Novel indan-1,3-dione derivatives: Design,green synthesis,effect against tomato damping-off disease caused by Fusarium oxysporum and in silico molecular docking study

An effective method for synthesizing series of twenty-two new compounds 1, 2a,b, 3, 4a,b, 5a-e, 7, 8, 9, 10, 12, 13a-d, 15a,b was performed starting from reaction of 1,2,3-indenetrione thiourea, and ethyl cyanoacetate under microwave irradiation and / or 2-(1,3-dioxo-1H-inden-2(3H)-ylidene) hydrazine carbothioamide with acetic anhydride. Chemical structure of the obtained products has been established by spectroscopic techniques including FTIR, ¹H NMR, ¹³C NMR, DEPT-135, and mass spectroscopy. The designed new compounds have been successfully examined in-vitro for their antifungal activities. The relation between the structure of the synthesized compounds and their activity against tomato damping-off disease caused by Fusarium oxysporum fungi was studied and favourable results were obtained. The antifungal studies indicated that compounds 1, 7, 4a and 5a-d exerted the highest antifungal activities, while 3 and 4b recorded the lowest effect. The obtained results confirmed the possibility of the application of ethyl 6′-amino-1,3-dioxo-2′-thioxo-1,2′,3,3′-tetrahydro-1′H-spiro[indene-2,4′-pyrimidine]-5′-carboxylate 1 as a new effective regulator of the vegetative growth of tomatoes. The molecular docking analysis was performed within succinate dehydrogenase (SDH) as a target enzyme in order to rationalize the promising findings obtained for the active compounds 1, 2a,b, 5a-d, 7, 8, 9, 10, 12, and 13a.     

Synthesis,spectral characterization and biological evaluation of novel 1-(2-(4,5-dimethyl-2-phenyl-1H-imidazol-1-yl)ethyl)piperazine derivatives

A simple, highly useful synthesis of 1-(2-(4,5-dimethyl-2-phenyl-1H-imidazol-1-yl)ethyl)piperazine derivatives is achieved by a four component cyclo condensation of diacetyl, aromatic aldehyde, 2-(piperazin-1-yl)ethanamine and ammonium acetate using SO₄²⁻/Y₂O₃ as a catalyst in ethanol. The synthesized compounds were characterized by IR, ¹H and ¹³C NMR and mass spectral studies. All the synthesized compounds were screened for their in vitro antimicrobial studies. Among the newly synthesized compounds 5d, 5e, 5h and 5m showed excellent antibacterial and antifungal activities when compared to the standard drugs.     

Quinoxalines XIV. Synthesis, H, C, N NMR spectroscopic, and quantum chemical study of 1H-pyrazolo[3,4-b]quinoxalines (flavazoles)

The synthesis of a series of 1H-pyrazolo[3,4-b]quinoxalines (flavazoles) by acylation, alkylation, halogenation, and aminomethylation of the parent compound is reported and their structure is investigated by ¹H, ¹³C, and ¹⁵N NMR spectroscopy. The restricted rotation about the partial C, N double bond of the N-acyl derivatives 7-10 is studied by dynamic NMR spectroscopy and the barriers to rotation are determined. In order to assign unequivocally the ¹⁵N chemical shifts of N-4 and N-9, in case of 3-substituted flavazoles, exemplary the ¹H, ¹³C, and ¹⁵N NMR chemical shifts of 34, 35, and 39 are also theoretically calculated by quantum chemical methods [ab initio at different levels of theory (HF/6-31G* and B3LYP/6-31G*)].     

Alkaloids of NIRAM,natural dye from Polygonum tinctorium,and their anti-inflammatory activities

Phytochemical investigation of EtOH extract of NIRAM, natural dye from Polygonum tinctorium, resulted in the purification of nine alkaloid compounds (1–9) including four new compounds (1–4). Structures of these new compounds were elucidated by 1D and 2D NMR (¹H and ¹³C NMR, ¹H–¹H COSY, ¹H–¹³C HSQC, ¹H–¹³C HMBC), IR, UV, HR-ESI-MS, and ECD spectra. Isolated compounds (1–9) were tested for their inhibitory effects on nitric oxide (NO) production in lipopolysaccharide (LPS)-activated BV-2 cells. Compounds 1–3, 5, and 7 showed potent NO production inhibitory activities, with IC₅₀ values of 3.88–22.87 μM.     

