First direct discrimination of chiral phosphine selenide (P=Se) derivatives by multinuclear magnetic resonance spectroscopy in the presence of a chiral dirhodium complex

Enantiomeric ratios of compounds with P=Se functionalities (phosphine selenides) can easily be determined by (1)H, (13)C, (31)P, and (77)Se NMR spectroscopic inspection of their diastereomeric complexes with (R)-Rh(2)(MTPA)(4) (MTPA-H identical with methoxytrifluoromethylphenylacetic acid; Mosher's acid). This is the first facile and rapid spectroscopic method for chiral recognition in this class of compounds. Whereas most complexation shifts Delta(delta) are moderate or even negligible, significant signal dispersions Delta(nu) can be observed. Some rationalization for the adduct formation mode is presented. NMR spectral characteristics of the free P=Se compounds 1-5 are described.     

Chiral mono and diamide derivatives of calix[4]arene for enantiomeric recognition of chiral amines

Novel chiral mono and diamide derivatives of calix[4]arene have been prepared from the aminolysis reaction of 5,11,17,23-tetra-tert-butyl-25,27-diethoxycarbonyl-methoxy-26,28-dihydroxycalix[4]arene 1 and 25,27-diethoxycarbonyl-methoxy-26,28-dihydroxycalix[4]arene 2 with chiral (S)-(-)-1-phenylethylamine (PEA) and (1S,2S)-(+)-2-amino-1-(4-nitrophenyl)-1,3-propanediol, respectively. Spectrophotometric titrations have been performed in CHCl(3) at 20-30 degrees C in order to obtain the binding constants (K) and the thermodynamic quantities (DeltaH and DeltaS) for the stoichiometric 1:1 inclusion complexation of various chiral amines with these new host compounds. Preliminary experiments were undertaken to confirm the complexation properties of receptors 9 and 13 with PEA by (1)H NMR in CDCl(3) at room temperature. The molecular recognition abilities and enantioselectivities for guests (R and S)-alpha-PEA and (R and S)-cyclohexylethylamine (CHEA) are discussed from a thermodynamic point of view.     

Atropisomeric 3-aryl-2-oxo-4-oxazolidinones and some thione analogues--enantiodifferentiation and ligand competition in applying the dirhodium method

The atropisomeric 2-oxo-4-oxazolidinones 1Z bind weakly to the rhodium atoms in the complex Rh(II)2 [(R)-(+)-MTPA]4 (Rh*, MTPA-H = methoxytrifluoromethylphenylacetic acid identical with Mosher's acid), presumably via the C-2 carbonyl oxygen atom. There are some 1H and 13C NMR signals in these compounds which show small dispersion effects suitable for enantiodifferentiation. In contrast, the thiocarbonyl sulfur atoms in 2Z and 3Z bind strongly so that significant complexation shifts (Delta delta) and diastereomeric dispersion effects (Delta nu) can be observed, and chiral discrimination and the determination of enantiomeric ratios of these thiocarbonyl compounds is easy. So, it is shown that--as expected--C=S is a much better binding site when competing with C=O. In compounds of Series 2 a "syn-methyl effect" was discovered which describes the dependence of dispersion effects of syn-oriented methyl groups 6 on the nature of the substituents Z. A mechanism of combined steric and electronic interaction influencing the conformational equilibria inside the adducts is proposed. Determination of absolute configurations by correlation fails, at least on the basis of the data available.     

Interactions of aluminium(III) with glycerolphosphates and glycerophosphorylcholine

The complexation of aluminium(III) with glycerol-1-phosphate (G1P) and glycerol-2-phosphate (G2P) in aqueous solutions has been studied as a function of pH, by pH-potentiometry, 31P NMR spectroscopy and ESI mass spectrometry. Various mononuclear complexes (MLH(2)(3+), MLH(2+), ML(+), ML(2)H, ML(2)(-)) and polynuclear species (M(3)L(3)H(-1)(2+), M(3)L(2)H(-n)((n-5)-) with n=5, 6, 7, M(2)L(2)H(-1)(+) ) are formed in the system where the full protonated ligands are noted LH(2). NMR experiments clearly show that G1P and G2P already interact with Al(III) at pH 1. The potentiometric results are confirmed by ESI measurements and 31P NMR studies. No metal ion-induced deprotonation and coordination of the alcoholic-OH functions seem to occur during the complexation. The situation is very different for the glycerophosphorylcholine ligand (GPC identical with LH). Only the complex ML(3+) is formed in aqueous solution with a relatively low formation constant (K=5 at 37 degrees C). This species is clearly identified in 31P and 27Al NMR spectra. The complexation study as a function of the temperature allowed us to determine the thermodynamic parameters of the complex formation. The complexation is not governed by the reaction enthalpy that is found to be positive but by the entropy that is largely positive.     

