Divergent Synthesis of Fluorinated Alkenes, Allenes, and Enynes via Reaction of 2-Trifluoromethyl-1,3-enynes with Carbon Nucleophiles.

Herein, inorganic base K3PO4 promoted divergent synthesis of CF3-substituted allenes, cyclopentenes, alkynes, and fluorinated enynes via regioselective nucleophilic addition of carbon nucleophiles to 2-trifluoromethyl-1,3-enynes was developed. With the choice of different carbon nucleophiles, various fluorinated compounds could be obtained under K3PO4/DMF reaction system. When malononitriles were used as nucleophiles, CF3-substituted allenes, cyclopentenes, and alkynes could be obtained, respectively. By using 1,3-dicarbonyl compounds as nucleophiles, ring-monofluorinated 4H-pyrans could be prepared, and 1,1-difluoro-1,3-enynes could be furnished with the participation of diethyl malonate. Moreover, these five kinds of fluorinated allenes, alkenes, and enynes are valuable building blocks.

3,4-Bisthiolated Pyrroles: Concise Construction and Their Electronic Properties.

3,4-Bisthiolated pyrroles constitute key cores in pyrrole-based semiconductors, and their electronic properties could be improved by the bisthio groups via the S-effect. Herein, a convenient method for the synthesis of 3,4-bisthiolated pyrroles has been developed through the AlCl3-catalyzed thiolation/cyclization of homopropargylic azides, and cyclic voltammetry and DFT calculations indicated that the desired 3,4-bisthiolated pyrroles had higher HOMO orbital energies and lower band gaps than the parent unsubstituted 2,5-diphenylpyrrole.

Enantioselective Cascade Biocatalysis for Deracemization of Racemic ß-Amino Alcohols to Enantiopure (S)-ß-Amino Alcohols by Employing Cyclohexylamine Oxidase and ω-Transaminase.

Optically active ß-amino alcohols are very useful chiral intermediates frequently used in the preparation of pharmaceutically active substances. Here, a novel cyclohexylamine oxidase (ArCHAO) was identified from the genome sequence of Arthrobacter sp. TYUT010-15 with the R-stereoselective deamination activity of ß-amino alcohol. ArCHAO was cloned and successfully expressed in E. coli BL21, purified and characterized. Substrate-specific analysis revealed that ArCHAO has high activity (4.15 to 6.34 U mg-1 protein) and excellent enantioselectivity toward the tested ß-amino alcohols. By using purified ArCHAO, a wide range of racemic ß-amino alcohols were resolved, (S)-ß-amino alcohols were obtained in >99 % ee. Deracemization of racemic ß-amino alcohols was conducted by ArCHAO-catalyzed enantioselective deamination and transaminase-catalyzed enantioselective amination to afford (S)-ß-amino alcohols in excellent conversion (78-94 %) and enantiomeric excess (>99 %). Preparative-scale deracemization was carried out with 50 mM (6.859 g L-1 ) racemic 2-amino-2-phenylethanol, (S)-2-amino-2-phenylethanol was obtained in 75 % isolated yield and >99 % ee.

NBS/DBU-Promoted One-Pot Three-Component Cycloaddition of Malonic Acid Derivatives, Nitrosoarenes, and Alkenes: Synthesis of Isoxazolidines.

A general DBU-mediated one-pot three-component cycloaddition reaction of easily accessible malonic acid derivatives, nitrosoarenes, and alkenes has been successfully established with the aid of NBS to provide direct access to highly functionalized isoxazolidine derivatives with generally good to excellent yields, broad functional group tolerance, and excellent regio- and diastereo-selectivities under mild conditions. The mechanism study shows that the NBS-mediated formation of bromomalonic acid derivatives from malonic acid derivatives and DBU-promoted synthesis of nitrone intermediates via the reaction of bromomalonic acid derivatives with nitrosoarenes are key steps.

Straightforward Approach toward Multifunctionalized Aziridines via Catalyst-Free Three-Component Reactions of α-Diazoesters, Nitrosoarenes, and Alkynes.

