Presence Of 4-dimethylaminopyridine Research Articles

Design, synthesis, and biological evaluation of novel pyridine acid esters of podophyllotoxin and esters of 4′-demethylepipodophyllotoxin

Podophyllotoxin and related analogs present numerous challenges associated with optimal antitumor activity and severe unpredictable toxicity. In the course of our ongoing investigation of quantitative structure–activity relationships to find biorational antitumor drugs, two series of pyridine acid ester derivatives of podophyllotoxin and 4′-demethylepipodophyllotoxin have been prepared by reacting the corresponding pyridine acids with the hydroxyl group of podophyllotoxin and 4′-demethyl epipodophyllotoxin in the presence of dimethylaminopyridine (DMAP) and N,N-dicyclohexylcarbodiimde (DCC). The structures of the compounds were extensively characterized by using 1H-nuclear magnetic resonance, mass spectroscopy, infrared, and elemental analysis and evaluated for their in vitro cytotoxicity on two neoplastic cell lines (P-388 murine leukemia, A-549 human lung carcinoma) using a MTT-based assay, the results indicated significantly higher efficacy of these compounds in comparison with the prototypical inhibitor etoposide. On the basis of the preliminary biological testing results, it suggested that the cytotoxic activity of OCH3 at C-4′ is more potent than that of its demethylated analogs and the podophyllotoxin substitution at C-4 may be optimal for synthesizing more potent cytotoxic compounds.

A simple and efficient method for synthesis of fluorine-containing saccharide esters and antiviral activity

Sixteen new fluorine-containing saccharide esters from fluorine-containing benzoic acids and α- O-acetylglycosyl bromide were synthesized in the presence of 4-dimethylaminopyridine (DMAP) and triethylamine (Et 3N) under mild conditions in good yields and their structures were clearly verified by IR, 1H NMR, MS and elemental analysis. This method has high stereospecificity, the configuration is unitary, the new synthesized compounds are all of β-configuration. The results of bioassay showed that these title compounds possess potential antiviral activities against tobacco mosaic virus (TMV).

Synthesis and Characterization of Triblock Copolymers Containing Amphiphilic Dendron

Dendrimers/dendrons are regularly branched macromolecules which have received a great amount of attention due to their structural and physical uniqueness. Recently, introduction of microphase-separation concept has been proved to lead to a self-assembling system which shares the morphological behavior of dendrimers/dendrons and linear block copolymers. However, dendron and linear polymer fused system has not been extended to complicated chain architectures. For example, triblock copolymers, they have potential to selforganize into complex and exciting nanostructures such as a ring and a knitting pattern which can not be expected in conventional diblock copolymer systems. Therefore, it would be an interesting challenge to study the influence of dendron architecture on self-assembled nanostructures in triblock copolymer systems. To this end, we have designed and synthesized a novel triblock copolymer which consists of a hydrophobic crystalline peripheries (docosyl chains), a hydrophilic part [dendritic core plus poly(ethylene oxide) (PEO)], and a hydrophobic amorphous coil [polyisoprene (PI)]. As shown in Scheme 1, the synthesis began with anionic polymerization of isroprene. In the first step isoprene was polymerized in cyclohexane with sec-butyllithium as an initiator. To convert the living PI end into hydroxy group, ethylene oxide was added and then subsequently oxyanion of the resulting PI chain was protonated with degassed methanolic HCl. In the next step potassium naphthalenide was used to remove the proton on the hydroxyl group resulting in PI-O−K+. Polymerization of ethylene oxide at the end of PI was performed in tetrahydrofuran in the presence of a five-fold excess of KCl with respect to PI-OH chain ends. The polymerization was terminated with degassed methanolic HCl. Then, the PI-b-PEO was functionalized with carboxylic acid by the reaction with succinic anhydride in the presence of 4-dimethylaminopyridine (DMAP). The structural analysis from gel permeation chromatography (GPC) and nuclear magnetic resonance (NMR) spectroscopy determines that the molecular weights of PEO and PI are 2170 and 3000 g/mol, respectively. Meanwhile, synthesis of an amphiphilic dendron (denoted as 4G-OH) was performed using a convergent synthetic method. The synthetic procedure consists of two organic reactions such as a Williamson etherification and hydroboration/oxidation reactions. Several iteration of these steps led to the monodisperse dendron, the synthetic details of which were reported previously. The triblock block copolymer was achieved through a simple esterification coupling reaction using N,N'-diisopropylcarbodiimide (DIPC) and 4-(dimethylamino)pyridiniump-toluene sulfonate (DPTS). In this reaction, a two fold excess of 4G-OH with respect to PI-b-PEO was used to

