Application of a classical least-squares regression method to the assay of 1,4-dihydropyridine antihypertensives and their photoproducts

A multicomponent UV spectrophotometric method using a classical least-squares (CLS) algorithm has been developed for the quantitative determination of 1,4-dihydropyridine (DHP) calcium antagonists and respective photoproducts. The procedure was optimized by defining a fractionation scheme for selecting the more useful wavelength ranges to be used in the calibration model. The method is potentially able to be extended to the other drugs of the same family. The recovery values from synthetic mixtures and commercial formulations were verified to be 99.09 and 97.85% for drug parents and degradation products, respectively. The sensitivity for the photoproducts determination was found to be below 0.8%. The results obtained from laboratory mixtures and commercial formulations were compared with those provided by UV derivative spectrophotometry.     

Synthesis of New 1,4-Dihydropyridine Derivatives Containing Thiazolyl Substituents

A series of 4-[2-methyl (or aryl) thiazole-4-yl]-2,6-dimethyl-3,5-diacetyl (or dibenzoyl) 1,4-dihydropyridines were synthesized using a modified Hantzsch reaction involving the condensation of the corresponding aldehyde with acetyl acetone or benzoyl acetone. The preparation of the corresponding aldehydes (2-methylthiazole-4-carboxaldehyde and some 2-arylthiazole-4-carboxaldehydes) was achieved by a simplified protocol of the published synthesis.     

Ultrasound-promoted green synthesis of 1,4-dihydropyridines using fuctionalized MWCNTs as a highly efficient heterogeneous catalyst

A new method for multi-component synthesis of 1,4-dihydropyridine derivatives (1,4-DHPs) in the presence of meglumine supported on multiwalled carbon nanotubes (MWCNTs@meglumine) as a new heterogeneous, highly efficient and reusable catalyst was investigated. The reaction was performed under ultrasonic irradiation in EtOH at room temperature. A new, highly efficient heterogeneous catalyst, short reaction times, high to excellent yield of products, and safe and clean conditions are the advantages of the presented method.     

Catalytic Synthesis of Fused 1,4-Dihydropyridines and 1,4-Dihydropyridine Derivatives Using Preyssler Heteropolyacids Catalyst

An efficient and convenient method for the synthesis of 1,4-dihydropyridines from β-dicarbonyl compounds, aldehydes, and ammonium acetate and the synthesis of fused 1,4-dihydropyridines from dimedone in the presence of Preyssler heteropolyacid catalyst are reported under reflux conditions with good to excellent yields. Preyssler heteropolyacid catalyst is easily prepared, stable (up to 300 °C), reusable, efficient, green and inexpensive.     

Synthesis and studies of calcium channel blocking and antioxidant activities of novel 4-pyridinium and/or N-propargyl substituted 1,4-dihydropyridine derivatives

The novel 1,4-dihydropyridine derivatives containing the cationic pyridine moiety at the position 4, and the N-propargyl group as a substituent at position 1 of the 1,4-DHP cycle were designed, synthesised, and assessed in biological tests. Among all the novel compounds, the 4-(N-dodecyl) pyridinium group-containing compounds 11 (without the N-propargyl group) and 12 (with the N-propargyl group) demonstrated the highest calcium antagonistic properties against neuroblastoma SH-SY5Y (IC₅₀ about 5–14 μM) and the vascular smooth muscle A7r5 cell (IC₅₀ – 0.6–0.7 μM) lines, indicating that they predominantly target the L-type calcium channels. These compounds showed a slight total antioxidant activity. At concentrations close to those of L-type calcium channel blocking ones, compound 12 did not affect mitochondrial functioning; also, no toxicity was obtained in vivo. The N-propargyl group as a substituent at position 1 of the 1,4-DHP cycle did not essentially influence the compounds’ activity. The 4-(N-dodecyl) pyridinium moiety-containing compounds can be considered as prototype molecules for further chemical modifications and studies as cardioprotective/neuroprotective agents.     

