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.

[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.

Three-dimensional spiral CT observation of the facet joints of the lower cervical spine and its clinical significance.

OBJECTIVE: By observing the 3D anatomy of normal adult cervical facet joints, using the picture archiving and communication system to measure its 3D parameters and discussing its clinical significance, the aim of this study was to provide a reliable morphological basis for the design and manufacture of lower cervical facet joint interface distractors. METHODS: We selected 200 patients who underwent cervical spine 3D spiral computed tomography (CT) examination in the imaging department of our hospital from September 2019 to May 2020 and whose spiral CT images showed no cervical spinal canal stenosis, cervical disc herniation, obvious bone hyperplasia, or infection. The anterior and posterior diameters of the facet joints on both sides of the cervical spine, the space between the joints, and the left and right diameters were measured on the sagittal, cross-sectional and coronal planes after reconstruction with 3D spiral CT. RESULTS: The anterior and posterior diameters of the facet joints of the cervical spine, the space between the joints, and the left and right diameters all increased from top to bottom along the cervical spine. The 3D parameters of the C2-3~C6-7 segments were significantly different between the male and female groups. CONCLUSION: The anteroposterior diameter, joint space interval, and left and right diameter of cervical facet joints are different in each segment and between the sexes. The lower cervical facet joint interface fusion device designed according to the measurement results can fully meet the needs of most patients.

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.

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.

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.

Manganese-Catalyzed Intermolecular Oxidative Annulation of Alkynes with γ-Vinyl Aldehydes: An Entry to Bridged Carbocyclic Systems.

Manganese-catalyzed intermolecular oxidative annulation of alkynes with γ-vinyl aldehydes involving acylation and alkylation is described, thus providing a scenario for the divergent synthesis of bridged carbocyclic systems. By means of this manganese-catalyzed alkyne dicarbofunctionalization strategy, three chemical bonds, including two C-C bonds and one C-H bond, are formed via an aldehyde C(sp2)-H oxidative functionalization/[4 + 2] annulation/protonation cascade.

Synthesis of Icaritin and ß-anhydroicaritin Mannich Base Derivatives and Their Cytotoxic Activities on Three Human Cancer Cell Lines.

BACKGROUND: Prenyl flavonoid icaritin (1) and ß-anhydroicaritin (2) are two natural products with important biological and pharmacological effects. such as antiosteoporosis, estrogen regulation and antitumor properties. OBJECTIVE: The present study investigates the synthesis and cytotoxic activities on three Human cancer cell lines (Hela, HCC1954 and SK-OV-3) of icaritin and ß-anhydroicaritin Mannich base derivatives in vitro models. METHOD: Preylated flavonoid icaritin (1) upon treatment with formic acid under microwave assistance gave another natural product ß-anhydroicaritin (2) in good yield (89%). Based on Mannich reaction of 1 or 2 with various secondary amines and formaldehyde, two series eighteen new 6-aminomethylated flavonoids Mannich base derivatives 3-11 and 12-20 were synthesized. Their cytotoxic potential against three human cancer cell lines (Hela, HCC1954 and SK-OV-3) were evaluated by the standard MTT method with cis-Platin and Paclitaxel as positive control. RESULTS: Our research showed that most of these flavonoid Mannich base derivatives displayed equal or higher (lower IC50 values) cytotoxic activities than the positive control cis-Platin. Some compounds possess the IC50 value below 10µM. Compounds 6-(diisopropylamino)methyl- and 6-morpholinylmethyl substituted ß-anhydroicaritin (15 and 19) showed selective cytotoxicity against HCC1954 cells (IC50 12.688 µM) and Hela cells (IC50 6.543 µM) respectively. CONCLUSION: Our finding most of icaritin and ß-anhydroicaritin Mannich base derivatives possessing moderate to potent cytotoxicity against these three cancer cells (Hela, HCC1954 and SK-OV-3). Compound 15 and 19 showed selective cytotoxicity against HCC1954 cells and Hela cells respectively, they are potential and selective anticancer agent and worthy of further development.

Synthesis of kaempferide Mannich base derivatives and their antiproliferative activity on three human cancer cell lines.

