Synthesis and antiviral activities of novel penta-1,4-diene-3-one oxime derivatives bearing a pyridine moiety

A series of novel penta-1,4-diene-3-one oxime ether derivatives bearing a pyridine moiety were designed and synthesized, and their antiviral activities against tobacco mosaic virus (TMV) were evaluated. The results of the biological assay indicated that most of the title compounds exhibit good antiviral activities against TMV at 500 μg/mL. In particular, the title compounds 5c, 5j, 5o and 5p showed remarkable curative activities against TMV, with EC₅₀ values of 274.8, 299.2, 251.8 and 287.7 μg/mL, respectively, which were superior to that of ribavirin (379.8 μg/mL). This study indicates that penta-1,4-diene-3-one oxime ether derivatives bearing a pyridine moiety can serve as potential alternative templates in the search for novel, highly efficient, anti-plant viral agents.     

2-(Benzo[d]thiazol-2-yl) phenyl-4-nitrophenyl alkyl/aryl substituted phosphoramidates: Synthesis,characterization and antimicrobial activity evaluation

A series of new 2-(benzo[d]thiazol-2-yl) phenyl-4-nitrophenyl alkyl/aryl substituted phosphoramidate derivatives (7a-j) of biological interest are synthesized in two steps via an in situ process without the isolation of the intermediate. 2-(Benzo[d]thiazol-2-yl) phenol (3) was treated with 4-nitrophenyl phosphorodichloridate(4) to obtain the monochloro intermediate, 2-(benzo[d]thiazol-2-yl)phenyl (4-nitrophenyl) phosphorochloridate(5). It was subsequently reacted with various amines, 6(a-j) to afford the desired title products. IR, NMR (¹H, ¹³C and ³¹P), mass spectral and elemental analysis are used to characterize the structures of the newly synthesized compounds. The antibacterial and antifungal activities are determined by the growth of inhibition of bacteria and fungi of the title compounds at two concentrations, 50 and 100 µg/mL, and minimum inhibitory concentrations to the active compounds. The compounds 7e, 7f and 7j exhibited promising inhibition activity against bacterial strains and 7c, 7e and 7i against A. niger and C. albicans and MIC values are in the range of 10.0–15.0 µg/mL.     

Synthesis,antibacterial, and antiviral activities of novel penta-1,4-dien-3-one derivatives containing a benzotriazin-4(3<Emphasis Type="Italic">H</Emphasis>)-one moiety

A series of penta-1,4-dien-3-one containing a benzotriazin-4(3H)-one moiety were prepared and evaluated for their antibacterial and antiviral activities. Bioassays indicated that some compounds exhibited good antibacterial and antiviral activities. Among them, the EC₅₀ values of compound 6d against Xanthomonas axonopodis pv. citri and compound 6l against Ralstonia solanacearum were, respectively, 22.45 and 34.77 μg/mL, which were better than that of thiodiazole copper (51.35 and 87.26 μg/mL, respectively). Meanwhile, some title compounds were found to show remarkable antiviral activities against tobacco mosaic virus (TMV). These results indicated that penta-1,4-dien-3-one derivatives containing benzotriazin-4(3H)-one moiety could play significant roles in searching for novel agrochemicals.     

Facile Access to Mono-Cinchona Alkaloid-Derived Ligands

Two facile accesses to mono-cinchona alkaloid-derived ligands, by conventional heating conditions and solvent-free microwave irradiation, are described. 1,4-Dichlorophthalazine (PHAL) or 3,6-dichloropyridazine (PYDZ) reacted with quinine (QN), cinchonine (CN), or cinchonidine (CND) by using CaH₂ as acid-bonding reagent in DMF at 90–100°C to provide mono-cinchona alkaloid-derived ligands 2a–f (87–95%) in 1.5 h. However, the coupling reactions were performed under solvent-free microwave conditions to yield 2a–f (64–89%) within 15 min.     

