Synthetic access to arsenic-containing phosphatidylcholines

We wish to disclose the first synthesis of 1-O-hexadecanoyl-2-O-((15-(dimethylarsinoyl)pentadecanoyl)oxy)-sn-glycero-3-phosphocholine, which belongs to the group of arsenic-containing phosphatidylcholines (AsPCs), recently discovered in herring caviar. The synthesized product will serve as a model compound to study biological and toxicological properties of arsenolipids in food.     

The water-soluble indolium-based fluorescence probes for detection of the extreme acidity or extreme alkalinity

In this work, 3,3′-(((1E,1′E)-(H,12H-5,11-methanodibenzo[b,f][1,5]diazocine-2,8-diyl)bis(ethene-2,1-diyl))bis(1,1-dimethyl-1H-benzo[e]indole-3-ium-2,3-diyl))bis(propane-1-sulfonate) (1), 3,3’-(((1E,1′E)-(6H,12H-5,11-methanodibenzo[b,f][1,5]diazocine-2,8-diyl)bis(ethene-2,1-diyl))bis(3,3-dimethyl-3H-indole-1-ium-2,1-diyl))bis(propane-1-sulfonate) (2), 2,2’-((1E,1′E)-(6H,12H-5,11-methanodibenzo[b,f][1,5]diazocine-2,8-diyl)bis(ethene-2,1-diyl))bis(1,3,3-trimethyl-3H-indol-1-ium) iodide (3) and 2,2’-((1E,1′E)-(6H,12H-5,11-methanodibenzo[b,f][1,5]diazocine-2,8-diyl)bis(ethene-2,1-diyl))bis(1,1,3-trimethyl-1H-benzo[e]indol-3-ium) iodide (4) were designed and synthesized by ethylene bridging of the N-substituted indolium salts and the Tröger’s Base (TB) framework. The probes exhibited a longer absorption and emission wavelength and the emission wavelength of them in dichloromethane (DCM) was more than 600 nm, performed a red fluorescence. All of the probes could work on the extreme acidic and the extreme alkaline environments and showed a good liner response in the working pH range. Especially, 2 and 4 were soluble in water and manifested a good pH sensing in a water system. Also, ¹H NMR analysis illustrated how these dyes worked as the pH-sensitive fluorescence probes. In addition, they performed excellent reversibility, high selectivity and good photostability.     

Synthesis and characterization of tetra-armed-thiosemicarbazone and its salen/salophen capped transition metal complexes: Investigation of their thermal and magnetic properties

In this work, we aimed to synthesize and characterize a novel tetra-directional ligand, (2E,2′E)-2,2′-((((2-(1,3-bis(4-((E)-(2-carbamothioylhydrazono)methyl)phenoxy)propan-2-ylidene)propane-1,3-diyl)bis(oxy))bis(4,1-phenylene))bis(methanylylidene))bis(hydrazinecarbothioamide) (5), including thiosemicarbazone group and its novel tetra-directional-tetra-nuclear Schiff base complexes. For this purpose, we used 1,4-dibromo-2,3-bis(bromomethyl)but-2-ene (2) as starting material. 4,4′-((2-(1,3-Bis(4-formylphenoxy)propan-2-ylidene)propane-1,3-diyl) bis(oxy))dibenzaldehyde (3) was synthesized by the reaction of an equivalent 1,4-dibromo-2,3-bis(bromomethyl)but-2-ene (2) and 4 equivalents of 4-hydroxybenzaldehyde. Then, compound 5 was synthesized in high yield (86%) by a condensation reaction of compound 3 with thiosemicarbazide (4). Finally, four novel tetra-nuclear Cr(III) or Fe(III) complexes of compound 5 were synthesized. The synthesized compounds were characterized using elemental analyses, ¹H NMR, Fourier transform–infrared spectrometry, liquid chromatography–mass spectrometry (ESI⁺), and thermal analyses. The metal ratios of the prepared complexes were determined using an atomic absorption spectrophotometer. We also investigated their effects on the magnetic behaviors of [salen, salophen, Cr(III)/Fe(III)] capped complexes. The complexes were found to be low-spin distorted octahedral Fe(III) and distorted octahedral Cr(III), all bridged by thiosemicarbazone.     

