Betulinic acid derivatives: a new class of α-glucosidase inhibitors and LPS-stimulated nitric oxide production inhibition on mouse macrophage RAW 264.7 cells

Chemical manipulation studies were conducted on betulinic acid (1), twenty-one new rationally designed analogues of 1 with modifications at C-28 were synthesized for their evaluation of inhibitory effects on α-glucosidase and LPS-stimulated nitric oxide production in mouse macrophage RAW 264.7 cells. Compound 2 (IC₅₀ = 5.4 μM) exhibited an almost 1.4-fold increase in α-glucosidase inhibitory activity on yeast α-glucosidase while analogues 5 (IC₅₀ 16.4 μM) and 11 (IC₅₀ 16.6 μM) exhibited a 2-fold enhanced inhibitory activity on NO-production than betulinic acid.     

Synthesis of novel zerumbone derivatives via regioselective palladium catalyzed decarboxylative coupling reaction: a new class of α-glucosidase inhibitors

A new strategy for the synthesis of novel zerumbone derivatives via a regioselective palladium catalyzed decarboxylative coupling reaction using arene carboxylic acids is described. The current methodology involves the repositioning of endocyclic double bond to exocyclic double bond of zerumbone. Preliminary in vitro analysis revealed that most of the newly synthesized derivatives are potent α-glucosidase enzyme inhibitors.     

Synthesis of new α-glucosidase inhibitors based on oleanolic acid incorporating cinnamic amides

A series of α-glucosidase inhibitors with the oleanolic acid core and different cinnamic amide ligands were designed and synthesized. Their preliminary structure-activity relationships were analyzed. In general, the compounds with 3,28-disubstituted oleanolic acid exhibited stronger activity than those 28-monosubstituted analogues, and variation of cinnamic amide substitution significantly affected α-glucosidase inhibition activities. Most of the compounds showed potent inhibitory activity against α-glucosidase with much greater efficacy than a typical α-glucosidase inhibitor, acarbose.     

Charge transfer molecular complexes of arylidene anthranilic acid derivatives with π-electron acceptors

X-Benzylidenesanthranilic acid molecular complexes with π-acceptors, tetracyanoethylene, 2,3-dichloro-5,6-dicyano-p-benzoquinone and chloranil, have been studied. The intramolecular hydrogen bonding that exists in such compounds greatly inhibits the transition of the nitrogen azomethine n-electrons. The formation constant values and molar extinction coefficients of the p-dimethyl-aminobenzylidenean-thranilic acid-DDQ CT complexes have been determined in CH₂Cl₂, C₂H₄Cl₂ and CHCl₃ in the temperature range 10–30°C. Such CT complexes are of strong n-π type.     

Synthesis and biological evaluation of coumarin derivatives containing oxime ester as α-glucosidase inhibitors

In this study, potent coumarin derivatives containing oxime ester 1 ～ 28 as α-glucosidase inhibitors were developed through a stepwise structure optimization, and the structure activity relationship was uncovered. Among them, compound 20 exhibited outstanding α-glucosidase inhibitory activity with IC₅₀ of 2.54 ± 0.04 μM compared to 640.57 ± 1.13 μM of Acarbose. Kinetic study ascertained that compound 20 was a reversible and uncompetitive α-glucosidase inhibitor. 3D fluorescence results showed that the interaction of compound 20 with α-glucosidase caused the changes of microenvironments and polypeptide backbone structure of α-glucosidase. CD spectra results revealed that compound 20 decreased the α-helix content and increased the β-sheet content. Molecular docking analysis indicated that compound 20 well located into the active site and mainly bind with Phe157, His239, His279, Tyr71, and Arg312 to reduce the catalytic activity of α-glucosidase.     

Synthesis of a new class of corrosion inhibitors derived from natural fatty acid: 13‐Docosenoic acid amide derivatives for oil and gas industry

As corrosion inhibitors, a series of new amide derivatives of 13‐docosenoic acid was synthesized in yields of above 90% by reacting 13-docosenoic acid with primary and secondary aliphatic and aromatic amines. The inhibition efficiencies (%IEs) of these compounds at various concentrations for the suppression of corrosion of mild steel in 1.00 M HCl exposed for 96 h (4 days) at temperatures in the range 298–333 K were measured via gravimetric corrosion measurements. At 100 ppm, all compounds yielded satisfactory corrosion %IE in 1.00 M HCl; compounds 2 and 7 exhibited remarkable %IE of 70.0 and 74.7%, respectively. The results of gravimetric measurements further revealed that compound 7 performed excellently at 60 °C, with %IE = 96.8 at 500 ppm. Quantum chemical density functional theory (DFT) calculations helped predict that compound 7 should have more aromatic character, enabling it to serve as a donor-center for the empty d-orbital of the metal atoms, leading to higher corrosion IE. The adsorption of the inhibitor molecules on the surface of mild steel followed the Langmuir adsorption model, and the free energy of adsorption (ΔG_ads) value indicated that the inhibitors are adsorbed through a combined physisorption and chemisorption mechanism to provide effective surface coverage.     

