Synthesis and antifungal activities of novel trifluoroethane derivatives with coumarin,indole and thiophene

A series of novel 1-(β-coumarinyl)-1-(β-indolyl)-1-(α-thiophenyl)trifluoroethane derivatives 5aaa-5hdb were prepared by one-pot reaction from 3-(trifluoroacetyl)coumarin with indole and α-substituted thiophene. Their structures were confirmed by ¹H NMR, ¹³C NMR, ¹⁹F NMR, HRMS and X-ray single crystal diffraction, and their antifungal activities against F. moniliforme, F. graminearum, F. oxysporum, R. solani and P. nicotianae were evaluated. The title compounds displayed significant to moderate in vitro antifungal activity when compared to the standard drug triadimefon. Among the synthesized compounds, compound 5bfa showed the highest inhibitor rate of 83.5 % at 0.500 mg/mL against R. solani, while compound 5ada displayed the highest inhibitor rate of 73.3 % at 0.500 mg/mL against F. graminearum.     

Synthesis and characterization of the two enantiomers of a chiral sigma-1 receptor radioligand: (S)-(+)- and (R)-(-)-[18F]FBFP

Racemic [¹⁸F]FBFP ([¹⁸F]1) proved to be a potent σ₁ receptor radiotracer with superior imaging properties. The pure enantiomers of unlabeled compounds (S)- and (R)-1 and the corresponding iodonium ylide precursors were synthesized and characterized. The two enantiomers (S)-1 and (R)-1 exhibited comparable high affinity for σ₁ receptors and selectivity over σ₂ receptors. The Ca²⁺ fluorescence assay indicated that (R)-1 behaved as an antagonist and (S)-1 as an agonist for σ₁ receptors. The ¹⁸F-labeled enantiomers (S)- and (R)-[¹⁸F]1 were obtained in >99% enantiomeric purity from the corresponding enantiopure iodonium ylide precursors with radiochemical yield of 24.4% ± 2.6% and molar activity of 86–214 GBq/µmol. In ICR mice both (S)- and (R)-[¹⁸F]1 displayed comparable high brain uptake, brain-to-blood ratio, in vivo stability and binding specificity in the brain and peripheral organs. In micro-positron emission tomography (PET) imaging studies in rats, (S)-[¹⁸F]1 exhibited faster clearance from the brain than (R)-[¹⁸F]1, indicating different brain kinetics of the two enantiomers. Both (S)- and (R)-[¹⁸F]1 warrant further evaluation in primates to translate a single enantiomer with more suitable kinetics for imaging the σ₁ receptors in humans.     

The reaction of perfluoroalkylcopper compounds with 1-bromo-1-perfluoroalkylethylenes

Perfluoroalkylcopper compounds [F_FCU], when they react with 1-bromo-1-perfluoroalkylethylenes 1, do not give the expected gem-disubstituted compounds 3, but the vic-disubstituted products 2 in 60–70% yields. These results show that the reaction does not proceed through a simple vinylic substitution. ¹H and ¹⁹F NMR data are given for the new compounds.     

Oligofluorene-based push-pull type functional materials for blue light-emitting diodes