α-Substituierte phosphonate—38: 1-dimethylamino-1-cyano-methanphosphonsäurediethylester,ein neues edukt zur darstellung von carbonsäuren, 1-cyanoenaminen und homoenolaten

Alkylation of 1-dimethylamino-1-cyanomethanephosphonic acid diethyl ester (8), easily obtainable from diethyl phosphite and the 0,N-acetal 9, yields 1-alkyl derivatives 14. Elimination of HCN converts 14 into 1-phosphonoenamines 6. Carbonyl compounds react with 8 to give 1-cyanoenamines 15 which may be hydrolyzed to from the homologous carboxylic acid. Alternatively, deprotonation of 15 yields the homoenolate anions 17 which can be alkylated or hydroxyalkylated, permitting chain extension of carbonyl compounds through introduction of an α-carboxyl and a β-alkyl group. Acid catalyzed hydrolysis of 8 results in cleavage of the PC bond, leading to the corresponding α-dimethylamino alkanoic acids. A phosphonic acid 11 can be obtained from 8 by application of the silylester method. An unambigous assignment of E/Z-isomers of the cyanoenamines 15 has been derived from ¹³C-NMR spectroscopy.     

Specificity of 15N NMR chemical shifts to the nature of substituents and tautomerism in substituted pyridine N-oxides

¹H, ¹³C, and ¹⁵N NMR chemical shifts have been measured for 2-aminopyridine N-oxide (1), its eleven derivatives (2–10, 13, 14), and 3-Cl and 3-Br substituted 4-nitropyridine N-oxides (11, 12). δ(¹⁵N) of pyridine ring nitrogen in 2-acetylaminopyridine N-oxides are 5.9–11.5 ppm deshielded from those in 2-aminopyridine N-oxides. When amino and acetylamino substituents are in 4-position, δ(¹⁵N) of ring nitrogen is 21.3 ppm deshielded in the acetylated derivative. The strong resonance interaction between 2-amino and 5-nitro groups reflects in the decrease of amino nitrogen shielding about 5.3–17.9 ppm. Also, ¹H and ¹³C NMR spectral data are in agreement with ¹⁵N NMR results reflected as deshielded amino protons and carbons C-2 and C-5. The pyridine nitrogen chemical shift in all amino- and acetylamino derivatives vary between ?101.2 and ?126.7 ppm, which has been connected with the tautomeric balance in our earlier studies.     

Silylmethyl and silylamino groups as ligands in tin(II), tin(IV), lead(II) and lead(IV) compounds—a multinuclear magnetic resonance study

We have studied tin(II), tin(IV), lead(II) and lead(IV) compounds of the type M[CH(SiMe₃)₂]₂ (5), M[N(SiMe₃)₂]₂ (6), M[N(SiMe₃)SiMe₂^tBu]₂ (7), Me₃MCH₂SiMe₃ (1), Me₃MCH(SiMe₃)₂ (3), Me₃MNHSiMe₂^tBu (2), Me₃MN(SiMe₃)₂ (4), Me₂M[N(SiMe₃)₂]₂, (8) and (Me₃M)₂NSiMe₂^tBu (9) by ¹³C, ¹⁵N, ²⁹Si, ¹¹⁹Sn and ²⁰⁷Pb NMR spectroscopy. In some cases, two-dimensional (2-D) ¹³C/¹H and ²⁹Si/¹H heteroscalar-correlated NMR spectra served for the comparison of the signs of the respective coupling constants [ⁿJ(M ¹³C), ²J(M²⁹Si) and ⁿJ(M¹H)]. The ¹³C and ¹⁵N NMR parameter of comparable compounds (replacement of the CH or CH₂ fragment by a nitrogen atom or the NH group, respectively), show analogous trends. In the monomeric M(II) compounds (5, 6, 7) the peculiar electronic situation at the metal is reflected by the extreme deshielding of the metal nuclei (e.g. δ²⁰⁷ Pb for 5b = +9110 ppm), by the strongly deshielded ¹³C (5) and ¹⁵N nuclei (6, 7), as well as by large negative contributions to the reduced nuclear spin—spin coupling constants ¹K(M¹³C) (5) and ¹K(M¹⁵N) (6). In the M(II) compounds 5 the ¹¹⁹Sn and, in particular, the ²⁰⁷Pb longitudinal and transverse nuclear relaxation is dominated by the chemical-shift-anisotropy mechanism. This is also true for 6 and 7, in which the transverse relaxation rate is further increased by scalar relaxation of the second kind owing to partially relaxed scalar coupling ¹J(M¹⁴N).     

