Visible light-driven photocatalytic sulfonative oxidation of benzyl secondary amines.

A method for the α-oxidation and sulfonation of benzyl secondary amines was developed utilizing Ir(III) or Eosin Y as the photocatalyst in the presence of O2 as a green oxidant. Using commercial substrates, 37 products from cyclic and acyclic benzylamines were achieved with good functional group compatibility in 48-87% yields. Furthermore, tetrahydroisoquinoline protected by an Ac or a Boc group was oxidized under standard conditions.

One-Pot, Metal-Free Synthesis of Allyl Sulfones in Water.

A one-pot dehydration cross-coupling reaction between allyl alcohols and sodium sulfinates that provides allyl sulfones in good to excellent yields is presented. Its broad substrate scope includes symmetrical and asymmetrical α,α-diaryl- and α-aryl-substituted allylic alcohols and aryl and alkyl sodium sulfinates. For asymmetrical allylic substrates, the E isomer predominates with examples of excellent stereoselectivity. Control experiments provide the basis for a proposed radical-mediated mechanism. The metal-free procedure applies cheap and commercially available tetrabutylammonium tribromide as the catalyst and H2O as the solvent. Notable features of this simple, efficient, weakly toxic, and environmentally benign strategy include mild and convenient operating conditions and readily accessible starting materials.

Metal-Free Oxidative Formation of Aryl Esters by Catalytic Coupling of Acyl and Sulfonyl Chlorides with Arylboronic Acids.

A practical and efficient synthesis of aryl esters was developed through metal-free oxidation. This reaction employs stable and readily available acyl or sulfonyl chlorides and arylboronic acids as the starting materials and proceeds under mild reaction conditions without additional precious metal catalysts. This new strategy exhibits broad substrate tolerance and operational simplicity and gives diverse aryl esters in moderate to high yields.

Design of a homologous series of molecular glassformers.

We design and synthesize a set of homologous organic molecules by taking advantage of facile and tailorable Suzuki cross coupling reactions to produce triarylbenzene derivatives. By adjusting the number and the arrangement of conjugated rings, the identity of heteroatoms, lengths of fluorinated alkyl chains, and other interaction parameters, we create a library of glassformers with a wide range of properties. Measurements of the glass transition temperature (Tg) show a power-law relationship between Tg and molecular weight (MW), with of the molecules, with an exponent of 0.3 ± 0.1, for Tg values spanning a range of 300-450 K. The trends in indices of refraction and expansion coefficients indicate a general increase in the glass density with MW, consistent with the trends observed in Tg variations. A notable exception to these trends was observed with the addition of alkyl and fluorinated alkyl groups, which significantly reduced Tg and increased the dynamical fragility (which is otherwise insensitive to MW). This is an indication of reduced density and increased packing frustrations in these systems, which is also corroborated by the observations of the decreasing index of refraction with increasing length of these groups. These data were used to launch a new database for glassforming materials, glass.apps.sas.upenn.edu.

InCl3-catalyzed one-pot synthesis of multi-substituted pyrano[2,3-c]pyrazole-4-carboxylic acid esters under ultrasound irradiation.

An efficient and simple procedure for the synthesis of 6-amino-5-cyano-4-phenyl-pyrano[2,3-c]pyrazole-4-carboxylic acid esters was developed via a one-pot reaction of ß-ketoester, hydrazine, benzoylacetate, and malononitrile in 50% EtOH catalyzed by InCl3 under ultrasound irradiation. This method is more economic, convenient, nontoxic, and environmentally friendly than established methods of pyranopyrazole synthesis. Target compounds were obtained in excellent yields of up to 95%.

Synthesis of Diarylated 4-Pyridylmethyl Ethers via Palladium-Catalyzed Cross-Coupling Reactions.

The direct arylation of weakly acidic sp3-hybridized C-H bonds via deprotonated cross-coupling processes (DCCP) is a challenge. Herein, a Pd(NIXANTPHOS)-based catalyst for the mono arylation of 4-pyridylmethyl 2-aryl ethers to generate diarylated 4-pyridyl methyl ethers is introduced. Furthermore, under similar conditions, the diarylation of 4-pyridylmethyl ethers with aryl bromides has been developed. These methods enable the synthesis of new pyridine derivatives, which are common in medicinally active compounds and in application in materials science.

Photoredox-Catalyzed Deoxygenative Intramolecular Acylation of Biarylcarboxylic Acids: Access to Fluorenones.

An efficient deoxygenative radical cyclization reaction has been reported for the synthesis of fluorenones by employing various biarylcarboxylic acids via photoredox catalysis. Attractive features of this process include generation of acyl radical, which quickly underdone intramolecular radical cyclization. This method marks the first photocatalytic intramolecular acyl radical coupling for constructing carbon-carbon bond, which further synthesizes the valuable fluorenone products with mild conditions, good yields, and good functional-group compatibility.

Rapid and efficient one-pot synthesis of spiro[indoline-3,4'-pyrano[2, 3-c]pyrazole] derivatives catalyzed by l-proline under ultrasound irradiation.