A series of new oligofluorene-based push-pull type blue light-emitting functional materials, namely, 2-(9H-carbazole-9-yl)-7-(4-cyanophenyl)-9,9-dihexylfluorene (F1), 7-(9H-carbazol-9-yl)-7′-(4-cyanophenyl)-2,2′-bi(9,9-dihexylfluorene) (F2), 7-(9H-carbazole-9-yl)-7″-(4-cyanophenyl)-2,2′:7′,2″-ter(9,9-dihexylfluorene) (F3), and 7-(9H-carbazole-9-yl)-7″′-(4-cyanophenyl)-2,2′:7′,2″:7″,2″′-quarter(9,9-dihexylfluorene) (F4) were synthesized and characterized. Their onset decomposition temperatures for the thermal bond cleavage and the glass-transition temperatures were in general increased with increasing number of fluorene units. In dilute toluene solution, the oligofluorenes exhibited main absorption peaks in the range of 343-370 nm, photoluminescence maxima from 403 to 410 nm, and absolute quantum yields (Φ_PLs) of higher than 87%. In contrast, the absorption spectra of these compounds in the thin films had no large differences from those in the solutions except for the slight peak red-shifts (2-8 nm). The main emission maxima of F1, F2, and F3 in the thin films were located at 418-420 nm, while the main emission of F4 was found to be shifted to 446 nm, followed by a shoulder peak at 421 nm. The Φ_PLs of these thin films were estimated in the range of 59.2-68.7%. The existence of the electron-pull and -push end groups could effectively tune the energy levels of the oligofluorenes. By using the organic light emitting device (OLED) configuration of ITO/PEDOT:PSS/oligofluorenes/TPBi/LiF/Al by solution-process, F4 displayed the best performance: the lowest turn-on voltage (4.1 V) and highest maximum luminance (2180 cd/m²) with maximal current efficiency of 1.17 cd/A. When F4 was fabricated into the optimized device of ITO/MoO₃/NPB/CBP:F4(1:4)/TPBi/LiF/Al by vapor deposition, highest brightness of 5135 cd/m² and current efficiency of 1.76 cd/A were achieved with the Commission Internationale de l’Eclairage (CIE) coordinates of (0.16, 0.09).     

Pseudapenes A–C,sesquiterpenoids from the marine-derived fungus Pseudallescheria apiosperma F52-1

Three sesquiterpenoids pseudapenes A–C (1–3) were isolated from the marine-derived fungus Pseudallescheria apiosperma F52-1. Pseudapene A (1) has an unprecedented 2-methyl-5-methylene-3-(2-methylbut-2-ene)-dicyclo(3, 3, 0)-octane carbon skeleton and pseudapenes B (2) and C (3) possess an unique 2-methyl-4-methylene-2-(2-methylpent-2-ene)-dicyclo(3, 2, 0)-heptane chemical scaffold. Their structures were determined by use of MS and NMR spectroscopic data, and ECD, optical rotation and ¹³C NMR calculations.     

Hyperinoids A and B,two polycyclic meroterpenoids from Hypericum patulum

Hyperinoids A (1) and B (2), two prenylated acylphloroglucinol related meroterpenoids, were isolated from Hypericum patulum. Compound 1 incorporates an unprecedented 11,12-dioxatetracyclo[5.4.3.0^1,7.0^4,14]tetradecane system, while 2 possesses a unique 10,11-dioxatetracyclo[5.3.3.0^1,7.0^4,13]tridecane system. Their structures were established by spectroscopic analysis and X-ray crystallographic data. Compounds 1 and 2 were identified as potent NF-κB inhibitors and suppressed the LPS-induced inflammatory responses in RAW 246.7 macrophages and primary mouse BMDM cells     

C-F?M interaction in anionic α-fluorovinyl rhenium oxycarbene complexes and their β-fluoroenolate analogs

The C-F?M⁺ interaction in anionic σ-(α-fluorovinyl)rhenium oxycarbene complexes, [RCFCFReC(O)R′(CO)₄]M (1-6), M = Na, Li, K is studied by ¹⁹F NMR in THF and Et₂O. The coordination of α-F to M⁺ results in an upfield shift of the corresponding ¹⁹F NMR signal and a decrease of ¹J_CF. The maximum shift is found for the Li salt of complex 4 in Et₂O (Δδ_Fα = 36.4 ppm), in which case a ⁷Li-¹⁹F spin-spin coupling is also observed (J_LiF = 40 Hz). The ΔE of C-F?M⁺ interaction and its effect on ¹⁹F shielding was further studied by DFT calculations using β-fluoroenolates as models, which confirmed a strong impact of CF-bond environment on the coordination ability of fluorine in these F,O-chelates. A compound with a β-fluoroenolate backbone but without rhenium, o-(α-fluorovinyl)phenolate 12, was prepared and studied by ¹⁹F NMR, and similarly showed indications of C-F?M⁺ interaction in THF solution. It is concluded that the donor ability of fluorine in the studied system is enhanced because of the conjugation of α-fluorovinyl group with the enolate π-system and back donation from the transition metal.     

