Isolation and structural elucidation of a novel homogenous polysaccharide from Tricholoma matsutake

A crude polysaccharide possessing antitumour, radiation-resistant and anti-ageing attributes was extracted from Tricholoma matsutake by water extraction and alcohol precipitation. From this crude polysaccharide, a homogeneous polysaccharide, TMP-5II, was successfully purified by Sephacryl S-300 column chromatography. The average molecular weight (M_w) of TMP-5II was 15.76 kDa. Monosaccharide analysis indicated that the homogeneous polysaccharide contained four different residues: d-glucose, d-galactose, d-mannose and d-fucose. Attenuated total reflectance infrared spectroscopy revealed characteristics typical of carbohydrate polymers and a peak typical of a β-type glycosidic bond. TMP-5II was selected for structural characterisation by nuclear magnetic resonance (NMR) analysis. According to ¹H NMR, ¹³C NMR and two-dimensional-NMR analysis, TMP-5II contains two kinds of linkages, β and α, at a ratio of 4:1. Preliminary results indicated that the polysaccharide had (1-4)-beta-pyran glucose as the main chain, and a branched chain in the O-6 location with fucose (1-2) mannose (1-3)-alpha-pyran galactose.     

Theoretical elucidation of structure-activity relationship of flavonoid antioxidants

AM1 method was employed to calculate flavonoid antioxidants, and the results obtained are as follows. Firstly, flavonoid hydroxyls at ortho position were more active than the hydroxyls at meta position in scavenging oxygen-free radicals, which resulted from the facts that (ⅰ) the former were stabilized by forming intramolecular hydrogen bond and (ⅱ) ortho benzoquinone formed in the former structures through resonance, which resulted in large percentage of distribution of spin density on ortho oxygen and low internal energy. Secondly, electron-attracting effect of ring C of chromone-flavonoids showed some passive effects on hydroxyls of ring A, making the OH less active. As ring C had little effect on ring B and hydroxyls of ring B in most flavonoids were at ortho position, the rule summarized from experiments showing that hydroxyls of ring B were more active in scavenging oxygen-free radicals was elucidated.     

Structural elucidation of gemifloxacin mesylate degradation product

Gemifloxacin mesylate (GFM), chemically (R,S)‐7‐[(4Z)‐3‐(aminomethyl)‐4‐(methoxyimino)‐1‐pyrrolidinyl]‐1‐cyclopropyl‐6‐fluoro‐1,4‐dihydro‐4‐oxo‐1,8‐naphthyridine‐3‐carboxylic acid methanesulfonate, is a synthetic broad‐spectrum antibacterial agent. Although many papers have been published in the literature describing the stability of fluorquinolones, little is known about the degradation products of GFM. Forced degradation studies of GFM were performed using radiation (UV‐A), acid (1 mol L^?1 HCl) and alkaline conditions (0.2 mol L^?1 NaOH). The main degradation product, formed under alkaline conditions, was isolated using semi‐preparative LC and structurally elucidated by nuclear magnetic resonance (proton – ¹H; carbon – ¹³C; correlate spectroscopy – COSY; heteronuclear single quantum coherence – HSQC; heteronuclear multiple‐bond correlation – HMBC; spectroscopy – infrared, atomic emission and mass spectrometry techniques). The degradation product isolated was characterized as sodium 7‐amino‐1‐pyrrolidinyl‐1‐cyclopropyl‐6‐fluoro‐1,4‐dihydro‐4‐oxo‐1,8‐naphthyridine‐3‐carboxylate, which was formed by loss of the 3‐(aminomethyl)‐4‐(methoxyimino)‐1‐pyrrolidinyl ring and formation of the sodium carboxylate. The structural characterization of the degradation product was very important to understand the degradation mechanism of the GFM under alkaline conditions. In addition, the results highlight the importance of appropriate protection against hydrolysis and UV radiation during the drug‐development process, storage, handling and quality control. Copyright © 2015 John Wiley & Sons, Ltd.     

Structural elucidation and NMR spectral assignment of three new furostanol saponins from the roots of Tupistra chinensis

Three new furostanol saponins (1–3) were isolated from the roots of Tupistra chinensis (T. chinensis). And their structures were elucidated on the basis of NMR and mass spectrometry (MS) spectral analysis. Copyright © 2009 John Wiley & Sons, Ltd.     

Isolation and structural elucidation of a polysaccharide with radiation-protective activity from Spirulina platensis

The structure of a radiation-protective sulfated polysaccharide, SP-APS, isolated from Spirulina platensis, was investigated by methylation analysis, partial acetolysis and 1H-NMR spec-troscopy. The repeating-unit of SP-APS as branched structures was elucidated.     

