Cobalt-Promoted Photoredox 1,2-Amidoamination of Alkenes with N-Sulfonamidopyridin-1-ium Salts and Free Amines.

A cobalt-promoted photoredox 1,2-amidoamination of alkenes with N-sulfonamidopyridin-1-ium salts and free amines for the synthesis of unsymmetrical vicinal diamines has been developed. The reaction handles N-(sulfonamido)pyridin-1-ium salts as the sulfonamidyl radical precursors and free amines as the nucleophilic terminating reagents to enable the formation of two new C(sp3)-N bonds in a single reaction step and offers a route to selectively producing unsymmetrical vicinal diamines with an exquisite selectivity and a good compatibility of functional groups.

Photo-controllable binding and release of HP2O73- using an azobenzene based smart macrocycle.

Herein, we describe the design and synthesis of an unusual azobenzene-bearing macrocycle 1, whose trans isomer was found able to 100% transform into its cis configuration under photoirradiation, for selectively recognizing HP2O73- with reversibly photo-controllable binding and release properties.

Co-Catalyzed Dual C5/C8-H Bond Functionalization of Imidazo[1,2-a]pyrazines with Disulfides and Grignard Reagents.

An efficient difunctionalization at C5/C8 of imidazo[1,2-a]pyrazines has been developed using disulfides and Grignard reagents under cheap cobalt catalysis. This one-pot, two-step, three-component transformation is performed under mild conditions; various Grignard reagents (aryl and alkyl) and disulfides are tolerated. Mechanistic studies and control experiments demonstrate this reaction proceeded via an anionic intermediate.

Synthesis and anti-proliferative activities of 5,6,7-trimethoxyflavones and their derivatives.

A series of 5,6,7-trimethoxyflavones 1a-1g and their derivatives 2a-2g, 3a-3d, 4 and 5, including the natural products 5,6,7-trimethoxy-4'-hydroxyflavone (1a), 5,6,7,3',4' -pentamethoxyflavone (sinensetin, 1 b), 5,6,7-trimethoxy-3',4'-methyl enedioxy flavone (1c), 5,6,7,3'-tetramethoxy-4,5'-methylenedioxyflavone (1e), 5,6,7, 3',4',5'-hextamethoxyflavone (1 g), 5-hydroxy-3,4,2',3',4'-pentamethoxy chal-cone (2 b), 5,4'-dihydroxy-6,7-dimethoxy flavone (cirsimaritin, 3a) and 5-hydroxy-6,7,3', 4'-tetramethoxyflavone (5-demethylsinensetin, 3 b), 3,5,6,7,3',4'-hexamethoxyflavone (3-methoxysinensetin, 4) and 5'-hydroxy-3,6,7,3',4'-pentamethoxyflavone (5) were synthesized. Their anti-proliferative activity in vitro was evaluated against a panel of four human cancer cell lines (Aspc-1, HCT-116, HepG-2 and SUN-5) by the CTG assay. The results showed that most of the synthetic compounds exhibited moderate to high anti-proliferative activities. In particular, compound 3c possess IC50 (5.30 µM) values below 10 µM against Aspc-1 cells and are worthy of further investigation.

[Study on the application of a new type of vertebral plate nail guide].

OBJECTIVE: To explore safety and accuracy of novel C2 laminar staple guide through in vitro experiments. METHODS: From January 2018 to June 2018, 40 patients who underwent three-dimensional CT of cervical spine were selected, including 21 males and 19 females, heighted from 165 to 180 cm with an average of (172.9±9.5) cm, aged from 38 to 55 years old (51.1±12.8) years old, excluding patients with axis lamina defect and hypoplasia. Two sets of 3D printed specimens were made from the three-dimensional CT data of cervical spine of each patient, and both of than were used for the in vitro nailing experiment. According to different nail placement methods, in vitro experimental part of this experiment was divided into guide nail placement group and hand nail placement group, 40 pieces in each group. At the same time, the three-dimensionalmodel of cervical spine of 40 patients was reconstructed on computer, and the ideal needle point data and inclination angle were obtained by computer simulation of the nail placement. This is 3D simulation nail placement group, 40 pieces. With vitro experiment, the risk level of screw placement, the position of needle exit point and inclination angle were measured in guide nail group and hand nail group. Based on the accuracy of needle point and inclination angle of nail path, the data of guide nail group, the hand nail group and 3D simulation nail group were compared, and the data of each group were statistically analyzed to determine the accuracy. RESULTS: In guide nail group, 75 screws were acceptable and 5 were dangerous. The acceptable rate was 94%, and the double cortical rate was 93%. There were 62 position-acceptable screws in hand nail group, and 18 positions were dangerous, with an acceptable rate of 78% and a double cortical rate of 33%. The difference between two groups was statistically significant (P<0.05). There was no significant difference in accuracy of needle exit point and inclination angle of nail path between guide nail group and 3D simulation nail group (P>0.05), but there was significant difference in the accuracy of needle exit point and inclination angle of nail path between hand nail group and 3D simulation nail group (P<0.05). CONCLUSION: The guide is universal, with stable structure, accurate guidance, and easy operation. It could be placed with bilateral lamina screws at the same time, shortening the time of nail placement, avoiding collision of two way cross screws, increase the rate of double cortex. Ultimately, efficiency and security can be improved.