Synthesis of Novel Spin‐Labeled Derivatives of Podophyllotoxin as Potential Antineoplastic Agents

Five novel nitroxyl spin‐labeled ester derivatives of podophyllotoxin have been prepared by reacting the corresponding N‐(1‐oxyl‐2,2,6,6‐tetramethyl‐4‐piperidinyloxycarbonyl) amino acids with the hydroxy group of podophyllotoxin in the presence of dimethylaminopyridine and N,N‐dicyclohexylcarbodiimide and evaluated as potential antitumor agents. All of the target compounds showed more significant cytotoxicity against P‐388 murine leukemia and A‐549 human lung carcinoma in vitro than etoposide.

The DMAP‐Catalyzed Acetylation of Alcohols—A Mechanistic Study (DMAP=4‐(Dimethylamino)pyridine)

The acetylation of tert-butanol with acetic anhydride catalyzed by 4-(dimethylamino)pyridine (DMAP) has been studied at the Becke3 LYP/6-311 + G(d,p)//Becke3 LYP/6-31G(d) level of theory. Solvent effects have been estimated through single-point calculations with the PCM/UAHF solvation model. The energetically most favorable pathway proceeds through nucleophilic attack of DMAP at the anhydride carbonyl group and subsequent formation of the corresponding acetylpyridinium/acetate ion pair. Reaction of this ion pair with the alcohol substrate yields the final product, tert-butylacetate. The competing base-catalyzed reaction pathway can either proceed in a concerted or in a stepwise manner. In both cases the reaction barrier far exceeds that of the nucleophilic catalysis mechanism. The reaction mechanism has also been studied experimentally in dichloromethane through analysis of the reaction kinetics for the acetylation of cyclohexanol with acetic anhydride, in the presence of DMAP as catalyst and triethylamine as the auxiliary base. The reaction is found to be first-order with respect to acetic anhydride, cyclohexanol, and DMAP, and zero-order with respect to triethyl amine. Both the theoretical as well as the experimental studies strongly support the nucleophilic catalysis pathway.

Synthesis and characterization of novel biodegradable superabsorbent hydrogels based on chitin and succinic anhydride

Synthesis of novel superabsorbent hydrogels has been investigated with the reaction of chitin and succinic anhydride (SA) in the presence of 4-dimethylaminopyridine as esterification catalyst in mixture of tetrabutylammnium fluoride and dimethylsulfoxide (TBAF/DMSO) or in mixture of lithium chloride and N-methyl-2-pyrrolidinone (LiCl/NMP), followed by NaOH neutralization. Interestingly, hydrogel was obtained in TBAF/DMSO without any crosslinking agent, which indicated the partial formation of diester between hydroxyl group of chitin and SA. On the contrary, products obtained in LiCl/NMP dissolved out during the absorbency test, which indicates that they consist mainly of linear polymer. The former absorbed water about 300 times of its dry weight, which is comparable with the conventional sodium polyacrylate superabsorbent hydrogel. Further, in aqueous NaCl solution, absorbency of the product hydrogels was higher than the sodium polyacrylate superabsorbent hydrogel. The products biologically degraded up to 70% after 20 days, which shows their good biodegradability.

SSZ‐51 — A New Aluminophosphate Zeotype: Synthesis, Crystal Structure, NMR, and Dehydration Properties.

AbstractFor Abstract see ChemInform Abstract in Full Text.

SSZ-51A New Aluminophosphate Zeotype: Synthesis, Crystal Structure, NMR, and Dehydration Properties

A new aluminophosphate zeotype framework structure, SSZ-51 (Al4(PO4)4F.C7N2H11·0.5H2O), has been prepared in the presence of 4-dimethylaminopyridine as a structure-directing agent and a fluoride ion-mineralizing agent. The structure of the material was solved using single-crystal X-ray diffraction at a synchrotron source. It is closely related to the structure of SAPO-40 (AFR) and contains intersecting channels delimited by 8- and 12-membered ring windows. The occluded structure-directing agent and fluoride can be calcined to yield a material with appreciable microporosity. The calcination and dehydration of SSZ-51 was followed using variable temperature synchrotron X-ray powder diffraction and showed that the adsorption of water at low temperatures leads to a loss in long-range order of the framework. The long-range order of the framework is regained by dehydration at temperatures above 100 °C.

A versatile metathesis reaction for the formation of labile bonds between group 13 and group 15 atoms.

