Metal-free nucleophilic 7,8-dearomatization of quinolines:Spiroannulation of aminoquinoline protected amino acids

Atom-and step-economy in IBX assisted diversity-oriented synthesis is achieved with a versatile AQ auxiliary α-amino acid analogs offering rapid access to polycyclic spiro-quinolines featuring a quaternary stereocenter in 20%–91% yields under mild conditions via 7,8-dearomatization of quinolines. Free of a preinstalled activation group is highlight of this intramolecular oxidation spiroannulation tandem reaction. This type of N-heterospirocycles, traditionally difficult to access, may open the door to a potentially interest scaffold for synthetic and medicinal chemistry.

Silver-catalyzed decarboxylative C-H functionalization of cyclic aldimines with aliphatic carboxylic acids

Silver-catalyzed decarboxylative C–H alkylation of cyclic aldimines with abundant aliphatic carboxylic acids has been realized under mild reaction conditions generating the corresponding products in moderate to good yields(32%–91%).In addition,a gram-scale reaction,late-stage modification of drug,synthetic transformation of the product,and further application of the catalytic strategy were also performed.Preliminary studies indicate that the reaction undergoes a radical process.

Synthesis of polycyclic spiro-fused indolines via IBX-mediated cascade cyclization

We report a 2-iodoxybenzoic acid(IBX)-mediated intarmolecular oxidative spiro-fused tandem cyclization reaction of tryptophan analogs bearing an N-arylamides side-chain to rapidly afford polycyclic spiroindolines featuring multiple stereocenters including a quaternary stereocenters under mild reaction conditions.Among them,a novelty azaphosphol idine-containing spiroindoline compound is synthesized for the first time.It may open the door to azaphos pholidine-containing spiroindoline compound of potential interest in synthetic and medicinal chemistry.A plausible mechanism is proposed.

Target-induced mimic enzyme deactivation based on mixed-node metal-organic frameworks for colorimetric assay of hydrogen sulfide

Accurate detection of hydrogen sulfide(H_(2)S)is of great significance for environmental monitoring and protection.We propose a colorimetric method for the detection of H_(2)S by the use of mixed-node Cu-Fe metal organic frameworks(Cu-Fe MOFs)as highly efficient mimic enzymes for target-induced deactivation.The Cu-Fe MOFs were synthesized by a simple solvothermal method and could catalyze the H_(2)O_(2)mediated oxidation of 3,30,5,50-tetramethylbenzidine(TMB)to oxTMB with a blue color.The presence of dissolved H_(2)S would deactivate the mimic enzymes,and then the blue color disappeared.The mechanism of the sensor was discussed by steady-state kinetic analysis.The designed assay was highly sensitive for H_(2)S detection with a linear range of 0à80 mmol/L and a detection limit of 1.6 mmol/L.Moreover,some potential substances in the water samples had no interference.This method with the advantages of low cost,high sensitivity,selectivity,and visual readout with the naked eye was successfully applied to the determination of H_(2)S in industrial wastewater samples.

Synthesis of planar chiral isoquinolinone-fused ferrocenes through palladium-catalyzed C-H functionalization reaction

(S,S)-Me-BI-DIME/Pd(0)-catalyzed ennantioselective C-H functionalization of N-ferrocenyl o-bromobenzanilides has been realized,affording isoquinolinone-fused ferrocenes with up to 97% ee.The products can be transformed into planar chiral ferrocenyl monophosphines,which demonstrate their preliminary application.

Metal-free synthesis of N-sulfonylformamidines via skeletal reconstruction of sulfonyl oximonitriles

We developed for the first time an unprecedented domino reaction of sulfonyl oximonitriles with secondary amines to streamline the synthesis of N-sulfonylformamidines in decent to high yields under mild reaction conditions.In addition,scale-up experiments and late-stage functionalization of drugs were also performed.Preliminary studies indicate that the loss of a cyano-/benzyloxy-group and a sulfonyl migration process are involved in this reaction.

BVAN08 enhances radiosensitivity via downregulation of DNA-PKcs towards hepatic tumor xenograft

Objective:To study the effects of the novel vanillin derivative BVAN08 on the radiosensitivity of hepatic cancer cells for the purpose of providing evidence for its potential use as a potential radiosensitive drug.Methods:Hepatic cancer Huh-7 cells labeled with luciferase were used to investigate the radiosensitivity induced by BVAN08 in vivo.Colony formation assays and flow cytometry were used to measure the apoptosis and radiosensitivity of Huh-7 cells in vitro produced by BVAN08.Histology and immunohistochemistry were used to evaluate the toxicity of BVAN08 in vivo.Results:BVAN08 induced apoptosis and cell cycle arrest of Huh-7 cells in a time-dependent manner.Moreover,BVAN08 combined with radiation increased the sensitivity of Huh-7 cells toγ-ray radiation and significantly inhibited tumor growth in vivo.The tumor inhibition rates of the BVAN08 treatment group,irradiation treatment group,and combined therapy group were 58%,38%,and 85%,respectively.The DNA-PKcs expression in tumor tissues of the BVAN08 treatment group was lower than that of the control group(P<0.01).BVAN08 inhibited the growth of Huh-7 cells in nude mice bearing tumors,without resulting in any noticeable side effects on bodyweight,livers,hearts,kidneys,or the number of peripheral white blood cells.Conclusions:As a natural food additive derivative,BVAN08 possesses the potential to be used as an effective anticancer drug to increase cell sensitivity to radiotherapy.