A rapid and efficient ultrasound-promoted one-pot synthesis of spiro[indoline-3,4'-pyrano[2,3-c]pyrazole] derivatives is described here. The reaction of substituted phenylhydrazine and dialkyl acetylenedicarboxylate with substituted isatin and malononitrile is catalyzed by l-proline to give good-to-excellent yields in water/ethanol (v/v, 1:1) at room temperature.

Simultaneous determination of seven ginsenosides in Du Shen Tang decoction by rapid resolution liquid chromatography (RRLC) coupled with tandem mass spectrometry.

A rapid quantification of seven ginsenosides in Du Shen Tang decoction, the decoction of the root of Panax ginseng was investigated by rapid resolution liquid chromatography coupled with tandem mass spectrometry (RRLC-MS/MS). All analytes including seven major constituents, namely ginsenoside-Re, Rg1, Rb1, Rc, Rb2, Rd and Rf were analysed simultaneously in short time and provide good linearity (r>0.9976), repeatability (RSD<5.67%), intra- and inter-day precisions (RSD<5.06%) with accuracies (94.65-105.31%) and recovery (93.76-106.82%) by using optimised methods. In addition, the content of seven ginsenosides in the decoction prepared by the root of 2-year-old, 4-year-old and 6-year-old Panax ginseng was also analysed. The results showed the concentration of ginsenosides detected in Du Shen Tang decoction was affected by the difference in collected times of the root of Panax ginseng. The established method could be used as a rapid and reliable approach for assessment of the quantity of Du Shen Tang decoction.

Cerium ammonium nitrate (CAN)-catalyzed four-component one-pot synthesis of multi-substituted pyrano[2,3-c] pyrazoles under ultrasound irradiation.

A convenient and efficient synthesis of multi-substituted dihydropyrano[2,3-c]pyrazole derivatives is reported. The four-component reaction of 4-hydrazinobenzoic acid, ß-keto esters, aromatic aldehydes, and malononitrile using 10 mol% CAN catalyst in water under ultrasound irradiation produced the target compounds in good-to-excellent yields. This method has advantages over conventional methods in being economic, non-toxic, and environmentally compatible due to its use of efficient and eco-friendly CAN catalyst and water solvent.

Simultaneous quantitation of seven alkaloids in processed Fuzi decoction by rapid resolution liquid chromatography coupled with tandem mass spectrometry.

A rapid analytical method based on rapid resolution LC coupled with MS/MS was first established to quantify seven alkaloids in processed Fuzi decoction. The chromatographic method was optimized to allow simultaneous analysis of all analytes in 5 min and demonstrated good linearity (r > 0.9995), repeatability (RSD < 4.36%), intra- and interday precisions (RSD < 5.07%) with good accuracies (97.76-105.08%) and good recovery (95.0-107.5%) of seven alkaloids, namely higenamine, benzoylhypaconine, benzoylmesaconine, benzoylaconine, aconitine, hypaconitine, and mesaconitine. The LODs for these markers were in the range of 2.30-17.00 pg/mL. Quantitative analysis of the seven alkaloids in Baifupian decoction and Heishunpian decoction showed that the content of the seven marker chemicals varied significantly and concluded that the quality of Fuzi was greatly affected by different processed methods. The developed method could be used as a rapid, sensitive, and reliable approach for assessment of the quality of processed Fuzi and related decoction.

Fragmentation characteristics and isomeric differentiation of flavonol O-rhamnosides using negative ion electrospray ionization tandem mass spectrometry.

RATIONALE: Flavonoids exhibit a wide range of biological activities. The differentiation and structural characterization of the flavonol O-rhamnosides and their isomers are important research topics. Electrospray ionization tandem mass spectrometry (ESI-MS(n) ) is an indispensable tool and has become an efficient method for the identification of bioactive natural products. METHODS: Negative ion ESI-MS(n) was used to characterize and differentiate flavonol O-rhamnosides and their isomeric compounds. The collision energies in collision-induced dissociation were varied to optimize the structural information. RESULTS: Flavonol 7-O-rhamnosides containing either a hydroxyl or a methoxyl group at the C-8 position clearly differed from their isomeric compounds, such as the flavonol 3-O-rhamnosides, in the product ion spectra of the [M-H](-) ions. The differences in the locations of the glycosyl group and OCH(3) group resulted in a significant change in the relative abundances of the Y(0)(-) and [Y(0) -H](-•) ions, and the formation of some characteristic ions, such as (1,3)A(0)(-) and [(1,3)A(0)-CH(3)](-•). CONCLUSIONS: An efficient ESI-MS(n) method for the structural identification and isomeric differentiation of flavonol O-rhamnosides was developed. The differences in the glycosyl type, and the glycosylation and methoxylation positions in the structures of isomeric flavonoids, can be determined using (-)ESI-MS(n) spectra. The formation and relative abundances of [Y(0)-H](-•) and Y(0) (-) ions, as well as the comparison of some diagnostic ions, are vital in the differentiation of isomeric flavonoids. These results have practical applications in the rapid identification of flavonol O-rhamnosides present in crude bioactive extracts.

