Preparative Isolation and Purification of Two Phenylpropanoids from Daphne giraldii Nitsche by HSCCC

Preparative high-speed counter-current chromatography (HSCCC) was successfully applied to purify phenylpropanoids from the stem and root bark of Daphne giraldii Nitsche, a traditional Chinese medicine. Their structures were identified on the basis of ¹H NMR and ¹³C NMR technology. The two-phase solvent system composed of n -hexane–ethyl acetate–methanol–water (2: 3: 0.5: 4, v/v/v/v) was selected for HSCCC. A total of 8.0 mg woonenoside XI (1) and 18.0 mg daphnetin (2) were obtained in one-step separation from 200 mg of the crude extract with purity of 96.0 and 99.1%, respectively, as determined by LC. And the major compound (2) showed antithrombotic activity in vitro.     

Dihydroisocoumarins and Dihydroisoflavones from the Rhizomes of Dioscorea collettii with Cytotoxic Activity and Structural Revision of 2,2′-Oxybis(1,4-di-tert-butylbenzene)

The investigation of the constituents of the rhizomes of Dioscorea collettii afforded one new dihydroisocoumarin, named (−)-montroumarin (1a), along with five known compounds—montroumarin (1b), 1,1′-oxybis(2,4-di-tert-butylbenzene) (2), (3R)-3′-O-methylviolanone (3a), (3S)-3′-O-methylviolanone (3b), and (RS)-sativanone (4). Their structures were elucidated using extensive spectroscopic methods. To the best of our knowledge, compound 1a is a new enantiomer of compound 1b. The NMR data of compound 2 had been reported but its structure was erroneous. The structure of compound 2 was revised on the basis of a reinterpretation of its NMR data (1D and 2D) and the assignment of the ¹H and ¹³C NMR data was given rightly for the first time. Compounds 3a–4, three dihydroisoflavones, were reported from the Dioscoreaceae family for the first time. The cytotoxic activities of all the compounds were tested against the NCI-H460 cell line. Two dihydroisocoumarins, compounds 1a and 1b, displayed moderate cytotoxic activities, while the other compounds showed no cytotoxicity.     

Isolation of N-Ethyl-2-pyrrolidinone-Substituted Flavanols from White Tea Using Centrifugal Countercurrent Chromatography Off-Line ESI-MS Profiling and Semi-Preparative Liquid Chromatography

N-Ethyl-2-pyrrolidinone-substituted flavanols (EPSF) are marker compounds for long-term stored white teas. However, due to their low contents and diasteromeric configuration, EPSF compounds are challenging to isolate. In this study, two representative epimeric EPSF compounds, 5′′′R- and 5′′′S-epigallocatechin gallate-8-C N-ethyl-2-pyrrolidinone (R-EGCG-cThea and S-EGCG-cThea), were isolated from white tea using centrifugal partition chromatography (CPC). Two different biphasic solvent systems composed of 1. N-hexane-ethyl acetate-methanol-water (1:5:1:5, v/v/v/v) and 2. N-hexane-ethyl acetate-acetonitrile-water (0.7:3.0:1.3:5.0, v/v/v/v) were used for independent pre-fractionation experiments; 500 mg in each separation of white tea ethyl acetate partition were fractionated. The suitability of the two solvent systems was pre-evaluated by electrospray mass-spectrometry (ESI-MS/MS) analysis for metabolite distribution and compared to the results of the CPC experimental data using specific metabolite partition ratio K_D values, selectivity factors α, and resolution factors R_S. After size-exclusion and semi-preparative reversed-phase liquid chromatography, 6.4 mg of R-EGCG-cThea and 2.9 mg of S-EGCG-cThea were recovered with purities over 95%. Further bioactivity evaluation showed that R- and S-EGCG-cThea possessed in vitro inhibition effects on α-glucosidase with IC₅₀ of 70.3 and 161.7 μM, respectively.     

