Identification of C-21 steroidal glycosides from the roots of Cynanchum chekiangense by high-performance liquid chromatography/tandem mass spectrometry

High-performance liquid chromatography coupled with electrospray tandem mass spectrometry (HPLC/ESI-MS/MS) was used to identify C-21 steroidal glycosides with immunological activities in roots of Cynanchum chekiangense. In the MS/MS spectra, fragmentation reactions of the [M + Na]⁺ were recorded to provide structural information about the glycosyl and aglycone moieties. To further confirm the fragments structures, off-line Fourier transform ion cyclotron resonance tandem mass spectrometry (FT-ICR-MS/MS) was also performed. In the study, four known steroidal glycosides cynascyroside C, chekiangensosides A and B, glaucoside H, and four novel steroidal glycosides chekiangensosides C, D, E and chekiangensoside A isomer were identified based on mass spectral data, NMR spectral data and standards. This is the first report on identifying steroidal glycosides in roots of C. chekiangense by HPLC/ESI-MS/MS directly, which could save time and material consuming efforts in traditional phytochemistry analysis.     

Synthesis and chiral recognition of novel chiral fluorescence receptors bearing 9-anthryl moieties

Two chiral fluorescence receptors 1 and 2 have been synthesized, and their structures characterized by IR, ¹H NMR, MS spectra and elemental analysis. The chiral recognition of the receptors was studied by ¹H NMR and fluorescence spectra. The results demonstrate that the receptors and tetrabutylammonium mandelate formed a 1:1 complex. Two receptors exhibit good chiral recognition abilities towards the enantiomers of tetrabutylammonium mandelate.     

Synthesis and characterization of novel chiral calix[4]arene bearing (R)-(+)-1-phenylethylamine bonded silica particles

Two novel chiral di- and tri-amide derivatives of p-tert-butylcalix[4]arene were synthesized by (R)-(+)-1-Phenylethylamine via convenient reactions and then immobilized on aminopropyl functionalized silica particles. The prepared chiral calix[4]arenes and their silica polymers (Calix-SP1 and Calix-SP2) were characterized using ¹H NMR, ¹³C NMR, FT-IR, and thermal and elemental analysis techniques.     

Synthesis and chiral recognition properties of two novel chiral calix[4]arene tartaric ester derivatives

Two new chiral calix[4]arene derivatives containing tartaric acid ester moieties were synthesized. The chiral calix[4]arenes are in a ‘cone’ conformation according to NMR spectroscopy. The chiral recognition capabilities of 1–4 toward the guests, 1,2-propanediol and serine methyl ester hydrochloride (SerOMe), were investigated (¹H NMR spectroscopy). The extraction properties of compounds 1 and 2 toward selected α-amino acid methyl esters were also studied.     

Asymmetric synthesis of new chiral long chain alcohols

Sixteen new chiral alcohols with alkyl (C₁₁–C₁₉) and aryl, substituted aryl, hetero aryl and biaryl groups 2a–2t were synthesized by three different asymmetric reduction methods from their corresponding ketones 1a–1t. Chiral NaBH₄ (method A), chiral BH₃ (method B) and chiral AIP (method C) were used as asymmetric reduction catalysts. Chiral NaBH₄ was modified by four different ligands 3a–3d, chiral BH₃ and chiral AIP by four different ligands 4a–4d. Ligand 4c was synthesized for the first time in this work. Chiral NaBH₄ generated chiral alcohols of (R)-configuration and chiral BH₃ and chiral AIP of (S)-configuration with high enantiomeric excesses, were analysed by chiral HPLC. In order to determine the ee values by chiral HPLC, sixteen corresponding racemic alcohols, synthesized by reducing their corresponding ketones via NaBH₄, were used for chiral resolution on a Daicel OD HPLC column. The sixteen starting ketones were synthesized in this study by Friedel–Craft acylation. The new chiral alcohols were characterized by IR, NMR, (¹H and ¹³C), MS, elemental analyses and specific rotation. The reduction methods A, B and C were applied to these ketones for the first time in this study and were compared with each other. The relationship between the structure of the ketone and the yield and the enantiomeric excess was discussed.     

The first catalytic asymmetric addition of diethylzinc to aldehyde promoted by chiral thiourea

A series of C₂-symmetric and asymmetric chiral thiourea derivatives were synthesized from commercial L-phenylalanine.All of the new compounds have been fully characterized by IR,¹H NMR,¹³C NMR,MS spectra and elemental analyses.The chiral thioureas were used as chiral ligands in the catalytic enantioselective ethylation of aldehydes with diethylzinc,the corresponding sec-alcohols were gained with excellent enantioselectivities（up to 87.1%ee） and high yields（up to 76.7%） after the conditions were optimized.     

