Solanidine isolation from Solanum tuberosum by centrifugal partition chromatography

The aim of this investigation was the preparative isolation of solanidine (aglycone of the two main potato glycoalkaloids: α‐chaconine and α‐solanine) from fresh Solanum tuberosum (cv. Pompadour) material by implementing a new preparation scheme using centrifugal partition chromatography (CPC). A setup for obtaining solanidine by hydrolysis of the glycoalkaloids found in the skin and sprouts of S. tuberosum was first developed. Then its isolation was carried out by the development of CPC conditions: the solvent system used for separation was ethyl acetate/butanol/water in the ratio 42.5:7.5:50 v/v/v, 0.6 g of crude extract were separated with a 8 mL/min flow rate of mobile phase while rotating at 2500 rpm. A run yielded 98 mg of solanidine (86.7 % recovery from the crude extract) in a one‐step separation. The purity of the isolated solanidine was over 98%. Thus, CPC has proven to be the method of choice to get solanidine of very high purity from S. tuberosum biomass in large quantities.     

Methylene Blue as a Photosensitizer and Redox Agent: Synthesis of 5‐Hydroxy‐1H‐pyrrol‐2(5H)‐ones from Furans

A highly efficient and general singlet‐oxygen‐initiated one‐pot transformation of readily accessible furans into 5‐hydroxy‐1H‐pyrrol‐2(5H)‐ones has been developed. The methodology was extended to the synthesis of other high‐value α,β‐unsaturated γ‐lactams. This useful set of transformations relies not only on the photosensitizing ability of methylene blue, but also on its redox properties: properties that have until now been virtually ignored in a synthetic context.     

Phosphoryl group differentiating α‐amino acids from β‐ and γ‐amino acids in prebiotic peptide formation

In recent years β‐amino acids have increased their importance enormously in defining secondary structures of β‐peptides. Interest in β‐amino acids raises the question: Why and how did nature choose α‐amino acids for the central role in life? In this article we present experimental results of MS and ³¹P NMR methods on the chemical behavior of N‐phosphorylated α‐alanine, β‐alanine, and γ‐amino butyric acid in different solvents. N‐Phosphoryl α‐alanine can self‐assemble to N‐phosphopeptides either in water or in organic solvents, while no assembly was observed for β‐ or γ‐amino acids. An intramolecular carboxylic–phosphoric mixed anhydride (IMCPA) is the key structure responsible for their chemical behaviors. Relative energies and solvent effects of three isomers of IMCPA derived from α‐alanine (2a–c), with five‐membered ring, and five isomers of IMCPA derived from β‐alanine (4a–e), with six‐membered ring, were calculated with density functional theory at the B3LYP/6‐31G** level. The lower relative energy (3.2 kcal/mol in water) of 2b and lower energy barrier for its formation (16.7 kcal/mol in water) are responsible for the peptide formation from N‐phosphoryl α‐alanine. Both experimental and theoretical studies indicate that the structural difference among α‐, β‐, and γ‐amino acids can be recognized by formation of IMCPA after N‐phosphorylation. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem 94: 232–241, 2003     

Studies on the Mass Spectra of N‐Aryl α,β‐Unsaturated γ‐Lactams

The mass spectra of a series of N‐aryl α,β‐unsaturated γ‐lactams were studied. Besides the molecular ion, the three characteristic fragments such as [M⁺‐29], [M⁺‐55], and [M⁺‐82] were commonly found in a series of N‐Aryl α,β‐unsaturated γ‐lactams in EI/MS. Further more the mechanism for the interpretation of these fragments is also de scribed.     

Development and validation of an ultra high‐performance liquid chromatographic method for the determination of a diastereomeric impurity in (+)‐pinoresinol diglucoside chemical reference substance

(+)‐Pinoresinol 4,4′‐di‐O‐β‐D ‐glucopyranoside ((+)‐PDG) is one of the major lignans with various pharmacological activities which could be isolated from Duzhong and other plant species. In this study, a diastereomeric impurity, (?)‐pinoresinol 4,4′‐di‐O‐β‐D ‐glucopyranoside ((?)‐PDG), the main impurity was identified in (+)‐PDG chemical reference substance (CRS) and a reliable chromatographic method for rapid purity determination of (+)‐PDG CRS was firstly developed. The optimal chromatographic condition was found to be using ACN/1,4‐dioxane–water (2.5:6:91.5, v/v/v) as mobile phase on a Waters Acquity UPLC HSS T3 column (2.1 mm×100 mm, 1.8 μm) with column temperature of 37°C. The method was validated and applied to determine the chromatographic purity of five (+)‐PDG CRS samples. The content of (?)‐PDG in four commercial (+)‐PDG CRS was 8.47–20.30%, whereas no (?)‐PDG was detected in our in‐house prepared (+)‐PDG CRS in which purity was confirmed to be 99.80%. The above results confirmed that this method is fast and highly efficient for purity determination of the (+)‐PDG CRS.     