Scale-Up Preparation of Crocins I and II from Gardenia jasminoides by a Two-Step Chromatographic Approach and Their Inhibitory Activity Against ATP Citrate Lyase

Crocins are highly valuable natural compounds for treating human disorders, and they are also high-end spices and colorants in the food industry. Due to the limitation of obtaining this type of highly polar compound, the commercial prices of crocins I and II are expensive. In this study, macroporous resin column chromatography combined with high-speed counter-current chromatography (HSCCC) was used to purify crocins I and II from natural sources. With only two chromatographic steps, both compounds were simultaneously isolated from the dry fruit of Gardenia jasminoides, which is a cheap herbal medicine distributed in a number of countries. In an effort to shorten the isolation time and reduce solvent usage, forward and reverse rotations were successively utilized in the HSCCC isolation procedure. Crocins I and II were simultaneously obtained from a herbal resource with high recoveries of 0.5% and 0.1%, respectively, and high purities of 98.7% and 99.1%, respectively, by HPLC analysis. The optimized preparation method was proven to be highly efficient, convenient, and cost-effective. Crocins I and II exhibited inhibitory activity against ATP citrate lyase, and their IC₅₀ values were determined to be 36.3 ± 6.24 and 29.7 ± 7.41 μM, respectively.     

Simultaneous Isolation and Purification of Mollugin and Two Anthraquinones from Rubia cordifolia by HSCCC

A preparative high-speed countercurrent chromatography (HSCCC) method for isolation and purification of three bioactive components, tectoquinone; 1-hydroxy-2-methylanthraquinone and mollugin from the Chinese medicinal plant Rubia cordifolia was successfully established. With a two-phase solvent system composed of light petroleum/ethanol/diethyl ether/water (5:4:3:1, v/v), 10 mg tectoquinone, 19 mg 1-hydroxy-2-methylanthraquinone and 16 mg mollugin were obtained from 100 mg of the crude petroleum extract in a one-step separation at a purity of 98.8, 95.8 and 98.3%, respectively. The structures of mollugin and anthraquinones were identified by ¹H NMR and ¹³C NMR.     

Separation and Purification of Baishouwubenzophenone, 4-Hydroxyacetophenone and 2,4-Dihydroxyacetophenone from Cynanchum auriculatum Royle ex Wight by HSCCC

A preparative high-speed counter-current chromatography method for isolation and purification of three acetophenones, baishouwubenzophenone, 4-hydroxyacetophenone and 2,4-dihydroxyacetophenone from the Chinese medicinal plant Cynanchum auriculatum Royle ex Wight was successfully established. With a two-phase solvent system composed of light petroleum (b.p. 60–90 °C)–ethyl acetate–methanol–water (4:9:6:6, v/v), about 20.2 mg compound 1, 35.0 mg compound 2 and 8.3 mg compound 3, each at over 95% purity as determined by LC, were obtained in one-step elution from 400 mg of the ethanol extract. The structures of these compounds were identified by UV, IR, ESI-MS, ¹H NMR and ¹³C NMR spectroscopy. Among them, compounds 2,4-dihydroxyacetophenone and 4-hydroxyacetophenone were obtained from C. auriculatum for the first time.     

Elucidation of Antioxidant Compounds in Moroccan Chamaerops humilis L. Fruits by GC–MS and HPLC–MS Techniques

The aim of this study was to characterize the phytochemical content as well as the antioxidant ability of the Moroccan species Chamaerops humilis L. Besides crude ethanolic extract, two extracts obtained by sonication using two solvents with increased polarity, namely ethyl acetate (EtOAc) and methanol-water (MeOH-H₂O) 80:20 (v/v), were investigated by both spectroscopy and chromatography methods. Between the two extracts, the MeOH-H₂O one showed the highest total polyphenolic content equal to 32.7 ± 0.1 mg GAE/g DM with respect to the EtOAc extract (3.6 ± 0.5 mg GAE/g DM). Concerning the antioxidant activity of the two extracts, the EtOAc one yielded the highest value (1.9 ± 0.1 mg/mL) with respect to MeOH-H2O (0.4 ± 0.1 mg/mL). The C. humilis n-hexane fraction, analyzed by GC–MS, exhibited 69 compounds belonging to different chemical classes, with n-Hexadecanoic acid as a major compound (21.75%), whereas the polyphenolic profile, elucidated by HPLC–PDA/MS, led to the identification of a total of sixteen and thirteen different compounds in both EtOAc (major component: ferulic acid: 104.7 ± 2.52 µg/g) and MeOH-H₂O extracts (major component: chlorogenic acid: 45.4 ± 1.59 µg/g), respectively. The attained results clearly highlight the potential of C. humilis as an important source of bioactive components, making it a valuable candidate to be advantageously added to the daily diet. Furthermore, this study provides the scientific basis for the exploitation of the Doum in the food, pharmaceutical and nutraceutical industries.     