Design,synthesis, biological activity evaluation and mechanism of action of myricetin derivatives containing thioether quinazolinone

Plant bacteria and viruses have a huge negative impact on food crops in the world. Therefore, it is important to create new and efficient green pesticides. In this paper, a series of myricetin derivatives containing quinazolinone sulfide were introduced. Good antibacterial and antiviral activities of the drug molecules 2-((3-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)propyl)thio)-6-fluoro-3-phenylquinazolin-4(3H)-one (T5) and 2-((4-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)butyl)thio)-6-methyl-3-phenylquinazolin-4(3H)-one (T15) respectively were found by biological activity screening. The value of dissociation constant (K_d) of compound T15 to TMV CP was 0.024 ± 0.006 μM, determined by Microscale thermophoresis (MST), which was far less than the value of 8.491 ± 2.027 μM of commercial drug ningnanmycin (NNM). The interaction between compound T15 and TMV CP was further verified by molecular docking. Compound T15 formed strong hydrogen bonds with residues SER:49 and SER:15 (1.92 Å, 2.20 Å, respectively), which were superior to the traditional hydrogen bonds formed by NNM with residue SER:215 (3.64 Å). In addition, the effects of compound T15 on the contents of chlorophyll and peroxidase (POD) in tobacco were studied, and the results indicated that compound T15 could enhance the disease resistance of tobacco plants to a certain extent.     

Unsymmetrical N and/or O-bridged calixarene derivatives: synthesis,structure and encapsulation of solvent molecules in the solid state

Eight unsymmetrical N and/or O-bridged calixarene derivatives were obtained by 1 (naphthalene-2,7-diol), 2 (bis(4-hydroxyphenyl)methanone), 3 (4,4′-methylenedianiline), 4 (3,3′-methylenedianiline), 5 (4,4′-oxydianiline) and 6 (4,4′-(perfluoropropane-2,2-diyl)dianiline) reacting with fragment a (4,4′-bis(dichloro-s-triazinyloxy)propane-2,2-diyldibenzene) and b (N,N′-bis(dichloro-s-triazinyl)-4,4′-methylenedianiline) under very mild reaction conditions via efficient fragment coupling strategy. We also obtained the crystal structure of 1a (tetraoxocalix[2](propane-2,2-diyldibenzene,naphthalene)[2]triazine) which can form a molecular capsule by two dimers with C–H?N and C–H?O quadruple hydrogen bonds, and it has the encapsulation ability toward solvent molecules.     

Synthesis of novel dipodal-benzimidazole,benzoxazole and benzothiazole from cyanuric chloride: Structural,photophysical and antimicrobial studies

In the present study, new benzimidazole, benzoxazole and benzothiazole derivatives were prepared and screened for antimicrobial activity. The structure of 4,4′-((6-(4-(diethylamino)phenyl)-1,3,5-triazine-2,4-diyl)bis(oxy))dibenzaldehyde (DIPOD) 5 was established from p-hydroxy benzaldehyde 4 and 4-(4,6-dichloro-1,3,5-triazin-2-yl)-N,N-diethylaniline 3. The reaction of DIPOD 5 with different o-phenylenediamine or o-amino phenol or o-amino thiophenol in ethanol gave benzimidazole, benzoxazole and benzothiazole 7. Novel heterocycles showed excellent broad-spectrum antimicrobial activity against bacterial strain (Escherichia coli, Staphylococcus aureus) and fungal strain (Candida albicans, Aspergillus niger) cultures. Activity data was compared with standard Streptomycin and Fluconazole drug. Photophysical and thermal properties of synthesized compounds were also studied.     

Bisthiourea: thermal and structural investigation

Bisthiourea derivatives 1,1′-(ethane-1,2-diyl)bis(3-phenylthiourea), 1,1′-(propane-1,3-diyl)bis(3-phenylthiourea), and 1,1′-(butane-1,4-diyl)bis(3-phenylthiourea) have been synthesized and characterized by IR, ¹H NMR, and ¹³C NMR. Suitable crystals of 1,1′-(propane-1,3-diyl)bis(3-phenylthiourea) were grown for single-crystal X-ray analysis and from the data it was observed that they organize into the P-1 space group. The thermal decomposition of these compounds has been studied by TG–DSC.     