Preparation of chiral α-diazophosphonic acid derivatives

The chiral α-diazophosphonic acid derivatives 3, 6 and 8 were prepared from (−)-ephedrine and (S,S)-N,N′-dimethyl-1,2-diaminocyclohexane; preliminary experiments suggest that the chiral auxiliary exerts little influence in the dirhodium(II) acetate catalysed OH and NH insertion reactions.     

Combining spiro-fused cyclohexadienone – tetrahydrofuran ring system with glycine: Asymmetric synthesis of a new class of α-amino acid derivatives

Herein, we present the asymmetric synthesis of spiro-fused cyclohexadienone – tetrahydrofuran-embedded glycine derivatives as a new class of nonproteinogenic α-amino acid derivatives. Starting from commercially available 2-allylphenols, key β-hydroxy-α-amino esters were synthesized via high-yielding multi-step reaction sequences involving Sharpless asymmetric dihydroxylation as the chirality induction step. PhI(OAc)₂-mediated oxidative dearomatization – spirocyclization of phenol-tethered β-hydroxy-α-amino esters efficiently produced the corresponding spiro-fused cyclohexadienone – tetrahydrofuran-embedded glycine derivatives, providing a general route to this hitherto-unreported class of compounds that are equipped with three privileged scaffolds (cyclohexadienone – tetrahydrofuran – α-amino ester).     

In vitro evaluation of novel mefenamic acid derivatives as potential α-glucosidase and urease inhibitors: Design,synthesis, in silico and cytotoxic studies

This study aim to synthesize new 1,3,4-oxadiazole derivatives incorporating mefenamic acid as promising α-glucosidase and urease inhibitors, potentially leading to the treatment of postprandial hyperglycemia as well as H. pylori related disorders. In this regards, we have designed a series of Mefenamic acid derivatives. The synthetic compounds were structurally elucidated through ¹H NMR, ¹³C NMR and HR-EIMS analysis. The biological evaluation of these derivatives against α-glucosidase and urease enzyme depicted some novel derivatives with potent inhibition against the said enzymes. All the derivatives exhibited potent inhibition against α-glucosidase enzymes with IC₅₀ ranging from 25.81 ± 1.63–113.61 ± 1.31 µM against standard drug acarbose (IC₅₀ = 375.82 ± 1.76 µM) while with respect to urease these derivatives possessed inhibitory potential varied between IC₅₀ = 8.04 ± 1.01–58.18 ± 1.03 µM against the standard thiourea (IC₅₀ = 21.0 ± 1.76 µM). The cell viability results revealed that all of the derivatives were found least cytotoxic. Furthermore, molecular docking studies of the most potent derivatives identify number of key features involved in binding interactions between potential inhibitors and the enzyme's active site.     

Biological evaluation of 9-(1H-Indol-3-yl) xanthen-4-(9H)-ones derivatives as noncompetitive α-glucosidase inhibitors: kinetics and molecular mechanisms

Structural Chemistry - The α-Glucosidase plays a key role in attenuation of postprandial hyperglycemia in diabetic patients. In this study, a class of 9-(1H-Indol-3-yl) xanthen-4-(9H)-ones...     

Complexes of heavy lanthanides witho-aminobenzoic acid

Anthranilates of Tb-Lu prepared in the reaction of the rare earth hydroxides withortho-aminobenzoic acid (anthranilic acid) have the general formulaLn(C₆H₄NH₂COO)₃·2H₂O whereLn=Tb, Dy, Ho, Er, Tm, Yb, Lu. The water molecules in the hydrated compounds are in the outer coordination sphere. On heating in air at 493K dehydration occurs and the anhydrous anthranilatesLn(C₆H₄NH₂COO)₃ are formed. On the basis of the IR spectra it was found that the metal in dihydrated anthranilates was simultaneously coordinated through amino and carboxyl groups whereas in anhydrous anthranilates only through the bidentate carboxyl group. From X-ray analysis it was stated that the anthranilatesLn(C₆H₄NH₂COO)₃·2H₂O are isostructural, whereas the anhydrous compoundsLn(C₆H₄NH₂COO)₃ are isostructural in the two groups Tb-Er and Tm-Lu.