High-Speed Counter-Current Chromatography Combined with Column Chromatography for Isolation of Methyllycaconitine from Delphinium pseudocyanthum

Preparative high-speed counter-current chromatography (HSCCC) combined with conventional column chromatography (CC) has been used for isolation and purification of methyllycaconitine from Delphinium pseudocyanthum. n-Hexane-ethyl acetate-methanol-water, 1:1:1:2 (v/v), was used as the solvent system for HSCCC. Separation of methyllycaconitine from an HSCCC fraction was successfully achieved by CC on silica gel using chloroform-methanol, 7:1 (v/v), as mobile phase. A total of 113.45 mg methyllycaconitine of purity >95% was obtained from 1.044 g extract of D. pseudocyanthum. Its structure was identified by MS and NMR.     

Strongly Basic Anion Exchange Resin Based on a Cross-Linked Polyacrylate for Simultaneous C.I. Acid Green 16, Zn(II), Cu(II), Ni(II) and Phenol Removal

The adsorption ability of Lewatit S5528 (S5528) resin for C.I. Acid Green 16 (AG16), heavy metals (Zn(II), Cu(II) and Ni(II)) and phenol removal from single-component aqueous solutions is presented in this study to assess its suitability for wastewater treatment. Kinetic and equilibrium studies were carried out in order to determine adsorption capacities, taking into account phase contact time, adsorbates’ initial concentration, and auxiliary presence (NaCl, Na₂SO₄, anionic (SDS) and non-ionic (Triton X100) surfactants). The pseudo-second-order kinetic model described experimental data better than pseudo-first-order or intraparticle diffusion models. The adsorption of AG16 (538 mg/g), phenol (14.5 mg/g) and Cu(II) (5.8 mg/g) followed the Langmuir isotherm equation, while the uptake of Zn(II) (0.179 mg^1−1/nL^1/n/g) and Ni(II) (0.048 mg^1−1/nL^1/n/g) was better described by the Freundlich model. The auxiliary’s presence significantly reduced AG16 removal efficiency, whereas in the case of heavy metals the changes were negligible. The column studies proved the good adsorption ability of Lewatit S5528 towards AG16 and Zn(II). The desorption was the most effective for AG16 (>90% of dye was eluted using 1 mol/L HCl + 50% v/v MeOH and 1 mol/L NaCl + 50% v/v MeOH solutions).     

Preparative Isolation and Purification of Flavonoids and Protocatechuic Acid from Sea Buckthorn Juice Concentrate (Hippophaë rhamnoides L. ssp. rhamnoides) by High-Speed Counter-Current Chromatography

High-speed counter-current chromatography (HSCCC)—a support free all liquid–liquid chromatography technique—has been successfully used for the preparative isolation of isorhamnetin 3-O-β-d-glucoside, isorhamnetin 3-O-β-rutinoside, quercetin 3-O-β-d-glucoside, syringetin 3-O-β-d-glucoside and protocatechuic acid from sea buckthorn juice concentrate (Hippophaë rhamnoides L. ssp. rhamnoides, Elaeagnaceae). The preparative HSCCC instrument was a multilayer coil planet centrifuge equipped with three preparative coils. Separation was performed with a two phase solvent system (n-hexane–n-butanol–water, 1:1:2 v/v/v) in ‘head-to-tail’ mode. Each injection of 4.1 g crude ethyl acetate extract yielded isorhamnetin 3-O-β-d-glucoside (95 mg), isorhamnetin 3-O-β-rutinoside (10 mg), quercetin 3-O-β-d-glucoside (5 mg), and protocatechuic acid (34 mg) with purities >98%. The flavonoid syringetin 3-O-β-d-glucoside (2 mg) was a novel compound for H. rhamnoides. Chemical structures of all compounds were determined by HPLC–ESI–MS–MS, 1D-NMR (¹H, ¹³C, DEPT 135) spectroscopy and for elucidation of glycosidic linkages 2D-NMR (HMBC) spectroscopy was used.     

