Regio-and Stereo-selective Bioreduction of Diketo-n-butylphosphonate by Baker''''s Yeast

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Synthesis of l‐ and d‐Ubiquitin by One‐Pot Ligation and Metal‐Free Desulfurization

Native chemical ligation combined with desulfurization has become a powerful strategy for the chemical synthesis of proteins. Here we describe the use of a new thiol additive, methyl thioglycolate, to accomplish one‐pot native chemical ligation and metal‐free desulfurization for chemical protein synthesis. This one‐pot strategy was used to prepare ubiquitin from two or three peptide segments. Circular dichroism spectroscopy and racemic protein X‐ray crystallography confirmed the correct folding of ubiquitin. Our results demonstrate that proteins synthesized chemically by streamlined 9‐fluorenylmethoxycarbonyl (Fmoc) solid‐phase peptide synthesis coupled with a one‐pot ligation–desulfurization strategy can supply useful molecules with sufficient purity for crystallographic studies.     

Analysis and Identification of the Chemical Constituents of Ding‐Zhi‐Xiao‐Wan Prescription by HPLC‐IT‐MSn and HPLC‐Q‐TOF‐MS

Ding‐Zhi‐Xiao‐Wan (DZXW) is a famous traditional Chinese medicine (TCM) formula, which is composed of four herbs, Ginseng Radix, Poria, Polygala Radix and Acori Tatarinowii Rhizoma. It has been popularly used for the treatment of emotional disease, like Alzheimer's disease, Parkinson's disease, depression, anxiety, forgetfulness and neurasthenia. In this research, a high‐performance liquid chromatography coupled with ion‐trap tandem mass spectrometry (HPLC‐IT‐MSⁿ) method along with a high‐performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry (HPLC‐Q‐TOF‐MS) method in negative ion mode was established to investigate the major constitutions in DZXW. The extracts were prepared by ultra‐sonication in ethyl acetate, n‐butanol, 95% ethanol and deionized water sequentially as well as in deionized water directly. A Kromasil C18 column was used to separate the extracts of DZXW. Acetonitrile and 0.1% aqueous formic acid (V/V) were used as the mobile phase. A total of 64 components were characterized, including 16 triterpenoids, 14 Polygala saponins, 10 oligosaccharide esters, 6 sucrose esters, 2 xanthone C‐glycosides and 16 ginsenosides.     

Lithium Cyanide Supported by O‐ and N‐Donors

A series of adducts of LiCN, namely [Li(Me₂CO₃)CN], [Li(Et₂CO₃)CN], and [Li(NMP)CN] (NMP = N‐methyl‐2‐pyrrolidone) were prepared by treatment of solvent‐free LiCN with the appropriate donor. The starting material for these approaches, donor‐free LiCN, was quantitatively prepared from Me₃SiCN and Li[Me] in diethyl ether at 0 °C. Alternatively, [Li(NMP)CN] was synthesized by metathesis reaction of LiCl with NaCN in the presence of stoichiometric amounts of NMP. Although [Li(Me₂CO₃)CN] and [Li(Et₂CO₃)CN] are water‐sensitive compounds and decompose at the exposure to air, [Li(NMP)CN] is stable in air, even at elevated temperatures. The thermal stability of [Li(NMP)CN] was proven by differential thermal analysis (DTA). [Li(NMP)CN] shows thermal stability up to temperatures of about 132 °C. To evaluate the cyanation ability the reactions of 1‐bromooctane and 3‐bromocyclohexene with unsupported LiCN, [Li(NMP)CN], and a mixture of NaCN/LiCl/NMP were investigated. We found that [Li(NMP)CN] as well as LiCl/NaCN/NMP are efficient cyanation reagents comparable to the expensive and air‐sensitive, donor‐free LiCN. A product of the chloride‐cyanide‐bromide exchange could be isolated and structurally characterized by X‐ray diffraction.     

Diamond‐ and Graphite‐Like Octacyanometalate‐Based Polymers Induced by Metal Ions

By using cyclohexane‐1,2‐diamine (chxn), Ni(ClO₄)₂ ? 6H₂O and Na₃[Mo(CN)₈] ? 4H₂O, a 3D diamond‐like polymer {[Ni^II(chxn)₂]₂[Mo^IV(CN)₈] ? 8H₂O}_n ( 1 ) was synthesised, whereas the reaction of chxn and Cu(ClO₄)₂ ? 6H₂O with Na₃[M^V(CN)₈] ? 4H₂O (M=Mo, W) afforded two isomorphous graphite‐like complexes {[Cu^II(chxn)₂]₃[Mo^V(CN)₈]₂ ? 2H₂O}_n ( 2 ) and {[Cu^II(chxn)₂]₃[W^V(CN)₈]₂ ? 2H₂O}_n ( 3 ). When the same synthetic procedure was employed, but replacing Na₃[Mo(CN)₈] ? 4H₂O by (Bu₃NH)₃[Mo(CN)₈] ? 4H₂O (Bu₃N=tributylamine), {[Cu^II(chxn)₂Mo^IV(CN)₈][Cu^II(chxn)₂] ? 2H₂O}_n ( 4 ) was obtained. Single‐crystal X‐ray diffraction analyses showed that the framework of 4 is similar to 2 and 3 , except that a discrete [Cu(chxn)₂]²⁺ moiety in 4 possesses large channels of parallel adjacent layers. The experimental results showed that in this system, the diamond‐ or graphite‐like framework was strongly influenced by the inducement of metal ions. The magnetic properties illustrate that the diamagnetic [Mo^IV(CN)₈] bridges mediate very weak antiferromagnetic coupling between the Ni^II ions in 1 , but lead to the paramagnetic behaviour in 4 because [Mo^IV(CN)₈] weakly coordinates to the Cu^II ions. The magnetic investigations of 2 and 3 indicate the presence of ferromagnetic coupling between the Cu^II and W^V/Mo^V ions, and the more diffuse 5d orbitals lead to a stronger magnetic coupling interaction between the W^V and Cu^II ions than between the Mo^V and Cu^II ions.     