An efficient strategy for the extraction and purification of lignans from Schisandra chinensis by a combination of supercritical fluid extraction and high‐speed counter‐current chromatography

An efficient strategy for extracting and separating five lignans from Schisandra chinensis (Turcz.) Baill has been developed using supercritical fluid extraction (SFE) and high‐speed counter‐current chromatography (HSCCC) in the present study. First, the extraction was performed by a preparative SFE system under 15 MPa of pressure at 36°C for 4 h. Then, the SFE extract was successfully separated and purified by HSCCC with a two‐phase solvent system composed of n‐hexane/ethyl acetate/methanol/water (6:4:5:5, 6:4:6:4, 6:4:8:2, v/v) in a stepwise elution mode. The fractions were analyzed by HPLC, and the chemical structures of the products were identified by ESI‐MS and ¹H NMR spectroscopy. As a result, a total of 12.5 mg of schisandrin at 98.0% purity, 7.1 mg of gomisin A at 98.1% purity, 1.8 mg of schisantherin B at 93.3% purity, 4.4 mg of deoxyschisandrin at 92.9% purity, and 6.8 mg of γ‐schisandrin at 89.1% purity were obtained from 300 mg crude extract in a one‐step purification.     

Enantioselective Syntheses of Substituted γ‐Butyrolactones

The previously described chiral 2‐acyloxathianes 5 (Scheme I) are used in two different enantioselective syntheses of γ‐butyrolactones. In one synthesis, Grignard addition, cleavage and reduction to carbinols RR'C(OH)CH₂OH is followed by tosylation, malonate homologation, lactonization, and removal of the carbomethoxy group to give optically active γ‐lactones. A modification of this synthesis (Scheme I) leads to optically active α‐methylene‐γ‐lactones. In the second synthesis, reaction of a bromomagnesium enolate with ketones 5 leads to β‐hydroxyesters, which, by appropriate sequences of reduction and cleavage (Scheme II) are converted to optically active α‐ or β‐hydroxy‐γ‐lactones.     

A New Route to N‐Aryl 2‐Alkenamides,N‐Allyl N‐Aryl 2‐Alkenamides,and N‐Aryl α,β‐Unsaturated γ‐Lactams from N‐Aryl 3‐(Phenylsulfonyl)propanamides

A series of N‐aryl 2‐alkenamides were produced efficiently by treating N‐aryl 3‐(phenylsulfonyl)‐propanamides with potassium tert‐butoxide in THF at 0°C. With out isolation, it was further treated with an additional equivalent of potassium tert‐butoxide and allyl bromide to give N‐allyl N‐aryl 2‐alkenamides in one pot in good yields. Followed by a ring‐closing metathesis reaction, these N‐allyl N‐aryl 2‐alkenamides were respectively converted into corresponding N‐aryl α,β‐unsaturated γ‐lactams in moderate yields.     

Cu(II) immobilized on guanidinated epibromohydrin‐functionalized γ‐Fe2O3@TiO2 (γ‐Fe2O3@TiO2‐EG‐Cu(II)): A highly efficient magnetically separable heterogeneous nanocatalyst for one‐pot synthesis of highly substituted imidazoles

A simple, efficient and eco‐friendly procedure has been developed using Cu(II) immobilized on guanidinated epibromohydrin‐functionalized γ‐Fe₂O₃@TiO₂ (γ‐Fe₂O₃@TiO₂‐EG‐Cu(II)) for the synthesis of 2,4,5‐trisubstituted and 1,2,4,5‐tetrasubstituted imidazoles, via the condensation reactions of various aldehydes with benzil and ammonium acetate or ammonium acetate and amines, under solvent‐free conditions. High‐resolution transmission electron microscopy analysis of this catalyst clearly affirmed the formation of a γ‐Fe₂O₃ core and a TiO₂ shell, with mean sizes of about 10–20 and 5–10 nm, respectively. These data were in very good agreement with X‐ray crystallographic measurements (13 and 7 nm). Moreover, magnetization measurements revealed that both γ‐Fe₂O₃@TiO₂ and γ‐Fe₂O₃@TiO₂‐EG‐Cu(II) had superparamagnetic behaviour with saturation magnetization of 23.79 and 22.12 emu g^?1, respectively. γ‐Fe₂O₃@TiO₂‐EG‐Cu(II) was found to be a green and highly efficient nanocatalyst, which could be easily handled, recovered and reused several times without significant loss of its activity. The scope of the presented methodology is quite broad; a variety of aldehydes as well as amines have been shown to be viable substrates. A mechanism for the cyclocondensation reaction has also been proposed.     