Pyrene-Benzimidazole Derivatives as Novel Blue Emitters for OLEDs

Three novel small organic heterocyclic compounds: 2-(1,2-diphenyl)-1H-benzimidazole-7-tert-butylpyrene (compound A), 1,3-di(1,2-diphenyl)-1H-benzimidazole-7-tert-butylpyrene (compound B), and 1,3,6,8-tetra(1,2-diphenyl)-1H-benzimidazolepyrene (compound C) were synthesized and characterized for possible applications as blue OLED emitters. The specific molecular design targeted decreasing intermolecular aggregation and disrupting crystallinity in the solid-state, in order to reduce dye aggregation, and thus obtain efficient pure blue photo- and electroluminescence. Accordingly, the new compounds displayed reasonably high spectral purity in both solution- and solid-states with average CIE coordinates of (0.160 ± 0.005, 0.029 ± 0.009) in solution and (0.152 ± 0.007, 0.126 ± 0.005) in solid-state. These compounds showed a systematic decrease in degree of crystallinity and intermolecular aggregation due to increasing steric hindrance, as revealed using powder X-ray diffraction analysis and spectroscopic studies. An organic light-emitting diode (OLED) prototype fabricated using compound B as the non-doped emissive layer displayed an external quantum efficiency (EQE) of 0.35 (±0.04)% and luminance 100 (±6) cd m⁻² at 5.5 V with an essentially pure blue electroluminescence corresponding to CIE coordinates of (0.1482, 0.1300). The highest EQE observed from this OLED prototype was 4.3 (±0.3)% at 3.5 V, and the highest luminance of 290 (±10) cd m⁻² at 7.5 V. These values were found comparable to characteristics of the best pure blue OLED devices based on simple fluorescent small-molecule organic chromophores.     

Separation and Purification of Three Flavonoids from Helichrysum arenarium (L.) Moench by HSCCC

Following an initial clean-up step on a Sephadex LH-20 column, high-speed countercurrent chromatography was successfully applied to the isolation and purification of three flavonoids from a crude sample of Helichrysum arenarium (L.) Moench. HSCCC was performed with a two-phase solvent system composed of ethyl acetate–water (1:1, v/v). Naringenin-7-O-β-d-glycoside (2.3 mg), isoquercitrin (3.5 mg), and astragalin (6.7 mg), with purities of 96.05%, 93.63%, 95.23%, respectively, were separated from 160 mg of crude sample in a one-step separation. The structure identification was by ¹H NMR and ¹³C NMR.     

Structural Relevance of Intramolecular H-Bonding in Ortho-Hydroxyaryl Schiff Bases: The Case of 3-(5-bromo-2-hydroxybenzylideneamino) Phenol

A new Schiff base compound, 3-(5-bromo-2-hydroxybenzylideneamino)phenol (abbreviated as BHAP) was synthesized and characterized by ¹H- and ¹³C- nuclear magnetic resonance and infrared spectroscopies. DFT/B3LYP/6-311++G(d,p) calculations were undertaken in order to explore the conformational space of both the E- and Z- geometrical isomers of the enol-imine and keto-amine tautomers of the compound. Optimized geometries and relative energies were obtained, and it was shown that the most stable species is the E-enol-imine form, which may exist in four low-energy intramolecularly hydrogen-bonded forms (I, II, V, and VI) that are almost isoenergetic. These conformers were concluded to exist in the gas phase equilibrium with nearly equal populations. On the other hand, the infrared spectra of the compound isolated in a cryogenic argon matrix (10 K) are compatible with the presence in the matrix of only two of these conformers (conformers II and V), while conformers I and VI convert to these ones by quantum mechanical tunneling through the barrier associated with the rotation of the OH phenolic group around the C–O bond. The matrix isolation infrared spectrum was then assigned and interpreted with help of the DFT(B3LYP)/6-311++G(d,p) calculated infrared spectra for conformers II and V. In addition, natural bond orbital (NBO) analysis was performed on the most stable conformer of the experimentally relevant isomeric form (E-enol-imino conformer V) to shed light on details of its electronic structure. This investigation stresses the fundamental structural relevance of the O–H···N intramolecular H-bond in o-hydroxyaryl Schiff base compounds.     