Simple protocols for NMR analysis of the enantiomeric purity of chiral diols

A three-component chiral derivatization protocol for determining the enantiopurity of chiral diols by (1)H NMR spectroscopic analysis is described here. The present approach involves the derivatization of 1,2- 1,3- and 1,4-diols with 2-formylphenylboronic acid and enantiopure alpha-methylbenzylamine. This method affords a mixture of diastereoisomeric iminoboronate esters whose ratio can be determined by integration of well-resolved diastereotopic resonances in their (1)H NMR spectra, thus enabling the determination of the enantiopurity of the parent diol. The protocol as described takes less than 90 min to complete.     

Phytoalexins from Pinus strobus bark infected with pinewood nematode, bursaphelenchus xylophilus

From the bark of Pinus strobus infected with pinewood nematode, Bursaphelenchus xylophilus, a stilbenoid 3-O-methyldihydropinosylvin and a flavanone (2S)-pinocembrin were isolated as active principles of inducibly produced antifungal compounds. The structures of the compounds were determined on the basis of spectroscopic analyses. Close investigations of spectroscopic analyses led to the complete assignment of 13C NMR and 1H NMR chemical shifts for the former compound and to the determination of the stereochemistry of the latter compound from P. strobus to be 2S. Furthermore, the distribution and time course accumulation of the identified compounds were investigated. The former compound was demonstrated to be nematocidal and the concentrations of the compound in the inoculated branches were sufficient enough to inactivate the pinewood nematode within one week after inoculation.     

Chemical constituents of leaves and stem bark of Plumeria obtusa

The continued studies on the constituents of the fresh leaves and stem bark of Plumeria obtusa Linn. have led to the isolation and characterization of four new triterpenoids, dammara-12,20(22)Z-dien-3-one (1), dammara-12,20(22)Z-dien-3beta-ol (2), olean-12-en-3beta,27-diol (3), and 27-hydroxyolean-12-en-3-one (4) and 12 known compounds, which included eight triterpenoids; dammara-3beta,20(S),25-triol (5), urs-12-en-3beta-hydroxy-27-Z-feruloyloxy-28-oic acid (6), 3beta-hydroxyolean-12-en-28-oic acid (7), 3beta,27-dihydroxylupan-29-ene (8), 3beta-hydroxylupan-29-en-28-oic acid (9), 3beta-hydroxyursan-12-en-28-oic acid (11), 3beta-hydroxy-27-p-coumaroyloxy-olea-12-en-28-oic acid (12) and urs-12-en-3-one (15); an iridoid 1alpha-plumieride (10); a cardenolide 3alpha,14beta-dihydroxy-17beta-card-20(22)-enolide (13); a fatty acid ester methyl n-octadecanoate (14) and a steroid 3beta-hydroxy-delta5-stigmastane (16). The new constituents were characterized through spectroscopic studies including 1D (1H and 31C NMR) and 2D (COSY-45, NOESY, J-resolved, HMQC and HMBC) NMR and chemical transformations. This is the first report on the isolation of dammarane triterpenoids from P. obtusa. Compounds 5 and 6 are hitherto unreported from P. obtusa. The known compounds were identified by comparison of their spectral data with those reported in the literature.     

Chiral purity determination of tobacco alkaloids and nicotine-like compounds by 1H NMR spectroscopy in the presence of 1,1′-binaphthyl-2,2′-diylphosphoric acid

The enantiomeric purity of several tobacco alkaloids and nicotine-like compounds was determined using ¹H NMR (300 MHz) spectroscopy in the presence of (-)-(R)-1,1′binaphthyl-2,2′-diylphosphoric acid (BNPPA) as a chiral complexing agent. The most significant signal splitting resulting from diastereoisomeric complexation are seen for chemical shifts in the proximity of the pyridinyl nitrogen. Chemical shift data exclude any contribution of the pyrrolidinyl protons to chiral recognition, but when the pyrrolidine ring is replaced by a piperidine ring, i.e., for compounds such as rac-anabasine and rac-anatabine, non-equivalence between enantiomers was observed for protons close to the piperidine ring. A new approach for the preparation of the pure (-)-(S)-and (+)-(R)-enantiomers of nornicotine, a tobacco alkaloid and metabolite of nicotine, was developed. The optically pure enantiomers thus obtained were used to establish the minimum sensitivity of the NMR spectroscopic method of chiral analysis. These findings provide a new, general, and facile method for the determination of enantiomeric purity of tobacco alkaloids and nicotine-like compounds. © 1996 Wiley-Liss, Inc.     