The heterocycles [{Me2AlE(SiMe3)2}x] (E=P–Bi) are powerful metathesis reagents in the presence of 4-dimethylaminopyridine (dmap), thus allowing the synthesis of previously unknown Group 13/15 compounds. Reactions with [Me3Mdmap] (M=In, Tl) proceed with E(SiMe3)2 transfer to form the corresponding heterocycles [{Me2InBi(SiMe3)2}3] and [{Me2TlE(SiMe3)2}2] (E=P, As), which were characterized by NMR and MS analysis, and by single-crystal X-ray diffraction.

High yield regioselective monobenzyloxycarbonylation of secondary alcohols in glycopyranoside series

The regioselective monobenzyloxycarbonylation of secondary alcohols in methyl 6- O-(4-methoxytrityl)-α- d-manno-, gluco- and galactopyranoside has been achieved in high yields (74–85%) by using benzyl chloroformate in the presence of 4-dimethylaminopyridine and/or 1,4-diazabicyclo[2.2.2]octane.

Synthesis and Some Pharmacological Properties of Elatidine Derivatives.

The pronounced myorelaxant activity of elatine (I) on both enteral and parenteral administration prompted us to study the medical applications of this alkaloid for the treatment of nervous diseases involving muscle tone disorders [1, 2]. Elatine can also be considered as a competitor for [ 125 I]-bungarotoxin (-BGT) in tests for binding to nicotinic acetylcholine receptors in the nervous system of mammals and insects, which makes possible to application of this agent in the diagnostics of Alzheimer’s disease and in the search for new highly effective insecticides [3]. Previously, an almost identical ability for such a competitive binding was established for elatine and its analog methyllicaconitine (II). The substitution of 2-aminobenzoyl for the 2-[(S)-methylsuccinimido]benzoyl fragment of the latter compound results in the formation of anthranoyllicoctonine (inuline, III) and is accompanied by a significant (about two orders of magnitude) decrease in competitive binding to -BGT [3]. In addition, passage from II to III is accompanied by a decrease (approximately fivefold) in the neuromuscular conductance blockade level in cats [4]. Thus, the pharmacological properties of derivatives of elatine depend on the nature of the substituents in various positions, in particular, in position 18 of the aconitane skeleton. In connection with this, we have synthesized and characterized the previously undescribed elatine analogs, anthranoyl elatidine (IV) and benzoyl elatidine (VII). Compound IV, obtained by acylating elatidine (VI) with isatoic anhydride in DMF solution in the presence of 4-dimethylaminopyridine (DMAP) acting as a catalyst [5], was characterized in the form of N-acetyl derivative V. Benzoyl elatidine VII was synthesized via interaction of elatidine VI with benzoyl chloride in the presence of pyridine. Previously [6, 7], we described the synthesis of elatidal

Determination of Methanol by 4-[N-Methyl, N-(1-naphthylmethyl)]-amino-4-oxo-butanoic Acid in Presence of 4-Dimethylaminopyridine and 1-Ethyl-3-(3-dimethylaminopropyl) Carbodiimide Hydrochloride as Catalysts

High performance liquid chromatography (HPLC) with chemically removable derivatizing reagents for the analysis of methanol has been developed. Methanol was derivatized with 4-[N-methyl, N-(1-naphthylmethyl)]-amino-4-oxo-butanoic acid (NAOB), using 4-dimethylaminopyridine (DMAP) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) as activators. NAOB and the activators are chemically removable and can be removed by aqueous base and acid treatment after derivatization to minimize reagent interference in chromatography. The method can simultaneously determine methanol, ethanol and 1-propanol. The proposed HPLC method was validated for linearity, specificity, accuracy and reproducibility. The method was applied to the analysis of methanol spiked in Ipecac fluid extract with a satisfactory recovery (>95%).

Study of 1-deoxy-1-(indol-3-yl)- l-sorbose, 1-deoxy-1-(indol-3-yl)- l-tagatose, and their analogs

