Generation of Glycosyl Radicals from Glycosyl Sulfoxides and Its Use in the Synthesis of C‐linked Glycoconjugates

We here report glycosyl sulfoxides appended with an aryl iodide moiety as readily available, air and moisture stable precursors to glycosyl radicals. These glycosyl sulfoxides could be converted to glycosyl radicals by way of a rapid and efficient intramolecular radical substitution event. The use of this type of precursors enabled the synthesis of various complex C‐linked glycoconjugates under mild conditions. This reaction could be performed in aqueous media and is amenable to the synthesis of glycopeptidomimetics and carbohydrate‐DNA conjugates.     

葡萄糖氧化酶催化荧光测定的非酶体系研究

多数氧化酶及其底物都是重要的临床检验指标[1]，目前普遍采用酶荧光法或酶显色法，通过氧化酶催化氧化底物生成H刃。，过氧化物酶（HRP）催化H刃2氧化生成荧光／生色底物，实现间接测定［’j．酶法测定的缺点是体系不稳定、反应条件苛刻、费用较高．最近Mitani等［’j报道了非酶法化学发光测定葡萄糖氧化酶，灵敏度高，但需要特殊试剂，且测定时间较长．我们用Fenton反应［‘j将H。O。转化为羟基自由基（“OH），进而氧化对苯二甲酸生成荧光物质，建立了荧光测定葡萄糖氧化酶的非酶法，详细研究了荧光指示剂的选择、Fenton试剂的改进…     

ENDOR AND ESR STUDIES OF RADICALS FORMED IN FRIEDEL-CRAFTS REACTIONS

The present study deals with the study of some Friedel-Crafts alkylating system and the accurate measurement of hyperfine coupling constants by ESR and ENDOR techniques. The results indicate that the observed ESR spectra are due to polycyclic aromatic radical cations formed from their parent hydrocarbons.It is suggested that benzyl halides produced in the Friedel-Crafts alkylating reaction undergo Scholl condensation reaction to give polycyclic aromatic hydrocarbons, which were converted into the corresponding polycyclic aromatic radical cations in the presence of aluminum chloride.     

Mechanistic Insights into the Radical S‐adenosyl‐l‐methionine Enzyme NosL From a Substrate Analogue and the Shunt Products

The radical S‐adenosyl‐l ‐methionine (SAM) enzyme NosL catalyzes the transformation of l ‐tryptophan into 3‐methyl‐2‐indolic acid (MIA), which is a key intermediate in the biosynthesis of a clinically interesting antibiotic nosiheptide. NosL catalysis was investigated by using the substrate analogue 2‐methyl‐3‐(indol‐3‐yl)propanoic acid (MIPA), which can be converted into MIA by NosL. Biochemical assays with different MIPA isotopomers in D₂O and H₂O unambiguously indicated that the 5′‐deoxyadenosyl (dAdo)‐radical‐mediated hydrogen abstraction is from the amino group of l ‐tryptophan and not a protein residue. Surprisingly, the dAdo‐radical‐mediated hydrogen abstraction occurs at two different sites of MIPA, thereby partitioning the substrate into different reaction pathways. Together with identification of an α,β‐unsaturated ketone shunt product, our study provides valuable mechanistic insight into NosL catalysis and highlights the remarkable catalytic flexibility of radical SAM enzymes.     

Scalable Photoelectrochemical Dehydrogenative Cross-Coupling of Heteroarenes with Aliphatic C−H Bonds

Heteroarenes are structural motifs found in many bioactive compounds and functional materials. Dehydrogenative cross-coupling of heteroarenes with aliphatic C−H bonds provides straightforward access to functionalized heteroarenes from readily available materials. Established methods employ stoichiometric chemical oxidants under conditions of heating or light irradiation. By merging electrochemistry and photochemistry, we have achieved efficient photoelectrochemical dehydrogenative cross-coupling of heteroarenes and C(sp³)−H donors through H₂ evolution, without the addition of metal catalysts or chemical oxidants. Mechanistically, the C(sp³)−H donor is converted to a nucleophilic carbon radical through H-atom transfer with chlorine atom, which is produced by light irradiation of anodically generated Cl₂ from Cl⁻. The carbon radical then undergoes radical substitution to the heteroarene to afford alkylated heteroarene products.     