A straightforward, catalyst-free atom- and step-economical approach for the synthesis of multisubstituted 1-arylaziridine-2-carboxylates via one-pot three-component reactions of α-diazoesters, nitrosoarenes, and alkynes has been described. This method could provide facile access to a variety of multifunctionalized aziridines in up to 91% yields under mild reaction conditions and features the catalyst-free strategy and use of cheap and readily accessible starting materials.

High throughput solid-phase screening of bacteria with cyclic amino alcohol deamination activity for enantioselective synthesis of chiral cyclic ß-amino alcohols.

OBJECTIVES: To screening of bacteria with cyclic amino alcohol deamination activity for enantioselective synthesis of chiral cyclic ß-amino alcohols. RESULTS: A new strain named Arthrobacter sp. TYUT010-15 with the (R)-selective deamination activity of cyclic ß-amino alcohol has been isolated from nature via a high throughput solid-phase screening method. The reaction conditions of TYUT010-15 were optimized. Using the resting cell of TYUT010-15 as the catalyst, kinetic resolution of trans-2-aminocyclopentanol, trans-2-aminocyclohexanol and cis-1-amino-2-indanol was carried out to afford (1S, 2S)-trans-2-aminocyclopentanol, (1S, 2S)-trans-2-aminocyclohexanol and (1R, 2S)-cis-1-amino-2-indanol in > 99% ee and 49.6-50% conversion. Four aromatic ß-amino alcohols and two amines were also resolved, (S)-ß-amino alcohols and (R)-amines were obtained in > 99% ee. Preparation experiment was conducted with 200 mM (23.2 g L-1) racemic trans-2-aminocyclohexanol, yielding the desired (1S, 2S)-trans-2-aminocyclohexanol in 40% isolated yield, > 99% ee and 5.8 g L-1 d-1 space time yields. CONCLUSIONS: This study provides a high throughput solid-phase method for screening of bacteria with cyclic amino alcohol deamination activity and a first example for practical preparation of chiral cyclic ß-amino alcohol by Arthrobacter sp. TYUT010-15.

Few-Layer Boron Nitride with Engineered Nitrogen Vacancies for Promoting Conversion of Polysulfide as a Cathode Matrix for Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries have become one of the most promising candidates as next-generation batteries, owing to their high specific capacity, low cost, and environmental benignity. Although many strategies have been proposed to restrain the shuttle of lithium polysulfides (LiPSs) through physical trapping and chemical binding, the sluggish kinetics of PS conversion still degrade the capacity, rate, and cycling performance of Li-S batteries. Herein, a novel kind of few-layer BN with engineered nitrogen vacancies (v-BN) has been developed as a cathode matrix for Li-S batteries. The positive vacancies in the BN nanosheets not only promote the immobilization and conversion of LiPSs, but also accelerate the lithium ion diffusion in cathode electrodes. Compared with pristine BN, the v-BN cathodes exhibit higher initial capacities from 775 mA h g-1 to 1262 mA h g-1 at 0.1 C and a high average coulombic efficiency of over 98 % during 150 cycles. Upon increasing the current density to 1 C, the cell still preserves a capacity of 406 mA h g-1 after 500 cycles, exhibiting a capacity decay of only 0.084 % per cycle. The new vacancy-engineered material provides a promising method for achieving excellent performance in Li-S batteries.

KOAc-Catalyzed One-Pot Three-Component 1,3-Dipolar Cycloaddition of α-Diazo Compounds, Nitrosoarenes, and Alkenes: An Approach to Functionalized Isoxazolidines.

A direct, highly efficient KOAc-catalyzed one-pot three-component approach for the preparation of various functionalized isoxazolidines via the 1,3-dipolar cycloaddition reactions of readily accessible diazo compounds, nitrosoarenes, and alkenes has been reported. The cheap and readily available catalyst and starting materials, excellent functional group compatibility, wide substrate scope, high yields, and excellent chemo-, regio-, and diastereoselectivities make this protocol an attractive alternative.