An efficient synthesis,spectral characterization,antimicrobial, and antioxidant activities of novel α-hydroxyphosphonates and α-hydroxyphosphinates

A simple, novel, and an efficient synthesis of α-hydroxy phosphonates (3a–d) and phosphinates (5a–f) has been accomplished from febuxostat aldehyde (1) with various dialkylphosphites (2) and dialkylphosphinates (4) in the presence of 1, 4-dimethylpiperazine as a strong base with good to excellent yields (78%–95%) is reported. The structures of the title compounds were established by elemental analysis and spectral data (IR, ¹H, ¹³C and ³¹P NMR, and LC-MS). All the title compounds (3a–d) and (5a–f) were tested for their antimicrobial and antioxidant activities. Bioassay results reveal that a few of the title compounds exhibited promising antimicrobial and antioxidant activities.     

Antiviral activity of aconite alkaloids from Aconitum carmichaelii Debx

Four diterpenoid alkaloids, namely, (a) hypaconitine, (b) songorine, (c) mesaconitine and (d) aconitine, were isolated from the ethanol root extract of Aconitum carmichaelii Debx. The antiviral activities of these alkaloids against tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV) were evaluated. Antiviral activity test in vivo showed that compounds a and c, which were C19-diterpenoid alkaloids, showed inactivation efficacy values of 82.4 and 85.6% against TMV at 500 μg/mL, respectively. By contrast, compound c presented inactivation activity of 52.1% against CMV at 500 μg/mL, which was almost equal to that of the commercial Ningnanmycin (87.1% inactivation activity against TMV and 53.8% inactivation activity against CMV). C19-Diterpenoid alkaloids displayed moderate to high antiviral activity against TMV and CMV at 500 μg/mL, dosage plays an important role in antiviral activities. This paper is the first report on the evolution of aconite diterpenoid alkaloids for antiviral activity against CMV.     

Lanthanide Triflate Catalyzed One-Pot Synthesis of Dihydropyrimidin-2(1H)-thiones by a Three-Component of 1,3-Dicarbonyl Compounds,Aldehydes, and Thiourea Using a Solvent-Free Biginelli Condensation

Abstract

Novel one-pot Biginelli-type reaction has been developed. Aromatic and aliphatic aldehydes with β-dicarbonyl compounds and thiourea in the presence of catalytic amount 5 mol% of Yb(OTf)₃ at 100° C for 60–90 min under solvent-free conditions proceeded smoothly to afford corresponding dihydropyrimidin-thiones. The yields of the classical Biginelli reaction can be increased from 20–50% to 81–91% while the reaction time was shortened from 18–48 h to 60–90 min. In addition the catalyst can be easily recovered and reused.     

Influence of Isosorbide on Glass‐Transition Temperature and Crystallinity of Poly(butylene terephthalate)

Copolyesters of isosorbide and 1,4‐butane diol were prepared by Ti(OBu)₄‐catalyzed transesterifications with dimethyl terephthalate in bulk at temperatures up to 250°C. The content of isosorbide was considerably lower than expected from the feed ratio and the molar masses were low, so that no DSC measurements were conducted. Copolycondensations of isosorbide and 1,4‐butane diol with terephthaloyl chloride were either performed in dichloromethane at 40°C or in toluene at 100°C. The second method gave the higher molar masses. However, both series of polycondensations had the content of isosorbide roughly paralleled the feed ratios in common. The DSC measurements revealed that even 6 mol% of isosorbide is sufficient to raise the glass‐transition temperature (T_g) by 10–12°C (up to 55°C). With 50 mol% of isosorbide, the T_g reaches 100°C. Yet, incorporation of isosorbide also reduces the melting temperature T_m and the degree of crystallinity, and a mol percentage above 30% prevents crystallization completely. In summary, incorporation of isosorbide allows for fine‐tuning of T_g and T_m of poly(butylene terephthalate) over a wide range.     