An improved process for chiron synthesis of the atorvastatin side chain

An improved and practical synthesis of tert-butyl ((4R,6R)-6-aminoethyl-2,2-dimethyl-1,3-dioxan-4-yl)acetate 3 has been developed for supplying this key chiral side-chain of atorvastatin by using a Blaise reaction of (S)-4-chloro-3-((trimethylsilyl)oxy)butanenitrile 7 and the Raney Ni catalyzed hydrogenation of tert-butyl 2-((4R,6R)-6-(-2-oximeethyl)-2,2-dimethyl-1,3-dioxan-4-yl)acetate 12 as the key steps. This nine-step route from (R)-epichlorohydrin afforded the target compound in 55% overall yield of high chemical and enantiomeric purity.     

Synthesis of a new sulfobetaine surfactant with double long alkyl chains and its performances in surfactant-polymer flooding

A new zwitterionic surfactant with double long alkyl chains, 3-((3-((1,3-bis (decyloxyl) propane-2-yl) oxy) -2-hydroxypropyl) dimethylamonio) -2-hydroxypropane-1-sulfonate (diC₁₀GE-HSB), was synthesized, and its performances in Surfactant-Polymer (SP) flooding were studied. As a hydrophobic surfactant diC₁₀GE-HSB solely cannot reduce Daqing crude oil/connate water IFT to ultralow, but ultralow IFT can be achieved by using binary mixtures of diC₁₀GE-HSB with various conventional hydrophilic surfactants such as α–olefin sulfonates, dodecyl polyoxyethylene (10) ether, and cetyl dimethyl hydroxypropyl sulfobetaine, over a wide total concentration range (0.625?～?10?mM) at reservoir temperature. This new sulfobetaine surfactant is therefore a good candidate for SP flooding free of alkali.     

Recyclization of ethyl 1-alkyl-5-benzoyl-6-methylsulfanyl-2-oxo-1,2-dihydropyridine-3-carboxylates into Bicyclic <Emphasis Type="Italic">N</Emphasis>-alkyl-5-benzoyl-2-oxo-1,2-dihydropyridine-3-carboxamide derivatives by the action of nitrogen-containing 1,4- and 1,5-binucleophiles

Reactions of ethyl 1-alkyl-5-benzoyl-6-methylsulfanyl-2-oxo-1,2-dihydropyridine-3-carboxylates with nitrogen-containing 1,4- and 1,5-binucleophiles (o-phenylenediamine, o-aminobenzenethiol, ethane-1,2-diamine, and propane-1,3-diamine) involved recyclization, leading to the formation of fused N-alkyl-5-benzoyl- 2-oxo-1,2-dihydropyridine-3-carboxamides, diethyl 6,6′-oxybis(1-alkyl-5-benzoyl-2-oxo-1,2-dihydropyridine-3-carboxylates), and diethyl 6,6′-[ethane-1,2-diyl(or propane-1,3-diyl)diimino]bis(1-alkyl-5-benzoyl-2-oxo-1,2-dihydropyridine-3-carboxylates), depending on the reactant ratio. The sequence of formation of intermediate recyclization products was determined.     

New chiral phosphine-phosphonites derived from (2R,3R)-dimethyl tartrate, (S)-binaphthol and (1R,2S)-ephedrine

The reaction of 2-lithiophenyldiphenylphosphine with phosphorus trichloride afforded the new unsymmetric phosphine, dichloro(2-diphenylphosphinophenyl)phosphine (4). Condensation of 4 with (a) (2R,3R)-dimethyl tartrate or (b) (S)-binaphthol in the presence of triethylamine gave new chiral phosphine-phosphonite ligands, (2R,3R)-[2-(2′-(diphenylphosphino)phenyl)-4,5-bis(carbomethoxy)-1,3,2-dioxaphospholane] ((2R,3R)-5) and (S)-[2-(diphenylphosphino)benzene][1,1′-binaphthalen-2,2′-diyl]phosphonite] ((S)-6). The analogous reaction of 4 with (1R,2S)-ephedrine using N-methylmorpholine as the base, gave [2-(2′-(diphenylphosphino)phenyl)-3,4-dimethyl-5-phenyl-1,3,2-oxazaphospholidine] (7) as a 95:5 mixture of diastereoisomers.     