Synthesis of 4-Sulfenyl Isoxazoles through AlCl3-Mediated Electrophilic Cyclization and Sulfenylation of 2-Alkyn-1-one O-Methyloximes.

An efficient method for the synthesis of 4-sulfenyl isoxazoles has been developed via AlCl3-mediated electrophilic cyclization/sulfenylation of 2-alkyn-1-one O-methyloximes. Remarkably, N-arylsulfanylsuccinimides are employed as electrophiles for the construction of 4-arylsulfanyl isoxazoles, and 4-alkylsulfanyl isoxazoles are accessed with dialkyl disulfides as electrophiles.

Synthesis and nano-Pd catalyzed chemoselective oxidation of symmetrical and unsymmetrical sulfides.

A highly chemoselective, efficient and nano-Pd catalyzed protocol for the rapid construction of sulfoxides and sulfones via the oxidation of symmetrical and unsymmetrical sulfides using H2O2 as an oxidant has been developed, respectively. The ready availability of starting materials, easy recovery and reutilization of the catalyst, wide substrate scope, and high yields make this protocol an attractive alternative. The process also involves the metal-free and microwave-promoted synthesis of symmetrical diarylsulfides, and FeCl3-mediated preparation of symmetrical diaryldisulfides through the reaction of arenediazonium tetrafluoroborates with Na2S·9H2O as a sulfur source. In addition, unsymmetrical sulfides were generated via the K2CO3-mediated reaction of arenediazonium tetrafluoroborates with symmetrical disulfides.

Copper(II)-Catalyzed Four-Component Oxysulfonylation/Diazenylation: Synthesis of α-Arylhydrazo-ß-keto Sulfones.

A new and convenient method for one-pot synthesis of α-arylhydrazo-ß-keto sulfones is developed via Cu (II)-catalyzed oxysulfonylation/diazenylation of alkenes. This four-component cascade reaction enables a series of α-arylhydrazo-ß-keto sulfone derivatives accessed from readily available alkenes, sulfinates, and diazonium salts under aerobic conditions. Furthermore, the 3-sulfonyl cinnolin-4(1 H)-one skeleton is successfully constructed from the corresponding α-arylhydrazo-ß-keto sulfone product under basic conditions.

One pot simultaneous preparation of both enantiomer of ß-amino alcohol and vicinal diol via cascade biocatalysis.

OBJECTIVES: To investigate the efficiency of a new cascade biocatalysis system for the conversion of R, S-ß-amino alcohols to enantiopure vicinal diol and ß-amino alcohol. RESULTS: An efficient cascade biocatalysis was achieved by combination of a transaminase, a carbonyl reductase and a cofactor regeneration system. An ee value of > 99% for 2-amino-2-phenylethanol and 1-phenyl-1, 2-ethanediol were simultaneously obtained with 50% conversion from R, S-2-amino-2-phenylethanol. The generality of the cascade biocatalysis was further demonstrated with the whole-cell approaches to convert 10-60 mM R, S-ß-amino alcohol to (R)- and (S)-diol and (R)- and (S)-ß-amino alcohol in 90-99% ee with 50-52% conversion. Preparative biotransformation was demonstrated at a 50 ml scale with mixed recombinant cells to give both (R)- and (S)-2-amino-2-phenylethanol and (R)- and (S)-1-phenyl-1, 2-ethanediol in > 99% ee and 40-42% isolated yield from racemic 2-amino-2-phenylethanol. CONCLUSIONS: This cascade biocatalysis system provides a new practical method for the simultaneous synthesis of optically pure vicinal diol and an ß-amino alcohol.

Resonance Rayleigh scattering assay for EGFR using antibody immobilized gold nanoparticles.