Dual Palladium/Copper-Catalyzed anti-Selective Intermolecular Allenylsilylation of Terminal Alkynes: Entry to (E)-Silyl Enallenes.

A palladium-/copper-cocatalyzed three-component trans-allenylsilylation of terminal alkynes with propargyl acetates and PhMe2SiBpin is described, which is driven by the regioselective allenylation of the alkyne with propargyl acetates and then silylation. This method allows the simultaneous incorporation of an allene and silicon across the C≡C bond and provides a highly chemo-, regio-, and stereoselective alkyne difunctionalization route to the synthesis of valuable (E)-silyl enallenes. The utility of this method is highlighted by late-stage derivatization of bioactive compounds.

External-oxidant-free amino-benzoyloxylation of unactivated alkenes of unsaturated ketoximes with O-benzoylhydroxylamines.

A new copper-catalyzed two-component amino-benzoyloxylation of unactivated alkenes of unsaturated ketoximes with O-benzoylhydroxylamines as the benzoyloxy sources is developed. Chemoselectivity of this method toward amino-benzoyloxylation or oxy-benzoyloxylation of alkenyl ketoximes relies on the position of the tethered olefins, and provides an external-oxidant-free alkene difunctionalization route that directly utilizes O-benzoylhydroxylamines as the benzoyloxy radical precursors and internal oxidants for the divergent synthesis of cyclic nitrones and isoxazolines.

A lattice topology optimization of cervical interbody fusion cage and finite element comparison with ZK60 and Ti-6Al-4V cages.

BACKGROUND: In current clinical practice, the most commonly used fusion cage materials are titanium (Ti) alloys. However, titanium alloys are non-degradable and may cause stress shielding. ZK60 is a bio-absorbable implant that can effectively avoid long-term complications, such as stress shielding effects, implant displacement, and foreign body reactions. In this study, we aimed at investigating the biomechanical behavior of the cervical spine after implanting different interbody fusion cages. METHODS: The finite element (FE) models of anterior cervical disc removal and bone graft fusion (ACDF) with a ZK60 cage and a Ti cage were constructed, respectively. Simulations were performed to evaluate their properties of flexion, extension, lateral bending, and axial rotation of the cervical spine. Moreover, a side-by-side comparison was conducted on the range of motion (ROM), the deformation of cages, the stress in the cages, bone grafts, and cage-end plate interface. Simultaneously, according to the biomechanical analysis results, the microporous structure of the ZK60 cage was improved by the lattice topology optimization technology and validation using static structure. RESULTS: The ROMs in the current study were comparable with the results reported in the literature. There was no significant difference in the deformation of the two cages under various conditions. Moreover, the maximum stress occurred at the rear of the cage in all cases. The cage's and endplate-cage interface's stress of the ZK60 group was reduced compared with the Ti cage, while the bone graft stress in the ZK60 fusion cage was significantly greater than that in the Ti fusion cage (average 27.70%). We further optimized the cage by filling it with lattice structures, the volume was decreased by 40%, and validation showed more significant biomechanical properties than ZK60 and Ti cages. CONCLUSION: The application of the ZK60 cage can significantly increase the stress stimulation to the bone graft by reducing the stress shielding effect between the two instrumented bodies. We also observed that the stress of the endplate-cage interface decreased as the reduction of the cage's stiffness, indicating that subsidence is less likely to occur in the cage with lower stiffness. Moreover, we successfully designed a porous cage based on the biomechanical load by lattice optimization.

Pedicle Screw Insertion: Is O-Arm-Based Navigation Superior to the Conventional Freehand Technique? A Systematic Review and Meta-Analysis.