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Die Komplexe der schweren Selteneerdmetalle mit Orthoaminobenzoesäure

Zusammenfassung Zur Darstellung der Verbindungen des TypsLn(C₆H₄NH₂COO)₃·2H₂O (mitLn=Tb bis Lu) wurde die berechnete Menge vonLn(OH)₃ und C₆H₄NH₂COOH-Lösung gemischt und bei 363K schnell zur Kristallisation gebracht. Die Produkte werden schnell abfiltriert, mit Wasser gewaschen und bis zur Gewichtskonstanz getrocknet. Die VerbindungenLn(C₆H₄NH₂COO)₃·2H₂O sind isostrukturell mit der Dichte ungefähr 1.6g·cm^–1 und geringer Löslichkeit in Wasser bei Raumtemperatur. Beim Erhitzen folgt zunächst Entwässerung bei 493 K, später Zersetzung zu Tb₄O₇ undLn ₂O₃. Die wasserfreien VerbindungenLn(C₆H₄NH₂COO)₃ sind isostrukturell in 2 Strukturtypen: Tb-Er and Tm-Lu. Die Infrarotspektren von wasserfreien Verbindungen und Doppelhydraten wurden registriert. Es wurde festgestellt, daß die Koordinierung der Seltenerdmetalle mit Liganden in den Dihydraten sowohl durch die Amino- als auch durch Carboxylgruppen erfolgt. In den wasserfreien Komplexen tritt die Koordinierung nur durch Carboxylgruppen auf.

     

Synthesis of new phthalocyanines substituted with four benzo[d]thiazol-2-ylthio groups

The synthesis of a new phthalonitrile derivative (4-(benzo[d]thiazol-2-ylthio)phthalonitrile), its metal-free phthalocyanine, and metallo-phthalocyanines are described. Phthalocyanines are formed in high yield with template synthesis. These compounds showed considerable solubility in CHCl₃, DMF and DMSO, a primary condition for potential applications. The newly synthesized compounds have been characterized by elemental analyses, UV-Visible spectra, IR and ¹H-NMR.     

The Reaction of (N-Isocyanimino)triphenylphosphorane with Anthranilic Acid Derivatives: One-Pot Synthesis of 2-Substituted 1,3,4-Oxadiazoles via Intramolecular Aza-Wittig Reaction

The reaction of anthranilic acid derivatives with (N-isocyanimino)triphenylphosphorane proceeds smoothly at room temperature to afford 2-substituted 1,3,4-oxadiazoles via an intramolecular aza-Wittig reaction in excellent yields under neutral conditions. The structures of the products were deduced from their IR, ¹H NMR, and ¹³C NMR spectra and mass spectrometry.     

Metal complexes of isonicotinic acid hydrazide

Complexes of platinum(IV), ruthenium(III), rhodium(III), iridium(III), gold(III), dioxouranium(II), zinc(II), cadmium(II), mercury(II) and manganese(II) with isonicotinic acid hydrazide were prepared and characterized on the basis of analytical, conductometric, magnetic susceptibility and spectral data. Platinum(IV) ruthenium(III), rhodium(III), iridium(III), dioxouranium(II) and manganese(II) form six-coordinate complexes while gold(III), zinc(II), cadmium(II) and mercury(II) form four coordinate complexes.     

Gadolinium triflate catalyzed alkylation of pyrroles: efficient synthesis of 3-oxo-2,3-dihydro-1H-pyrrolizine derivatives

Novel 2-alkylated pyrrole derivatives were synthesized regioselectively by Gd(OTf)₃ catalyzed addition reactions of pyrrole to substituted dimethyl 2-benzylidenemalonate derivatives under mild reaction conditions. 2-Alkylated pyrrole derivatives are used for the construction of the 3-oxo pyrrolizine skeleton. Intramolecular cyclization of alkylated pyrrole derivatives afforded new diastereoselective 3-oxo-2,3-dihydro-1H-pyrrolizine derivatives with good to high yields.     

Alkylation and acylation of basic salts of anthranilic acid

The O-nucleophilicity of basic anthranilic acid salts was documented, analyzed, and utilized in synthesis. Specifically substitutions leading to esters instead of secondary amines, and formation of anthranilic acid anhydrides were studied.