The visible absorbance maximum of 2-hydroxy-1,4-naphthoquinone as a novel probe for the hydrogen bond donor abilities of solvents and solvent mixtures

Summary The electronic absorption spectra of 2-hydroxy-1,4-naphthoquinone (HNQ) in one- and two-component solvents are discussed. The visible absorption of this reagent has been shown to arise from a charge-transfer transition of the zwitterionic tautomer stabilized by a hydrogen bond donating solvent. The formation constant of the 1:1 hydrogen bonded complex with methanol, ethanol, andn-propanol has been determined at 25 °C from the spectral behaviour in mixed solvents. The tautomerization equilibrium ofHNQ in aqueous ethanol is demonstrated and characterized. The dependence of the absorbance maximum ofHNQ on the hydrogen bond donor ability of the solvent in the visible spectrum, as measured by theTaft-Kamlet parameter, has been established. Experimentally derived evidence is supplied to justify the recommendation ofHNQ as a novel probe for hydrogen bond donor ability in pure solvents and in mixed aqueous solvents.

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Das Absorptionsmaximum von 2-Hydroxy-1,4-naphthochinon im sichtbaren Bereich als neues Maß für die Wasserstoffbrückenbindungsbildungsfähigkeit von Lösungsmitteln und Lösungsmittelgemischen

Zusammenfassung Die Absorptionsspektren von 2-Hydroxy-1,4-naphthochion (HNQ) in Ein- und Zweikomponentensystemen werden diskutiert. Die Absorption im sichtbaren Bereich stammt von einemcharge-transfer — Übergang des zwitterionischen Tautomers, das über Wasserstoffbrückenbindungen zum Lösungsmittel stabilisiert wird. Die Bildungskonstanten der binären Komplexe mit Methanol, Ethanol undn-Propanol wurden aus spektroskopischen Daten in Lösungsmittelgemischen bei 25 °C emittelt. Das Tautomeriegleichgewicht vonHNQ in wäßrigem Ethanol wird iskutiert. Die Abhängigkeit des Absorptionsmaximums vonHNQ vond der Wasserstoffbrückenbindungsbildungsfähigkeit des Lösungsmittels wird mittels desT aft-Kamlet — Parameters beschrieben. Experimentelle Ergebnisse ermutigen zur Verwendung vonHNQ als neue Testsubstanzfür die Wasserstoffbrückenbindungsbildungsfähigkeit von reinen und gemischten Lösungsmitteln.

     

Use of green alternative solvents in dispersive liquid-liquid microextraction: A review

Dispersive liquid-liquid microextraction is one of the most widely used microextraction techniques currently in the analytical chemistry field, mainly due to its simplicity and rapidity. The operational mode of this approach has been constantly changing since its introduction, adapting to new trends and applications. Most of these changes are related to the nature of the solvent employed for the microextraction. From the classical halogenated solvents (e.g., chloroform or dichloromethane), different alternatives have been proposed in order to obtain safer and non-pollutants microextraction applications. In this sense, low-density solvents, such as alkanols, switchable hydrophobicity solvents, and ionic liquids were the first and most popular replacements for halogenated solvents, which provided similar or better results than these classical dispersive liquid-liquid microextraction solvents. However, despite the good performances obtained with low-density solvents and ionic liquids, researchers have continued investigating in order to obtain even greener solvents for dispersive liquid-liquid microextraction. For that reason, in this review, the evolution over the last five years of the three types of solvents already mentioned and two of the most promising solvent alternatives (i.e., deep eutectic solvents and supramolecular solvents), have been studied in detail with the purpose of discussing which one provides the greenest alternative.     

Synthesis and Photochemistry of Novel 3,5-Diacetyl-1,4-dihydropyridines. II [1]

Summary. In continuation of previous work some novel 3,5-diacetyl-1,4-dihydropyridine derivatives were synthesized and their photochemical behavior was studied under oxygen and argon atmosphere. Oxidation of the dihydropyridine ring and formation of pyridine derivatives was the result of the reaction. The presence of oxygen affects not only on the rate of oxidation, but also the formation of some unidentified by-products was observed on irradiation under this atmosphere.     