A highly selectivity determination of epidermal growth factor receptor (EGFR) has been described in the article. Antibody immobilized cysteamine (Cys) functionalized gold nanoparticles (AuNP) were proposed as immunosensors, and resonance Rayleigh scattering (RRS) was used for detection. First, Cys stabilized AuNPs (Cys-AuNP) were prepared by the reduction of chloroauric acid with sodium borohydride in the presence of Cys. Further, anti-EGFR antibody (Cetuximab, C225) was covalently linked to the Cys-AuNP by carbodiimide-mediated amidation protocol to yield the C225-AuNP immunoprobe. The prepared conjugations were characterized by ultraviolet-visible (UV-vis) spectroscopy, transmission electron microscopy (TEM), Fourier transform infrared (FT-IR) and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). Based on the specific binding of C225 to EGFR, an RRS method was established to determine the concentration of EGFR. Under the optimal conditions, the concentration of EGFR was related to the intensity of RRS in the range 30-130 ng ml-1 with a low detection limit of 4.0 ng ml-1 . Meanwhile, the proposed immunosensor exhibited excellent selectivity and anti-interference property. The method was applied to the determination of EGFR in human serum and cancer cell lysate samples with satisfactory results.

Dye sensitized photoelectrochemical immunosensor for the tumor marker CEA by using a flower-like 3D architecture prepared from graphene oxide and MoS2.

The authors describe a dye-sensitized photoelectrochemical immunoassay for the tumor marker carcinoembryonic antigen (CEA). The method employs the rhodamine dye Rh123 with red color and absorption maximum at 500 nm for spectral sensitization, and a 3D nanocomposite prepared from graphene oxide and MoS2 acting as the photoelectric conversion layer. The nanocomposite with flower-like 3D architectures was characterized by transmission electron microscopy, scanning electron microscopy, X-ray powder diffraction, and UV-vis diffuse reflectometry. A photoelectrochemical sandwich immunoassay was developed that is based on the use of the nanocomposite and based on the specific binding of antibody and antigen, and by using a secondary antibody labeled with Rh123 and CdS (Ab2-Rh123@CdS). Under optimal conditions and at a typical working voltage of 0 V (vs. Hg/HgCl2), the photocurrent increases linearly 10 pg mL-1 to 80 ng mL-1 CEA concentration range, with a 3.2 pg mL-1 detection limit. Graphical abstract Flower-like GO-MoS2 complex with high efficiency of electron transport was synthesized to construct photoelectrochemical platform. The sandwich-type immunoassay was built on this platform based on specific binding of antigen and antibody. Carcinoembryonic antigen in sample was detected sensitively by using sensitization of rhodamine dye Rh123 as signal amplification strategy.

Amplified photoelectrochemical immunoassay for the tumor marker carbohydrate antigen 724 based on dye sensitization of the semiconductor composite C3N4-MoS2.

The authors describe an amplified photoelectrochemical immunoassay for the tumor marker carbohydrate antigen 724 (CA724). The method employs a C3N4-MoS2 semiconductor as the photoelectric conversion layer. The nanocomposite was characterized by transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray powder diffraction, and UV-vis diffuse reflectometry. The dye eosin Y was encapsulated into CaCO3 nanospheres which then were used as labels for antibody against CA724. In addition, Fe3O4 nanospheres were employed as magnetic platform for constructing photoelectrochemical sandwich immunoassay. The CaCO3 nanospheres can be dissolved with aid of ethylene diamine tetraacetic acid (EDTA) and the carried eosin Y in CaCO3 is released. The released dyes sensitizes the C3N4-MoS2 semiconductor, which induces photocurrent amplification. Under optimal conditions and at a typical working voltage of 0 V (vs. SCE), the photocurrent increases linearly in the range of 0.05 mU mL-1 to 500 mU mL-1 of CA724, with a 0.02 mU mL-1 detection limit. Graphical abstract The C3N4-MoS2 complex, with high efficiency of electron transport, was synthesized to construct a photoelectrochemical analytical platform. A sandwich-type immunoassay was established on the surface of magnetic beads. Carbohydrate antigen 724 in sample was detected sensitively by using sensitization of released eosin Y as signal amplifiery.