On the alkaloids of strychnos—xxxvi: The alkaloids of strychnos hirsuta spruce exbentham; two new β-carbolinic alkaloids,strychnohirsutine and tetradehydrostrychnohirsutine

The structures and configurations of two new β-carbolinic alkaloids, strychnohirsutine 1 and tetra-dehydrostrychnohirsutine 2, isolated from stem and root bark of Strychnos hirsuta, were reported. ¹H NMR data of N,O-diacetylstrychnohirsutine 5 and ¹H and ¹³C NMR data of O-acetyltetradehydrostrychnohirsutine 4 were listed. Alkaloid 1 was converted into 2 by catalytic dehydrogenation.     

Reactivity of M(en)Cl2 (M = Pd/Pt,en = 1,2-diaminoethane) with N,N′-bis(salicylidene)-p-phenylenediamine: Binding with hexafluorobenzene

Schiff base N,N′-bis(salicylidene)-p-phenylenediamine (LH₂) complexed with Pt(en)Cl₂ and Pd(en)Cl₂ provided [Pt(en)L]₂ · 4PF₆ (1) and Pd(Salen) (2) (Salen = N,N′-bis(salicylidene)-ethylenediamine), respectively, which were characterized by their elemental analysis, spectroscopic data and X-ray data. A solid complex obtained by the reaction of hexafluorobenzene (hfb) with the representative complex 1 has been isolated and characterized as 3 (1 · hfb) using UV–Vis, NMR (¹H, ¹³C and ¹⁹F) data. A solid complex of hfb with a reported Zn-cyclophane 4 has also been prepared and characterized 5 (4 · hfb) for comparison with complex 3. The association of hfb with 1 and 4 has also been monitored using UV–Vis and luminescence data.     

Synthesis and biological evaluation of 1-(4-(4-(4-[18F]fluorobenzyl)-1-piperazinyl)butyl)indolin-2-one as dopamine D4 receptor ligand

A potential dopamine D₄ receptor ligand, 1-(4-(4-(4-fluorobenzyl)-1-piperazinyl)butyl)indolin-2-one (4) was synthesized through a four-step process and its affinity and selectivity for dopamine D₂-like receptors was determined through in vitro receptor binding assay. [¹⁸F]4 was prepared using a one-pot two-step method with total radiochemical yield 21.2 % (decay-corrected). The molar radioactivity was around 135 GBq/μmol and the radiochemical purity was greater than 95.5 %. The partition coefficient (Log P) of [¹⁸F]4 was determined to be 2.10 ± 0.30 through octanol experiment. The in vivo biodistribution and the competitive distribution of [¹⁸F]4 in rat exposed that the tracer passes through blood–brain-barrier (BBB) and may specifically bind to D₄ receptor. Metabolite analysis revealed that there was no metabolism of [¹⁸F]4 in brain. Conclusively, these preliminary results demonstrated that [¹⁸F]4 shows promises as a radioligand for the in vivo study of dopamine D₄ receptor.     

Determination of the geometrical configuration of the polyen chain of monocis C40-carotenoids—I: A 13C NMR study of monocis zeaxanthins and monocis capsorubins

¹³C NMR studies reveal that the polyen chain of neo-zeaxanthin A (2) and that of neo-capsorubin A (5) have 13-cis configuration, while those of neo-zeaxanthin B (3) and neo-capsorubin B (6) have 9-cis geometrical configuration. ¹³C NMR data on the corresponding all-trans carotenoids (1 and 4) are also reported.     