The conformational dependence of 15n13c spin spin coupling constants

2-Azabicyclo(2.2.2)octan-3-One 1, N-isopropylpivaloylamide 2 and 4-azatricyclo(4.3.1.1^3,8)undecan-5-one 3 have been prepared with a ¹⁵N label. The amides were reduced to the corresponding amines 2-azabicy-clo(2.2.2)octane 4, N-isopropyl-N-neopentylamine 5 and 4-azatricyclo(4.3.1.1^3,8)undecane 6. The ¹³C spectra of these compounds and their hydrochlorides were measured and the ¹⁵N¹³C spin coupling constants interpreted in terms of their conformational dependence.     

Rifamycin antibiotics—new compounds and synthetic methods. Part 1: Study of the reaction of 3-formylrifamycin SV with primary alkylamines or ammonia

Within the study covering the search for new methods of synthesis of rifamycin antibiotics, the reactions of 3-formylrifamycin SV (2) with primary amines or ammonia were studied. In the reaction of 2 with methylamine, unstable 3-methyliminomethylrifamycin SV (8) was formed, which was further oxidised to stable 3-methyliminomethylrifamycin S (9). In the reaction of 2 with ammonia, N,15-didehydro-15-deoxo-pyrimido-(4,5-b)rifamycin SV (10), a new compound with a chromophore system enlarged by a pyrimidine ring, was obtained. The product of its reduction with sodium borohydride—(11)—was also isolated. The structures of the compounds and an explanation of the synthesis mechanism have been proposed on the basis of mass spectrometry results as well as (1D) and (2D) ¹H- and ¹³C NMR analysis. In vitro antituberculous activity of the new compounds have been investigated.     

Polybrominated oxydiphenol derivatives from the sponge dysidea herbacea: Structure determination by analysis of 13C spin-lattice relaxation data for quaternary carbons and 13C-1H coupling constants

Five polybrominated oxydiphenol derivatives have been isolated from various Great Barrier Reef collections and one Fijian collection of the sponge Dysidea herbacea: 3,4',5,6,6'-hexabromo-2, 2'-oxydiphenol (11), 3,4',5,6,6'-pentabromo-2,2'-oxydiphenol (12), 3.4',5,6,6'-pentabromo-2,2'-oxydiphenol 1-methyl ether (13), 3,4,4',5,6'-pentabromo-2,2'-oxydiphenol 1,1'-dimethyl ether (14) and 3,4',5,6'-tetrabromo-2,2'-oxydiphenol 1'-methyl ether (15).The structure of the first member of this series is determined by a new method involving ¹³C spin-lattice relaxation data. The contributions of nearby hydrogens to quaternary carbon spin-lattice relaxation times are calculated for various possible structures and compared with the experimental data, leading to an unequivocal proof of structure. The structures of the remaining compounds in the series are established principally by analysis of ¹³C chemical shifts and ¹³C-¹H coupling constants.     

Pyrazolonderivate VII Synthese und Struktur von Metallchelatkomplexen mit 4-aminomethylen-Δ2-pyrazolinon-(5)-ligaden

In the reaction of 4-aminomethylene-Δ²-pyrazolin-5-ones with metal acetates new chelate complexes with a ligand-metal ratio of 2:1 are formed. For structural investigations¹⁵N-labeled compounds and azomethines of the pyrazole type are also prepared. The¹⁵N-,¹³C-, and¹H-chemical shifts have been measured in CDCl₃. Chemical shifts as well as coupling constantsnJ (¹³C?¹⁵N)n=1, 2;² J (HC=¹⁵N);² J (=CH?¹⁵N) are discussed with regard to the structure of metal complexes and azomethines. It has been shown that complex formation causes a considerable change of the π-electron structure within the merocyanin part.     

Synthesis,characterization and in vitro antimicrobial screening of quinoline nucleus containing 1,3,4-oxadiazole and 2-azetidinone derivatives

A series of 3-chloro-1-(aryl)-4-(2-(2-chloro-6-methylquinolin-3-yl)-5-(pyridin-4-yl)-1,3,4-oxadiazol-3(2H)-yl)-4-ethyl-azetidin-2-ones (V)_1–12 have been synthesized and characterized by IR, ¹H NMR, ¹³C NMR and mass spectra. Synthesized compounds were screened for their antibacterial activity against four different strains like Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Streptococcus pyogenes, while antifungal activity was determined against three different strains like Candida albicans, Aspergillus niger and Aspergillus clavatus. On the basis of statistical analysis, it has been observed that compounds gave significant co-relation.     