Visible‐Light‐Induced Nickel‐Catalyzed Negishi Cross‐Couplings by Exogenous‐Photosensitizer‐Free Photocatalysis

The merging of photoredox and transition‐metal catalysis has become one of the most attractive approaches for carbon–carbon bond formation. Such reactions require the use of two organo‐transition‐metal species, one of which acts as a photosensitizer and the other one as a cross‐coupling catalyst. We report herein an exogenous‐photosensitizer‐free photocatalytic process for the formation of carbon–carbon bonds by direct acceleration of the well‐known nickel‐catalyzed Negishi cross‐coupling that is based on the use of two naturally abundant metals. This finding will open new avenues in cross‐coupling chemistry that involve the direct visible‐light absorption of organometallic catalytic complexes.     

Silyl‐Terminated Ethylene‐co‐Norbornene Copolymers by Organotitanium‐Based Catalysts

Ethylene (E) and norbornene (N) were copolymerized in the presence of PhSiH₃ as chain‐transfer agent with [Ti(η⁵:η¹‐C₅Me₄SiMe₂NBu^t)(η¹‐Me)₂] precatalyst combined with [Ph₃C][B(C₆F₅)₄]. The silane was introduced at chain‐ends of E‐co‐N copolymers with concomitant reinitiation of the growing polymer chain. The concentrations of the silane and polymer molecular weight are inversely correlated. The characteristic signals of  SiH₂Ph chain‐ends were observed by ¹H NMR. The Si heteroatom is predominantly adjacent to ethylene units in E‐co‐N copolymers with high N content.

     

Separation and quantification of double‐ and triple‐layered rotavirus‐like particles by CZE

Virus‐like particles have been successfully used as safe vaccines, as their structure is identical to their native counterparts but devoid of the viral genetic material. However, production of these complex structures is not easy, as recombinant proteins must assemble into virus‐like particles. Techniques to differentiate assembled and soluble proteins, as well as assembly intermediaries often present in a sample, are required. An example of complex virus‐like particles mixture occurs when rotavirus proteins are recombinantly expressed. Rotavirus‐like particles (RLP) can be single (sl), double (dl), or triple layered (tl). The use of RLP preparations as vaccines requires their complete characterization, including separation and quantification of each RLP in a sample. In this work, CZE was evaluated for the separation and quantification of dl and triple‐layered rotavirus‐like particles (tlRLP). A fused‐silica capillary with a deoxycholate running buffer efficiently separated dl and tlRLP in RLP preparations, as they migrated in two discrete peaks with electrophoretic mobilities of 1.24±0.04 and 2.95±0.03 Ti, respectively. Standard curves for dl and tlRLP were generated, and the response was linearly proportional to analyte concentration. The methodology developed was quantitative, specific, accurate, precise, and reproducible. CZE allowed the quantitative characterization of RLP preparations, which is required for evaluation of immunogens, for process development, and for quality control protocols.     

Solvent‐free condensation of aromatic aldehydes and 2,3‐dimethyl‐1‐phenyl‐3‐pyrazolin‐5‐one by p‐toruenesulfonic acid

Solvent‐free condensation easily occurred by mixing aromatic aldehydes and 2,3‐dimethyl‐1‐phenyl‐3‐pyrazoline‐5‐one (antipyrine) in the presence of p‐toluenesulfonic acid as a solid acid catalyst at room temperature to give the corresponding disubstituted products as sole products in high yields.     

Vesicles Formed by Oligostyrene‐block‐Oligoaniline‐block‐Oligostyrene Triblock Oligomer

Novel π‐conjugated coil–rod–coil triblock oligomers containing optoelectronic active oligoaniline segments were synthesized. The block oligomer can self‐assemble into diverse aggregating morphologies including spherical micelles and thin‐layer vesicles in THF, which is found associated with the removing of the protecting groups of oligoaniline segments. A possible mechanism was proposed to explain the self‐assembly behavior changes in which chain conformation variation of the aniline segments initiated from deprotection of the nitrogen atoms is pointed to be the key factor that dominates the transition process.