Validation of the Antioxidant and Enzyme Inhibitory Potential of Selected Triterpenes Using In Vitro and In Silico Studies,and the Evaluation of Their ADMET Properties

The antioxidant and enzyme inhibitory potential of fifteen cycloartane-type triterpenes’ potentials were investigated using different assays. In the phosphomolybdenum method, cycloalpioside D (6) (4.05 mmol TEs/g) showed the highest activity. In 1,1-diphenyl-2-picrylhydrazyl (DPPH*) radical and 2,2′-azino-bis(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS) cation radical scavenging assays, cycloorbicoside A-7-monoacetate (2) (5.03 mg TE/g) and cycloorbicoside B (10) (10.60 mg TE/g) displayed the highest activities, respectively. Oleanolic acid (14) (51.45 mg TE/g) and 3-O-β-d-xylopyranoside-(23R,24S)-16β,23;16α,24-diepoxycycloart-25(26)-en-3β,7β-diol 7-monoacetate (4) (13.25 mg TE/g) revealed the highest reducing power in cupric ion-reducing activity (CUPRAC) and ferric-reducing antioxidant power (FRAP) assays, respectively. In metal-chelating activity on ferrous ions, compound 2 displayed the highest activity estimated by 41.00 mg EDTAE/g (EDTA equivalents/g). The tested triterpenes showed promising AChE and BChE inhibitory potential with 3-O-β-d-xylopyranoside-(23R,24S)-16β,23;16α,24-diepoxycycloart-25(26)-en-3β,7β-diol 2′,3′,4′,7-tetraacetate (3), exhibiting the highest inhibitory activity as estimated from 5.64 and 5.19 mg GALAE/g (galantamine equivalent/g), respectively. Compound 2 displayed the most potent tyrosinase inhibitory activity (113.24 mg KAE/g (mg kojic acid equivalent/g)). Regarding α-amylase and α-glucosidase inhibition, 3-O-β-d-xylopyranoside-(23R,24S)-16β,23;16α,24-diepoxycycloart-25(26)-en-3β,7β-diol (5) (0.55 mmol ACAE/g) and compound 3 (25.18 mmol ACAE/g) exerted the highest activities, respectively. In silico studies focused on compounds 2, 6, and 7 as inhibitors of tyrosinase revealed that compound 2 displayed a good ranking score (−7.069 kcal/mole) and also that the ΔG free-binding energy was the highest among the three selected compounds. From the ADMET/TOPKAT prediction, it can be concluded that compounds 4 and 5 displayed the best pharmacokinetic and pharmacodynamic behavior, with considerable activity in most of the examined assays.     

Antileishmanial Effects of Acetylene Acetogenins from Seeds of Porcelia macrocarpa (Warm.) R.E. Fries (Annonaceae) and Semisynthetic Derivatives

As part of our continuous studies involving the prospection of natural products from Brazilian flora aiming at the discovery of prototypes for the development of new antiparasitic drugs, the present study describes the isolation of two natural acetylene acetogenins, (2S,3R,4R)-3-hydroxy-4-methyl-2-(n-eicos-11′-yn-19′-enyl)butanolide (1) and (2S,3R,4R)-3-hydroxy-4-methyl-2-(n-eicos-11′-ynyl)butanolide (2), from the seeds of Porcelia macrocarpa (Warm.) R.E. Fries (Annonaceae). Using an ex-vivo assay, compound 1 showed an IC₅₀ value of 29.9 μM against the intracellular amastigote forms of Leishmania (L.) infantum, whereas compound 2 was inactive. These results suggested that the terminal double bond plays an important role in the activity. This effect was also observed for the semisynthetic acetylated (1a and 2a) and eliminated (1b and 2b) derivatives, since only compounds containing a double bond at C-19 displayed activity, resulting in IC₅₀ values of 43.3 μM (1a) and 23.1 μM (1b). In order to evaluate the effect of the triple bond in the antileishmanial potential, the mixture of compounds 1 + 2 was subjected to catalytic hydrogenation to afford a compound 3 containing a saturated side chain. The antiparasitic assays performed with compound 3, acetylated (3a), and eliminated (3b) derivatives confirmed the lack of activity. Furthermore, an in-silico study using the SwissADME online platform was performed to bioactive compounds 1, 1a, and 1b in order to investigate their physicochemical parameters, pharmacokinetics, and drug-likeness. Despite the reduced effect against amastigote forms of the parasite to the purified compounds, different mixtures of compounds 1 + 2, 1a + 2a, and 1b + 2b were prepared and exhibited IC₅₀ values ranging from 7.9 to 38.4 μM, with no toxicity for NCTC mammalian cells (CC₅₀ > 200 μM). Selectivity indexes to these mixtures ranged from >5.2 to >25.3. The obtained results indicate that seeds of Porcelia macrocarpa are a promising source of interesting prototypes for further modifications aiming at the discovery of new antileishmanial drugs.     