Synthesis and characterization of new ferrocenyl bishydrazones

New ferrocenyl bishydrazones (2a–2d) have been efficiently obtained from 1,1′-ferrocenedicarboxaldehyde by a straightforward synthesis. The four new compounds have been fully characterized by NMR (¹H, ¹³C), high-resolution mass spectroscopy, and the molecular structure of compounds (2a–2d) has been elucidated by X-ray diffraction on single crystals.     

Structure of seven new vibsane-type diterpenoids from Viburnum awabuki

Seven new vibsane-type diterpenoids, 6-O-methyl-6,7-dihydroxyvibsanin B (1), 4-hydroxyvibsanin A (2), 14(R*),15-epoxyneovibsanin B (3), 14(S*),15-epoxyneovibsanin B (4), (8Z)-neovibsanin B (5), 18-O-methylvibsanin C (6), and (8Z)-vibsanin E (7), have been isolated from the leaves of Viburnum awabuki. Their structures have been elucidated by molecular mechanics 2 (MM2) calculations and comparison of the spectroscopic data, including ¹³C NMR data, with those of previously known compounds. Moreover, neovibsane-type diterpenoids 3, 4, and 5 enhanced the neurite outgrowth of NGF-mediated PC12 cells at a concentration of 40 μM.     

Synthesis,insecticidal activities,and SAR studies of novel piperazine-containing heterocyclic mono-/di-/tri-amide derivatives

Diamide compounds such as chlorantraniliprole, a famous anthranilic diamide insecticide targeting the insect ryanodine receptor (RyR), have received continuous attention in pesticide research during the past 15 years owing to their excellent insecticidal potentials. With the aim of discovering new heterocyclic pesticides used for crop protection, based on the structural information of compound M from the reported pharmacophore-based virtual screening for RyR insecticides and diamide compound, a series of new heterocyclic mono-, di-, and tri-amide derivatives containing piperazine moiety have been synthesized in this paper. The new compounds were identified and confirmed by melting point, ¹H NMR, ¹³C NMR and HRMS. Compound M was firstly validated for insecticidal activities, and the new synthesized compounds were all made comprehensive insecticidal evaluations against diamondback moth and oriental armyworm. The bioassay results showed that some of the compounds exhibit favorable insecticidal potentials, particularly some novel piperazine-containing heterocyclic mono-/di-/tri-amide derivatives such as 8g, 14a, 15a, 15g, 15i, 15j, 15k, 15l, and 15m could be used as new insecticidal leading structures for further study (e.g., towards diamondback moth, 15i-15m LC₅₀: 0.0022−0.0081 mg/L). The structure-activity relationships of the compounds discussed in detail provide useful guidance for further design and development of new insecticides.     

Axially chiral thioamides of acrylic acid: correlated and uncorrelated internal rotations

In acrylic thioamides (Scheme. 1), two intramolecular motions are possible: thiocarbonyl–nitrogen (C–N) and alkenyl–carbonyl (C–C) rotations. Since the two mobile molecular fragments can interact by steric and by resonance effects, we intended to demonstrate the existence of correlated in addition to the above uncorrelated motions. For each of the three thioamides chosen, at least two of the four stereoisomers were enriched by crystallization and by liquid chromatography on nonracemic sorbents. Thereby axial chirality of acrylic thioamides was proven for the first time. Thermal equilibrations were monitored quantitatively by time-dependent ¹H NMR spectroscopy in the presence of a nonracemic additive, a method which, to our knowledge, has not previously been described. These kinetic results were evaluated by a simulation program with reference to uncorrelated and correlated rotations (Fig. 4, Fig. 5, Fig. 6). We have shown that all of these motions occur in thioamide 14. The enantiomers of thioamide 13 do not interconvert directly. However, indirect, two-step enantiomerizations in 13 have been proven one of the two steps consisting of correlated rotations. The latter are, therefore, possible in acrylic thioamides, a class of compounds which differ considerably from the molecules for which correlated motions were hitherto known.     