Structural elucidation of rat biliary metabolites of corynoxeine and their quantification using LC‐MSn

Corynoxeine (COR) is one of 4 bioactive oxindole alkaloids in Uncaria species. In this work two phase I metabolites, namely 11‐hydroxycorynoxeine (M1) and 10‐hydroxycorynoxeine (M2), and two phase II metabolites, namely 11‐hydroxycorynoxeine 11‐O‐β‐d ‐glucuronide (M3) and 10‐hydroxycorynoxeine 10‐O‐β‐d ‐glucuronide (M4), were detected in rat bile after oral dose of COR (0.105 mmol/kg), by optimized high‐performance liquid chromatography–tandem mass spectrometry (LC‐MSⁿ) with electrospray ionization in positive ion mode. Structures of M1–4 were determined by LC‐MSⁿ, nuclear magnetic resonance, circular dichroism and high‐resolution MS spectra. COR and its metabolites in rat bile were quantified by LC‐MSⁿ. The LC‐MSⁿ quantification methods for COR and its metabolites yielded a linearity with coefficient of determination ≥0.995 from 5.0 × 10^?10 to 5.0 × 10^?7 m . The recoveries of stability tests varied from 96.80 to 103.10%. Accuracy ranged from 91.00 to 105.20%. Relative standard deviation for intra‐day and inter‐day assay was <5.0%. After the oral dose 0.14% of COR was detected in rat bile from 0 to 8 h, in which in total 97.8% COR biotransformed into M1–4. M1 and M2 yielded 48.1 and 49.7%, which successively glucuronidated to M3 and M4 at 47.2 and 43.8%, respectively. Copyright © 2014 John Wiley & Sons, Ltd.     

Structural analysis and anticomplement activity of a novel homogenous polysaccharide isolated from Juniperus tibetica kom

Abstract

Juniperus tibetica Kom., a common forest species in Tibet, has been traditionally used in Tibetan medicine to treat rheumatic arthritis. In order to investigate the effective substances of J. tibetuca, anticomplent assay-guided fractionation using gradient anion-exchange chromatography and gel permeation chromatography was applied to the crude polysaccharides of the twigs and leaves of J. tibetica and led to the isolation of a homogenous polysaccharide, YB-PS. It exhibited a robust anticomplement activity (CH₅₀: 461?±?10?μg/mL) through the classical pathway of complement system activation by targeting complement components C1q, C3, C4 and C5. The structure of YB-PS was studied by monosaccharide composition and methylation analyses, 1?D, 2?D NMR data and scanning electron microscope. The results indicated that YB-PS was composed of Ara, Gal, and Glc with a molar ratio of 5.8:3.0:1.2. Its backbone was comprised of 1,3-linked α-Araf, 1,3,5-linked α-Araf, 1,2,4-linked α-Galp, and 1,3-linked α-Glcp with terminal α-Araf, β-Galp and 1,4-linked β-Galp as branches. YB-PS was found to have a sheet structure with smooth surface. This study provided scientific foundation for YB-PS as a potential complement inhibitor to treat diseases involved with excessive activation of the complement system.     

Structure elucidation of a novel group of dithiocarbamate derivatives using 1D and 2D NMR spectroscopy

Compounds 1-7 form a novel group of dithiocarbamates, first synthesized from the reaction of a series of primary amines with carbon disulfide and 3-bromo ethyl pyruvate in the presence of anhydrous potassium phosphate. Structure elucidation of this group of compounds was accomplished using extensive 1D and 2D NMR spectroscopic studies, including (1)H, (13)C, COSY, NOESY, HSQC, and gHMBC experiments. The distinction between the linear structures I, II and the cyclic structure III was made mainly on the basis of the analysis of the cross peak between H-2 and H-4a in the COSY spectra, in combination with the long-range correlation between H-2 and C-4, 6 in the gHMBC spectra.     

Synthesis and antitumor activity of novel pyridazinone derivatives containing 1,3,4-thiadiazole moiety

Abstract

A series of novel pyridazinone derivatives containing the 1,3,4-thiadiazole moiety were synthesized and characterized by ¹H NMR, 13C NMR, spectroscopies HRMS and IR. Among them, the structure of compound 5c (2-(Tert-butyl)?4-chloro-5-((5-((2-ethylphenyl)amino)?1,3,4-thiadiazol-2-yl)thio)pyridazin-3(2H)-One) was unambiguously confirmed via single crystal X-ray diffraction analysis. The inhibitory activity of all the target compounds against MGC-803 and Bcap-37 was determined by MTT assay, with doxorubicin (the inhibition rates were 95.5?±?0.4% and 95.7?±?1.0% respectively) as a control. The preliminary results showed that the inhibitory activity of compound 5n (2-(Tert-butyl)?4-chloro-5-((5-((3-fluorophenyl)amino)?1,3,4-thiadiazol-2-yl)thio)pyridazin-3(2H)-One) was superior to the others. The inhibition rates of MGC-803 and Bcap-37 cells were 86.3?±?2.2% and 92.3?±?0.6% at a concentration of 10?μmol/L, respectively. The preliminary structure-activity relationship showed that when the 2-position of the benzene ring was substituted by a methyl group, such as compound 5j (2-(Tert-butyl)?4-chloro-5-((5-((2,3-dimethylphenyl)amino)?1,3,4-thiadiazol-2-yl)thio)pyridazin-3(2H)-One), it exhibited good anticancer activity on MGC-803 cells. Besides, introducing fluorine, chlorine, or trifluoromethyl group onto the benzene ring, such as compound 5?m (2-(Tert-butyl)?4-chloro-5-((5-((4-(trifluoromethoxy)phenyl)amino)?1,3,4-thiadiazol-2-yl)thio)pyridazin-3(2H)-One), displayed good anticancer activity on MGC-803 and Bcap-37 cells.     