BACKGROUND: Although O-arm-based navigation (ON) has been considered a better choice than the conventional freehand (FH) technique for spine surgery, clinical evidence showing the accuracy of ON compared with the FH technique is limited. The purpose of this study was to evaluate the accuracy of pedicle screw insertion under ON compared with the FH technique. METHODS: The Cochrane Library, Ovid, Web of Science, PubMed, Embase, and CNKI online databases were searched up to January 2020. Because only a few randomized controlled trials were anticipated, prospective and retrospective comparative studies were also evaluated to compare the accuracy of pedicle screw insertion between ON and FH. Statistical analysis was performed using Stata 16.0. The primary outcomes extracted from articles that met the selection criteria were expressed as odds ratios for dichotomous outcomes with a 95% confidence interval. A χ2 test and I2 statistics were used to evaluate heterogeneity. RESULTS: A total of 20 reviews were included in this meta-analysis without identifying additional studies from the references of published articles. These reviews included 1422 patients and 9982 screws. ON was used to insert 4797 pedicle screws and 5185 pedicle screws were inserted using the conventional FH technique with C-arm assistance. The meta-analysis showed that ON is significantly more accurate than FH pedicle screw insertion (odds ratio, 2.46; 95% confidence interval, 1.92-3.16; I2 = 43.4%; P = 0.021). I2 indicates that the studies have a moderate statistical heterogeneity; subgroup analysis decreased heterogeneity significantly. CONCLUSIONS: Compared with conventional methods, navigation provides greater accuracy in the placement of pedicle screws, accelerates the insertion, and reduces the complications associated with screw insertion. However, it may increase exposure time to radiation, which may harm the patient's or surgeon's health.

Brønsted Acid-Catalyzed Asymmetric Friedel-Crafts Alkylation of Indoles with Benzothiazole-Bearing Trifluoromethyl Ketone Hydrates.

An efficient Brønsted acid-catalyzed asymmetric Friedel-Crafts alkylation of indoles with benzothiazole-bearing trifluoromethyl ketone hydrates as electrophiles has been developed. The mild organocatalytic reactions proceeded well with low catalyst loading to afford a range of enantioenriched α-trifluoromethyl tertiary alcohols containing both benzothiazole and indole rings with excellent yields and enantioselectivities.

Dicarbonylative benzannulation of 3-acetoxy-1,4-enynes with CO and silylboranes by Pd and Cu cooperative catalysis: one-step access to 3-hydroxyarylacylsilanes.

A new, general Pd/Cu-cocatalysed dicarbonylative benzannulation of 3-acetoxy-1,4-enynes with CO and silylboranes is described. The method utilizes CO as both a one-carbon (C1) unit and an external addition functional reagent to achieve an unprecedented dicarbonylative benzannulation process, and represents a facile, efficient route to 3-hydroxyarylacylsilanes. Mechanistically, the silyl-Cu intermediate formed from CuF2 and silylboranes, and silyl-Pd intermediate generated by transmetallation are two key factors for successfully targeting the reaction and selectivity.

A novel mitochondria-targeted near-infrared (NIR) probe for detection of viscosity changes in living cell, zebra fishes and living mice.

Viscosity is a key factor that determines the diffusion-controlled processes in biological systems. The matrix of mitochondria contains various enzymes and other proteins with high density, and the diffusion of which are severely restricted by the cristae, making it the most crowded place in the cells. Herein, we reported a new near-infrared probe NV-1 with increased Stokes shift for monitoring viscosity changes in mitochondria. A remarkable increase of the fluorescence was observed in glycerol compared with which was observed in methanol at 744 nm. The probe was applied for measuring viscosity changes not only in mitochondria, but also in vivo (in zebra fishes and mice).

Visible-Light Induction/Brønsted Acid Catalysis in Relay for the Enantioselective Synthesis of Tetrahydroquinolines.

An efficient method merging Brønsted acid catalysis with visible-light induction for the highly enantioselective synthesis of tetrahydroquinolines has been developed. This mild process directly transforms 2-aminoenones into 2-substituted tetrahydroquinolines with excellent enantioselectivities through a relay visible-light-induced cyclization/chiral phosphoric acid-catalyzed transfer hydrogenation reaction.

Annulation Cascades of N-Allyl- N-((2-bromoaryl)ethynyl)amides Involving C-H Functionalization.

An annulation cascades of N-allyl- N-((2-bromoaryl)ethynyl)amides with terminal alkynes or 1,3-dicarbonyls involving C-H functionalization for producing 2,3-functionalized indoles has been first developed by means of Cu catalysis. The method is enabled by the formation of the ketenimine intermediates to deliver 2,3-disubstituted indoles through a sequence of aza-Claisen rearrangement, C-H functionalization, Ullmann C-N coupling, and cyclization.

Synthesis and antiproliferative activities of aminoalkylated polymethoxyflavonoid derivatives.

A series of novel aminoalkylated polymethoxyflavonoid derivatives 3-11 was synthesised from 5-hydroxy-3,7,3',4'-tetramethoxyflavonoid (1) through extending alkoxy chain at the 5-position, and introducing amine hydrogen bond receptor at the end of the side chain. Their antiproliferative activities were evaluated in vitro on a panel of three human cancer cell lines (Hela, HCC1954 and SK-OV-3). The results showed that all the target compounds exhibited antiproliferative activities against investigated cancer cells with IC50 values of 9.51-53.33 µM. Compounds 5, 7, 8, 11 on Hela cells and compounds 4-9, 11 on HCC1954 exhibited more potency as compared to positive control cis-Platin.

