2-(4-β-D-吡喃阿洛糖苷-苯基)-5-取代芳基-1,3,4-噁二唑的合成及镇静活性研究

以豆腐果苷为原料, 与取代苯甲酰肼反应生成中间体4-β-D-吡喃阿洛糖苷-苯甲醛取代苯甲酰腙(2a～2g), 在溴作催化剂的条件下发生关环反应, 合成了一系列豆腐果苷类似物3a～3g. 所有化合物结构经IR, ¹H NMR以及MS谱得以证实. 初步药理实验结果表明, 化合物3a, 3c, 3f与豆腐果苷相比有更好的镇静活性.     

无溶剂合成1,3,5-三芳基-2-芳酰基环己醇衍生物和晶体结构

在NaOH存在下室温研磨查尔酮与丙二腈,可以有效地得到1,3,5-三芳基-2-芳酰基环己醇衍生物,本合成方法反应时间短、操作简单、产率高,符合绿色化学特点.产物结构经过红外、核磁、元素分析和高分辨质谱确证,并对3b做了单晶衍射测定.     

Asymmetric cycloaddition of β,γ-unsaturated α-ketoesters with electron-rich alkenes catalyzed by a chiral Er(OTf)3/N,N'-dioxide complex: highly enantioselective synthesis of 3,4-dihydro-2H-pyrans

The asymmetric inverse-electron-demand hetero-Diels-Alder (HDA) reactions of β,γ-unsaturated α-ketoesters with electron-rich alkenes were investigated, with an N,N'-dioxide/erbium(III) complex employed as the catalyst. Quantitative conversion of the β,γ-unsaturated α-ketoesters and excellent enantioselectivities (up to >99% ee) and diastereoselectivities (up to >99:1 d.r.) were observed for a broad range of substrates by using a 0.5-0.05 mol% catalyst loading under mild reaction conditions. The reaction could be scaled up to the gram scale with the same results. In addition, this was the first application of Er(OTf)(3) to the asymmetric inverse-electron-demand HDA reaction and it behaved as an efficient catalyst. Moreover, the synthetic utility of this methodology was demonstrated with the synthesis of key intermediates of some natural products.     

Improving confidence in detection and characterization of protein N-glycosylation sites and microheterogeneity

Protein glycosylation is one of the most common post-translational modifications, estimated to occur in over 50% of human proteins. Mass spectrometry (MS)-based approaches involving different fragmentation mechanisms have been frequently used to detect and characterize protein N-linked glycosylations. In addition to the popular Collision-Induced Dissociation (CID), high-energy C-trap dissociation (HCD) fragmentation, which is a feature of a linear ion trap orbitrap hybrid mass spectrometer (LTQ Orbitrap), has been recently used for the fragmentation of tryptic N-linked glycopeptides in glycoprotein analysis. The oxonium ions observed with high mass accuracy in the HCD spectrum of glycopeptides can be combined with characteristic fragmentation patterns in the CID spectrum resulting from consecutive glycosidic bond cleavages, to improve the detection and characterization of N-linked glycopeptides. As a means of automating this process, we describe here GlypID 2.0, a software tool that implements several algorithmic approaches to utilize MS information including accurate precursor mass and spectral patterns from both HCD and CID spectra, thus allowing for an unequivocal and accurate characterization of N-linked glycosylation sites of proteins.     

催化动力学光度法测定青霉素G及其机理研究

研究了在青霉素G存在下双氧水氧化苋菜红的褪色反应,建立了催化动力学光度法测定微量青霉素G的方法.方法线性范围为0.20～4.00μg/mL,回归方程y=-0.015p(μg/mL)+0.311,r=0.9998;方法线性范围为4.00～50.0μg/mL,回归方程y=0.001p(μg/mL)+0.280,r=0.99...     

4-卤代苯甲酸铽配合物荧光性能的研究

以4-氯苯甲酸(4-ClBA)、4-溴苯甲酸(4-BrBA)和4-碘苯甲酸(4-IBA)为配体合成了三种4-卤代苯甲酸铽的稀土配合物Tb(4-ClBA)3,Tb(4-BrBA)3和Tb(4-IBA)3,紫外可见光吸收光谱表明,相同摩尔浓度的Tb(4-IBA)3的紫外吸收最强,Tb(4-BrBA)3的紫外吸收强度次之,Tb(4-ClBA)3的紫外吸收最弱,而荧光发射光谱表明,Tb(4-IBA)3和Tb(4-BrBA)3的荧光发射强度远小于Tb(4-ClBA)3的.从配体的结构及配体能级、稀土离子Tb3+能级、配体到稀土离子之间的能量传递等角度对该试验结果进行了分析探讨,结果表明苯甲酸对位的碘原子、溴原子和氯原子与苯环上的碳原子所形成的碳卤键热振动的不同是造成三种稀土配合物荧光强度差别较大的本质原因.     

A multistage pathway for human prion protein aggregation in vitro: from multimeric seeds to β-oligomers and nonfibrillar structures

Aberrant protein aggregation causes numerous neurological diseases including Creutzfeldt-Jakob disease (CJD), but the aggregation mechanisms remain poorly understood. Here, we report AFM results on the formation pathways of β-oligomers and nonfibrillar aggregates from wild-type full-length recombinant human prion protein (WT) and an insertion mutant (10OR) with five additional octapeptide repeats linked to familial CJD. Upon partial denaturing, seeds consisting of 3-4 monomers quickly appeared. Oligomers of ~11-22 monomers then formed through direct interaction of seeds, rather than by subsequent monomer attachment. All larger aggregates formed through association of these β-oligomers. Although both WT and 10OR exhibited identical aggregation mechanisms, the latter oligomerized faster due to lower solubility and, hence, thermodynamic stability. This novel aggregation pathway has implications for prion diseases as well as others caused by protein aggregation.     

In situ encapsulation of laccase in nanofibers by electrospinning for development of enzyme biosensors for chlorophenol monitoring

A biosensor based on Trametes versicolor laccase (Lac) was developed for the determination of phenolic compounds. The biosensor was prepared by in situ electrospinning of a mixture of polyvinyl alcohol (PVA), Lac, PEO-PPO-PEO (F108) and gold nanoparticles (Au NPs), where F108 was used as an enzyme stabilizing additive and Au NPs was used to enhance the conductivity of the biosensor. Laser confocal scanning microscopy and electrochemical impedance spectroscopy proved that the enzyme was successfully encapsulated into the electrospun nanofibers. Under the optimal conditions, the lowest detection limit was found to be 0.04 μM (S/N = 3) for 2,4-DCP and the highest detection limit was found to be 12.10 μM for 4-CP. The sensitivity of the biosensor obtained in the linear range for chlorophenols followed the sequence 2,4-dichlorophenol (2,4-DCP) > 2,4,6-trichlorophenol (2,4,6-TCP) > 4-chlorophenol (4-CP). The sensing performance for chlorophenols was attributed to the suitable electrochemical interface of PVA/F108/Au NPs/Lac, resulting from biocompatibility, a high surface area-to-volume ratio (10.42 m(2) g(-1)) and superior mechanical properties of the electrospun nanofibers. The biosensor exhibited good repeatabilities of 7.6%, 2.8% and 9.0% (R.S.D.) and reproducibilities of 14.9%, 10.4% and 13.7% (R.S.D.) for 4-CP, 2,4-DCP and 2,4,6-TCP, respectively. Lac retained 65.8% of its initial activity after a 30-day storage period.