one of the central topics in organic chemistry. Although unprecedented alkoxyl-radical-induced transformations have drawn a lot of attention, compared to selective C-H activation, selective radical O-H activation remains less explored. Herein, we report a novel selective radical O-H activation strategy of diols by combining spatial effects with proton-coupled electron transfer (PCET). It was found that DMSO is an essential reagent that enables the regioselective transformation of diols. Mechanistic studies indicated the existence of the alkoxyl radical and the selective interaction between DMSO and hydroxyl groups. Moreover, the distal C-C cleavage was realized by this selective alkoxyl-radical-initiation protocol.

A computational study of N-hydroxyphthalimidecatalyzed aerobic oxidative cleavage of alkenes is carried out employing density functional theory and high-level coupled-cluster methods, such as coupled-cluster singles and doubles with perturbative triples [CCSD(T)]. Our results demonstrate that the reaction proceeds through the alkoxyl radicals, as opposed to the mechanism suggested by Jiao and co-workers (Org. Lett. 2012, 14, 4158-4161), in which the reaction proceeds via formation of the dioxetane ring. The barriers for the formation of dioxetane derivatives are computed to be higher than SO kcal mol(-1), while the barriers for the formation of alkoxyl radicals are as low as 13 kcal mol(-1). Our results also demonstrate that epoxide derivatives can be formed as intermediates or byproducts under the reaction conditions.

Alkoxyl radicals play important roles in various fields of chemistry. Understanding their reactivity is essential to applying their chemistry for industrial and biological purposes. Hydrogen-atom t...

A mild and convenient method for the synthesis of reverse glycosyl fluorides (RGFs) has been developed that is based on the silver-promoted radical dehydroxymethylative fluorination of carbohydrates. A salient feature of the reaction is that furanoid and pyranoid carbohydrates furnish structurally diverse RGFs bearing a wide variety of functional groups in good to excellent yields. Intramolecular hydrogen atom transfer experiments revealed that the reaction involves an underexploited radical fluorination that proceeds via β-fragmentation of sugar-derived primary alkoxyl radicals. Structurally divergent RGFs were obtained by catalytic C-F bond activation, and our method thus offers a concise and efficient strategy for the synthesis of reverse glycosides by late-stage diversification of RGFs. The potential of this method is showcased by the preparation and diversification of sotagliflozin, leading to the discovery of a promising SGLT2 inhibitor candidate.

The intermolecular radical addition to the carbonyl group is difficult due to the facile fragmentation of the resulting alkoxyl radical. To date, the intermolecular radical addition to ketones, a valuable approach to construct quaternary carbon centers, remains a formidable synthetic challenge. Here, we report the first visible-light-induced intermolecular alkyl boronic acid addition to α-ketoacids enabled by the Lewis acid activation. The

An iron-catalyzed decarboxylative olefination of unstrained carbon-carbon bonds via alkoxyl radical induced C-C bond cleavage is presented. This protocol features mild conditions (room temperature, redox-neutral), good substrate scope and functional group compatibility, as well as excellent stereoselectivity, thus providing a facile access to the distal alkenyl ketones.

We report the first example of oxazoline-/copper-catalyzed alcohol oxidation to generate the alkoxyl radical under additive-free conditions. The resulting alkoxyl radical addition to alkene enables useful C-O bond-forming and selective C(sp3)-C(sp3) radical-radical dimerization/radical-trapping reactions, providing direct access to the 3a,3a'-bisfuro[2,3-b]indoline scaffold for the first time and a wide range of 3-alkoxyl furoindolines with high efficiency.

A new lipophilic spin-trapping flow-injection electron spin resonance (LFI-ESR) system was developed for quantitative detection of DMPO spin-adduct of alkoxyl radical (RO•), which was produced by t...

A challenging deoxygenation of alkoxyl radicals from readily accessible alcohol derivatives was developed, affording facile synthesis of functionalized alkenes with good functional group tolerance under mild reaction conditions. Because alkoxyl radicals can easily undergo β-fragmentations or hydrogen abstractions, this new strategy for deoxygenation of alkoxyl radicals is highly valuable. Moreover, mechanistic studies revealed that the electron-neutral phosphine acts as the deoxygenation reagent.