Structural elucidation and complete assignment of a novel class of sulfonamides: bridgehead tricyclic sultams

Endocyclic sulfonamide templates bearing both an exocyclic ketone function and an internal olefin underwent reaction with a variety of hydroxylamines to effect an intramolecular nitrone–olefin cycloaddition to afford a new class of compounds suitable for derivatization by high‐throughput medicinal chemistry. Structural elucidation via complete assignment of the ¹H and ¹³C NMR spectra of this new class of compounds was achieved using gradient‐COSY, gradient heteronuclear multiple quantum‐coherence spectroscopy and gradient heteronuclear multiple bond correlation spectroscopy. Additionally, double pulsed field gradient spin echo–nuclear Overhauser effect experiments were carried out in order to study the spatial conformation of this new type of molecule and assess the stereo‐ and regio‐selectivity of the chemical transformation. The unequivocal molecular framework and structural conformation was confirmed by X‐ray diffraction. Copyright © 2002 John Wiley & Sons, Ltd.     

Structural Characterization of a Polysaccharide from Gastrodia elata and Its Bioactivity on Gut Microbiota

A novel homogeneous polysaccharide named GEP-1 was isolated and purified from Gastrodia elata (G. elata) by hot-water extraction, ethanol precipitation, and membrane separator. GEP-1, which has a molecular weight of 20.1 kDa, contains a polysaccharide framework comprised of only glucose. Methylation and NMR analysis showed that GEP-1 contained 1,3,6-linked-α-Glcp, 1,4-linked-α-Glcp, 1,4-linked-β-Glcp and 1,4,6-linked-α-Glcp. Interestingly, GEP-1 contained citric acid and repeating p-hydroxybenzyl alcohol as one branch. Furthermore, a bioactivity test showed that GEP-1 could significantly promote the growth of Akkermansia muciniphila (A. muciniphila) and Lacticaseibacillus paracasei (L. paracasei) strains. These results implied that GEP-1 might be useful for human by modulating gut microbiota.     

Spirodionic acid, a novel metabolite from Streptomyces sp., part 1: structure elucidation and Diels-Alder-type biosynthesis

Spirodionic acid (1), a novel microbial metabolite with a spiro[4.5]decene skeleton, the 6-ethyl-2H-pyrone 5, dihydrosarkomycin (6), and other metabolites were isolated from the strain Streptomyces sp. Tü 6077. Structural elucidation was accomplished by NMR spectroscopic and mass-spectrometric studies, and the biosyntheses of compounds 1, 5, and 6 were investigated by feeding experiments with (13)C-labeled precursors. All results indicate a biogenetic sequence with metabolite 5 and sarkomycin (7) as precursors in the formation of spirocyclus 1 through an intermolecular Diels-Alder-type reaction.     

Structural properties and antioxidant activities of polysaccharide from fruit bodies of Pholiota nameko

A polysaccharide named PNP was extracted and purified from Pholiota nameko. The total sugar content of PNP was 95.29% and the molecular weight was 1.89 × 10³ kDa. The structural features of PNP were investigated by the combination of chemical and instrumental analysis such as UV spectrophotometer, specific rotation determination, FT-IR, methylisation analysis and Congo red. The results showed that the optical rotation of PNP was +120° and that it had a triple-helical structure. Besides, PNP was mainly composed of glucose and mannose at the molar ratio of 4.24:1.00. The backbone of PNP was composed of (1→3)-linked-Glc and (1→3)-linked-Man whereas the branches of (1→3,6)-linked- Glc, (1→3,6)-linked-Man and T- Glc. Consistenting with the results of UV–Vis spectra, FT-IR spectroscopy and ¹H NMR, indicated that PNP was a complex of polysaccharides and polyphenols. In vitro antioxidant results suggested that PNP was processed with certain scavenging capacity.     