Effect of Molecular Interactions on Electron‐Transfer and Antioxidant Activity of Bis(alkanol)selenides: A Radiation Chemical Study

Understanding electron‐transfer processes is crucial for developing organoselenium compounds as antioxidants and anti‐inflammatory agents. To find new redox‐active selenium antioxidants, we have investigated one‐electron‐transfer reactions between hydroxyl (^.OH) radical and three bis(alkanol)selenides (SeROH) of varying alkyl chain length, using nanosecond pulse radiolysis. ^.OH radical reacts with SeROH to form radical adduct, which is converted primarily into a dimer radical cation (>Se∴Se<)⁺ and α‐{bis(hydroxyl alkyl)}‐selenomethine radical along with a minor quantity of an intramolecularly stabilized radical cation. Some of these radicals have been subsequently converted to their corresponding selenoxide, and formaldehyde. Estimated yield of these products showed alkyl chain length dependency and correlated well with their antioxidant ability. Quantum chemical calculations suggested that compounds that formed more stable (>Se∴Se<)⁺, produced higher selenoxide and lower formaldehyde. Comparing these results with those for sulfur analogues confirmed for the first time the distinctive role of selenium in making such compounds better antioxidants.     

THF: An Efficient Electron Donor in Continuous Flow Radical Cyclization Photocatalyzed by Graphitic Carbon Nitride

Mesoporous graphitic carbon nitride (mpg‐C₃N₄) was found to be an efficient heterogeneous photocatalyst for the metal‐free radical cyclization of 2‐bromo‐1,3‐dicarbonyl compounds. Reactions leading to functionalized cyclopentanes proceed under mild conditions and can be conducted in a continuous flow photoreactor. Compared to the batch reaction, the use of a continuous flow reactor resulted in a significant reduction in reaction time (complete conversion of 0.04 mmol of substrate in a batch was achieved after 4 h, whereas in a flow reactor the same amount of substrate was fully converted into a product within 40 min). Mechanistic studies of the reaction showed that THF plays not only the role of solvent, but is also a crucial hydrogen and electron donor.     

In Situ Direct Mechanistic Transformation from FeCl3-Catalyzed Living Cationic to Radical Polymerizations

A trivalent iron chloride (FeCl₃) catalyst induced both living cationic and radical polymerizations of various monomers in the presence of an appropriate additive or ligand to yield polymers with controlled molecular weights and narrow molecular-weight distributions. The in-situ mechanistic transformation from a living cationic to a radical growing species during the styrene polymerization was achieved in a FeCl₃-based system with the simple addition of phosphine followed by an elevation of the reaction temperature. The growing cationic species was effectively converted into the radical species to produce a series of block copolymers that consist of styrene and various acrylic monomers.     

Scalable Photoelectrochemical Dehydrogenative Cross‐Coupling of Heteroarenes with Aliphatic C−H Bonds

Heteroarenes are structural motifs found in many bioactive compounds and functional materials. Dehydrogenative cross‐coupling of heteroarenes with aliphatic C?H bonds provides straightforward access to functionalized heteroarenes from readily available materials. Established methods employ stoichiometric chemical oxidants under conditions of heating or light irradiation. By merging electrochemistry and photochemistry, we have achieved efficient photoelectrochemical dehydrogenative cross‐coupling of heteroarenes and C(sp³)?H donors through H₂ evolution, without the addition of metal catalysts or chemical oxidants. Mechanistically, the C(sp³)?H donor is converted to a nucleophilic carbon radical through H‐atom transfer with chlorine atom, which is produced by light irradiation of anodically generated Cl₂ from Cl^?. The carbon radical then undergoes radical substitution to the heteroarene to afford alkylated heteroarene products.     