The oxidation of alcohols to carbonyl compounds using air as the terminal oxidant is highly desirable. As described in previous reports, the abstraction of α-H of the alcohol is the most important step, and it typically requires not only a metal catalyst but also complex ligands, co-catalysts and bases. Herein, we report a practical and efficient method for the oxidation of primary alcohols, secondary alcohols, 1,2-diols, 1,2-amino alcohols, and other α-functionalized alcohols using a commercially available catalyst, Mn2(CO)10, and no additives. Preliminary mechanistic studies indicated that an alkoxyl radical intermediate existed in our system, and a plausible mechanism consistent with the experimental results and literature was proposed.

Peroxyl radicals participate in multiple processes involved in critical changes to cells, tissues, pharmacueticals and foods. Some of these reactions explain their association with degenerative pathologies, including cardiovascular and neurological diseases, as well as cancer development. Azocompounds, and particularly AAPH (2,2'-Azobis(2-methylpropionamidine) dihydrochloride), a cationic water-soluble derivative, have been employed extensively as sources of model peroxyl radicals. A considerable number of studies have reported mechanistic data on the oxidation of biologically-relevant targets, the scavenging activity of foods and natural products, and the reactions with, and responses of, cultured cells. However, despite the (supposed) experimental simplicity of using azocompounds, the chemistry of peroxyl radical production and subsequent reactions is complicated, and not always considered in sufficient depth when analyzing experimental data. The present work discusses the chemical aspects of azocompounds as generators of peroxyl (and other) radicals, together with their contribution to our understanding of biochemistry, pharmaceutical and food chemistry research. The evidence supporting a role for the formation of alkoxyl (RO•) and other radicals during thermal and photochemical decomposition of azocompounds is assessed, together with the potential influence of such species on the reactions under study.

The anomeric alkoxyl radical β-fragmentation (ARF) of carbohydrates possessing an electron-withdrawing group (EWG) at C2, promoted by PhI(OAc)2/I2, gives rise to an acyclic iodide through which a pentavalent atom of phosphorus can be introduced via the Arbuzov reaction. After selective hydrolysis and subsequent cyclization, the phosphonate or phosphinate intermediates can be converted into 2-deoxy-1-phosphahexopyranose and 2-deoxy-1-phosphapentopyranose sugars. The ARF of carbohydrates with an electron-donor group (EDG) at C2 proceeds by a radical-polar crossover mechanism, and the cyclization occurs by nucleophilic attack of a conveniently positioned phosphonate or phosphinate group to the transient oxocarbenium ion. This alternative methodology leads to 5-phosphasugars with a 4-deoxy-5-phosphapentopyranose framework. The structure and conformation of the 2-oxo-1,2-oxaphosphinane and 2-oxo-1,2-oxaphospholane ring systems in different carbohydrate models have been studied by NMR and X-ray crystallography., Financial support by the Investigation Programs of the Ministerio de Economía y Competitividad (No. CTQ2010-18244), Fundación CajaCanarias (No. 2015-BIO08) and the Gobierno de Canarias (No. ProID2017010017) is acknowledged. D.H.-G. thanks the Ministerio de Economía y Competitividad for a fellowship.

Inert chemical bond cleavage and functionalization reactions provide expedient synthetic routes and are fundamental in organic synthesis. Alkoxyl radicals enable inert chemical bond cleavages by hydrogen atom transfer and β-fragmentation reactivity; however their further synthetic transformations and functional group compatibility are limited by traditional alkoxyl radical generation methods. Recently, visible-light-induced alkoxyl radical generation methods have emerged and led to new advancements in inert chemical bond cleavage reactions and subsequent functionalization, with excellent chemoselectivity and functional group compatibility. In this Feature Article, the generation of alkoxyl radicals by different visible-light-induced methods and their common or distinct reactivity are discussed, which are categorized by C(sp3)-H, C(sp3)-C(sp3), and C(sp3)-X bond cleavages and subsequent transformations.