Multiblock copolymer synthesis via controlled radical polymerization in aqueous dispersions. Part 1: Synthesis of S-tert-alkyl-N,N-alkoxycarbonylalkyldithiocarbamates

In a novel two- or three-step synthetic route, S-(1,4-phenylenebis(propane-2,2-diyl)) bis(N-methyldithiocarbamate) is reacted at low temperature with various alkyl chloroformates to form various S-tert-alkyl-N,N-alkoxycarbonylmethyl-dithiocarbamate RAFT agents. Also an alternative and novel synthetic route towards S-(1,4-phenylenebis(propane-2,2-diyl)) bis(N-methyldithiocarbamate), is proposed.     

Arsenic-containing ribofuranosides and dimethylarsinic acid in green seaweed,Codium fragile

Three water-soluble arsenic compounds were isolated from the green seaweed Codium fragile. These compounds were identified as 1-glycerophosphoryl-2-hydroxy-3-[5′-deoxy-5′-(dimethylarsinoyl)-β-ribofuranosyloxy]propane (1a), 1′ -(1,2-dihydroxypropyl)-5′ -deoxy-5′ -(dimethylarsinoyl)-β-ribofuranoside (1b), and dimethylarsinic acid ((CH₃)₂AsOOH). The structures of these compounds were ascertained by ¹H NMR spectroscopy. Compounds 1a and 1b accounted for 60 % and dimethylarsinic acid for 5% of the water-soluble arsenic.     

Asymmetric transfer hydrogenation of acetophenone derivatives with novel chiral phosphinite based η-p-cymene/ruthenium(II) catalysts

Enantioselective reduction of prochiral ketones to optically active secondary alcohols is an important subject in synthetic organic chemistry because the resulting chiral alcohols are extremely useful, biologically active compounds. The new chiral ligands (2R)-2-[benzyl{(2-((diphenylphosphanyl)oxy)ethyl)}amino]butyldiphenylphosphinite, 1 and (2R)-2-[benzyl{(2-((dicyclohexylphosphanyl)oxy)ethyl)}amino]butyldicyclohexylphosphinite, 2 and the corresponding ruthenium(II) complexes 3 and 4 have been prepared. The structures of these complexes have been elucidated by a combination of multinuclear NMR spectroscopy, IR spectroscopy and elemental analysis. ³¹P-{¹H} NMR, DEPT, ¹H-¹³C HETCOR or ¹H-¹H COSY correlation experiments were used to confirm the spectral assignments. These ruthenium(II)-phosphinite complexes have been used as catalysts for the asymmetric transfer hydrogenation of acetophenone derivatives. Under optimized conditions, aromatic ketones were reduced in good conversions and in moderate to good enantioselectivities (up to 85% ee).     

A new synthesis of 1,3-difunctionalized 2-sulfonamidopropane derivatives via regioselective ring opening reactions of 2-(bromomethyl)-1-sulfonylaziridines by substituted arylsulfonamides

The novel functionalized N,N′-[2-(arylsulfonamido)propane-1,3-diyl]bis(N-allylarylsulfonamide) and N,N′-[2-(methylsulfonamido)propane-1,3-diyl]bis(N-benzylarylsulfonamide) derivatives have been prepared from 2-(bromomethyl)-1-sulfonylaziridines for the first time using substituted arylsulfonamides in the presence of sodium methoxide under catalyst-free condition in good yields.     

Efficient stereocontrolled synthesis of C-glycosides using glycosyl donors substituted by propane 1,3-diyl phosphate as the leaving group

α- and β-Glycosyl cyanides, per-O-acetyl-1,2-O-1-cyanoethylidenes and C-allyl glycopyranosides were efficiently prepared by treatment of 2,3,4-tri-O-acetyl-α,β-l-rhamno-, l-fuco- and 2,3,4,6-tetra-O-acetyl-α,β-d-galactopyranosyl propane-1,3-diyl phosphates with trimethylsilyl cyanide (TMSCN) and allyltrimethylsilane in the presence of trimethylsilyl triflate (TMSOTf). Similarly 2,3,4,6-tetra-O-benzyl-α,β-d-manno- and d-glucopyranosyl propane-1,3-diyl phosphates were employed in the synthesis of C-glycosides.     

