DCC) And 4-dimethylaminopyridine Research Articles

STUDY OF THE INHIBITORY EFFECTS OF VITAMIN E DERIVATIVES ON MITOCHONDRIAL COMPLEX II SUBUNIT USING MOLECULAR DOCKING

Objective: The goal of this study was to create vitamin E derivatives and explore their potential anticancer properties using a computational approach. Methods: The Steglich method was used for the synthesis of the vitamin E-fatty acid (pentanoic acid, heptanoic acid, and octanoic acid) derivatives, with N,N'-dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP) as the catalysts. The structure of the synthesized products was determined by ultraviolet-visible (UV-Vis) spectroscopy, fourier transform infrared (FTIR) spectroscopy, and liquid chromatography-mass spectrometry (LC-MS). Molecular docking was carried out on the succinate dehydrogenase (SDH) enzyme using AutoDockTools. Results: α–Tocopherol pentanoate (α–TP), α–tocopherol heptanoate (α–TH), and α–tocopherol octanoate (α–TO) were the three vitamin E derivatives synthesized in this study. Based on the results of molecular docking, the novel compounds (α–TP, α–TH, and α–TO) generated bond energies of-10.57,-9.61, and-9.20 kcal/mol, respectively. Conclusion: All newly synthesized compounds exhibited lower binding affinity values than α–tocopherol (α–T). This confirms that these compounds might not provide greater advantages than α-tocopherol in terms of inhibitory effects on mitochondrial complex II (CII).

Rivet-Inspired Modification of Aramid Fiber by Decorating with Silica Particles to Enhance the Interfacial Interaction and Mechanical Properties of Rubber Composites.

A rivet–inspired method of decorating aramid fiber (AF) with silica particles (SiO2) is proposed to produce SiO2@AF hybrid materials that have largely enhanced interfacial interaction with the rubber matrix. AF was firstly surface-modified with polyacrylic acid (PAA) to obtain PAA–AF, and SiO2 was silanized with 3-aminopropyltriethoxysilane to obtain APES–SiO2. Then, SiO2@AF was prepared by chemically bonding APES–SiO2 onto the surface of PAA–AF in the presence of dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP). With the incorporation of SiO2@AF into the rubber matrix, SiO2@AF hybrid materials with high surface roughness can play a role as ‘rivets’ to immobilize large numbers of rubber chains on the surface. The tear strength and tensile strength of rubber composite that filling 4 phr SiO2@AF are dramatically increased by 97.8% and 89.3% compared to pure rubber, respectively. Furthermore, SiO2@AF has superiority in enhancing the cutting resistance of rubber composites, in contrast with unmodified AF and SiO2. SiO2@AF is suitable to be applied as a novel reinforcing filler in rubber composites for high performance.

Polyethyleneimine Nanofibers Functionalized with Tetradentate Schiff Base Complexes of Dioxomolybdenum(VI) as Efficient Catalysts for Epoxidation of Alkenes

AbstractThree tetradentate Schiff base ligands (H2L1‐3) were prepared from the reaction of 5‐sustituted‐2‐hydroxybenzaldehydes and 3,4‐diaminobenzoic acid. The obtained ligands were reacted with molybdenyl acetylacetonate in ethanol to prepare the corresponding dioxomolybdenum(VI) complexes (MoO2L1‐3) in good yields (80‐82%). Immobilization of the abovementioned complexes on polyethyleneimine (PEI) was achieved via condensation of carboxylic functional groups of the complex with amine functional groups of the polymer in presence of dicyclohexylcarbodiimide (DCC) and 4‐dimethylaminopyridine (DMAP). The obtained hybrid materials were then converted to electrospun nanofibers and used as recyclable catalysts for the epoxidation of alkenes.