The alkoxyl radical is an essential and prevalent reactive intermediate for chemical and biological studies. Here we report the first donor-acceptor complex-enabled alkoxyl radical generation under metal-free reaction conditions induced by visible light. Hantzsch ester forms the key donor-acceptor complex with N-alkoxyl derivatives, which is elucidated by a series of spectrometry and mechanistic experiments. Selective C(sp3)-C(sp3) bond cleavage and allylation/alkenylation is demonstrated for the first time using this photocatalyst-free approach with linear primary, secondary, and tertiary alkoxyl radicals.

Carbon–carbon bond cleavage/functionalization is synthetically valuable, and selective carbonyl−C(sp3) bond cleavage/alkynylation presents a new perspective in constructing ynamides, ynoates, and ynones. Reported here is the first alkoxyl-radical-enabled carbonyl−C(sp3) bond cleavage/alkynylation reaction by photoredox catalysis. The use of novel cyclic iodine(III) reagents are essential for β-carbonyl alkoxyl radical generation from β-carbonyl alcohols, including alcohols with high redox potential (Epox >2.2 V vs. SCE in MeCN). β-Amide, β-ester, and β-ketone alcohols yield ynamides, ynoates, and ynones, respectively, for the first time, with excellent regio- and chemoselectivity under mild reaction conditions.

Multiple free-radical scavenging (MULTIS) activity in cattle and human sera was evaluated with electron spin resonance spectroscopy. Scavenging rates against six active species, namely hydroxyl radical, superoxide anion, alkoxyl radical, alkylperoxyl radical, methyl radical, and singlet oxygen were quantified. The difference in the electron spin resonance signal intensity in the presence and absence of the serum was converted into the scavenging rates. Comparative MULTIS measurements were made in sera from eight beef cattle, three fetal calves and fifteen healthy human volunteers. Further, we determined the MULTIS value of albumin, the most abundant component in serum. MULTIS values in cattle sera indicated higher scavenging activity against most free radical species tested than human sera. In particular, cattle serum scavenging activities against superoxide and methyl radical were higher than human serum by 2.6 and 3.7 fold, respectively. In cattle serum, albumin appears to play a dominant role in MULTIS activity, but in human serum that is not the case. Previous data indicated that the abundance of uric acid in bovine blood is nearly 80% less than humans; however, this difference does not explain the deviation in MULTIS profile.

The generation and fate of 2,3,6-icosa-O-methyl-β-cyclomaltoheptaos-6-O-yl radical under reductive conditions is described. Two radical cascade reactions are involved: the main one is triggered by a 1,8-HAT of the hydrogen at 5C. The radical can reach the anomeric hydrogen at 1C three sugar units ahead using a six-step sequence. The different hydrogen donor ability of the group 14 hydrides permits one to selectively stop the cascade at 5C, 2C, and 4C to obtain β-CD with a β-l-Idop unit, acyclic hepta-, and hexa-saccharide structures, respectively., Financial support by the Investigation Programs of theMinisterio de Economía y Competitividad (No. CTQ2010-18244), Fundación CajaCanarias (No. 2015-BIO08) and the Gobierno de Canarias (No. ProID2017010017) is acknowledged.

A direct approach to β-iodophosphonates and β-iodophosphine oxides from 2,3-dideoxy-3-phosphoryl carbohydrate derivatives has been achieved by using the anomeric alkoxyl radical 1,2-fragmentation protocol. The reaction has been conducted on carbohydrate derivatives under mild conditions with (diacetoxyiodo)benzene and molecular iodine. Subsequent dehydroiodination afforded the corresponding vinylphosphonates and vinylphosphine oxides.