Aggregation behavior of imidazolium-based chiral surfactant in aqueous solution

A novel imidazolium-based chiral surfactant with a Y-type hydrophobic chain, (S)-(+)-1-(2,3-bis(octanoyloxy)propyl)-3-methylimidazolium chloride ([Bopmim]Cl), was synthesized. The aggregation behavior of [Bopmim]Cl in aqueous solution was then investigated by surface tension, electrical conductivity, ¹H NMR, and fluorescence measurements. Compared with [C₁₂mim]Cl, the critical micelle concentration for [Bopmim]Cl is lower, indicating that the novel chiral surfactant has superior capacity to form micelles. A larger value of pC ₂₀, a greater minimum area per surfactant molecule (A _min), a smaller degree of counterion binding (β), and a looser aggregate are caused by the relatively larger Y-type hydrophobic chain of [Bopmim]Cl. Furthermore, analysis of the ¹H NMR spectra revealed that the introduced Y-type hydrophobic chain may prevent the hydrophobic group from forming an extended chain configuration and cause a changeover from trans to gauche conformations upon micellization. The micelles of the novel chiral surfactant may provide some potential applications in the stereochemical recognition of surfaces or of biological structures.     

Synthesis of spiro-cyclopropane derivatives containing multiple chiral centers

Tandem asymmetric double Michael addition/internal nucleophilic substitution of the novel chiral source, 5-(l-menthyloxy)-3-bromo-2(5H)-furanone with nucleophilic alcohol compounds has been investigated. The tandem asymmetric reaction can afford four new stereogenic centers with one reaction and give optically pure spiro-cyclopropane derivatives 5a--5d which are difficult to obtain by routine methods. The synthetic method for 5a--5d was studied in detail and the new compounds were identified on the basis of their analytical data and spectroscopic data, such as [α]~(20),IR,~1H NMR,~(13)C NMR, MS and elementary analysis. The absolute configuration of the sprio [5-l-menthyloxy-3-bromo butyrolactocyclopropane-3″, 3′(4′-methyloxy-5′-menthyloxybutyrolactone)] (5a) was established by X-ray crystallography. The work can provide important synthetic strategy in synthesis of some new optically active spiro-cyclopropane analogues and some biologically active molecules with complex structure.     

A new 20-membered macrocyclic dilactam: an unexpected product of a tri-n-butyltin hydride-mediated radical reaction

The tri-n-butyltin hydride-mediated reaction of methyl 3-O-allyl-4,6-di-O-benzyl-2-deoxy-2-(2-iodobenzoylamino)-α-d-glucopyranoside affords an unexpected benzomacrodilactam. The structure of this new 20-membered macrocyclic dilactam has been elucidated by electrospray mass and tandem mass spectrometry (ESI-MS/MS) and by ¹H, ¹³C NMR spectroscopy, COSY, TOCSY, HMQC and HMBC experiments.     

New chiral auxiliaries derived from (S)-α-phenylethylamine as chiral solvating agents for carboxylic acids

The two new diastereoisomeric chiral auxiliaries 1a and 1b were synthesized conveniently and effectively. ¹H NMR was employed to investigate their chiral recognition ability. Compared with (S)-PEA, these new chiral auxiliaries exhibited better enantioselectivity towards the carboxylic acids we had chosen.     

Synthesis of a chiral N-heterocyclic carbene bearing a m-terphenyl-based phosphate moiety as an anionic N-substituent and its application to copper-catalyzed enantioselective boron conjugate additions

A chiral N-heterocyclic carbene (NHC) ligand 1a bearing a m-terphenyl-based phosphate moiety as an anionic N-substituent has been developed. A rhodium complex [Rh(1a)(cod)]₂ was synthesized and its structure was characterized by NMR and ESI-MS spectroscopy. This ligand gave high enantioselectivities in copper-catalyzed enantioselective boron conjugate additions to an α,β-unsaturated ester to give a chiral β-boryl ester.     