Resorcinarene-centered amphiphilic star-block copolymers: Synthesis, micellization and controlled drug release

Eight-arm star-shaped poly(ɛ-caprolactone)-block-poly(ethylene glycol)s (SPCL-b-PEG) have been prepared by a combination of controlled ring-opening polymerization (CROP) and coupling reaction. First, eight-arm star-shaped poly(ɛ-caprolactone)s (SPCL) with a resorcinarene core were synthesized using octamethyl tetraundecylresorcinarene octaacetate as octa-initiator and yttrium tris(2,6-di-tert-butyl-4-methylphenolate) [Y(DBMP)3] as catalyst. Then the coupling reaction was carried out between SPCLs and carboxyl-terminated methoxy poly(ethylene glycol)s (mPEG-COOH) in the presence of N,N′-dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP), resulting in eight-arm star-shaped SPCL-b-PEGs with controlled molecular weight and well-defined architecture. Furthermore, these amphiphilic eight-arm SPCL-b-PEGs could self-assemble into micelles with low critical micellar concentrations (CMC), which was characterized by fluorescent spectroscopy. Moreover, indomethacin loaded micelles with high drug loading content and high encapsulation efficiency can be prepared, which is probably due to the highly branched architecture. The morphologies of micelles were characterized by transmission electron microscopy (TEM), which exhibited diverse nanostructures as the drug loading contents varied. In vitro drug release of indomethacin from SPCL-b-PEG micelles was carried out in PBS, from which a sustained release behavior was observed. SPCL-b-PEG micelles did not show significant cytotoxicity at copolymer concentrations up to 1000 mg/L, making them very promising for drug delivery.

Dynamic Kinetic Resolution of L-Threonine-derived α-Bromo Esters for Asymmetric Synthesis of α-Amino Esters

Many chiral alcohols have successfully been used as a chiral auxiliary for the dynamic resolution of -halo esters in nucleophilic substitution. 1 L-Threonine is a proteinogenic -amino acid that bears a chiral alcohol group. However, so far L-threonine has not been used as a chiral auxiliary for the dynamic resolution of -halo esters. We herein report the first example of L-threonine-mediated dynamic kinetic resolution of -bromo esters in nucleophilic substitution with various amine nucleophiles. Treatment of N-acetyl L-threonine isopropyl ester with racemic -bromo phenylacetic acid in the presence of dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP) provided -bromo ester (RS)-1 in 70% yield with about 50:50 diastereomeric ratio (dr). When the mixture of (S)-1 and (R)-1 was treated with p-anisidine (1.2 equiv), tetrabutylammonium iodide (TBAI, 1.0 equiv) and diisopropylethylamine (DIEA, 1.0 equiv) in CH2Cl2 at room temperature for 12 h, amino ester 8a was produced in 63% yield with 84:16 dr as shown in Table 1, entry 1. Also, six different N-protection groups of L-threonine were examined for the substitution with p-anisidine as shown in entries 2-7. The reactions of 2, 3, 4, and 7 bearing N-pivaloyl, N-Boc, Nbenzoyl, and N,N-dibenzyl groups gave slightly better drs ranging from 88:12 to 86:14, while the reactions of 5 and 6 bearing N-p-methoxybenzoyl and N-2-pyridinylcarbonyl groups gave lower drs compared to the reaction of 1. The dr and yield of the substitutions in Table 1 imply that -bromo carbon center is configurationally labile with respect to the rate of substitution and L-threonine-derived -bromo esters

Click synthesis by Diels-Alder reaction and characterisation of hydroxypropyl methylcellulose-based hydrogels