Coordination Chemistry of a Bis(Tetrazine) Tweezer: A Case of Host-Guest Behavior with Silver Salts

The carbon-carbon cross-coupling of phenyl s-tetrazine (Tz) units at their ortho-phenyl positions allows the formation of constrained bis(tetrazines) with original tweezer structures. In these compounds, the face-to-face positioning of the central tetrazine cores is reinforced by π-stacking of the electron-poor nitrogen-containing heteroaromatic moieties. The resulting tetra-aromatic structure can be used as a weak coordinating ligand with cationic silver. This coordination generates a set of bis(tetrazine)-silver(I) coordination complexes tolerating a large variety of counter anions of various geometries, namely, PF₆⁻, BF₄⁻, SbF₆⁻, ClO₄⁻, NTf₂⁻, and OTf⁻. These compounds were characterized in the solid state by single-crystal X-ray diffraction (XRD) and diffuse reflectance spectroscopy, and in solution by ¹H-NMR, mass spectrometry, electroanalysis, and UV-visible absorption spectrophotometry. The X-ray crystal structure of complexes {[Ag(3)][PF₆]}_∞ (4) and {[Ag(3)][SbF₆]}_∞ (6), where 3 is 3,3′-[(1,1′-biphenyl)-2,2′-diyl]-6,6′-bis(phenyl)-1,2,4,5-tetrazine, revealed the formation of 1D polymeric chains, characterized by an evolution to a large opening of the original tweezer and a coordination of silver(I) via two chelating nitrogen atom and some C=C π-interactions. Electrochemical and UV spectroscopic properties of the original tweezer and of the corresponding silver complexes are reported and compared. ¹H-NMR titrations with AgNTf₂ allowed the determination of the stoichiometry and apparent stability of two solution species, namely [Ag(3)]⁺ and [Ag(3)₂]²⁺, that formed in CDCl₃/CD₃OD 2:1 v/v mixtures.     

Synthesis and biological evaluation of new pyrazolebenzene-sulphonamides as potential anticancer agents and hCA I and II inhibitors

Cancer is a disease characterized by the continuous growth of cells without adherence to the rules that healthy normal cells obey. Carbonic anhydrase I and II (CA I and CA II) inhibitors are used for the treatment of some diseases. The available drugs in the market have limitations or side effects, which bring about the need to develop new drug candidate compound(s) to overcome the problems at issue. In this study, new pyrazole-sulphonamide hybrid compounds 4-[5-(1,3-benzodioxol-5-yl)-3-aryl-4,5-dihydro-1 H -pyrazol-1-yl]benzenesulphonamides (4a - 4j) were designed to discover new drug candidate compounds. The compounds 4a - 4j were synthesized and their chemical structures were confirmed using spectral techniques. The hypothesis tested was whether an introduction of methoxy and polymethoxy group(s) lead to an increased potency selectivity expression (PSE) value of the compound, which reflects cytotoxicity and selectivity of the compounds. The cytotoxicity of the compounds towards tumor cell lines were in the range of 6.7 – 400 µM. The compounds 4i (PSE₂ = 461.5) and 4g (PSE₁ = 193.2) had the highest PSE values in cytotoxicity assays. Ki values of the compounds were in the range of 59.8 ± 3.0 - 12.7 ± 1.7 nM towards hCA I and in the range of 24.1 ± 7.1 - 6.9 ± 1.5 nM towards hCA II. While the compounds 4b, 4f, 4g, and 4i showed promising cytotoxic effects, the compounds 4c and 4g had the inhibitory potency towards hCA I and hCA II, respectively. These compounds can be considered as lead compounds for further research.     

Preparative Isolation of Imperatorin, Oxypeucedanin and Isoimperatorin from a Traditional Chinese Herb Using a HSCCC Strategy Based on Optimization of Rapid Flow Rate

Preparative high-speed counter-current chromatography has been used successfully for the isolation and purification of imperatorin, oxypeucedanin and isoimperatorin from traditional Chinese herb “bai zhi”—Angelica dahurica (Fisch. ex Hoffm) Benth. et Hook using high-speed counter-current chromatography (HSCCC). This was achieved in two stages. The first stage used a high flow HSCCC protocol with a two-phase solvent system composed of n-hexane–ethyl acetate–methanol–water (HEMW) with volume ratios of 5:5:5:5, v/v which isolated isoimperatorin but co-eluted imperatorin and oxypeucedanin. The second stage used HEMW 5:5:4:6, v/v at low flow rate to resolve the co-eluted components from the first stage. The flow rate was optimized by preparative HSCCC. 300 mg of the crude extract was separated, yielding 18.5 mg of imperatorin, 8.3 mg of oxypeucedanin and 9.8 mg of isoimperatorin all at a high purity of over 98%.     