Synthesis of novel well-defined chain-end-functionalized polystyrenes with dendritic chiral ephedrine moieties and their applications as highly enantioselective diethylzinc addition to N-diphenylphosphinoyl arylimines

A series of novel well-defined chain-end-functionalized polystyrenes having 2, 4, 8, and 16 chiral ephedrine moieties dendritically distributed at their hyperbranched chain-ends were quantitatively synthesized. Their well-defined architectures were fully confirmed by elemental analysis, FTIR, SEC as well as by ¹H and ¹³C NMR spectroscopies. These polymers were precisely controlled in the molecular weight and molecular weight distribution as well as well-defined in chain-end-functionalities. These dendritic chiral polymers serve as highly enantioselective chiral ligands in the enantioselective addition of diethylzinc to a series of N-diphenylphosphinoyl arylimines. Among them, chiral dendrimer having eight ephedrine moieties at the chain-ends afforded the corresponding enantiomerically enriched phosphinoylamides in good to high yields with enantioselectivities up to 93% ee. The obtained enantioselectivities are comparable with those obtained by using N-benzylephedrine and its corresponding copolymer as chiral ligands.     

Synthesis, curing kinetics and thermal properties of novel difunctional chiral and achiral benzoxazines with double chiral centers

Novel difunctional chiral and achiral benzoxazine monomers were synthesized from the reaction of bisphenol A with paraformaldehyde and primary amines, including S-(+)-3-methyl-2-butylamine and rac-(±)-3-methyl-2-butylamine, by solventless method. The chemical structures of chiral and achiral benzoxazines were identified by fourier transform infrared, nuclear magnetic resonance (¹H NMR and ¹³C NMR). The curing behavior and non-isothermal curing kinetics of chiral and achiral benzoxazine monomers were investigated by differential scanning calorimeter (DSC). Isoconversional methods based on Friedman and Kissinger–Akahira–Sunose were applied to analyze the curing process of chiral and achiral benzoxazines. The thermal properties of cured polymers were characterized by DSC and thermogravimetry. The results suggested that the optical purity and stereo-configuration for chiral and achiral benzoxazines have definite influence on curing behavior and thermal properties despite the same chemical structure. Chiral benzoxazine displayed typical characteristics of difunctional benzoxazines. Achiral benzoxazine showed distinctly double peaks in DSC exotherms due to the presence of racemic and mesomeric isomers. The thermal properties of achiral polybenzoxazine were slightly higher than those of chiral polybenzoxazine, and were much higher than those of other bisphenol A-C₃–C₈ linear aliphatic amine-based polybenzoxazines because of tight packing, low free volume, and abundant intramolecular and intermolecular hydrogen bonds in network structure of polymers.     

Catalytic asymmetric Henry reaction using copper(II) chiral tridentate Schiff-base complexes and their polymer-supported complexes

A series of chiral tridentate Schiff-base ligands and their polymer-supported ligands were conveniently prepared and introduced as copper(II) chiral complexes for the asymmetric Henry reaction. The structures of these ligands have been characterized by IR, ¹H NMR, ¹³C NMR and MS. The experimental results showed that the corresponding β-nitro alcohols were obtained in moderate to high yields (up to 98%) with up to 98% ee under mild conditions. The complex catalyst forming from copper(II) polymer-supported ligands could be recycled by a simple filtration and reused 6 times at least with similar good catalytic effect (about 94% yield and 90% ee).     

Synthesis of cis-1,2-diol-type chiral ligands and their dioxaborinane derivatives: Application for the asymmetric transfer hydrogenation of various ketones and biological evaluation

Two cis-1,2-diol-type chiral ligands (T ₁ and T ₂ ) and their tri-coordinated chiral dioxaborinane (T _(1–2) B _(1–2) ) and four-coordinated chiral dioxaborinane adducts with 4-tert-butyl pyridine sustained by N → B dative bonds (T _(1–2) B _(1–2) -N) were synthesized and characterized by various spectroscopic techniques such as NMR (¹H, ¹³C, and ¹¹B), FT-IR and UV–Vis spectroscopy, LC–MS/MS, and elemental analysis. It was suggested that both ferrocene and trifluoromethyl groups played key roles in the catalytic and biological studies because they could tune the solubility of the chiral dioxaborinane complexes and adjust the strength of intermolecular interactions. To assess the biological activities of newly synthesized chiral dioxaborinane compounds, DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging, reducing power, antibacterial, DNA binding, and DNA cleavage activities were tested. Then, all chiral dioxaborinane complexes were investigated as catalysts for the asymmetric transfer hydrogenation of various ketones under suitable conditions. The results indicated that the chiral dioxaborinane catalysts performed well with high yields.     

Electrospray ionization multistage tandem mass spectrometry of penta- and hexa-substituted aryloxycyclotriphosphazenes

Several penta- and hexa-substituted aryloxycyclotriphosphazenes were synthesized and investigated by electrospray ionization tandem mass spectrometry (ESI-MSⁿ). Their main fragmentation pathways are proposed based on the MSⁿ and accurate mass data. An apparent hydrolysis reaction is an important fragmentation process exhibited in the ESI-MS/MS spectra for all of them. Also interesting is the intramolecular electrocyclic ring closure observed in ESI-MS/MS spectra of them. These observations may have some potential applications in the distinction between the mass spectra of penta- and hexa-substituted hexachlorocyclotriphosphazene derivatives.     