Four diastereomers of 2-[(trimethylammonium)-methyl]-5-methyltetrahydrofuran-3-ol, trivially named isomuscarine, allo-isomuscarine, epi-isomuscarine, and epiallo-isomuscarine, were prepared as bromide salts from 2,4-like and 2,4-unlike diastereomers of 3-(4-hydroxyhex-5-en-2-oxy)-4-methylthiazole-2(3H)-thione. The strategy for constructing the tetrahydrofuran nucleus of the isomuscarines uses alkenoxyl radical 5-exo-bromocyclization, occurring 2,3-cis-selectively for the 2,4-like-4-hydroxyhex-5-en-2-oxyl radical, and 2,3-trans-selectively for the 2,4-unlike diastereomer. A fraction of 4-hydroxyhex-5-en-2-oxyl radicals cyclizes 6-endo-selectively providing 5-bromo-2-methyltetrahydropyran-4-ols in yields between 3 and 15%. Substituting trimethylamine for bromide in 5-exo-bromocyclized products furnishes isomuscarine bromides, which were structurally characterized by X-ray diffraction and NMR-spectroscopy.

The reaction of dihydroartemisinin (DHA) with solvated electrons (e(solv)(-)) generated under radiolytic conditions showed high pH dependence. The reduction performed under neutral conditions led to the formation of compound P1 deriving from the initial alkoxyl radical as the only detectable product. (C) 2013 Elsevier Ltd. All rights reserved.

A new general methodology for the synthesis of chiral vinylphosphonate and vinylphosphine oxide carbohydrate derivatives has been developed using the anomeric alkoxyl radical fragmentation reaction as the key step. The synthetic sequence proceeded via β-iodophosphonate and β-iodophosphine oxide intermediates, which may be interesting synthons for the introduction of phosphorus into organic molecules. These vinylphosphonates could be easily transformed into 2-methylene-1-phosphapentofuranoses (3-methylene-1,2-oxaphospholanes) and β-aminophosphonates, isosteres of biologically active α-methylene-γ-lactones and β-amino acids, respectively., This work was supported by the Investigation Programs (CTQ2010-18244 and CTQ2007-67492) of the Ministerio de Economía y Competitividad and (SolSub20081000192 and ProID20100088) of the Gobierno de Canarias. D.H.-G. thanks the Ministerio de Economía y Competitividad for a fellowship.

The carbonyl products of the reactions of hydroxyl radicals with three vicinal diols (ethane-1,2-diol, propane-1,2-diol and butane-2,3-diol) have been identified and quantified. Hydroxyl radicals were produced by gamma-radiolysis of N2O-saturated aqueous solutions. The reactions result in the formation of alkoxyl radicals (similar to 15%) followed by beta-fragmentation, and alpha-hydroxyl alkyl radicals that undergo H2O elimination. The latter process is part of a radical chain reaction at higher diol concentrations.

Reported herein is the first visible-light-induced formation of alkoxyl radicals from N-alkoxyphthalimides, and the Hantzsch ester as the reductant is crucial for the reaction. The selective hydrogen atom abstraction by the alkoxyl radical enables C(sp(3))-H allylation and alkenylation reactions under mild reaction conditions at room temperature. Broad substrate variations, including a structurally complexed steroid, undergo the C(sp(3))-H functionalization reaction effectively with high regio- and chemoselectivity.

The mass spectra of highly toxic cycloalkyl alkylfluorophosphonates can be divided into two components: organophosphorus and hydrocarbon. The organophosphorus component is a generalized spectral image of a taxonomic group among those forming a homologous series of cycloalkyl alkylfluorophosphonates. The hydrocarbon component is interpreted as a spectrum of the cycloolefin which is the main product of cycloalkyl alkylfluorophosphonate fragmentation. A method for simulation of the electron ionization mass spectra of these compounds is proposed.

The oxidation of cumene in the presence of a mixture of two initiators, azobisisobutyronitrile and benzoyl peroxide, revealed the antagonistic effect of their action. This phenomenon was explained using mathematical simulation of the process by means of analyzing kinetic schemes. It was shown that the antagonistic effect is a result of formation of alkoxyl radicals at the stage of combination of cumene peroxyl radicals and their further participation in cross-termination reactions with initiator radicals. The temperature dependence of the initiators’ effect has been analyzed.