Catalysis of Radical Reactions: A Radical Chemistry Perspective

The area of catalysis of radical reactions has recently flourished. Various reaction conditions have been discovered and explained in terms of catalytic cycles. These cycles rarely stand alone as unique paths from substrates to products. Instead, most radical reactions have innate chains which form products without any catalyst. How do we know if a species added in “catalytic amounts” is a catalyst, an initiator, or something else? Herein we critically address both catalyst‐free and catalytic radical reactions through the lens of radical chemistry. Basic principles of kinetics and thermodynamics are used to address problems of initiation, propagation, and inhibition of radical chains. The catalysis of radical reactions differs from other areas of catalysis. Whereas efficient innate chain reactions are difficult to catalyze because individual steps are fast, both inefficient chain processes and non‐chain processes afford diverse opportunities for catalysis, as illustrated with selected examples.     

The synthesis of carbohydrate-derived acylsilanes and their intramolecular free radical cyclizations with the formation of polyoxygenated cyclopentanes

A convenient way for the synthesis of acylsilanes from arabinose, lyxose, and ribose is developed. All the chiral centers of the carbohydrate templates are conserved, and only the reducing end is transformed into the acylsilane functional group. The non-reducing end of the templates can be converted into a bromide. These bromo acylsilanes undergo efficient intramolecular radical cyclizations to give polyoxygenated cyclopentanes.     

Stereoselection at the Steady State: The Design of New Asymmetric Reactions

Not a new principle , but a shrewd analysis of stereoconvergent reactions is leading to new and highly efficient asymmetric reactions. A prochiral compound can be converted through a clever combination of competing reactions, one of which must be stereoselective, into a sole chiral product (shown above). The strategy is reviewed by using a radical cyclization reaction as an example.     

The study of intramolecular tandem radical cyclizations of acylsilanes with radicalphiles attached on silicon

Radical cyclizations of acylsilanes with radicalphilic pendant introduced on silicon proceeded in a tandem fashion to give spiro products containing a cyclic silyl ether skeleton. Because the alkoxysilyl group can be replaced with a hydroxy group through oxidation, the spiro silyl ethers can be converted into diols. In the case with a radical intermediate carrying 2-oxa-3-sila-6-heptenyl skeleton, products derived from 1,7-endo cyclization were obtained in good yields.     

A simple method to convert atom transfer radical polymerization (ATRP) initiators into reversible addition fragmentation chain-transfer (RAFT) mediators

A simple method to convert atom transfer radical polymerization (ATRP) initiators into reversible addition fragmentation chain-transfer (RAFT) mediators is reported. Poly(methylmethacrylate) (PMMA), poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) and poly(ethylene glycol) (PEG) ATRP initiators were converted into their corresponding RAFT analogues using modified ATRP conditions for polymer chain activation in presence of bis(thiobenzoyl) disulphide.     

S-亚基谷胱甘肽对亚油酸过氧化和苯乙烯聚合的抑制作用的研究

研究了S－亚硝基谷胱甘肽（GSNO）对偶氮二异丁腈(AIBN)引发亚油酸过氧化 和苯乙烯聚合的抑制作用。GSNO的抑制作用可能归结为反应中生砀氮氧自由基的抑 制活性。EPR证据表明,含有AIBN和GSNO的DMSO溶液在无氧和50 ℃下,生成了谷胱 甘肽巯基,2－氰基－2－丙基氮氧自由基。     

Photocatalytic Sulfonylcarbocyclization of Alkynes Using SEt as a Traceless Directing Group: Access to Cyclopentenes and Indenes

Cyclopentenes and indenes are important structural scaffolds in synthetic, medical, and material chemistry. Cyclization of alkynes via remote C?H functionalization is an appealing approach to construct these motifs due to its high efficiency and step-economy. Herein, a traceless directing group strategy was designed to reverse the regioselectivity of radical addition which enabled an unprecedented photocatalytic sulfonylcarbocyclization of terminal alkynes by forming C?C bond on inert C(sp³)?H bond. It offers a facile access to decorated cyclopentenes and indenes under mild conditions. The resultant products could be converted into a set of valuable molecular scaffolds, including a key intermediate of AM-6226. Mechanistic experiments suggest a radical cascade pathway comprising a Markovnikov-type sulfonylation, 1,5-hydrogen atom transfer, 5-endo-trig cyclization, and β-elimination. This study lays further groundwork for the use of anti-Baldwin 5-endo-trig radical cyclization in rapidly assembling five-membered carbocycles.     