Facile synthesis of chiral <Emphasis Type="Italic">N</Emphasis>-glycosylated amino acids

Five designed chiral glycosylated amino acids have been synthesized for the first time by coupling of 1,3,4,6-tetra-O-acetyl-β-D-glucosamine sulfate (2), previously prepared by direct acetylation of D-glucosamine hydrochloride with acetic anhydride, with chiral Fmoc-protected amino acids and DIC, HOBt, and DIEA under mild conditions. The structures of these new compounds were characterized by IR, ¹H NMR, and ¹³C NMR spectroscopy and ESI MS.     

Synthesis of novel chiral Schiff base and amino alcohol derivatives of calix[4]arene and chiral recognition properties

In the present study, the synthesis and liquid phase extraction properties towards some amino acid methylesters and amino alcohols of Schiff base and amino alcohol substituted calix[4]arene are reported. The Schiff base substituted calix[4]arene 5 has been synthesized via condensation reaction involving 5,17-diformyl-11,23-di-tert-butyl-25,27-di[3-(4-formylphenoxy)propoxy]-26,28 dihydroxycalix[4]arene 4 and (R)-(?)-2-phenylglycine methyl ester in CHCl₃:MeOH. To give the amino alcohol substituted calix[4]arene 6, the synthesized chiral compound 5 was reduced by LiAlH₄. The new chiral Schiff base and amino alcohol derivatives of calix[4]arene have been characterized by a combination of FT-IR, ¹H NMR, ¹³C NMR, FAB-MS and elemental analysis. Also, the extraction behaviors of 5 and 6 towards some selected amino acid methylesters and amino alcohols have been studied by liquid–liquid extraction.     

Novel 2H-[1,2,4]thiadiazolo[2,3-a]pyrimidine derivatives bearing chiral S(−)-2-(4-chlorophenyl)-3-methylbutyric acid moiety: Design,synthesis and herbicidal activity

A series of S(?)-2-(4-chlorophenyl)-N-(5,7-disubstituted-2H-[1,2,4]-thiadiazolo[2,3-a]pyrimidin-2-ylidene)-3-methylbutanamide derivatives were designed and synthesized. The structures of all the newly synthesized compounds had been identified by elemental analysis, ¹H NMR, MS and optical rotation. Their herbicidal activities were evaluated against a variety of weeds. The preliminary results showed that most of the target compounds had moderate inhibitory activities and selectivities against root and stalk of monocotyledon and dicotyledon plants. More importantly, the chiral target compounds showed improved herbicidal activities to some extent over their racemic counterparts against a variety of tested weeds, which might be contributed by the introduction of chiral active unit. The present work provided a novel class of chirality-based thiadiazolopyrimidine derivatives with potent herbicidal activities for further optimization.     

Exploration of chiral drugs as references for chiral discrimination of valsartan and voriconazole by tandem mass spectrometry

The use of mass spectrometry for chiral recognition and quantification has attracted great interest owing to its speed, sensitivity, specificity, and tolerance. However, searching for chiral selectors in chiral analyses using mass spectrometry is still problematic. In this study, chiral drugs could be applied as references for the chiral recognition and enantiomeric quantification of valsartan and voriconazole. Two novel pairs of metal-bound diastereomeric complex ions were detected by mass spectrometry, namely, nickel (II)-bound dimeric ions [Ni^II (2R,5S-emtricitabine) (S-valsartan)-H]⁺ and [Ni^II (2R,5S-emtricitabine) (R-valsartan)-H]⁺ and copper (II)-bound dimeric ions [Cu^II (S,S,S-enalaprilat) (2S,3R-voriconazole)-H]⁺ and [Cu^II (S,S,S-enalaprilat) (2R,3S-voriconazole)-H]⁺. The resulting diastereomers were successfully identified based on the relative intensities of their characteristic fragments using tandem mass spectrometry. The logarithm of the characteristic fragment ion abundance ratio exhibited a good linear relationship with the enantiomeric excess. Density functional theory calculations were also performed to elucidate the mechanism of the structural differences observed in the MS results. This established approach proves that chiral drugs can serve as ligands for the rapid recognition and quantitative analysis of other chiral drugs without a chiral chromatographic column or complex sample pretreatment.