Comparative Study of Catalytic Potential of TBAB,BTEAC, and CTAB in One-Pot Synthesis of 1,4-Dihydropyridines Under Aqueous Medium

Convenient and straightforward tetrabutylammonium bromide (TBAB), benzyltrienthylammonium chloride (BTEAC), and cetyltrimethylammonium bromide (CTAB) catalyzed synthesis of 1,4-dihydropyridines (1,4-DHPs) in water was established for the first time. The catalytic potential of phase-transfer catalysts (PTCs) in three different concentrations was envisioned. Aryl aldehydes and hetero aryl aldehydes afforded good yields of 1,4-DHPs in TBAB and BTEAC reactions. In particular, furfuraldehyde and thienyl-2-carbaldehyde produced excellent yields. Isolation of the products through nonchromatographic methods, good to excellent yields, and benign reaction conditions are the major advantages of this protocol.     

Isopropanol dehydration via extractive distillation using low transition temperature mixtures as entrainers

Low transition temperature mixtures (LTTMs), also known as deep eutectic solvents, show properties that make them suitable as entrainers for extractive distillation. Two different low transition temperature mixtures were considered as potential entrainers for the extractive distillation of the azeotropic mixture (isopropanol + water). (Lactic acid + choline chloride) (2:1) and (glycolic acid + choline chloride) (3:1) were selected for this work. (Vapor + liquid) equilibrium measurements of the pseudo-binary systems (isopropanol + LTTM) and (water + LTTM) were measured at different concentrations of LTTM in a pressure range of 10 to 100 kPa. (Vapor + liquid) equilibrium data of the pseudo-ternary system (isopropanol + water + LTTM) were also measured at constant pressure (100 kPa) and constant LTTM molar fraction of 0.05 and 0.1. It was found that these LTTMs cannot break the azeotrope at those concentrations. However, the azeotrope was displaced to a much higher isopropanol concentration. The NRTL model was successfully applied to fit the experimental data.     

Silica Chloride/NaNO 2 as a Novel Heterogeneous System for the Oxidation of 1,4-Dihydropyridines Under Mild Conditions via In Situ Generation of NOCl

A combination of silica chloride and sodium nitrite in the presence of wet SiO 2 were used as an effective oxidizing agent for the oxidation of dihydropyridines to their corresponding pyridine derivatives under mild and heterogeneous conditions in moderate to excellent yields.     

Stereocontrolled Oxidative Additions upon 1,4-Dihydropyridines: Synthesis of Hexahydrofuro[2,3-b]pyridine and Hexahydropyrano[2,3-b]pyridine Derivatives

trans-α-Alkoxy-β-halotetrahydropyridines are synthesized in a very efficient single step by stereocontrolled N-halosuccinimide (NXS)–promoted alcohol addition to the enamine group in N-alkyl-1,4-dihydropyridines. These compounds are cyclized using sodium cyanoborohydride in the presence of 2,2′-azobis(2-methylpropionitrile), azabisisobutyronitrile (AIBN) (cat.), and tributylstannane (cat.), affording hexahydrofuro[2,3-b]pyridine and hexahydropyrano[2,3-b]pyridine derivatives. The cyclized product undergoes ring-opening reaction by a nucleophile in the presence of Lewis acid to afford highly functionalized tetrahydropyridines.     

Oxidation of cationic 1,4-dihydropyridine derivatives as model compounds for putative gene delivery agents

A new synthetic approach to cationic pyridine derivatives is described here. Two different strategies for the synthesis of 1,1′-{[3,5-bis(ethoxycarbonyl)-4-phenylpyridine-2,6-diyl]dimethylene}bispyridinium salts have been developed. The key step of the first strategy relies on electrochemical and chemical oxidation of cationic 1,4-dihydropyridines; the second one involves nucleophilic substitution of pyridine dibromo derivatives.     