AbstractThe Diels-Alder reaction was used to fabricate hydroxypropyl methylcellulose-based hydrogels. First, hydroxypropylmethylcellulose (HPMC) was modified by a carboxyl-containing diene molecule (SFA) which was synthesised from furfurylamine and succinic anhydride. Second, dienophile groups were introduced into HPMC by the coupling reaction with N-maleoyl alanine (AMI) using N,N′-dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP). Subsequently, the asprepared furan- and maleimide-modified HPMC were dissolved in water and gelation was observed at a pre-determined temperature after a period of time. The samples thus obtained were characterised by FTIR, NMR, SEM, etc. The gelation time changing with temperature, concentration of the solution, and solvent was measured. It was found that gelation time decreased with increasing temperature and concentration of the solution, and that water had a rate-accelerating effect on Diels-Alder reaction. The swelling behaviour indicates that the hydrogels have a high swelling ratio in water and the swelling ratio increases with the increasing temperature. Taking into consideration that the HPMC-based hydrogels are prepared under mild reaction conditions with an adjustable gelation time and thermal stability, the method described here has a potential application in biomaterials, especially in the areas of tissue-engineering and drug-controlled release carriers.

SYNTHESIS OF REDUCTIVELY DEGRADABLE COMB-LIKE CATIONIC POLYMER

A reductively degradable cationic polymer with comb-like architecture was synthesized by a combination of polycondensation and reversible addition and fragmentation chain transfer radical polymerization(RAFT).First,the direct polycondensation of decanediol,3,3′-dithiodipeopionic acid and malic acid was carried out using scandium triflate as catalyst.Due to the chemoselectivity of scandium triflate for esterification,the secondary hydroxyl groups of malic units were not esterified during the polycondensation process,resulting in functional polyester with numerous disulfide bones and hydroxyl groups.Then the pendant hydroxyl groups were modified into dithioester form in the presence of N,N′-dicyclohexylcarbodiimide(DCC) and 4-dimethylaminopyridine(DMAP),to give a macromolecular chain transfer agent,which could be used as multifunctional backbone to prepare comb-like polymer by "grafting from" method.Finally,the poly(2-(dimethylamino)ethyl methacrylate)(PDMAEMA) side chains were attached to the backbone via RAFT polymerization of 2-(dimethylamino)ethyl methacrylate.The comb-like architecture of the copolymer was characterized by 1H-NMR and GPC.The reducible degradation of the comb-like polycation was studied in the presence of tributylphosphane as reducing agent,which demonstrated the cleavage of disulfide bonds in the backbone under reductive environment,resulting in low molecular weight PDMAEMA oligomers.This comb-like cationic polymer may have potential applications in gene delivery,which is being investigated in our research group.

Synthesis and Esterification of 3‐Ferrocenyl Acrylic Acid in Ionic Liquid

Abstract3‐Ferrocenyl acrylic acid, synthesized from ferrocenecarboxaldehyde and propandioic acid in water‐insoluble ionic liquid (1‐butyl‐3‐methylimidazolium hexafluorophosphate, [BMIM]PF6) at 85 °C in high yield, was transformed to a series of 3‐ferrocenyl acrylate of alcohols and phenols in water‐soluble ionic liquid (1,3‐dimethylimidazolium dimethylphosphate, [DMIM]Me2PO4) at room temperature in the presence of dicyclohexylcarbodiimide (DCC) and 4‐dimethylaminopyridine (DMAP).

Synthesis and Anti-tumor Activity Evaluation of Rhein-Aloe Emodin Hybrid Molecule

To improve the anti-tumor effects of rhein and aloe-emodin, a rhein-aloe-emodin hybrid molecule (RH-AE) was synthesized from rhein and aloe-emodin in the presence of dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP). Chemical and spectroscopic methods, such as 1H and 13C NMR spectroscopy, and HR-ESIMS were used for the structure identification of RH-AE. Using the cell counting kit-8 (CCK-8) assay, the in vitro anti-tumor effects were compared between RH-AE, rhein and aloe-emodin on human hepatoma HepG2, human nasopharyngeal carcinoma CNE, human lung cancer NCI-H460, human ovarian cancer SK-OV-3, and human cervical cancer Hela cells. The results showed that the half inhibitory concentration (IC50) of RH-AE on HepG2, CNE, NCI-H460, SK-OV-3, and Hela cells were significantly lower than those of rhein and aloe-emodin. This showed that RH-AE has a better in vitro anti-tumor effect than rhein and aloe-emodin.