Reaction of thiourea with formaldehyde and simplest aliphatic diamines

N,N′-Bis(hydroxymethyl)thiourea reacted with propane-1,3-diamine at a molar ratio of 2 : 1 to give 5,5′-propane-1,3-diylbis(1,3,5-triazinane-2-thione), whereas 1,3,5,7,11,13,15,17-octaazatricyclo[15.3.1.1^7,11]-docosane-4,14-dithione was obtained in the reaction with equimolar amounts of the reactants. Tricyclic product was also formed in the three-component condensation of thiourea with formaldehyde and propane-1,3-diamine at a ratio of 1 : 3 : 1. The reactions of N,N′-bis(hydroxymethyl)thiourea with ethane-1,2-diamine (2 : 1) and of thiourea with formaldehyde and butane-1,4-diamine (1 : 2 : 1) afforded 5,5′-(ethane-1,2-diyl)bis(1,3,5-triazinane-2-thione) and 5,5′-(butane-1,4-diyl)bis(1,3,5-triazinane-2-thione), respectively.     

Three-component reaction of methyl 2,4-dioxo-4-phenylbutanoate and methyl 2,4-dioxopentanoate with aromatic aldehydes and propane-1,2-diamine and chemical properties of the products

The reactions of methyl 2,4-dioxo-4-phenylbutanoate and methyl 2,4-dioxopentanoate with a mixture of an aromatic aldehyde and propane-1,2-diamine, depending on the initial reactant ratio, gave 4-acyl-1-(2-aminopropyl)-5-aryl-3-hydroxy-2,5-dihydro-1H-pyrrol-2-ones and 1,1′-(propane-1,2-diyl)bis(4-acetyl-3-hydroxy-5-phenyl-2,5-dihydro-1H-pyrrol-2-one). Reactions of substituted 1-(2-aminopropyl)-2,5-dihydro-1H-pyrrol-2-ones with aromatic amines and hydrazines were studied, and the structure of one of the products, 5-(2-aminopropyl)-3,4-diphenylpyrrolo[3,4-c]pyrazol-6-one, was proved by X-ray analysis.     

New benzimidazole derivatives: Design,synthesis, docking,and biological evaluation