One-Pot Synthesis of N-Substituted 4-Aryl-1,4-dihydropyridines Under Solvent-Free Conditions and Microwave Irradiation

Summary.  The three-component condensation of benzaldehyde derivatives, alkyl propiolates, and primary amines catalyzed by silica gel, zeolite HY, montmorillonite K-10, and acidic alumina under microwave irradiation gave N-substituted 4-aryl-1,4-dihydropyridines in short reaction times and high yields. The best results were obtained with silica gel. Received March 26, 2001. Accepted (revised) June 18, 2001     

Deep eutectic solvents as green media for efficient extraction of terpene trilactones from Ginkgo biloba leaves

Deep eutectic solvents (DESs)-based ultrasonic extraction of terpene trilactones (TTLs) from Ginkgo biloba leaves was efficiently developed. Sixteen DESs were prepared, and DESs composed of choline chloride-urea (ChCl-U) and betaine-ethylene glycol (BE-EG) gave higher TTL extraction yields than the present, most efficient solvent 70% ethanol. The extraction conditions were further optimized, and the optimum conditions were as follows: taking BE-EG containing 40% (w/w) water as the extraction solvent, 1:10 of G. biloba leaves powder-to-solvent ratio, and ultrasonic treatment at 45°C and 100?W for 20?min. A total extraction yield of 1.94?±?0.03?mg/g was obtained under the optimum conditions, which indicated that 99.37% of TTLs could be extracted from the G. biloba leaves powder by a single extraction. Moreover, the polyamide resin was used to recover the TTLs in DES extracting solution, and recovery yield of 95.1% was attained. Therefore, BE-EG containing 40% (w/w) water was a potential alternative solvent for TTLs extraction from G. biloba leaves.     

Towards green synthesis of nanoparticles: From bio-assisted sources to benign solvents. A review

Current advancements in green synthesis of materials especially nanoparticles have led to conservation of natural and non-renewable resources along with reduction in environmental pollution. Development of cost-effective, simple and eco-friendly routes for the synthesis of nanoparticles is very important. All over the world, a wide variety of biogenic sources have been put to trial as a source of green agents to facilitate synthesis process. In addition to this, environmentally benign solvents are also being used these days in order to promote green synthesis. In this review, an attempt has been made to familiarise the readers with the different green routes for the synthesis of nanoparticles.     

A new protocol to synthesize 1,4-dihydropyridines by using 3,4,5-trifluorobenzeneboronic acid as a catalyst in ionic liquid: synthesis of novel 4-(3-carboxyl-1H-pyrazol-4-yl)-1,4-dihydropyridines

3,4,5-Trifluorobenzeneboronic acid catalysed, ionic liquid mediated facile synthesis of 4-pyrazolyl 1,4-dihydropyridines at room temperature by the cyclocondensation of ethyl 3-aminocrotonate, pyrazole aldehyde and a β-keto ester is reported. The procedure adopted was found to be eco-benign, facile at room temperature and better than the conventional, [bmim]Cl mediated and InCl₃ catalysed, [bmim]Cl mediated 1,4-dihydropyridine syntheses.     

Reactions of cyclic enaminoketones with benzylidenemalononitriles. Synthesis of new fused heterocyclic systems containing the 1,4-dihydropyridine fragment

The reactions of cyclic enaminoketones with benzylidenemalononitriles were examined and a new procedure was developed for the synthesis of fused heterocyclic systems containing the 1,4-dihydropyridine ring, viz., thienopyrimidoquinolines and furopyrimidoquinolines. The characteristic features of the reactions and the structures of the resulting compounds were investigated.     

Cubane derivatives 1. Synthesis and molecular structures of the esters of 1,4-cubanedicarboxylic acid

An effective method of esterification of 1,4-cubanedicarboxylic acid with alkylsulfuric acids is proposed. The derivatives of alkanols with substantially different pK_a Valus are obtained in high yields. Molecular structures of the esters obtained are confirmed by various methods. The X-ray study showed a remarkable effect of the nature of an alkyl radical on the geometry of the cubane core.Translated fromIzyestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp.668–672, April, 1994.The authors thank Dr. G. V. Lagodzinskaya for analyzing the NMR spectra and for useful discussions.     

Synthesis of unsaturated 1,4-heteroatom-containing benzo-fused heterocycles using a sequential isomerization-ring-closing metathesis strategy

A small library of 1,4-benzodioxins and 4H-1,4-benzoxazines was synthesized from the corresponding bis-allyloxy precursors by way of an initial isomerization to the bis-vinyloxy compounds, followed by a ring-closing metathesis using the second generation Grubbs' catalyst (G2). A related strategy, starting from benzene-1,2-dithiol and 2-mercaptophenol, afforded benzodithiin and 1,4-benzoxathiin, respectively.