Synthesis of 4-(2,2-dibromovinyl)phenol and its one-pot esterification

In situ treatment of 4-(2,2-dibromovinyl)phenol, which was prepared from 4-hydroxybenzaldehyde and carbon tetrabromide in CH2Cl2 under Corey–Fuchs conditions, with a diverse range of acids in the presence of dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP) gave the corresponding esters in high yields.

Synthesis of ( S)-naproxen-benzotriazole and its application as chiral derivatizing reagent for microwave-assisted synthesis and indirect high performance liquid chromatographic separation of diastereomers of penicillamine, cysteine and homocysteine

( S)-Naproxen-benzotriazole was synthesized by the reaction of ( S)-naproxen with 1 H-benzotriazole using coupling reagent dicyclohexyl carbodiimide and 4-dimethylamino pyridine (DCC/DMAP). It was used as chiral derivatizing reagent for microwave irradiated synthesis of diastereomers of penicillamine, cysteine and homocysteine. The diastereomers were separated by reversed phase high performance liquid chromatography using gradient elution of triethylammonium phosphate (pH 3.5)–acetonitrile (30–65% within 30 min). The method was validated for accuracy, precision, and limit of detection.

Synthesis of and Tautomerism in 3-Acyltetramic Acids

The synthesis of 3-acyltetramic acids, the substructure of bioactive natural products, via O-acylation of tetramic acids with carboxylic acids followed by acyl migration, has been investigated. This acylation sequence is mediated by N,N'-dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP) and is very sensitive to the nature of the nitrogen substituent (R(1)), the nature of the carboxylic acid (R(2)CO(2)H), and the amount of DMAP. Acylation of N-acyl tetramic acids with an alkyl carboxylic acid using 1.3 equiv of DMAP (with 1.1 equiv of DCC) unexpectedly gave the 3-acyltetramic acid directly as a result of acyl migration induced by excess amounts of DMAP. On the other hand, N-unsubstituted, N-alkyl, and N-acyl tetramic acids with alkyl and aromatic carboxylic acids gave the O-acyl tetramic acids by using only 0.1 equiv of DMAP (with 1.1 equiv of DCC); these could be further rearranged to the acyl product by treatment with excess DMAP. The tautomeric equilibrium of these 3-acyltetramic acids in solution was found to strongly depend on the nitrogen substituent group (R(1)) rather than the 3-acyl group.

Synthesis of an Inorganic–Organic Hybrid Material Based on Polyhedral Oligomeric Silsesquioxane and Polystyrene via Nitroxide-Mediated Polymerization and Click Reactions

Synthesis of an inorganic–organic hybrid polymeric material composed of polystyrene and polyhedral oligomeric silsesquioxane (POSS) was carried out via nitroxide-mediated polymerization (NMP) and Click reaction. First, 4-chloromethyl styrene was polymerized in bulk at 125°C using AIBN and 4hydroxy-TEMPO as the initiator and stable free radical, respectively. Reaction of poly(4-chloromethyl styrene) (PCMS) with NaN3 in DMF yielded azide side-functional polystyrene. In the other step, acetylene functional POSS was obtained by Steglich esterification of 3-hydroxypropylheptaisobutyl-POSS, C31H70O13Si8 (POSS-OH) and propiolic acid in the presence of N,N′-dicyclohexylcarbodiimide (DCC) and 4-dimethylamino pyridine (DMAP). Finally, Huisgen 1,3-dipolar cycloaddition between alkyne and azide functionalities afforded POSS side-chain functional polystyrene. The obtained hybrid polymer was characterized using 1H-NMR, 29Si-NMR, FT-IR, GPC and DSC. The DSC analysis showed that the T g of azide side-chain functional polystyrene (PS-N3) was enhanced by 14°C upon POSS attachment.