The aim of this study was to synthesize novel enaminonitrile derivatives starting from 2-aminobenzimidazole and utilize this derivative for the preparation of novel heterocyclic compounds and assess their function for biological activity screening. The key precursor N-(1H-benzo[d]imidazol-2-yl)carbonohydrazonoyl dicyanide (2) was prepared in pyridine by coupling of diazotized 2-aminobenzimidazole (1) with malononitrile. Compound 2 was subjected to react with various secondary amines such as piperidine, morpholine, piperazine, diphenylamine, N-methylglucamine, and diethanolamine in boiling ethanol to give the acrylonitriles (2Z)-2-((1H-benzo[d]imidazol-2-yl)diazenyl)-3-amino-3-(piperidin-1-yl)acrylonitrile (3), (2Z)-2-((1H-benzo[d]imidazol-2-yl)diazenyl)-3-amino-3-morpholinoacrylonitrile (4), (2Z)-2-((1H-benzo[d]imidazol-2-yl)diazenyl)-3-amino-3-(piperazin-1-yl)acrylonitrile (5), (2Z)-2-((1H-benzo[d]imidazol-2-yl)diazenyl)-3-amino-3-(diphenylamino)acrylonitrile (6), (2Z)-2-((1H-benzo[d]imidazol-2-yl)diazenyl)-3-amino-3-(methyl((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)amino)acrylonitrile (7), and (2Z)-2-((1H-benzo[d]imidazol-2-yl)diazenyl)-3-amino-3-(bis(2-hydroxyethyl)amino)acrylonitrile (8), respectively. It has been found that the behaviour of nitrile derivative 2 towards hydrazine hydrate to the creation of 4-((1H-benzo[d]imidazol-2-yl)diazenyl)-1H-pyrazole-3,5-diamine (9). The reaction of malononitrile with compound 2 in an ethanolic solution catalyzed with sodium ethoxide afforded 4-amino-1-(1H-benzo[d]imidazol-2-yl)-6-imino-1,6-dihydropyridazine-3,5-dicarbonitrile (11). Moreover, malononitrile reacted with 7 in a boiling ethanolic sodium ethoxide solution to give 2-(5-((1H-benzo[d]imidazol-2-yl)diazenyl)-4-amino-6-(methyl((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)amino)pyrimidin-2-yl)acetonitrile (14). Heating 7 in boiling acetic anhydride and pyridine afforded (2R,3R,4R,5S)-6-(((1E)-2-((1-acetyl-1H-benzo[d]imidazol-2-yl)diazenyl)-1-(N-acetylacetamido)-2-cyanovinyl)(methyl)amino)hexane-1,2,3,4,5-pentayl pentaacetate (15). When compound 15 is heated for a long time in refluxing DMF including a catalytic of TEA, cyclization occurs to give the corresponding (2R,3R,4R,5S)-6-((1-acetyl-3-((1-acetyl-1H-benzo[d]imidazol-2-yl)diazenyl)-4-amino-6-oxo-1,6-dihydropyridin-2-yl)(methyl)amino)hexane-1,2,3,4,5-pentayl pentaacetate (16). In addition, triethyl orthoformate was reacted with compound 7 in the presence of acetic anhydride to afford the corresponding ethoxymethyleneamino derivative (2R,3R,4R,5S)-6-(((1E)-2-((1-acetyl-1H-benzo[d]imidazol-2-yl)diazenyl)-2-cyano-1-(((E) ethoxymethylene)amino)vinyl)(methyl)amino)hexane-1,2,3,4,5-pentayl pentaacetate (17). Also, it has been found that heating a mixture of 7 with DMF/DMA in anhydrous xylene yielded compound (1E)-N'-((1E)-2-((1H-benzo[d]imidazol-2-yl)diazenyl)-2-cyano-1-(methyl((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)amino)vinyl)-N,N-dimethylformimidamide (18). In addition, compound 7, when reacted with several acid anhydrides, allowed the matching phthalimide derivatives 19–26. The results showed that compound 14 has significantly higher ABTS and antitumor activities than the other compounds. Molecular modelling was also studied for compounds 22 and 24. The viability of four many cell lines—the African green monkey kidney epithelial cells (VERO), human breast adenocarcinoma cell line (MCF-7), human lung fibroblast cell line (WI-38), and human hepatocellular liver carcinoma cell line (HepG2) was examined to determine the antitumor activities of the newly synthesized compounds. Also, it was found that compounds 9, 11, 15, 16, 22, 23, 24 and 25 are strong against HepG2 cell lines, while 16, 22, and 25 are strong against WI-38 cell lines. Moreover, it was also found that compounds 16 and 22 are strong against VERO cell lines. On the other hand, compounds 7, 14, 15, 16, and 22 are strong while the rest of the other compounds are moderate against the MCF-7 cell line. The result of docking showed that compound 24 got stabilized inside the pocket with a very promising binding score of ? 8.12 through hydrogen bonds with Arg184 and Lys179, respectively.     

New synthesized ligands for detection of heavy metal ions

Some new chemo-sensors (4,4'-((1E,1′E)-(2,2′-dichloro-[1,1′-biphenyl]-4,4′-diyl)bis(diazene-2,1-diyl))bis(3,5-dihydroxybenzoic acid), 4-((E)-(4-(N-(4-((E)-(4-carboxy-2,6-dihydroxyphenyl)diazenyl)phenyl)sulfamoyl)phenyl)diazenyl)-3,5-dihydroxybenzoic acid, 4-((E)-(4-((4-((E)-(4-carboxy-2,6-dihydroxyphenyl)diazenyl)-2-sulfophenyl)amino)phenyl)diazenyl)-3,5-dihydroxybenzoic acid) were synthesized. These synthesized sensors were then characterized by FTIR, TLC, UV–Visible spectrophotometry, and NMR techniques. The sensors showed the best results for detection of all type of heavy metal ions simply by changing the colour of metal ion solution and by shifting in the λ_max values of sensors due to interactions.