Synthesis of the [(η6-p-cymene)Ru(dppb)Cl]PF6 complex and catalytic activity in the transfer hydrogenation of ketones

Catalysis under mild conditions is of great importance to various chemistry areas, particularly for the development of novel active compounds and for natural products modifications, among others. In this study, the synthesis, characterization, and evaluation of the catalytic activity of a new ruthenium(II) compound, [(η⁶-p-cymene)Ru(dppb)Cl]PF₆ (A) where dppb=1,4-bis(diphenylphosphine)butane, is presented. Catalytic activity of the new Ru(II) compound was tested on hydrogen transfer reaction in various substrates, acetophenone, benzophenone, cyclohexanone, and methyl-ethyl-ketone. Potassium hydroxide was used as base, whereas isopropanol served as both solvent and hydrogen source. Samples comprising substrate: base: catalyst at a 200?:?20?:?1 ratio were poured into 5 mm tubes and monitored in situ at 40, 50, and 60 °C in a 600 MHz NMR spectrometer. The complex was active in the transfer hydrogenation of ketones, achieving conversions superior to 90% within 4 h at 60 °C, which suggests under mild conditions. Therefore, in situ monitoring the reactions through ¹H NMR was a valuable technique to establish the possible catalytic mechanism of Ru(II) precatalyst.     

Synthesis of 6-Substituted/Unsubstituted- 7,9-diaryl-1,2,4,8-tetraazaspiro[4.5]- decan-3-thiones

Abstract

Some 2,6-diarylpiperidin-4-one thiosemicarbazones (1a–8a), obtained from the corresponding 2,6-diarylpiperidin-4-ones (1–8) on oxidative cyclization with H₂O₂ at 0°C provide 7,9-diaryl-1,2,4,8-tetraaza spiro[4.5]decan-3-thiones (1b–8b) in excellent yields. The structures of these compounds have been established on the basis of their elemental, analytical and spectral data.     

1,4‐Diaryl and Schiff's base [1,2,3]‐triazole derivative liquid crystalline compounds

Regioselective synthesis of [1,2,3]‐triazoles based on the ‘click‐reaction’, involving the Cu(I)‐catalysed 1,3‐dipolar cycloaddition of aryl azide to terminal arylacetylenes, was successfully employed in the preparation of two series of non‐linear mesogens, based on 1,4‐diaryl‐[1,2,3]‐triazole (Ia–e) and with Schiff's base units (IIa–c). Their mesophases were characterized by polarizing optical microscopy and differential scanning calorimetry. All final compounds exhibited preferentially the SmC phase. In addition, compounds of series I showed weak blue fluorescence in solution (λ_{max. em.} = 380–386 nm) with poor quantum yields and a Stokes shift of around 90 nm.     

Synthesis of 2,3,8,9-Dibenzo-5,6-(substituted)benzo-1,4-dithio-7-oxacyclonona-2,5,8-trienes and some electrophilic substitution reactions

Treatment of 5-(2-hydroxyaryl)thianthreniumyl perchlorates 1 with sodium hydride in tetrahydrofuran at reflux gave the title compounds 5 in excellent yields. For the reactivities of the compounds 5 , the selected compounds 5 were subjected under the conditions of electrophilic substitution reactions. Bromination of 5,6-{3-(2-butyl)benzo}-2,3,8,9-dibenzo-1,4-dithio-7-oxacyclonona-2,5,8-triene ( 5f ) in acetic acid at 60° afforded two bromo compounds 9 (22%) and 10 (69%), which were oxidized by m-chloroperbenzoic acid to give tetraoxides 11 (95%) and 12 (97%), respectively. Treatment of 5f with acetyl chloride in the presence of aluminum chloride in carbon disulfide at 0° gave an acetylated compound 13 (58%). Nitration of 5f with nitric acid in acetic acid at 50° gave a nitro compound 17 (15%) together with 1,4-dioxide 7e (22%) and a 5-oxide 18 (3%) whose regiochemistry has not been established. On the other hand, 5,6-(3-methylbenzo)-2,3,8,9-dibenzo-1,4-dithio-7-oxacyclonona-2,5,8-triene ( 5a ) reacted with acetyl chloride under the same conditions to give two acetylated compounds 15 (33%) and 16 (18%). The mechanism for the formation of 5 and the structural elucidation of these compounds are discussed.     