Preparative separation of bioactive compounds from essential oil of Flaveria bidentis (L.) Kuntze using steam distillation extraction and one step high‐speed counter‐current chromatography

In order to utilize and control the invasive weed, bioactive compounds from essential oil of Flaveria bidentis (L.) Kuntze were studied. Steam distillation extraction and one step high‐speed counter‐current chromatography were applied to separate and purify the caryophyllene oxide, 7,11‐dimethyl‐3‐methylene‐1,6,10‐dodecatriene, and caryophyllene from essential oil of Flaveria bidentis (L.) Kuntze. The two‐phase solvent system containing n‐hexane/acetonitrile/ethanol (5:4:3, v/v/v) was selected for the one step separation mode according to the partition coefficient values (K) of the target compounds and the separation factor (α). The purity of each isolated fraction after a single high‐speed counter‐current chromatography run was determined by high performance liquid chromatography. A 3.2 mg of caryophyllene oxide at a purity of 92.6%, 10.4 mg of 7,11‐dimethyl‐3‐methylene‐1,6,10‐dodecatriene at a purity of 99.1% and 5.7 mg of caryophyllene at a purity of 98.8% were obtained from 200 mg essential oil of Flaveria bidentis (L.) Kuntze. The chemical structures of these components were identified by GC‐MS, ¹H‐NMR, and ¹³C‐NMR.     

Separations of antifungal compounds in capillary electrophoresis with two anionic cyclodextrins

CD‐CZE methods were developed for complete stereoisomeric separations of a series of six γ‐lactam analogues, of which some were neutral, or cationic depending on the background electrolyte nature. The tested cyclodextrin was the versatile sulfobutylether‐ β‐CD, used either in a phosphate buffer using capillaries dynamically coated with polyethylene oxide or in a borate buffer using uncoated capillaries. Long‐end and short‐end modes and concentration variations of chiral selectors allowed finding conditions of complete separation of four out of the six derivatives (i.e., 1 , 2 , 3, and 4 ) in short run times, confirming their broad range of applications. To separate the two last compounds, the highly sulfated‐ γ‐CD was examined as chiral selector in acidic phosphate conditions. The enantiomers of the γ‐lactam analogues 5 and 6 were baseline resolved with 5.5 and 4%, respectively as concentration in the buffer.     

Chemical synthesis of poly‐γ‐glutamic acid by polycondensation of γ‐glutamic acid dimer: Synthesis and reaction of poly‐γ‐glutamic acid methyl ester

α‐Methyl glutamic acid (L ‐L )‐, (L ‐D )‐, (D ‐L )‐, and (D ‐D )‐γ‐dimers were synthesized from L ‐ and D ‐glutamic acids, and the obtained dimers were subjected to polycondensation with 1‐(3‐dimethylaminopropyl)‐3‐ethylcarbodiimide hydrochloride and 1‐hydroxybenzotriazole hydrate as condensation reagents. Poly‐γ‐glutamic acid (γ‐PGA) methyl ester with the number‐average molecular weights of 5000∼20,000 were obtained by polycondensation in N,N‐dimethylformamide in 44∼91% yields. The polycondensation of (L ‐L )‐ and (D ‐D )‐dimers afforded the polymers with much larger |[α]_D | compared with the corresponding dimers. The polymer could be transformed into γ‐PGA by alkaline hydrolysis or transesterification into α‐benzyl ester followed by hydrogenation. © 2001 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 39: 732–741, 2001     

Preparation and purification of canthinone and β‐carboline alkaloids from Picrasma quassioides based on bioautography and mass‐spectrometry‐directed autopurification system