An efficient three component one-pot synthesis of 5-amino-7-aryl-7,8-dihydro-[1,2,4] triazolo[4,3-a]-pyrimidine-6-carbonitriles.

A series of novel 5-amino-7-aryl-7,8-dihydro-[1,2,4] triazolo[4,3-a]-pyrimidine-6-carbonitriles were synthesized by a one-pot reaction of 3-amino-1,2,4-triazole, malononitrile and aryl aldehydes in the presence of 20 mol% NaOH in ethanol under heating or ultrasonic irradiation. The structures of the target compounds were confirmed by inspection of their (1)H- NMR, (13)C-NMR, IR and MS spectra. The advantages of this method are short reaction times, good yields, high selectivity and operational simplicity.

Seasonal variations in metabolite profiling of the fruits of Ligustrum lucidum Ait.

The metabolite profiling of fruits of the herb Ligustrum lucidum Ait collected during different months has been performed using ultra-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC/QTOFMS) and multivariate statistical analysis techniques. The markers such as oleuropein acid, neonuezhenide, specnuezhenide, oleuropein and ligustrosidic acid accountable for such variations were identified through the loadings plot of principal component analysis (PCA), and the tentative identification of the markers is completed by comparing the mass spectra and retention times with those of reference compounds and/or tentatively assigned by matching empirical molecular formulae and MS/MS data with those of the known compounds published. Furthermore, one of the chemical markers, such as specnuezhenide, which is water-soluble, biologically active and also the predominant compound in this crude drug, was quantified by ultra-performance liquid chromatography coupled with a tunable UV detector (UPLC-TUV). The developed UPLC method provides good linearity (r(2)=0.9991), repeatability (RSD=2.96%), intra- and inter-day precisions (RSD=0.21%, 0.96%), with accuracies of 99.18-100.26% and a recovery of specnuezhenide of 97.57%. The fruits of L. lucidum Ait collected from August to December were tested. The results clearly show that the fruits of L. lucidum Ait harvested in October have the highest yields of specnuezhenide. It is also noted that the variations of content of specnuezhenide obtained by both methods have a strong correlation. This suggests that the newly proposed strategy is a reliable and simple method for the rapid discrimination of subtle variations, within the same plant species or strains, due to different seasonal collection times.

A study of characteristic fragmentation of isoflavonoids by using negative ion ESI-MSn.

Isoflavone mono-O-glycosides were investigated by electrospray ionization tandem mass spectrometry with a quadrupole linear ion trap mass spectrometer in negative ion mode. Isoflavonoids having different positions of glycosylation or methylation were differentiated according to the relative abundances of Y(0)(-) and [Y(0)-H](-•) ions generated from the [M-H](-) ion. It is found that the site of glycosyl or methyl group significantly affects relative abundances of the Y(0)(-) and [Y(0)-H](-•) ions. In addition, the characteristic ion [Y(0)-2H](-) was observed in the product ion spectrum of genistein 7-O-ß-D-glucoside and was also detected, together with the [Y(0)-CH(3)](-•) and [Y(0)-H-CH(3)](-) ions in the product ion spectra of glycitin and 6-methoxy genistein 7-O-ß-D-glucoside. The structures of isoflavonoids can be characterized and identified according to the formation of these diagnostic ions. The results obtained from this investigation can promote the rapid identification of isoflavonoids in crude plant extracts.

Structural characterization of flavonol 3,7-di-O-glycosides and determination of the glycosylation position by using negative ion electrospray ionization tandem mass spectrometry.

Flavonol 3,7-di-O-glycosides were investigated by negative ion electrospray ionization tandem mass spectrometry using a quadrupole linear ion trap (LIT) mass spectrometer. The results indicate that the fragmentation behavior of flavonol 3,7-di-O-glycosides is substantially different from that of their isomeric mono-O-diglycosides. In order to characterize a flavonoid as a flavonol 3,7-di-O-glycoside, both [Y3(0) - H]-* and [Y(0) - 2H]- ions should be present in [M - H]- product ion spectrum. The MS(3) product ion spectra of Y3(0)-, [Y3(0) - H]-* and Y7(0)- ions generated from the [M - H]- ion provide sufficient structural information for the determination of glycosylation position. Furthermore, the glycosylation positions are determined by comparing the relative abundances of Y3(0)- and Y7(0)- ions and their specific fragmentation patterns with those of flavonol mono-O-glycosides. In addition, a [Y3(0) - H]-* ion formed by the homolytic cleavage of 3-O glycosidic bond with high abundance points to 3-O glycosylation, while a [Y(0) - 2H]- ion formed by the elimination of the two sugar residues is consistent with glycosylation at both the 3-O and 7-O positions. Investigation of negative ion ESI-MS(2) and MS(3) spectra of flavonol O-glycosides allows their rapid characterization as flavonol 3,7-di-O-glycoside and their differentiation from isomeric mono-O-diglycosides, and also enables their direct analysis in crude plant extracts.