Design, Synthesis and Characterization of A Novel Cationic Polymer Poly(lactic acid-b-L-lysine)

A novel biodegradable block copolymer poly(lactic acid-b-lysine) (PLA-b-PLL) has been synthesized and characterized in this study. This product was synthesized via a five-step reaction: Synthesis of hydroxyl-tailed poly(lactic acid) (PLA) by the ring-opening polymerization (ROP) of D,L-lactide in the presence of stannous octoate (Sn(OCt)2) as initiator; coupling N-t-butoxycarbonyl-L-phenylalanine to hydroxyl-tailed PLA using dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP); the amino-tailed PLA was obtained through de-protection of the Boc-protective group in trifluoroacetic acid (TFA) solution; and then ring-opening polymerization of N ϵ -(Z)-lysine-N-carboxyanhydride (NCA) using the amino-tailed PLA as macro-initiator; finally removal of the Cbz-protective group of PLA-b-poly(N ϵ -(Z)-L-lysine) (PLA-b-PLL(Z) in a mixed hydrobromic acid/acetic acid solution to give the target copolymer. The characterization of this copolymer and its precursors were performed by 1H-NMR, FTIR and GPC. The block copolymer PLA-b-PLL, combining the characteristics of an aliphatic polyester and poly(amino acids), could be of potential interest in a variety of medical applications, such as the fields of targeted drug delivery and gene delivery systems.

2‐(Prenyloxymethyl)benzoyl (POMB) as a New Temporary Protecting Group for Alcohols.

AbstractFor Abstract see ChemInform Abstract in Full Text.

2-(Prenyloxymethyl)benzoyl (POMB) as a new temporary protecting group for alcohols

The 2-(prenyloxymethyl)benzoyl (POMB) group was introduced in high yields to hydroxyl functions using the crystalline reagent, 2-(prenyloxymethyl)benzoic acid, in the presence of dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP). 2-(Prenyloxymethyl)benzoic acid is readily available, in two steps, from phthalide in 65% overall yield. The POMB group can be cleaved, in two steps, by treatment with 2,3-dichloro-5,6-dicyanoquinone (DDQ) followed by intramolecular lactonisation of the resulting hydroxy ester induced by a catalytic amount of Yb(OTf) 3·H 2O. The reaction conditions are compatible with the presence of a number of protecting groups such as isopropylidene, benzyl, acetyl, chloroacetyl, benzoyl, levulinoyl, Fmoc and Boc groups.

Asymmetric synthesis of ( S)-ibuprofen by esterification with amides of ( S)-lactic acid as chiral auxiliaries: experimental and theoretical results

A novel synthesis of chiral ibuprofen by a dynamic kinetic resolution process is described. The racemic ibuprofen was converted into the corresponding diastereomeric mixtures of esters with amides of ( S)-lactic acid as chiral auxiliaries, using dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP) as condensation agents. The reactions afforded predominantly one of the two diastereomers with good diastereomeric ratios. The reasons of the stereoselectivity were also investigated by molecular mechanic calculations, using MM2 force fields.

Potential tumor or organ-imaging agents, 24. Radioiodinated pregnenolone esters

A series of radioiodinated pregnenolone esters was prepared in an effort to find an agent that would be rapidly and selectively taken up by adrenal cortical tissue. Achievement of such a goal would provide the basis for the development of an adrenal imaging agent having several advantages over those agents currently available for clinical use. The radioiodinated esters for this study were readily prepared by treating pregnenolone with the appropriate iodobenzoic acid in the presence of dicyclohexylcarbodiimide (DCC) and 4-dimethylamino-pyridine (DMAP). The resulting esters were readily labeled with radioiodine by isotope exchange with sodium iodide-125 in pivalic acid. Subsequent tissue distribution studies in rats revealed that those esters displaying the most stability towards hydrolysis achieved the highest concentration in adrenal cortical tissue. For example, the 2,3,5-triiodobenzoate ( 6) showed an adrenal uptake of 23% of administered dose per gram of tissue at 0.5 hours. The achievement of high levels of radioactivity in the adrenal with this agent at early time periods warrants further evaluation of this agent in other animals.