Treatment of various 3-aryl-1-propanols with 1,3-diiodo-5,5-dimethylhydantoin (DIH) in ethyl acetate or 1,2-dichloroethane under irradiation with a tungsten lamp gave the corresponding chroman derivatives in good to moderate yields. The present reaction proceeds via the initial formation of an alkoxyl radical and the radical cyclization onto the aromatic ring, followed by the oxidation of the formed radical intermediate with DIH to provide the chroman derivative. The same treatment of o-biphenyldimethylcarbinol, o-phenylbenzoic acid, and o-alkylbenzoic acids with DIH provided the corresponding chroman derivatives and lactone derivatives in good yields, respectively.

The oxygen radical absorbance capacity (ORAC) method employs a water soluble azo-radical initiator, AAPH (2,2’-azobis(2-amidinopropane) dihydrochloride) as a free radical generator, by which the fluorescent probe fluorescein is damaged to result in the loss of fluorescence. Antioxidants can protect the probe from the damage and the degree of protection is quantified. Because AAPH has been used as a lipid-peroxidation reagent, “oxygen radical” in ORAC is generally accepted as peroxyl radicals; however, in the present spin trapping experiments using a newly developed spin trap, CYPMPO, there was no indication of peroxyl-radical formation in AAPH decomposition in aqueous media. These spin trapping studies demonstrated that alkoxyl (RO·) radical adduct was the sole product of AAPH decomposition. In contrast, alkyl-peroxyl (ROO·) radical was spin-trapped during the decomposition of a lipid soluble azo-radical initiator AIBN (azobis(isobutyronitrile)) in non-aqueous media. We speculate that alkyl-peroxyl radicals are short-lived in water, rapidly converted into alkoxyl radicals. Although the possibility that ORAC method monitors peroxyl-radical scavenging activity cannot be completely eliminated, spin trapping evidence strongly indicates that ORAC method is a scavenging capacity assay for alkoxyl radicals.

The investigated set of 6-exo-trig cyclizations occurs irreversibly and justifies the use of tetrahydropyran-derived transition structures for rationalizing 2,6-cis, 2,5-trans, and 2,4-cis stereoselectivity in ring-closure reactions of 1-, 2-, and 3-phenyl-6-methyl-5-hepten-1-oxyl radicals. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

The primary alkoxyl radical generated by reaction of 1-(2-hydroxyethyl)-glycosides with (diacetoxyiodo)benzene (DIB) and iodine can undergo regioselective intramolecular hydrogen abstraction (IHA) reactions to furnish four different dioxabicyclic systems derived from carbohydrates. The results strongly suggest that the regiocontrol and feasibility of the cyclisation are dependant not only on geometric and stereoelectronic factors, but also on polar and thermochemical factors. The correct selection of the substituents at the precursors can favour the 1,6-IHA against the 1,5-IHA pathway.

The fragmentation of primary alkoxyl radicals has been scarcely used in synthesis since other competing processes (such as oxidation or hydrogen abstraction) usually predominate. However, when serine derivatives were used as substrates, the scission took place in excellent yields. Tandem scission-allylation, -alkylation, or -arylation reactions were subsequently developed. This one-pot methodology was applied to the synthesis of unnatural amino acids, which are useful synthetic blocks or amino acid surrogates in peptidomimetics.

Primary, secondary, and tertiary alkoxyl radicals add exo -selectively to the olefinic π-bond in bicyclo[2.2.1]heptene to afford exo -2-alkoxybicyclo[2.2.1]hept-3-yl radicals, which are trapped with BrCCl 3 preferentially from the endo face to furnish β-bromohydrine ethers in 23–67% yield.

Complete saturation of a single six-membered ring on fullerene C60 has been achieved. The critical step in this first synthesis of a fully characterized 1,2,3,4,5,6-hexaadduct consisted of a remarkable double 5-exo-trig addition of alkoxyl radicals promoted by lead tetraacetate. Two possible opening pathways ([2 + 2 + 2] retrocycloadditions) for the newly synthesized compound were explored using quantum mechanical calculations. We found that the oxa bridges in the hexaadduct prevent ring opening through the retro[2 + 2 + 2] mechanism due to the high activation barrier and endothermicity of the reaction.