Synthesis of complex macromolecules using iterative copper(0)‐mediated radical polymerization

Copper(0) mediated radical polymerization is an efficient and versatile polymerization technique which allows the control of acrylates and methacrylates with an unprecedented maintenance of end group fidelity (～100%) during the polymerization. In this highlight, we summarize recent works using Cu(0)‐mediated radical polymerization for the synthesis of multiblock copolymers via an iterative approach. This approach has been successfully implemented for the synthesis of decablock copolymers, constituted of blocks with a degree of polymerization ranging from 3–4 to 100 units as well as for the preparation of multiblock star polymers. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 2083–2098     

Decarbonylative Radical Coupling of α‐Aminoacyl Tellurides: Single‐Step Preparation of γ‐Amino and α,β‐Diamino Acids and Rapid Synthesis of Gabapentin and Manzacidin A

A new radical‐based coupling method has been developed for the single‐step generation of various γ‐amino acids and α,β‐diamino acids from α‐aminoacyl tellurides. Upon activation by Et₃B and O₂ at ambient temperature, α‐aminoacyl tellurides were readily converted into α‐amino carbon radicals through facile decarbonylation, which then reacted intermolecularly with acrylates or glyoxylic oxime ethers. This mild and powerful method was effectively incorporated into expeditious synthetic routes to the pharmaceutical agent gabapentin and the natural product (?)‐manzacidin A.     

Synthesis of di‐ and tetra‐adducts by addition of polystyrene macroradicals onto fullerene C60

Br‐terminated polystyrenes of controlled molar masses and low polydispersities prepared by atom transfer radical polymerization (ATRP) can be converted to macroradicals using an appropriate catalytic complex (CuBr/bipyridine/100 °C). The addition of this macroradicals PS° to 6–6 bonds of C₆₀ follows a specific atom transfer radical addition mechanism that favors the grafting of even number of chains onto the fullerene core. This peculiar mechanism, resulting from the properties of C₆₀, offers an easy synthetic route toward well‐defined di‐ and tetra‐adducts. In these adducts the disturbance of the electronic structure of the fullerene is kept at its minimum, as only one double bond needs to be opened on the C₆₀ to add two PS chains and only two double bonds are converted to single bonds in the tetra‐adduct. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 3456–3463, 2004     

Perspective on metal-mediated polar monomer/alkene copolymerization

A major unsolved problem in polymer synthesis is the design of efficient metal-mediated systems for the copolymerization of alkenes with polar vinyl monomers, such as acrylates and methacrylates. There are several reasons for the absence of efficient transition metal-based insertion copolymerization catalysts. First, following insertion, the ester group of the acrylate coordinates to the metal thereby hindering subsequent monomer coordination. A second reason stems from the preferred 2,1-insertion of acrylates into metal-carbon bonds resulting in the placement of the ester group on the α-carbon. This makes the metal-alkyl species particularly prone to homolysis because of the enhanced stability of the resultant alkyl radical, one that is essentially the same as the propagating species in radical-initiated acrylate polymerization. In this perspective we focus on this issue of facile metal-carbon bond homolysis, especially following acrylate insertion, using examples from our own work. We suggest ways to circumvent these issues, for example forcing 1,2-insertion by imposing steric crowding at the metal. Finally, we discuss the danger of relying on radical traps as probes for polymerization mechanism. Radical traps can react with metal-hydrides and attenuate metal-centered nonradical reactions. However, even when radical traps fail to stop an observed polymerization, it may be wrong to conclude that a nonradical mechanism is at work since the traps can be destroyed under certain reaction conditions.