Synthesis,thermal property and antifungal evaluation of pyrazine esters

Synthesis, thermal properties, as well as antifungal assessment of pyrazine esters were handed in this work. The metal-free esterification of pyrazinyl methanol and acid chloride derivatives in a stoichiometric ratio yielded the following compounds: pyrazin-2-ylmethyl benzoate (3a), (5-methylpyrazin-2-yl) methyl benzoate (3b), 1-(pyrazin-2-yl) ethyl benzoate (3c), 2-(pyrazin-2-yl) ethyl benzoate (3d), pyrazin-2-ylmethyl pivalate (3e). The spectral results totally showed that the synthesis conditions used permitted the compounds to be produced with great yield. The characterization included ¹H NMR, ¹³C NMR, IR, HRMS and organoleptic tests. Their thermal degradation process was examined by using the TG (thermogravimetry) and DSC (differential scanning calorimeter) methods. The pyrolysis products of the pyrazine esters in inert and oxidative atmospheres were analyzed by the Py-GC/MS (pyrolysis–gas chromatography/mass spectrometry) method. It revealed that 3a–3e were totally evaporated throughout the pyrolysis experiments at low temperatures. And they evaporated with high relative contents in pure nitrogen (86.12%–94.17%) and oxidative (75.01%–88.85%) atmospheres, with only a small amount decomposing into a series of substances. Additionally, the in vitro antifungal effects of compounds 3a–3e against R. solani, P. nicotianae, F. oxysporum, F. graminearum, and F. moniliforme were further investigated using the mycelial growth rate methodology. The findings shown that compound 3c has 94% and 80% inhibitor rates at 0.5 mg/ml against R. solani and P. nicotianae, respectively, with an EC₅₀ value (half maximum effective concentration) of 0.0191 mg/ml and 0.1870 mg/ml, respectively. Similarly, that of compounds 3a and 3b exhibited 82% and 91% at 0.5 mg/ml against R. solani, with an EC₅₀ value of 0.0209 mg/ml and 0.0218 mg/ml, respectively. The molecular docking of compound 3c with SDH (Succinate dehydrogenase) was preliminarily performed to reveal the binding modes in active pocket and analyze the interactions between the molecules and the protein.     

Vinylamine—XIV : Untersuchungen zur substituentenabhängigkeit der imin-enamin-tautomerie an N-aryl-vinylaminen

The dependence of the equilibrium on R¹ in imine-enamine tautomeric compounds 1 and 2 has been investigated by NMR measurements in nitrobenzene-d₅. The equilibrium was determined by the influence of R¹ on the enamine. A Hammett correlation was observed only in case of m-substitution. The p-substituted compounds show supplement stabilization and destabilization effects which cannot be described by σ-values. A linear free enthalpy relationship exists between 1 and 2. Under the conditions of measurement, 1I is more favored than 2I by 1·6 kcal/mole.     

Cribrarione A, a new antimicrobial naphthoquinone pigment from a myxomycete Cribraria purpurea

Cribrarione A (1), a new dihydrofuranonaphthoquinone pigment with antimicrobial activity against Bacillus subtilis has been isolated from a myxomycete Cribraria purpurea and its structure was elucidated by spectral data. The ¹H-¹³C long-range couplings through an intramolecular hydrogen bond were clearly observed in the HMBC spectrum of 1.     

Arnequinol A and arnequinone A,two unique meroterpenoids from Arnebia euchroma

Arnequinol A(1), featuring an unprecedented 6/6/3 tricyclic carbon skeleton fused with a heptatomic oxo-bridge, together with arnequinone A(2) bearing a highly conjugated methyl-shifting benzogeijerene skeleton, were isolated from Arnebia euchroma. Their structures were elucidated by extensive spectroscopic methods and quantum chemical calculations of the13C nuclear magnetic resonance(NMR) data and electronic circular dichroism(ECD) spectra. The plausible biosynthetic pathways for 1 and 2 were p...     