Investigations of molecular recognition aspects related to the enantiomer separation of 2-methoxy-2-(1-naphthyl)propionic acid using quinine carbamate as chiral selector: An NMR and FT-IR spectroscopic as well as X-ray crystallographic study

The chiral recognition mechanism of a cinchona alkaloid-based chiral stationary phase (CSP) showing high enantiomer discrimination potential for 2-methoxy-2-(1-naphthyl)propionic acid (MalphaNP acid) was investigated. Conformational and structural analyses of the 1:1 complexes of 9-O-(tert-butylcarbamoyl) quinine selector (SO) and MalphaNP acid (selectand, SA) were carried out employing NMR spectroscopy in solution, Fourier-transform infrared (FT-IR) spectroscopy, and solid-state X-ray diffraction analysis. Intramolecular NOEs of a soluble analogue of the CSP afforded the conformational states of the free and complexed form of the selector. The (1)H-NMR spectra revealed that the free form of the SO constitutes anti-open as well as anti-closed and/or syn-closed conformers. Upon complexation with the (S)-MalphaNP acid enantiomer to form the more stable diastereomeric associate, a conformational transition of the selector takes place, resulting in the synthesis of the anti-open conformer nearly exclusively. FT-IR spectra reveal that, besides the primary ion-pairing interaction, stereoselective hydrogen bonding stabilizes the more stable complex via the amide hydrogen of the SO. X-ray diffraction analysis of 9-O-(tert-butylcarbamoyl)quinine and (S)-MalphaNP acid complex further revealed the occurrence of a bidentate H-bond-mediated ionic interaction between SO and SA as well as the lack of pi-pi interaction in the 1:1 complex, and corroborated the conclusions derived from spectroscopic and chromatographic studies.     

Investigation of the inclusion behavior of chlorogenic acid with hydroxypropyl-β-cyclodextrin

The inclusion complexation behavior of chlorogenic acid (CGA) with the hydroxypropyl-β-cyclodextrin (HP-β-CD) was investigated in both solution and the solid state by UV-vis and fluorescence spectroscopy, infrared spectroscopy (IR), NMR spectroscopy as well as differential scanning calorimetry (DSC). The experimental results indicate that CGA is able to form an inclusion complex with HP-β-CD. The inclusion complex has a stoichiometry of 1:1 and the formation constant was calculated to be 155.7 M⁻¹. The antioxidant activity of CGA on complexation with HP-β-CD increased as compared to uncomplexed CGA. NMR spectroscopic studies show that the aromatic ring and the vinyl group of CGA are deeply included inside the CD cavity.     

Enantiomeric recognition of chiral 3,3-bridged-1,1'-binaphthol dimer toward alpha-phenylethylamine and alpha-amino acid ester

The 1,1'-binaphthol-based dimers with p-phenylenebis(2-ethynyl) spacer, (+)-6 and (+)-2, were synthesized as chiral host compounds. (1)H NMR, UV-vis, and fluorescent titration were used to evaluate the enantiomeric recognition abilities of the chiral host dimers toward the guest amine 7 and alpha-amino acid ester 8. The chiral BINOL-based dimers were found to have good enantiomeric recognition ability. The computer simulation of the host-guest complex molecules was carried out to describe the conformational changes of both naphthyl ring in the molecule of chiral host dimer after complexation with the guest molecule.     