Synthesis and antiproliferative activities of thioxoflavonoids on three human cancer cells.

Two series of fifteen novel thioxoflavonoids 2a-2h and 4a-4g were synthesized from corresponding flavonoids 1a-1h and 3a-3g by reacting with Lawesson's reagent, respectively. Their in vitro antiproliferative activities were evaluated on a panel of three human cancer cell lines (Hela, HCC1954 and SK-OV-3) using cell counting kit-8 (CCK-8) assay. The results showed that most of the target compounds exhibited moderate to good antiproliferative activities against the three human cancer cell lines. In particular, thioxoflavonoids 2f and 2g showed the strongest antiproliferative activity on all three human cancer cell lines with IC50 values ranging from 3.34 to 4.67 µM, 4f showed the best antiproliferative activity on Hela cells (IC50 2.30 µM), 2e showed the best antiproliferative activity on HCC1954 cells (IC50 2.13 µM) and SK-OV-3 cells (IC50 2.33 µM). The antiproliferative activities may be involved in their antioxidant activity, which can be speculated by their ability to scavenge free radicals and by their capacity of affecting key redox enzymes.

Primary aminomethyl derivatives of kaempferol: hydrogen bond-assisted synthesis, anticancer activity and spectral properties.

A series of primary aminomethyl derivatives of kaempferol were synthesized by a combination strategy involving two steps of the Mannich reaction and SN2 nucleophilic substitution. The structures of the products show that the preferential aminomethylations are in the position C-6 or C-8 of the A-ring of kaempferol, especially the latter. Interestingly, the experimental data indicate that the intermolecular hydrogen bonding plays a key role in the formation of primary aminomethyl products of kaempferol. The formation of appropriate hydrogen bonds between strong nucleophilic amino acids and phenol is essential for the smooth reaction of the SN2 nucleophilic substitution. The SN2 mechanism hypothesis involving a hydrogen bond-assisted process was also supported by the density functional theory (DFT) analysis. An antiproliferative test of synthetic compounds shows the moderate to potent cytotoxic activity against three human cancer cell lines (HeLa, HCC1954, and SK-OV-3) by the CCK-8 assay. Compound 4e shows selective antiproliferative activity against HeLa cells with a low IC50 value (4.27 µm) and is worthy of further development. Another interesting result is that the maximum emission bands for most metal complexes are located at about 480 nm, but the ones for Tm and Yb complexes appear at about 533 nm.

A novel mitochondria-targeted rhodamine analogue for the detection of viscosity changes in living cells, zebra fish and living mice.

Monitoring the intracellular viscosity changes is crucial for better understanding diffusion-controlled cellular processes. Herein, we synthesized a novel phenyl-substituted imidazole-fused rhodamine analogue RV-1 with a long absorption wavelength at 573 nm and a large Stokes shift of about 82 nm for monitoring the changes in cellular viscosity. The new probe RV-1 showed a very strong fluorescence emission at around 655 nm, with a 48.5-fold enhancement of fluorescence intensity from methanol to 99% glycerol. Significantly, the innovative probe RV-1 was successfully applied for the detection of viscosity changes not only in living cells, but also in zebra fish and living mice.

Discovery of potent and selective acetylcholinesterase (AChE) inhibitors: acacetin 7-O-methyl ether Mannich base derivatives synthesised from easy access natural product naringin.

Naringin, as a component universal existing in the peel of some fruits or medicinal plants, was usually selected as the material to synthesise bioactive derivates since it was easy to gain with low cost. In present investigation, eight new acacetin-7-O-methyl ether Mannich base derivatives (1-8) were synthesised from naringin. The bioactivity evaluation revealed that most of them exhibited moderate or potent acetylcholinesterase (AChE) inhibitory activity. Among them, compound 7 (IC50 for AChE = 0.82 ± 0.08 µmol•L-1, IC50 for BuChE = 46.30 ± 3.26 µmol•L-1) showed a potent activity and high selectivity compared with the positive control Rivastigmine (IC50 for AChE = 10.54 ± 0.86 µmol•L-1, IC50 for BuChE = 0.26 ± 0.08 µmol•L-1). The kinetic study suggested that compound 7 bind to AChE with mix-type inhibitory profile. Molecular docking study revealed that compound 7 could combine both catalytic active site (CAS) and peripheral active site (PAS) of AChE with four points (Trp84, Trp279, Tyr70 and Phe330), while it could bind with BuChE via only His 20.