Picrasma quassioides (D. Don) Benn. is a widely used traditional Chinese medicine for anti‐inflammation and antibiosis. Canthinone and β‐carboline alkaloids are the main characteristic constituents that possess diverse pharmacological effects, such as anti‐inflammatory and anti‐infectious properties. In this study, bioautography in thin‐layer chromatography indicated that the antiradical activity compound may be alkaloids. Then, a simple, fast, and efficient method was established for the separation and purification of two types of alkaloids from P. quassioides by mass‐spectrometry‐directed autopurification system. Eight alkaloids were isolated and purified in this one‐step methodology. Among them, five compounds ( 3 , 95.1%, 58.8 mg; 4 , 98.4%, 71.7 mg; 6 , 97.8%, 365.4 mg; 7 , 97.7%, 172.7 mg; 8 , 98.2%, 180.3 mg) were obtained in large amounts with extremely high purities. Then, the antiradical activities of the isolates showed that 4‐methoxy‐5‐hydroxycanthin‐6‐one ( 6 ) exhibited obvious 1,1‐diphenyl‐2‐picryl‐hydrazyl free radical scavenging activity with an IC₅₀ value of 84.037 μM. This study offers a new method for the preparation of targeted bioactive alkaloids in P. quassioides. This work also provides a reference for the separation of other targeted chemical components with potential activities from traditional Chinese herbal medicines.     

Combinative application of pH‐zone‐refining and conventional high‐speed counter‐current chromatography for preparative separation of caged polyprenylated xanthones from gamboge

An efficient method for the preparative separation of four structurally similar caged xanthones from the crude extracts of gamboge was established, which involves the combination of pH‐zone‐refining counter‐current chromatography and conventional high‐speed counter‐current chromatography for the first time. pH‐zone‐refining counter‐current chromatography was performed with the solvent system composed of n‐hexane/ethyl acetate/methanol/water (7:3:8:2, v/v/v/v), where 0.1% trifluoroacetic acid was added to the upper organic stationary phase as a retainer and 0.03% triethylamine was added to the aqueous mobile phase as an eluter. From 3.157 g of the crude extract, 1.134 g of gambogic acid, 180.5 mg of gambogenic acid and 572.9 mg of a mixture of two other caged polyprenylated xanthones were obtained. The mixture was further separated by conventional high‐speed counter‐current chromatography with a solvent system composed of n‐hexane/ethyl acetate/methanol/water (5:5:10:5, v/v/v/v) and n‐hexane/methyl tert‐butyl ether/acetonitrile/water (8:2:6:4,v/v/v/v), yielding 11.6 mg of isogambogenic acid and 10.4 mg of β‐morellic acid from 218.0 mg of the mixture, respectively. The purities of all four of the compounds were over 95%, as determined by high‐performance liquid chromatography, and the chemical structures of the four compounds were confirmed by electrospray ionization mass spectrometry and NMR spectroscopy. The combinative application of pH‐zone‐refining counter‐current chromatography and conventional high‐speed counter‐current chromatography shows great advantages in isolating and enriching the caged polyprenylated xanthones.     

CoOOH Nanosheets with High Mass Activity for Water Oxidation

Endowing transition‐metal oxide electrocatalysts with high water oxidation activity is greatly desired for production of clean and sustainable chemical fuels. Here, we present an atomically thin cobalt oxyhydroxide (γ‐CoOOH) nanosheet as an efficient electrocatalyst for water oxidation. The 1.4 nm thick γ‐CoOOH nanosheet electrocatalyst can effectively oxidize water with extraordinarily large mass activities of 66.6 A g^?1, 20 times higher than that of γ‐CoOOH bulk and 2.4 times higher than that of the benchmarking IrO₂ electrocatalyst. Experimental characterizations and first‐principles calculations provide solid evidence to the half‐metallic nature of the as‐prepared nanosheets with local structure distortion of the surface CoO_6?x octahedron. This greatly enhances the electrophilicity of H₂O and facilitates the interfacial electron transfer between Co ions and adsorbed ‐OOH species to form O₂, resulting in the high electrocatalytic activity of layered CoOOH for water oxidation.     

Magnetic nanoparticle γ‐Fe2O3‐immobilized 1,5,7‐triazabicyclo[4.4.0]dec‐5‐ene as a highly recyclable and efficient nanocatalyst for the synthesis of α′‐oxindole‐α‐hydroxyphosphonates

Magnetic nanoparticle γ‐Fe₂O₃‐immobilized 1,5,7‐triazabicyclo[4.4.0]dec‐5‐ene as a novel magnetic nanocatalyst was synthesized and characterized. The nanoparticle reagent catalyzed efficiently the synthesis of α′‐oxindole‐α‐hydroxyphosphonates from isatins and dimethyl phosphate under solvent‐free conditions at 60 °C. More importantly, the catalyst could be easily recovered by an external magnet and reused six times without significant loss of activity. Copyright © 2014 John Wiley & Sons, Ltd.     