Enantioseparation of chiral alcohols by complex formation and subsequent supercritical fluid extraction

The very first application of supercritical fluid extraction (SFE) on enantioseparation of alcohols is discussed. Resolution of three chiral alcohols (trans-2-chloro-cyclohexanol, trans-2-bromo-cyclohexanol, and trans-2-iodo-cyclohexanol) were performed by partial complexation with (-)-O,O'-dibenzoyl-(2R,3R)-tartaric acid monohydrate (DBTA). DBTA formed diastereomeric complexes with all S,S-enantiomers stable enough to extract the unreacted alcohols with supercritical carbon dioxide. Resolution efficiency increased with the size of halogen substituents, and by the proper selection of molar ratio, pure (-)-R,R-trans-2-iodo-cyclohexanol (ee > 99%, yield: 39%) or (+)-S,S-trans-2-iodo-cyclohexanol (ee = 98%, yield: 8%) were prepared in one process step. Achieved resolution efficiency values were much higher in all resolution procedures than in any other known enantioseparation of these racemic compounds. The developed method offers an environmentally friendly, efficient alternative of currently applied resolution processes, also on a preparative scale.     

Formation and structure in aqueous solution of complexes between vanadium(V) and aminohydroxamic acids that potentiates vanadium’s insulinomimetic activity: l-glutamic γ-hydroxamic and l-aspartic-β-hydroxamic acids

The full speciation of the vanadium(V) complexation systems with two aminohydroxamic acids, aspartic-β- and glutamic-γ-hydroxamic acid, has been determined using potentiometric and spectroscopic techniques. Formation constants were calculated in a systematic study at different ligand to metal molar ratios and the coordination types are proposed. An almost constant value of the ⁵¹V NMR signal in neutral medium can be attributed to two (1:1 and 1:2 metal to ligand ratios) similar structures, both of which can be either protonated or deprotonated. The two ligands have a carboxylic group in the structure and show comparable biological activities. In this work analogous complexation behavior at physiological conditions was found despite the presence of two or three methylenic groups between the amino and hydroxamate groups. The carboxylic groups are quite distant from the hydroxamic groups and are not involved directly in the coordination process. Therefore the coordination structures are related to that found in the vanadium(V)-β-alaninehydroxamic acid in which there is not a carboxylic group.     

NMR studies of chiral discrimination relevant to the enantioseparation of N-acylarylalkylamines by an (R)-phenylglycinol-derived chiral selector

Recently, it was reported that the chiral recognition ability of (R)-N-3,5-dinitrobenzoyl phenylglycinol derivative was examined as a new HPLC chiral stationary phase (CSP 1) for the resolution of racemic N-acylnaphthylalkylamines. However, the mechanism of chiral discrimination on the CSP remained elusive until now. In this study, a spectroscopic investigation of the chiral discrimination mechanism of CSP 1 was undertaken using mixtures of (R)-N-3,5-dinitrobenzoyl phenylglycinol-derived chiral selector (2) and each of the enantiomers of N-acylnaphthylalkylamines (3) by NMR study. First, the differences in free energy changes (DeltaDeltaG) upon diastereomeric complexation in solution between the complex of each isomer with chiral selector 2 by NMR titration were calculated. The values were then compared with those estimated by chiral HPLC. The chemical shift changes of each proton on the chiral selector and analytes were also checked and it was found that the chemical shift changes decreased continuously as the acyl group on analytes increased in length. This observation was consistent with the HPLC data. From these experimental results, the interaction mechanism of chiral discrimination between the chiral selector and the analytes is more precisely explained.     

Simple protocols for NMR analysis of the enantiomeric purity of chiral primary amines

A simple three-component chiral derivatization protocol for determining the enantiopurity of chiral primary amines by 1H NMR spectroscopic analysis is described here. The method involves condensation of the amines with 2-formylphenylboronic acid and enantiopure 1,1'-bi-2-naphthol. This approach affords a mixture of diastereoisomeric iminoboronate esters whose ratio can be determined by the integration of well-resolved diastereotopic resonances in their 1H NMR spectra, thus enabling the enantiopurity of the parent amine to be determined easily. The protocol, as described, takes less than 90 min to complete.     

Phenolic and other constituents of fresh water fern Salvinia molesta

Two glycosides, 6'-O-(3,4-dihydroxy benzoyl)-beta-D-glucopyranosyl ester (1), and 4-O-beta-d-glucopyranoside-3-hydroxy methyl benzoate (2), along with five known compounds methyl benzoate (3), hypogallic acid (4), caffeic acid (5), paeoniflorin (6) and pikuroside (7) were isolated for the first time from a fresh water fern Salvinia molesta D.S. Mitch. These compounds showed a potent antioxidant radical scavenging activity in a non-physiological assay. Their structures were determined by NMR spectroscopic and CID mass spectrometry techniques.     