The product distributions observed after visible light irradiation of a series of 1-alkylcycloalkanols ( 1 – 3 ) and bis(pyridine)iodonium tetrafluoroborate (IPy 2 BF 4 ), have been compared with those observed after irradiation of the same substrates in the presence of (diacetoxy)iodobenzene (DIB) and I 2 , i.e. under bona fide conditions for alkoxyl radical generation. The observation of very similar product distributions with the two systems strongly supports the previous hypothesis that alkoxyl radical intermediates are formed after photolysis of substrates 1 – 3 in the presence of IPy 2 BF 4 .

1,1,1-Trihaloalkanes of the types R–CCl 2 I, R–CClBrI, and R–CBr 2 I belonging to 1,1,1-trihalo-1-deoxy- d -arabinitol series of alditols were prepared and fully characterized by anomeric alkoxyl radical fragmentation of the corresponding 2,2-dihalo-2-deoxy- d - arabino -hexopyranose derivatives. The analogous diiodohalo compounds R–CClI 2 and R–CBrI 2 could not be prepared by this methodology. The results strongly suggest that the stability of the mixed trihalo alditols decreases with increasing bulkiness of the halogen atoms.

Various 2-substituted 1,3-dioxolanes, 1,3-dioxanes, and tetrahydrofurans were obtained selectively in good to moderate yields from the corresponding alcohols with PSDIB in the presence of iodine under irradiation conditions. Moreover, PSDIB was repeatedly used for the same reactions keeping good yield of the cyclic product.

Novel entry to synthesize medium-sized cycloalkanones is described. Thus, employment of catalytic (2+2)-cycloaddition for cyclic silyl enol ether followed by radical mediated ring-opening reaction provided medium-sized γ-halocycloalkanones.

The fast flow method with laser induced fluorescence detection of CH3C(O)CH2 was employed to obtain the rate constant of k1 (298 K) = (1.83 ± 0.12 (1σ)) × 1010 cm3 mol−1 s−1 for the reaction CH3C(O)CH2 + HBr CH3C(O)CH3 + Br (1, −1). The observed reduced reactivity compared with n-alkyl or alkoxyl radicals can be attributed to the partial resonance stabilization of the acetonyl radical. An application of k1 in a third law estimation provides ΔfH(CH3C(O)CH2) values of −24 kJ mol−1 and −28 kJ mol−1 depending on the rate constants available for reaction (-1) from the literature. © 2005 Wiley Periodicals, Inc. Int J Chem Kinet 38: 32–37, 2006

Polar bromocyclizations of bishomoallylic alcohols (nucleophilic oxygen), which have methyl and/or phenyl substituents located at positions 1, 4, and/or 5, and cyclizations of the derived alkenoxyl radicals (electrophilicoxygen) followed by bromine atom trapping from BrCCl 3 , proceed with complementary regio-selectivities.

Relative-rate experiments have been carried out, at several different temperatures between 240 and 340 K, to determine the Arrhenius rate parameters for the isomerization of the 1-pentoxyl, 2-pento...

A new synthesis of (−)-muscarine, (+)- allo -muscarine, (−)- epi -muscarine, and (−)- epiallo -muscarine has been devised which utilizes selective alkoxyl radical cyclizations for constructing tri-substituted tetrahydrofuran units. Photolysis of (2 R ,3 S )- N -(3-benzoyloxy-5-hexen-2-oxy)-4-methylthiazole-2(3 H )thione in the presence of BrCCl 3 provided (2 R ,3 S ,5 S )-3-benzoyloxy-5-bromomethyl-2-methyltetrahydrofuran as the major product and the corresponding (2 R ,3 S ,5 R )-isomer as the minor. These building blocks were converted into enantiomerically pure (+)- allo -muscarine (from the major alkoxyl radical cyclization product) and (−)-muscarine (from the minor product). Temperature and substituent effects on the diastereoselectivity of the underlying alkoxyl radical cyclization have been investigated. (−)- epi -Muscarine and (−)- epiallo -muscarine have been prepared likewise, starting from (2 R ,3 R )- N -(3-benzoyloxy-5-hexen-2-oxy)-4-methylthiazole-2(3 H )thione.