     

Synthesis of 3‐aminomethylidenechroman‐2‐carboxamides by a Sequential One‐pot Three Component Reaction and by Post‐Passerini Condensation Modification

3‐Arylaminomethylidenechroman‐2‐carboxamide has been synthesized by a one‐pot three component reaction among 3‐formylchromone, aromatic amine, and cyclohexyl isocyanide. 3‐(N‐alkylsubstitued/unsubstituted)aminomethylidenechroman‐2‐carboxamides were synthesized by heating Passerini products derived from chromone‐3‐carbaldehyde with different aliphatic primary amines. The products obtained from the reactions of aliphatic primary amines readily form chromeno[2,3‐c]pyrrole when heated in acetic acid. Bischromanones have also been synthesized using this methodology.     

Asymmetric Substitutions of 2‐Lithiated N‐Boc‐piperidine and N‐Boc‐azepine by Dynamic Resolution

Proton abstraction of N‐tert‐butoxycarbonyl‐piperidine (N‐Boc‐piperidine) with sBuLi and TMEDA provides a racemic organolithium that can be resolved using a chiral ligand. The enantiomeric organolithiums can interconvert so that a dynamic resolution occurs. Two mechanisms for promoting enantioselectivity in the products are possible. Slow addition of an electrophile such as trimethylsilyl chloride allows dynamic resolution under kinetic control (DKR). This process occurs with high enantioselectivity and is successful by catalysis with substoichiometric chiral ligand (catalytic dynamic kinetic resolution). Alternatively, the two enantiomers of this organolithium can be resolved under thermodynamic control with good enantioselectivity (dynamic thermodynamic resolution, DTR). The best ligands found are based on chiral diamino‐alkoxides. Using DTR, a variety of electrophiles can be used to provide an asymmetric synthesis of enantiomerically enriched 2‐substituted piperidines, including (after Boc deprotection) the alkaloid (+)‐β‐conhydrine. The chemistry was extended, albeit with lower yields, to the corresponding 2‐substituted seven‐membered azepine ring derivatives.     

Tetrahydro‐1,5‐benzoxazepines and tetrahydro‐1H‐1,5‐benzodiazepines by a tandem reduction‐reductive amination reaction

A tandem reduction‐reductive amination reaction has been applied to the synthesis of (±)‐4‐alkyl‐2,3,4,5‐tetrahydro‐1,5‐benzoxazepines and (±)‐4‐alkyl‐1‐benzoyl‐2,3,4,5‐tetrahydro‐1H‐1,5‐benzodiazepines. The nitro aldehydes and ketones required for 1,5‐benzoxazepine ring closures were prepared by nucleophilic aromatic substitution of the alkoxides from several 3‐buten‐1‐ol derivatives with 2‐fluoro‐1‐nitrobenzene followed by ozonolysis. Precursors for the 1,5‐benzodiazepines were prepared by similar addition of N‐(3‐butenyl)benzamide anions to 2‐fluoro‐1‐nitrobenzene followed by ozonolysis. Catalytic hydrogenation of the nitro carbonyl compounds using 5% palladium‐on‐carbon in methanol then gave the target heterocycles by a tandem reduction‐reductive amination sequence. The 1,5‐benzoxazepines were isolated in high yield following chromatographic purification; the 1,5‐benzodiazepines were isolated as solids directly from the hydrogenation mixture and possessed differentiated functionality on the two nitrogen atoms.     

Decoupled Thermo‐ and pH‐Responsive Hydrogel Microspheres Cross‐Linked by Rotaxane Networks

Rotaxane cross‐linked (RC) microgels that exhibit a decoupled thermo‐ and pH‐responsive volume transition were developed. The pH‐induced changes of the aggregation/disaggregation states of cyclodextrin in the RC networks were used to control the swelling capacity of the entire microgels. Different from conventional thermo‐ and pH‐responsive microgels, which are usually obtained from copolymerizations involving charged monomers, the RC microgels respond to temperature as intended, even in the presence of charged functional molecules such as dyes in the microgel dispersion. The results of this study should lead to new applications, including drug delivery systems that require a retention of their smart functions even in environments that may contain foreign ions, for example, in in vivo experiments.     

Near‐Infrared Free‐Radical and Free‐Radical‐Promoted Cationic Photopolymerizations by In‐Source Lighting Using Upconverting Glass

A method is presented for the initiation of free‐radical and free‐radical‐promoted cationic photopolymerizations by in‐source lighting in the near‐infrared (NIR) region using upconverting glass (UCG). This approach utilizes laser irradiation of UCG at 975 nm in the presence of fluorescein (FL) and pentamethyldiethylene triamine (PMDETA). FL excited by light emitted from the UCG undergoes electron‐transfer reactions with PMDETA to form free radicals capable of initiating polymerization of methyl methacrylate. To execute the corresponding free‐radical‐promoted cationic polymerization of cyclohexene oxide, isobutyl vinyl ether, and N ‐vinyl carbazole, it was necessary to use FL, dimethyl aniline (DMA), and diphenyliodonium hexafluorophosphate as sensitizer, coinitiator, and oxidant, respectively. Iodonium ions promptly oxidize DMA radicals formed to the corresponding cations. Thus, cationic polymerization with efficiency comparable to the conventional irradiation source was achieved.