Alkaline degradation of the ascorbigen 2- C-[(indol-3-yl)methyl]-α- l - xylo-hex-3-ulofuranosono-1,4-lactone ( 1a) led to a mixture of 1-deoxy-1-(indol-3-yl)- l-sorbose ( 2a) and 1-deoxy-1-(indol-3-yl)- l-tagatose ( 3a). The mixture of diastereomeric ketoses underwent acetylation and pyranose ring opening under the action of acetic anhydride in pyridine in the presence of 4-dimethylaminopyridine (DMAP) with the formation of a mixture of ( E)-2,3,4,5,6-penta- O-acetyl-1-deoxy-1-(indol-3-yl)- l- xylo-hex-1-enitol ( 4a) and ( E)-2,3,4,5,6-penta- O-acetyl-1-deoxy-1-(indol-3-yl)- l- lyxo-hex-1-enitol ( 5a), which were separated chromatographically. Deacetylation of 4a or 5a afforded cyclised tetrols, tosylation of which in admixture resulted in 1-deoxy-1-(indol-3-yl)-3,5-di- O-tosyl-α- l-sorbopyranose ( 12a) and 1-deoxy-1-(indol-3-yl)-4,5-di- O-tosyl-α- l-tagatopyranose ( 13a). Under alkaline conditions 13a readily formed 2-hydroxy-4-hydroxymethyl-3-(indol-3-yl)cyclopenten-2-one ( 15a) in 90% yield. Similar transformations were performed for N-methyl- and N-methoxyindole derivatives.

4-Dimethylaminopyridine as a catalyst in heroin synthesis

In this paper, we describe an acetylating method for fast synthesis of heroin from morphine in the presence of 4-dimethylaminopyridine (4-DMAP) as a catalyst. In the reaction which led to heroin formation, the morphine base was subjected to a solution made up of 4-DMAP (catalyst), methylene chloride (solvent) and acetic anhydride (acetylating agent). We showed that in comparison with classic acetylating procedures, reaction time can be reduced from at least several hours at elevated temperatures to <10 min at room temperature. In general, reaction time is dependant on the molar concentration ratio between morphine and 4-DMAP.

Kinetic of catalytic sucrose esterification in aqueous media

The process of sucrose esterification in the presence of a homogeneous catalyst was developed directing the reaction to the production of weakly substituted esters. Esterification of sucrose was processed with octanoyl chloride in a discontinuous reactor, in presence of 4-dimethylaminopyridine as catalyst. The process was operated in a time interval ranging from 0 to 80 min, at temperatures from 288 to 303 K, pH=10 and at atmospheric pressure. The following conversion levels were obtained: octanoyl chloride 11-84%, primary monoester production of 9-67%, secondary monoesters of 1.3-17%. Activation energies ranging from 158 l to 300 kJ/mol characterized the stages of the process, among them the stage of formation of the DMAP/RCOCl complex (162.43 kJ/mol). The increase in primary monoesters yield due to the temperature rise, leads to an increase in the rate of the direct reaction as well as in the speed of secondary monoester conversion to primary monoesters, quantifying a selectivity in primary isomers in the following positions sequence: 6> 1" > 6".

SYNTHESIS AND SOME PHARMACOLOGICAL PROPERTIES OF ELATIDINE DERIVATIVES

The pronounced myorelaxant activity of elatine (I) on both enteral and parenteral administration prompted us to study the medical applications of this alkaloid for the treatment of nervous diseases involving muscle tone disorders [1, 2]. Elatine can also be considered as a competitor for [ 125 I]-bungarotoxin (-BGT) in tests for binding to nicotinic acetylcholine receptors in the nervous system of mammals and insects, which makes possible to application of this agent in the diagnostics of Alzheimer’s disease and in the search for new highly effective insecticides [3]. Previously, an almost identical ability for such a competitive binding was established for elatine and its analog methyllicaconitine (II). The substitution of 2-aminobenzoyl for the 2-[(S)-methylsuccinimido]benzoyl fragment of the latter compound results in the formation of anthranoyllicoctonine (inuline, III) and is accompanied by a significant (about two orders of magnitude) decrease in competitive binding to -BGT [3]. In addition, passage from II to III is accompanied by a decrease (approximately fivefold) in the neuromuscular conductance blockade level in cats [4]. Thus, the pharmacological properties of derivatives of elatine depend on the nature of the substituents in various positions, in particular, in position 18 of the aconitane skeleton. In connection with this, we have synthesized and characterized the previously undescribed elatine analogs, anthranoyl elatidine (IV) and benzoyl elatidine (VII). Compound IV, obtained by acylating elatidine (VI) with isatoic anhydride in DMF solution in the presence of 4-dimethylaminopyridine (DMAP) acting as a catalyst [5], was characterized in the form of N-acetyl derivative V. Benzoyl elatidine VII was synthesized via interaction of elatidine VI with benzoyl chloride in the presence of pyridine. Previously [6, 7], we described the synthesis of elatidal