A new naphthoquinone analogue and antiviral constituents from the root of Rhinacanthus nasutus

Rhinacanthus nasutus (L.) Kurz (Acanthaceae) is known as traditional medicine for the treatment of fungal and herpes virus infections. A new naphthoquinone racemate, rhinacasutone (1) together with seven known compounds, rhinacanthone (2), rhinacanthins C, D, N, Q, and E (3–7), and heliobuphthalmin (8) were isolated from root of R. nasutus. Their structures were determined on the basis of extensive spectroscopic methods, including 1D-, 2D-NMR and MS data. All the isolated compounds were tested for their antiviral activities against PR8, HRV1B, and CVB3-infected vero cells. Compounds 3–6 exhibited significant antiviral activities with the IC₅₀ value ranging from 0.03 to 23.7 μM in all three infections.     

Synthesis and biological activity of ethyl 2-(5-methyl-3-arylisoxazole-4-carboxamido)-4-alkylthiazole-5-carboxylate

A series of novel ethyl 2-(5-methyl-3-arylisoxazole-4-carboxamido)-4-alkylthiazole-5-carboxylates I-1-6 were synthesized. The structures of all target compounds were characterized by ¹H NMR, ¹³C NMR, IR, MS and elemental analyses. Their fungicidal and herbicidal activities were evaluated. The results of preliminary bioassays show that the title compounds I-4 possess 20–50% inhibition against most of the tested plants at the dosage of 150 g ai/ha, while the title compounds I-1-5 possess 32–58% inhibition against FusaHum graminearum, Thanatephorus cucumeris, Botrytis cinereapers and Fusarium oxysporum in vitro at the concentration of 100 mg/L.     

Interaction of RuIII(EDTA) with cellular thiols and O2: biological implications thereof

Reaction of [Ru^III(EDTA)(CyS)]^2? (edta^4? = ethylenediaminetetraacetate; CySH = cysteine) with molecular oxygen (O₂) has been studied as a function of pH (4.0–8.0) and cysteine concentration (0.2–2.0 mM) at room temperature (25 °C). Biological activities of the [Ru(EDTA)]/CySH/O₂ system pertaining to cleavage of supercoiled plasmid DNA to its nicked open circular form has been explored in this work. Results are discussed in regard to the reaction of the ruthenium(III)-complex with molecular oxygen) and a working mechanism is proposed for the biological activities of the ruthenium(III)-complex in the presence of O₂.     

Two copper complexes based on nitronyl nitroxide with different halides: structures and magnetic properties

Complexes based on different halogen-substituted nitronyl nitroxide radicals and Cu(II), Cu₃(hfac)₆(NIT-Ph-F)₂ (1) and Cu₃(hfac)₆(NIT-Ph-Cl)₂ (2) (hfac = hexafluoroacetylacetonate; NIT-Ph-F = 2-(4′-fluorophenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide; NIT-Ph-Cl = 2-(4′-chlorphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide), were synthesized and characterized structurally and magnetically. X-ray crystal structure analyses show that 1 and 2 have similar centrosymmetric five-spin structures consisting of three Cu(II) ions bridged by two nitroxide ligands. The Cu(II) is coordinated by six oxygens to form an octahedron, while the five coordination of the terminal Cu(II) ion is square pyramidal. Magnetic measurements reveal strong antiferromagnetic interactions between Cu(II) ions and radicals in 1 (J = ?38.9 cm^?1) and weak antiferromagnetic interactions between Cu(II) ions and radicals in 2 (J = ?1.23 cm^?1), which may be explained by the bond length of the Cu–O_rad (2.468(2) Å) in 1, which is shorter than that (2.514(2) Å) in 2, and the dihedral angle (73.17(1)°) of the plane O7–O8–Cu(2)–O7A–O8A with the moiety O5–N1–C11–N2–O6 in 1 is smaller than (77.82(1)°) in 2.     

SYNTHESIS OF SOME BICYCLIC OXAZOLO- AND OXAZEPINOPYRIMIDINE DERIVATIVES

Oxazolopyrimidine compounds 2(a–c) and 3(a–e) were synthesized by a simple one-pot condensation reaction of the pyrimidine derivative 1 with 1,2-dibromoethane and 2-bromopropanoic acid, respectively. In a similar way the oxazepinopyrimidine compounds 4(a–b) were synthesized by reaction of 1 and 1,4-dichlorobutane in dioxane under reflux condition. The yields of products following recrystallization were of the order of 55–85%.     