Kaempferide (3,5,7-trihydroxy-4'-methoxyflavone, 1), a naturally occurring flavonoid with potent anticancer activity in a number of human tumour cell lines, was first semisynthesized from naringin. Based on Mannich reaction of kaempferide with various secondary amines and formaldehyde, nine novel kaempferide Mannich base derivatives 2-10 were synthesized. The aminomethylation occurred preferentially in the position at C-6 and C-8 of the A-ring of kaempferide. All the synthetic compounds were tested for antiproliferative activity against three human cancer cell lines (Hela, HCC1954, SK-OV-3) by the standard MTT method. The results showed that compounds 1, 2 and 5-10 were more potent against Hela cells with IC50 values of 12.47-28.24 µM than the positive control cis-platin (IC50 41.25 µM), compounds 5, 6, 8 and 10 were more potent against HCC1954 cells with IC50 values of 8.82-14.97 µM than the positive control cis-platin (IC50 29.68 µM), and compounds 2, 3, 5, 6 and 10 were more potent against SK-OV-3 cells with IC50 values of 7.67-18.50 µM than the positive control cis-platin (IC50 21.27 µM).

Novel Potent and Selective Acetylcholinesterase Inhibitors as Potential Drugs for the Treatment of Alzheimer's Disease: Synthesis, Pharmacological Evaluation, and Molecular Modeling of Amino-Alkyl-Substituted Fluoro-Chalcones Derivatives.

A new series of-fluoro chalcones-substituted amino-alkyl derivatives (3a˜3l) were designed, synthesized, characterized and evaluated for the inhibitory activity against acetylcholinesterase and butyrylcholinesterase. The results showed that the alteration of fluorine atom position and amino-alkyl groups markedly influenced the activity and the selectivity of chalcone derivates in inhibiting acetylcholinesterase and butyrylcholinesterase. Among them, compound 3l possesses the most potent inhibitory against acetylcholinesterase (IC50  = 0.21 ± 0.03 µmol/L), and the highest selectivity for acetylcholinesterase over butyrylcholinesterase (IC50 (BuChE)/IC50 (AChE) = 65.0). Molecular modeling and enzyme kinetic study on compound 3l supported its dual acetylcholinesterase inhibitory profile, simultaneously binding at the catalytic active and peripheral anionic site of the enzyme.

Synthesis and acetylcholinesterase inhibitory activity of Mannich base derivatives flavokawain B.

A novel series of flavokawain B derivatives, chalcone Mannich bases (4-10) were designed, synthesized, characterized, and evaluated for the inhibition activity against acetylcholinesterase (AChE). Biological results revealed that four compounds displayed potent activities against AChE with IC50 values below 20µM. Moreover, the most promising compound 8 was 2-fold more active than rivastigmine, a well-known AChE inhibitor. The logP values of 4-10 were around 2 which indicated that they were sufficiently lipophilic to pass blood brain barriers in vivo. Enzyme kinetic study suggested that the inhibition mechanism of compound 8 was a mixed-type inhibition. Meanwhile, the molecular docking showed that this compound can both bind with the catalytic site and the periphery of AChE.

Three new vibralactone-related compounds from cultures of Basidiomycete Boreostereum vibrans.

Three new compounds, named as vibralactones K-M (1-3), together with vibralactone (4) have been isolated from cultures of the Basidiomycete Boreostereum vibrans. Their structures were determined on the basis of spectroscopic evidences (1D and 2D NMR, HRMS, UV, and IR data), chemical methods and literature data. None of the compounds was cytotoxic against five human cancer cell lines and showed inhibitory activity on the pancreatic lipase.

Three new compounds from the cultures of basidiomycete Boreostereum vibrans.

Three new compounds, vibranether (1), myrrhlalkyldiol (2), vibralactone H (3), together with three known compounds, 2-methyl-6-p-tolylheptane-2,3-diol (4), 2-hydroxy-2-methyl-6-p-tolylheptan-3-one (5), and vibralactone (6), were isolated from the cultures of the basidiomycete Boreostereum vibrans. Their structures were determined on the basis of spectroscopic evidences (1D and 2D NMR, HRMS, UV, and IR data), chemical methods, and the literature data. The new compounds displayed no significant cytotoxicities against five human cancer cell lines (IC50>40 µM).

Synthesis and cytotoxicity of chalcones and 5-deoxyflavonoids.

Chalcones 1~8 and 5-deoxyflavonoids 9~22 were synthesized in good yields by aldol condensation, Algar-Flynn-Oyamada reaction, glycosidation, and deacetylation reaction, respectively, starting from 2-acetyl phenols substituted by methoxy or methoxymethoxy group and appropriately benzaldehydes substituted by methoxy, methoxymethoxy group, or chlorine. Among them, 13 and 17~22 are new compounds. The cytotoxicity bioassays of these chalcones and 5-deoxyflavonoids were screened using the sulforhodamine B (SRB) protein staining method, and the results showed that compounds 2, 4, 5, 6, 10, 15, and 19 exhibited moderate cytotoxicity against the cancer cell line of MDA-MB-231, U251, BGC-823, and B16 in comparison with control drugs (HCPT, Vincristine, and Taxol).