氨基乙内酰脲类BACE1抑制剂的特征结构与作用机制

对BACE1抑制剂的研究与开发已成为目前治疗阿尔兹海默症的主要研究方向之一。本文选取105个氨基乙内酰脲类BACE1抑制剂作为研究对象,借助比较分子相似性指数(Comparative Molecular Similarity Index, CoMSIA)和分子对接方法,建立定量构效关系预测模型,研究影响化合物抑制活性的特征结构信息,揭示该类抑制剂与靶标之间的作用模式。结果表明,模型(Q_²=0.45, R_²ncv=0.87, R_²pre=0.85)具有较强的预测能力,抑制剂主要占据了靶标的S3、S1和S2"位点,其主要作用力类型为氢键力。实验所得模型和信息可为日后研究开发新型高效的BACE1抑制剂提供一定的理论指导,节省研究时间与费用。     

Preparation,structure elucidation,and antioxidant activity of new bis(thiosemicarbazone) derivatives

Schiff-base–bearing new bis(thiosemicarbazone) derivatives were prepared from terephthalaldehyde and various thiosemicarbazides. FT–IR, ¹H NMR, ¹³C NMR, and UV–Vis spectroscopic methods and elemental analysis were used to elucidate the identification of the synthesized molecules. The in vitro antioxidant activity of the synthesized compounds was analysed with the 1,1-diphenyl-2-picryl hydrazyl free-radical–trapping process. The synthesized compounds exhibited lower antioxidant activity than the standard ascorbic acid. IC₅₀ values of the synthesized molecules measured from 3.81 ± 0.01 to 29.05 ± 0.11 μM. Among the synthesized compounds, compound 3 had the best antioxidant activity. Moreover, this study explained the structure–activity relationship of the synthesized molecules with different substituents in radical trapping reactions.     

Structural characterization of xylo-oligosaccharides from corncob residues

The structure of xylo-oligosaccharides (XOSs) derived from corncob residues was elucidated by means of FT-IR, GC-MS, ESI-CID-MS/MS, and 2D-NMR. GC-MS analysis confirmed that the partially methylated acetyl alditol derivatives of XOS were 1,5-Ac₂-2,3,4-Me₃-xylitol and 1,4,5-Ac₃-2,3-Me₂-xylitol. The C- and Y-type ions from glycosidic bond cleavage and ^0,2A (?60) and ^0,2A-H₂O (?78) ions from cross-ring cleavage of XOS were produced in ESI-CID-MS/MS. Both results indicated that the XOSs were (1→4)-linked xylans with a degree of polymerization from 2 to 7. The anomeric configuration and glycosidic linkage of XOSs were determined by 2D-NMR. Eventually, it was suggested that the structure of these XOSs was β-Xyl-(1→4)-[β-Xyl-(1→4)]_n-α/β-Xyl (n = 0–5) without other substituents.     

Separation, purification and structure elucidation of a polysaccharide from root of Cudrania tricuspidata

A water-soluble polysaccharide (CPS-0) was obtained from the root of Cudrania tricuspidata (Carr.) Bur., by hot water extraction (70°C), deproteination using enzymolysis and Sevag method, precipitation with ethanol, and fractionation through DEAE-Sephadex A-50 chromatography. The purity of CPS-0 was determined by HPLC and the structure was elucidated by monosaccharide composition analysis, methylation analysis, GC, GC-MS, NMR spectral (¹H-NMR, ¹³C-NMR, HMQC), UV, IR, and elemental analysis. The CPS-0 was found to contain glucose residues only. The average repeating unit is a decasaccharide having a backbone consisting of 1,4-linked α-D-glucopyranosyl residues to which the side chain consisting of terminal and 1,4-linked α-D-glucopyranosyl residues was attached at position 6 of the branching residues. __________ Translated from Chemical Journal of Chinese Universities, 2007, 28(6): 1088–1091 [译自: 高等学校化学学报]     

Chemical structure and biological activity of steroidal saponins from Furcraea gigantea

A new bisdesmosidic furostanol saponin, along with a known spirostanol saponin, furcreastatin, were isolated from Furcraea gigantea Vent. (Agavaceae). The structure of the new saponin was elucidated as 3-[(O-6-deoxy-α-L-mannopyranosyl-(1→4)-O-β-D-glucopyranosyl-(1å 3)-O-[O-β-D-glucopyranosyl-(1→3)-β-D-glucopyranosyl-(1→2)-O-β-D-glucopyranosyl-(1→4)-β-D-galactopyranosyl)oxy]-(3β, 5α, 25R)-26-(β-D-glucopyranosyloxy)-22-hydroxyfurost-12-one. The structural identification was performed using a combination of spectroscopic techniques and chemical conversions. Furcreastatin showed a powerful haemolytic effect in the in vitro assay, but the new bisdesmosidic furostanol saponin demonstrated only a significant inhibition of the capillary permeability activity.