The reactivity of 2,2-dimethyl-5-methoxyindan-1-ol ( 1 ) and 2,2-dimethyl-6-methoxytetral-1-ol ( 2 ) radical cations has been studied both in acidic and basic solution. At pH≤4 both 1 + and 2 + undergo C α H deprotonation as the exclusive reaction with k =4.6×10 4 and 3.2×10 4 s −1 , respectively. In basic solution 1 + and 2 + behave as oxygen acids undergoing − OH-induced αOH deprotonation in a diffusion controlled process ( k −OH ≈10 10 M −1 s −1 ). An intermediate alkoxyl radical is formed which undergoes a 1,2-hydrogen atom shift in competition with CC β-scission (with 1 + ) or as the exclusive pathway (with 2 + ). A behavior which is interpreted in terms of the greater ease of ring-opening of a five membered ring as compared to a six-membered one.

Addition of various organic O-centered radicals XO• {i.e. (alkoxycarbonyl)oxyl radicals, ROC(O)O•, [(alkoxycarbonyl)acyl]oxyl radicals, ROC(O)C(O)O•, (carbamoyl)oxyl radicals, R2NC(O)O•, alkoxyl radicals, RO•, and nitroxyl radicals, R2NO•} to alkynes initiates an oxidative radical cyclization cascade, which is terminated by release of a C- or N-centered radical X•. This finding clearly highlights the generality of the recently discovered concept of self-terminating radical oxygenations, through which C≡C triple bonds may be converted into carbonyl groups under very mild reaction conditions. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

10 pages, 2 figures, 2 tables, 7 schemes.-- PMID: 12816493 [PubMed].-- Printed version published Jun 27, 2003., The β-fragmentation of primary alkoxyl radicals, described in many cases as low-yielding and plagued by side reactions, can proceed in satisfactory yields using carbohydrate substrates. The only reaction that can compete significantly with the β-scission is the intramolecular hydrogen abstraction. The ratio of β-fragmentation to hydrogen abstraction can be varied according to the reaction conditions, the stereochemistry of the substituents (e.g., α- or β-anomeric substituents), and the protecting groups chosen. The carbohydrate substrates are easily prepared, and the mild reaction conditions are compatible with most functional groups. The β-scission reaction provides an expedient way toward shorter and less common sugar series and also toward α,ω-differently substituted cyclic ethers. These units are useful building blocks and are present in many natural products with interesting biological activity., This work was supported by the Investigation Programmes PB96-1461 and PPQ2000-0728 of the Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica, Dirección General de Investigación, Ministerio de Ciencia y Tecnología, Spain. We also thank the financial support from FEDER funds. D.H. thanks C.S.I.C.-Comunidad de Canarias for a fellowship.

The oxidation of proteins by free radicals is thought to play a major role in many oxidative processes within cells and is implicated in a number of human diseases as well as ageing. This review summarises information on the formation of radicals on peptides and proteins and how radical damage may be propagated and transferred within protein structures. The emphasis of this article is primarily on the deleterious actions of radicals generated on proteins, and their mechanisms of action, rather than on enzymatic systems where radicals are deliberately formed as transient intermediates. The final section of this review examines the control of protein oxidation and how such damage might be limited by antioxidants.

The autoxidation of six esters, neopentyl butanoate, 2,2-dimethylpropanoate, 3,3-dimethylbutanoate, 2,2-dimethylbutanoate, 2-methylbutanoate and 1,1-[2H2]-neopentyl butanoate, has been studied at 438 K. The reaction products were determined for each system and key reactions leading to the formation and further reactions of the primary products have been identified.Primary products include a range of hydroperoxides which lead to the formation of keto- and hydroxy-esters. Large amounts of neopentanol and the parent carboxylic acid are formed from each ester. It is shown that these are principally oxidation, and not hydrolysis, products.The relative rates of autoxidation of the first five esters mirror the relative rates of attack that occur on reaction with alkoxyl radicals; the sites of attack are on both the alkyl and acyl groups, with the α-alkyl hydrogen atoms on the ester showing particular vulnerability compared to the acyl hydrogen atoms. The analysis of products from the deuterated ester supports this conclusion. p