Synthesis and properties of novel poly(N-oxyimide)s

Novel poly(N-oxyimide)s (PNOI) were synthesized by the room temperature polycondensation of N,N′-dihydroxypyromellitimide (I) with dichloro compounds in N,N-dimethylformamide (DMF) in the presence of triethylamine both as base as well as catalyst. The dichloro compounds used were 1,4-bis(chloromethyl)-2,5-dimethylbenzene (II), 1,5-bis(chloromethyl)-2,4-dimethylbenzene (III), 1,4-bis(chloromethyl)-2,5-dimethoxybenzene (IV) and 1,4-dichlorobut-2-yne (V). Polymer synthesis, characterization, and properties such as density, viscosity, solubility, crystallinity, and thermal stability were described. Two model compounds, viz. (i) MNOI-1 from N-hydroxyphthalimide and a dichloro compound (III), (ii) MNOI-2 from I and benzyl chloride were also synthesized to confirm the formation of polymers. The polymers thus obtained had high intrinsic viscosities in the range 1.09–1.18 dl/g. The thermal decomposition of the polymers started around 260°C with 20–25% decomposition and about 50% weight loss was observed at 400°C.     

Cytotoxic,antitumour-promoting and inhibition of protein denaturation effects of flavonoids,isolated from Potentilla evestita Th. Wolf

This study was designed to evaluate the isolated flavonoids (chrysin 1, and umbelliferone 2) from Potentilla evestita for cytotoxic, antitumour-promoting and inhibition of protein denaturation activities. The results showed marked cytotoxic effect of compounds 1 and 2 in brine shrimp cytotoxic assay at various concentrations with LD₅₀ of 34.5 and 31.8 mg/mL, respectively. In Epstein–Barr-virus early antigen activation assay, both compounds 1 and 2 illustrated significant antitumour-promoting effect with IC₅₀ values of 462 and 308 mol ratio/32 pmol TPA, respectively. The cytotoxic and antitumour-promoting effects of compounds were strongly supported by inhibition of protein denaturation activity with IC₅₀ of 119 and 112 μg/mL, respectively. In conclusion, both compounds possess strong cytotoxic, antitumour-promoting and inhibition of protein denaturation activities.     

Influence of alkyl substituents in 1,3-diethyl-2-thiobarbituric acid on the coordination environment in M(H2O)2(1,3-diethyl-2-thiobarbiturate)2 M = Ca2+, Sr2+

Two new isostructural complexes, [Ca(H₂O)₂(μ₂-Detba-O,O′)₂]_n (1) and [Sr(H₂O)₂(μ₂-Detba-O,O′)₂]_n (2) (HDetba = 1,3-diethyl-2-thiobarbituric acid), were synthesized and characterized by single-crystal and powder X-ray diffraction analysis, TG-DSC, FT-IR, and emission spectroscopy. The single-crystal X-ray diffraction data revealed that 1 and 2 are polymeric where M²⁺ (M = Ca, Sr) is a six-coordinate octahedral binding four Detba^? ions and two water molecules. The octahedra are linked through bridging Detba^? ions forming a 2-D layer. Two intermolecular hydrogen bonds O–H…S in the crystal form a 3-D net. The comparison of M(Detba)₂ and M(Htba)₂ (H₂tba = 2-thiobarbituric acid) structures showed that the coordination number of metals in M(Detba)₂ does not exceed six and there are no π–π interactions, unlike compounds with Htba^?; Detba^? ions are only bridges in HDetba coordination compounds. Thermal decomposition of 1 and 2 includes dehydration, which mainly ends at 200 °C, and organic ligand oxidation at 300–350 °C with a release of CO₂, SO₂, H₂O, NH₃, and isocyanate. Upon excitation at 220 nm, 1 and 2 exhibit an intense emission maximum at 557 nm.