A positive-working alkaline developable photoresist based on partially tert-Boc-protected calix[4]resorcinarene and a photoacid generator

A positive working low-molecular-weight photoresist based on partially t-Boc protected tetra-C-methylcalix[4]resorcinarene (t-Boc C-4-R) and a photoacid generator (PAG), diphenyliodonium 9,10-dimethoxyanthracene-2-sulfonate (DIAS) has been developed. t-Boc C-4-Rs were prepared by the reaction of C-4-R with di-tert-butyl dicarbonate in the presence of 4-dimethylaminopyridine (DMAP). A clear film cast from a 20 wt% t-Boc C-4-R solution in cyclohexanone showed high transparency to UV above 300 nm. The appropriate t-Boc protecting ratio was about 60 mol% in view of adhesion, deprotection temperature and dissolution rate. The photoresist consisting of 60 mol% t-Boc C-4-R (95 wt%) and DIAS (5 wt%) showed a sensitivity of 13 mJ cm−2 and a contrast of 12.6 when it was exposed to 365 nm light and postbaked at 105 °C for 90 s, followed by developing with a 2.38 wt% aqueous tetramethylammonium hydroxide (TMAH) solution at room temperature. A fine positive image featuring 1.5 µm of minimum line and space patterns was observed on the film of the photoresist exposed to 40 mJ cm−2 of UV-light at 365 nm by the contact mode.

An improved derivatization method for sensitive determination of fatty acids by high-performance liquid chromatography using 9-(2-hydroxylethyl)-carbazole as derivatization reagent with fluorescence detection

Tagging techniques with reagents used for fluorescent detection for short and long-chain fatty acids using high-performance liquid chromatography are evaluated in terms of the tagging reactions, handing, flexibility, stability of the reagents. Emphasis is given to the applications of the tagging techniques to relatively high molecular mass fatty acids. The fatty acids or carboxylic compounds were derivatized to their corresponding esters with 9-(2-hydroxy ethyl)-carbazole (HEC) in acetonitrile at 60°C with N, N′-carbonyldiimidazole (CDI) as a coupling agent in the presence of 4-dimethylaminopyridine (DMAP). A mixture of esters of C1−C20 fatty acids was completely separated with 45 min using gradient elution on a reversed-phase C18 column. The maximum fluorescence emission for the derivatized fatty acids is at 365 nm (λex 293 nm). Studies on derivatization conditions indicated that fatty acids react rapidly and smoothly with HEC in the presence of CDI and DMAP in acetonitrile to give the corresponding sensitively fluorescent derivatives. The application of this method to the analysis of long chain fatty acids in plasma is also investigated. The LC separation shows good selectivity and reproducibility for fatty acids derivatives. The relative standard deviations (n=6) for each fatty acid derivative are <5.0%. The detection limits are at 38–57 fmol levels for C14−C20 fatty acids and lower levels for <C14 fatty acids.

Simple derivatization method for sensitive determination of fatty acids with fluorescence detection by high-performance liquid chromatography using 9-(2-hydroxyethyl)-carbazole as derivatization reagent

A simple and sensitive method for the determination of short and long-chain fatty acids using high-performance liquid chromatography with fluorimetric detection has been developed. The fatty acids were derivatized to their corresponding esters with 9-(2-hydroxyethyl)-carbazole (HEC) in acetonitrile at 60°C with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride as a coupling agent in the presence of 4-dimethylaminopyridine (DMAP). A mixture of esters of C 1–C 20 fatty acids was completely separated within 38 min in conjunction with a gradient elution on a reversed-phase C 18 column. The maximum fluorescence emission for the derivatized fatty acids is at 365 nm ( λ ex 335 nm). Studies on derivatization conditions indicate that fatty acids react proceeded rapidly and smoothly with HEC in the presence of EDC and DMAP in acetonitrile to give the corresponding sensitively fluorescent derivatives. The application of this method to the analysis of long chain fatty acids in plasma is also investigated. The LC separation shows good selectivity and reproducibility for fatty acids derivatives. The R.S.D. ( n=6) for each fatty acid derivative are <4%. The detection limits are at 45–68 fmol levels for C 14–C 20 fatty acids and even lower levels for <C 14 fatty acids.

Condensation Between Isocyanates and Carboxylic Acids in the Presence of 4-Dimethylaminopyridine (DMAP), a Mild and Efficient Synthesis of Amides

Condensation Between Isocyanates and Carboxylic Acids in the Presence of 4-Dimethylaminopyridine (DMAP), a Mild and Efficient Synthesis of Amides