A high-throughput microtiter plate assay for the discovery of active and enantioselective amino alcohol-specific transaminases.

Chiral vicinal amino alcohols are important chiral building blocks and intermediates in the pharmaceutical industry. The transaminase (TAm) catalyzed kinetic resolution of racemic amino alcohols provides a straightforward approach to access these important compounds. This study describes the development of a novel microtiter plate assay to screen vicinal amino alcohol-specific TAms using a tetrazolium red-based colorimetric assay to monitor the rate of α-hydroxy ketone formation at 510 nm. This approach is the first to determine the Michaelis-Menten parameters for a recombinant TAm (PpbauA) from Pseudomonas putida NBRC14164. The corresponding Vmax and KM values for both enantiomers of 2-amino-1-propanol and 2-amino-1-butanol were obtained, and the calculated kinetic E-factors of PpbauA toward 2-amino-1-propanol and 2-amino-1-butanol are 3 (S) and 6 (R), respectively. The method is sensitive and exhibits low level background coloration. Moreover, this method can be used to detect transaminase activity and enantioselectivity toward amino alcohols in a high-throughput format. Additionally, this simple method is compatible with the most widely used (R)- and (S)-selective transaminases and may be a broadly applicable tool for screening transaminases from a transaminase mutant library.

AlCl3-Catalyzed Intramolecular Cyclization of N-Arylpropynamides with N-Sulfanylsuccinimides: Divergent Synthesis of 3-Sulfenyl Quinolin-2-ones and Azaspiro[4,5]trienones.

Switchable ortho/ipso-cyclization of N-arylpropynamides induced with N-sulfanylsuccinimides as general sulfur reagents is reported. In the presence of MeOH, para-fluoro N-arylpropynamides exclusively undergo the ipso-cyclization to give 3-sulfenyl azaspiro[4,5]trienones. Two kinds of bioactive heterocycles, benzothieno-[3,2-b]quinoline and -[2,3-c]quinolone, have been directly and efficiently prepared from the corresponding sulfenylated products.

Intermolecular sulfenoamination of alkenes with sulfonamides and N-sulfanylsuccinimides to access ß-sulfonylamino sulfides and dihydrobenzothiazines.

An acid-catalyzed intermolecular sulfenoamination reaction of alkenes is developed with sulfonamides as the nitrogen source and N-sulfanylsuccinimides as the sulfur source. This methodology provides a straightforward and general way to synthesize various ß-sulfonylamino sulfides with high regio- and diastereoselectivity. The developed method was coupled with intramolecular C-N coupling in a one-pot procedure to afford a series of dihydrobenzothiazine derivatives, a kind of important heterocycle used as biologically active compounds in medicinal chemistry.

Synthesis of 3-Sulfenylated Coumarins: BF3·Et2O-Mediated Electrophilic Cyclization of Aryl Alkynoates Using N-Sulfanylsuccinimides.

A simple and efficient metal-free sulfenylation/cyclization of aryl alkynoates has been developed, obtaining various 3-sulfenylated coumarins in moderate to excellent yields. In the presence of BF3·Et2O, the stable and readily accessible N-sulfanylsuccinimides were employed as electrophiles to induce the 6-endo-dig electrophilic cyclization of alkynoates. The reaction using substrates bearing a methoxy group on the phenoxy ring proceeded in an exclusively distinct pathway via either ipso sulfenylcyclization or sulfenylation of the phenoxy ring depending on the different locations of the methoxy substituent. The resulting 3-sulfenylated coumarins can be readily transformed to 3-sulfinylated or 3-sulfonylated coumarins under different oxidation conditions.

Palladium-catalyzed direct C-H arylation of pyridine N-oxides with potassium aryl- and heteroaryltrifluoroborates.

An efficient ligand-free Pd(OAc)2-catalyzed selective arylation of pyridine N-oxides using potassium (hetero)aryltrifluoroborates as coupling partners via C-H bond activation was achieved in the presence of TBAI. This approach has a broad substrate scope and shows moderate to high yields.