土壤真菌Curvularia affinis HS-FG-196抗肿瘤化学成分的再研究

为对土壤真菌Curvularia affinis HS-FG-196的次级代谢产物及其体外抗肿瘤活性进行进一步研究。实验采用大孔吸附树脂HP-20树脂柱、硅胶柱、凝胶LH-20柱及半制备高效液相色谱柱从Curvularia affinis HS-FG-196的发酵培养物中分离得到六个单体化合物(1～6)。利用~1H NMR、¹³C NMR、~1H-~1H COSY、HMQC、HMBC、IR、UV和MS等波谱分析方法对其进行了结构鉴定,分别是:pyrenocine S (1)、pyrenocine B (2)、pyrenocine E (3)、pyrenocine I (4)、pyrenochaetic acid B (5)和pyrenochaetic acid C (6),其中化合物1是新化合物。对所得单体化合物进行了体外抗肿瘤活性测试,结果显示化合物1、2、3对肿瘤细胞A549、HCT-116、ACHN、K562和HepG2表现出较强的活性。     

Monitoring proton dissociation and solution conformation of chiral ytterbium complexes with near-IR CD

The ytterbium complex [Yb((S)-THP)](3+) ((S)-THP = (1S,4S,7S,10S-tetrakis(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecane) is investigated in solution through NMR, near-IR absorption, and CD spectroscopy. Quantitative analysis of the paramagnetic pseudocontact NMR shift shows Lambda helicity of the ligand cage around the metal. The NIR CD spectrum recorded at acidic pH is found to be very similar to that of [Yb((R)-DOTMA)](-) ((R)-DOTMA = (1R,4R,7R,10R)-alpha,alpha',alpha',alpha'-tetramethyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), which in solution assumes a twisted square antiprism (TSA) conformation. The similarity of the NIR CD spectra is discussed, and it is the first proof of the Lambda(lambda,lambda,lambda,lambda) conformation of [Yb((S)-THP)](3+). NIR CD spectra recorded in the pH range of 2-9 allow one to easily follow proton dissociation and to calculate the pK of this equilibrium in water (pK(A) = 6.4 +/- 0.1). This value agrees well with that determined for [Lu((S)-THP)](3+) using potentiometric methods. This demonstrates once again that NIR CD spectroscopy is a powerful technique for investigating the solution structure and dynamics of these complexes.     

大花地不容块根生物碱成分的研究

为研究大花地不容块根的生物碱成分,该研究采用酸提碱沉法从大花地不容块根中提取出总生物碱,通过硅胶柱色谱法和制备液相色谱技术对大花地不容块根的总生物碱提取物进行分离纯化,并利用波谱学手段对化合物进行结构鉴定。结果表明:(1)从总生物碱提取物中分离得到11个化合物,分别鉴定为青藤碱(1)、青风藤碱(2)、斯帝酚灵碱(3)、瑞枯灵(4)、异紫堇定(5)、紫堇单酚碱(6)、巴婆碱(7)、sukhodianine(8)、荷包牡丹碱(9)、7-氧代克班宁(10)和巴马汀(11)。(2)体外细胞毒性测试显示,大花地不容总生物碱和其主成分青藤碱对人类肺癌细胞A549的IC₅₀值分别为7.5×10^-4 g·mL^-1和6.59×10^-9 g·mL^-1。化合物2、3、4、7、8、9和10系首次从大花地不容中分离得到。大花地不容块根中含有吗啡烷、原阿朴啡、阿朴啡、苄基四氢异喹啉和原小檗碱5种类型的生物碱。     

Isolation of alpha-glusosidase inhibitors from hyssop (Hyssopus officinalis)

alpha-Glucosidase inhibitory activity was found in aqueous methanol extracts of dried hyssop (Hyssopus officinalis) leaves. Active principles against alpha-glucosidase, prepared from rat small intestine acetone powders, were isolated and characterized. The structures of these isolated compounds were determined to be (7S, 8S)-syringoylglycerol-9-O-(6'-O-cinnamoyl)-beta-D-glucopyranoside and (7S, 8S)-syringoylglycerol 9-O-beta-D-glucopyranoside by analysis of physical and spectroscopic data (FDMS, 1H NMR, 13C NMR, HMQC, and HMBC experiments) together with chemical syntheses.