Synthesis of β‐Substituted γ‐Aminobutyric Acid Derivatives through Enantioselective Photoredox Catalysis

β‐Substituted chiral γ‐aminobutyric acids feature important biological activities and are valuable intermediates for the synthesis of pharmaceuticals. Herein, an efficient catalytic enantioselective approach for the synthesis of β‐substituted γ‐aminobutyric acid derivatives through visible‐light‐induced photocatalyst‐free asymmetric radical conjugate additions is reported. Various β‐substituted γ‐aminobutyric acid analogues, including previously inaccessible derivatives containing fluorinated quaternary stereocenters, were obtained in good yields (42–89 %) and with excellent enantioselectivity (90–97 % ee). Synthetically valuable applications were demonstrated by providing straightforward synthetic access to the pharmaceuticals or related bioactive compounds (S)‐pregabalin, (R)‐baclofen, (R)‐rolipram, and (S)‐nebracetam.     

Preparative and scaled‐up separation of high‐purity α‐linolenic acid from perilla seed oil by conventional and pH‐zone refining counter current chromatography

α‐Linolenic acid is an essential omega‐3 fatty acid needed for human health. However, the isolation of high‐purity α‐linolenic acid from plant resources is challenging. The preparative separation methods of α‐linolenic acid by both conventional and pH‐zone refining counter current chromatography were firstly established in this work. The successful separation of α‐linolenic acid by conventional counter current chromatography was achieved by the optimized solvent system n‐heptane/methanol/ water/acetic acid (10:9:1:0.04, v/v), producing 466 mg of 98.98% α‐linolenic acid from 900 mg free fatty acid sample prepared from perilla seed oil with linoleic acid and oleic acid as by‐products. The scaled‐up separation in 45× is efficient without loss of resolution and extension of separation time. The separation of α‐linolenic acid by pH‐zone refining counter current chromatography was also satisfactory by the solvent system n‐hexane/methanol/water (10:5:5, v/v) and the optimized concentration of trifluoroacetic acid 30 mM and NH₄OH 10 mM. The separation can be scaled up in 180× producing 9676.7 mg of 92.79% α‐linolenic acid from 18 000 mg free fatty acid sample. pH‐zone refining counter current chromatography exhibits a great advantage over conventional counter current chromatography with 20× sample loading capacity on the same column.     

γ‐Butyrolactone Copolymerization with the Well‐Documented Polymer Drug Carrier Poly(ethylene oxide)‐block‐poly(ε‐caprolactone) to Fine‐Tune Its Biorelevant Properties

Polymeric drug carriers exhibit excellent properties that advance drug delivery systems. In particular, carriers based on poly(ethylene oxide)‐block‐poly(ε‐caprolactone) are very useful in pharmacokinetics. In addition to their proven biocompatibility, there are several requirements for the efficacy of the polymeric drug carriers after internalization, e.g., nanoparticle behavior, cellular uptake, the rate of degradation, and cellular localization. The introduction of γ‐butyrolactone units into the hydrophobic block enables the tuning of the abovementioned properties over a wide range. In this study, a relatively high content of γ‐butyrolactone units with a reasonable yield of ≈60% is achieved by anionic ring‐opening copolymerization using 1,5,7‐triazabicyclo[4.4.0]dec‐5‐ene as a very efficient catalyst in the nonpolar environment of toluene with an incorporated γ‐butyrolactone content of ≈30%. The content of γ‐butyrolactone units can be easily modulated according to the feed ratio of the monomers. This method enables control over the rate of degradation so that when the content of γ‐butyrolactone increases, the rate of degradation increases. These findings broaden the application possibilities of polyester‐polyether‐based nanoparticles for biomedical applications, such as drug delivery systems.     

Oxidative N‐Heterocyclic Carbene‐Catalyzed γ‐Carbon Addition of Enals to Imines: Mechanistic Studies and Access to Antimicrobial Compounds

The reaction mechanism of the γ‐carbon addition of enal to imine under oxidative N‐heterocyclic carbene catalysis is studied experimentally. The oxidation, γ‐carbon deprotonation, and nucleophilic addition of γ‐carbon to imine were found to be facile steps. The results of our study also provide highly enantioselective access to tricyclic sulfonyl amides that exhibit interesting antimicrobial activities against X. oryzae, a bacterium that causes bacterial disease in rice growing.