Perfluoro alkyl 1,3-diketonates of cyclic and acyclic secondary amines

Cyclic and acyclic secondary amines were quaternized with perfluoroalkyl 1,3-diketones to form secondary ammonium perfluoroalkyl 1,3-diketonates in good yields. Saturated cyclic secondary amines, including morpholine, N-acetylmorpholine, 3-methyl-N-acetylpiperidine, 2,2,6,6-tetramethyl-4-aminopiperidine, 4,4-dimethylimidazoline, 1,3-bispiperidine propane, and acyclic secondary amines, di(n-propyl) amine, di(isopropyl) amine, di(n-butyl) amine, and di(isobutyl) amine were reacted with various fluorine-containing 1,3-diketones (1-5) to yield the corresponding 1,3-diketonates (6-29). The compounds were characterized by ¹H, ¹⁹F, and ¹³C NMR, electrospray MS, and elemental analyses. Melting points and T_g values were obtained by DSC. Thermal decomposition data (5% weight loss temperature) were recorded by TGA. X-ray single-crystal structures show that 9 and 26 crystallize in monoclinic space group P2(1)/c.     

A convenient synthesis of 2β,3α-dihydroxyurs-12-en-28-oic acid as a natural diastereoisomer of corosolic acid

2β,3α-Dihydroxyurs-12-en-28-oic acid（6） is a naturally occurring diastereoisomer of corosolic acid with glycogen phosphorylase inhibitory activity.A new strategy for the semi-synthesis of 6 was developed.Using the commercially available ursolic acid（1） as the starting materials,6 was synthesized through five facile reactions with a high stereoselectivity and an overall yield of 47.3%.The structure of 6 was confirmed by optical rotation.ESI-MS,¹H NMR and ¹³C NMR data.     

Vincamajorines A and B,monoterpenoid indole alkaloids with new carbon skeletons from Vinca major

Two new monoterpenoid indole alkaloids, vincamajorines A (1) and B (2), were isolated from Vinca major. Their structures were elucidated by means of 1D and 2D NMR, and HREIMS spectroscopic data. The relative and absolute configurations were deduced by comparing the experimental ¹³C NMR, ECD spectra, and OR data with those theoretically calculated. Vincamajorine A (1) represents a new C₂₀ carbon skeleton arranged compactly in seven rings, and vincamajorine B (2) is an alkaloid with an unprecedented 6/5/7/5/6 pentacyclic ring system. A possible biosynthetic pathway was also proposed for the formation of 1 and 2.     

Synthesis, structural characterisation and biological activity of novel N-(ferrocenylmethyl)benzene-carboxamide derivatives

A series of N-(ferrocenylmethyl)benzene-carboxamide derivatives (4a-f) have been synthesised by coupling ferrocenylmethyl amine 3 with benzoic acid and various substituted fluorobenzoic acids using the standard 1,3-dicyclohexylcarbodiimide (DCC), 1-hydroxybenzotriazole (HOBt) protocol. All compounds were fully characterised using a combination of ¹H NMR, ¹³C NMR, ¹⁹F NMR, DEPT-135, ¹H-¹H COSY and ¹H-¹³C COSY (HMQC) spectroscopy and electrospray ionisation mass spectrometry (ESI-MS). The compounds 4a, 4d, 4e and 4f exhibited cytotoxic effects on the MDA-MB-435-S-F breast cancer cell line. Single crystal X-ray crystallographic data for 4d is also presented.     

Mycopyranone: A 8,8ˈ-binaphthopyranone with potent anti-MRSA activity from the fungus Phialemoniopsis sp.

A new 8,8?-binaphthopyranone (mycopyranone, 1) was isolated from a solid fermentation of Phialemoniopsis sp. (fungal strain MSX61662), and the structure was elucidated via analysis of the NMR and HRESIMS data. The axial chirality of 1 was determined to be M by ECD. The central chirality at C-4/C-4? was assigned through a modified Mosher’s method, while the absolute configuration at C-3/C-3? was deduced based on analysis of the ³J_H-3-H-4 values and NOESY correlations. Compound 1 was evaluated for its antimicrobial properties against Staphylococcus aureus SA1199 and a clinically relevant methicillin-resistant S. aureus strain (MRSA USA300 LAC strain AH1263). Compound 1 inhibited the growth of both strains in a concentration dependent manner with IC₅₀ values in the low μM range. Molecular docking indicated that compound 1 binds to the FtsZ (tubulin-like) protein in the same pocket as viriditoxin (2), suggesting that 1 targets bacterial cell division.