Synthesis and structures of nickel(II) and copper(II) compounds of 5,5,7,13-tetramethyl-13-nitro-1,4,8,11-tetraazacyclotetradecane and the 13-ethyl-5,5,7-trimethyl-homologue

Reduction by NaBH₄ of the imine functions of (5,7,7,13-tetramethyl-13-nitro-1,4,8,11-tetraazacyclotetradec-4-ene)-nickel(II) and -copper(II), and of their 13-ethyl-5,7,7-trimethyl-homologues, yield the nitro-substituted cyclic tetraamine cations (5,5,7,13-tetramethyl-13-nitro-1,4,8,11-tetraazacyclotetradecane)-nickel(II) and -copper(II), [M(neh)]²⁺, and (13-ethyl-5,5,7-trimethyl-homologues, [M(nph)]²⁺, respectively. The nickel(II) cations form square–planar, singlet ground, state salts with poorly coordinating anions and octahedral, triplet ground state, compounds with additional ligands, trans-β-[Ni(neh)A₂], A⁻ = Cl⁻, NCS⁻ and trans-β-[Ni(neh)A₂](ClO₄)₂, X = NH₃, MeCN, all with nitrogen configuration III, 1R,4R,8S,11S = β. With oxalate the chain-polymeric compound catena-trans-β-[Ni(neh)(μ-C₂O₄)]_n · 3n(H₂O) is formed. Folded macrocycle compounds cis-α-[Ni(neh)(C₅H₇O₂)]ClO₄ and cis-α-[{Ni(neh)}₂(C₂O₄)](ClO₄)₂ are formed with the chelates acetylacetonate and oxalate, with configuration 1R,4R,8R,11R = α. These react with HClO₄ to form metastable α-[Ni(neh)](ClO₄)₂ with retention of configuration. The copper(II) cations form crimson salts with poorly coordinating anions and compounds of the type β-[Cu(neh)A]ClO₄ of varying shades of blue with coordinating anions. Structures of singlet ground state square–planar nickel(II) compounds β-[Ni(neh)](ClO₄)₂ · H₂O, β-[Ni(neh)](ClO₄)₂, β-[Ni(neh)]₂[ZnCl₃(OH₂)]₂[ZnCl₄] · H₂O and α-[Ni(neh)](ClO₄)₂, the triplet ground state chain-polymeric compound catena-trans-β-[Ni(neh)(μ-C₂O₄)]_n · 3n(H₂O) and of square–pyramidal β-[Cu(nph)Cl]ClO₄ are reported.     

Synthesis,Antibacterial, and Antioxidant Evaluation of Novel Series of Condensed Thiazoloquinazoline with Pyrido,Pyrano, and Benzol Moieties as Five- and Six-Membered Heterocycle Derivatives

A novel synthesis of thiazolo[2,3-b]quinazolines 4(a–e), pyrido[2′,3′:4,5]thiazolo[2,3-b]quinazolines {5(a–e), 6(a–e), and 7(a–e)}, pyrano[2′,3′:4,5]thiazolo[2,3-b]quinazolines 8(a–e), and benzo[4,5]thiazolo[2,3-b]quinazoloine9(a–e) derivatives starting from 2-(Bis-methylsulfanyl-methylene)-5,5-dimethyl-cyclohexane-1,3-dione 2 as efficient α,α dioxoketen dithioacetal is reported and the synthetic approaches of these types of compounds will provide an innovative molecular framework to the designing of new active heterocyclic compounds. In our study, we also present optimization of the synthetic method along with a biological evaluation of these newly synthesized compounds as antioxidants and antibacterial agents against the bacterial strains, like S. aureus, E. coli, and P. aeruginosa. Among all the evaluated compounds, it was found that some showed significant antioxidant activity at 10 μg/mL while the others exhibited better antibacterial activity at 100 μg/mL. The results of this study showed that compound 6(c) possessed remarkable antibacterial activity, whereas compound 9(c) exhibited the highest efficacy as an antioxidant. The structures of the new synthetic compounds were elucidated by elemental analysis, IR, ¹H-NMR, and ¹³C-NMR.