The first platinum(IV) complexes involving aromatic cytokinins or cyclin-dependent kinase inhibitors derived from 6-benzylaminopurine: X-ray structures of

A series of Pt(IV) complexes with cytokinins or CDK-inhibitors derived from 6-benzylaminopurine (Bap) of the composition [Pt^IV(LH⁺)Cl₅] (1–14), where LH⁺ stands for protonated form of the Bap derivative (1–12), Boh = 6-(benzylamino)-2-[(3-hydroxypropyl)amino]-9-isopropylpurine, bohemine (13) and Ros = 6-(benzylamino)-2-[(1-hydroxymethylpropyl)amino]-9-isopropylpurine, roscovitine (14), have been prepared.They have been fully characterized by microanalysis, conductivity, FT-IR, ¹H, ¹³C, ¹⁵N and ¹⁹⁵Pt NMR and ES+ mass spectroscopy.It has been found that the cytokinin molecule is coordinated via N9 atom to platinum(IV) and N1, N7-protonated in case of complexes 1–12, and N7 coordinated and N1-protonated in case of complexes with CDK inhibitors (13 and 14).Predicted molecular geometries of the complexes have been supported by DFT calculations at the B3LYP level with the 6-311+G^**/LANL2DZ and aug-cc-pVDZ/LANL2DZ basis sets.All of the compounds have been tested in vitro for their cytotoxicity against four human cancer cell lines: malignant melanoma (G361), osteogenic sarcoma (HOS), chronic myelogenous erythroleukemia (K562) and breast adenocarcinoma (MCF7).The best result has been achieved for complex 14, where IC₅₀ = 17 μM against K562. The molecular structures of two ionic pair compounds have been determined by a single crystal X-ray analysis.     

Unambiguous structure elucidation of the reaction products of 3-acyl-4-methoxy-1-methylquinolinones with hydroxylamine via NMR spectroscopy

Reaction of 3-acyl-4-methoxy-1-methylquinolinones 2a,b with hydroxylamine has been investigated under different experimental conditions. Whereas compound 2a gives rise selectively and exclusively to the regioisomeric isoxazolo[4,5-c]- or isoxazolo[4,3-c]quinolin-4(5H)one (compound 3a or 4a, respectively), reaction of 2b always led to a mixture of the required isoxazole together with the oxazole derivative. Structural elucidation of all products has been independently achieved by multinuclear (¹³C and ¹⁵N) magnetic resonance spectroscopy.     

NMR study of some sydnones,isosydnones, and isothiosydnones

Multinuclear¹H,¹³C,¹⁴N,¹⁵N, and¹⁷O NMR data are presented for some sydnones, isosydnones and isothiosydnones. The type of valence tautomerism shown in (Fig. 1) is not observed for the compounds studied. At high pH compounds2 and12 are found to undergo transformations. The more suitable NMR parameters are reported for establishing the structures of mesoionic compounds containing three heteroatoms in the five-membered conjugated ring. Someab initio GIAO calculations on a model structure of sydnones and related compounds have been performed.     

Quinoline-pyrimidine hybrid compounds from 3-acetyl-4-hydroxy-1-methylquinolin-2(1H)-one: Study on synthesis,cytotoxicity, ADMET and molecular docking

Some novel 2-amino-6-aryl-4-(4′-hydroxy-N-methylquinolin-2′-on-3′-yl)pyrimidines have been synthesized from α,β-unsaturated ketones of 3-acetyl-4-hydroxy-N-methylquinolin-2-one by reaction of corresponding α,β-unsaturated ketones with guanidine hydrochloride. The purity and structure of the obtained products have been confirmed by thin layer chromatography, IR, ¹H NMR, ¹³C NMR, HSQC, HMBC and MS spectra. All the synthesized of 3-(2-amino-6-arylpyrimidin-4-yl)-4-hydroxy-1-methylquinolin-2(1H)-ones 6a-i were screened for their in vitro cytotoxic activity against human hepatocellular carcinoma HepG2 and squamous cell carcinoma KB cancer lines. Compounds 6b and 6e had the best activity in the series, with IC₅₀ values equal to 1.33 μM. Compounds 6a-g exhibited weak or insignificant activity with liver cancer cell lines HepG2, while compounds 6a and 6g had more powerful activity in this sequence, with IC₅₀ values equal to 47.99 and 89.38 μM, respectively. ADMET properties showed that compounds 6b, 6e, and 6f possessed the drug-likeness behavior. Cross-docking results indicated that two hydrogen bonding interactions in the binding pocket, as potential ligand binding hot-spot residues for compounds 6b and 6e, may be one of the mechanisms of action responsible for the higher cytotoxic effect on HepG2 and KB cells.