Glyconectin Cell Adhesion Epitope, β-d-GlcpNAc3S-(1→3)-α-l-Fucp,Is Involved in Blastulation of Lytechinus pictus Sea Urchin Embryos

Glycans, as the most peripheral cell surface components, are the primary candidates to mediate the initial steps of cell recognition and adhesion via glycan–glycan binding. This molecular mechanism was quantitatively demonstrated by biochemical and biophysical measurements at the cellular and molecular level for the glyconectin 1 β-d-GlcpNAc3S-(1→3)-α-l-Fucp glycan structure (GN1). The use of adhesion blocking monoclonal antibody Block 2 that specifically recognize this epitope showed that, besides Porifera, human colon carcinoma also express this structure in the apical glycocalyx. Here we report that Block 2 selectively immune-precipitate a Mr 580 × 10³ (g580) acidic non-glycosaminoglycan glycan from the total protein-free glycans of Lytechinus pictus sea urchin hatched blastula embryos. Immuno-fluorescence confocal light microscopy and immunogold electron microscopy localized the GN1 structure in the apical lamina glycocalyx attachments of ectodermal cells microvilli, and in the Golgi complex. Biochemical and immune-chemical analyses showed that the g580 glycan is carrying about 200 copies of the GN1 epitope. This highly polyvalent g580 glycan is one of the major components of the glycocalyx structure, maximally expressed at hatched blastula and gastrula. The involvement of g580 GN1 epitope in hatched blastula cell adhesion was demonstrated by: (1) enhancement of cell aggregation by g580 and sponge g200 glycans, (2) inhibition of cell reaggregation by Block 2, (3) dissociation of microvilli from the apical lamina matrix by the loss of its gel-like structure resulting in a change of the blastula embryonal form and consequent inhibition of gastrulation at saturating concentration of Block 2, and (4) aggregation of beads coated with the immune-purified g580 protein-free glycan. These results, together with the previous atomic force microscopy measurements of GN1 binding strength, indicated that this highly polyvalent and calcium ion dependent glycan–glycan binding can provide the force of 40 nanonewtons per single ectodermal cell association of microvilli with the apical lamina, and conservation of glycocalyx gel-like structure. This force can hold the weight of 160,000 cells in sea water, thus it is sufficient to establish, maintain and preserve blastula form after hatching, and prior to the complete formation of further stabilizing basal lamina.     

4-(4-甲氧基苯亚甲基)-2-苯基-5(4H)-噁唑酮纳米带的可控制备及光学特性研究

选取大π共轭体系4-(4-甲氧基苯亚甲基)-2-苯基-5(4H)-噁唑酮作为研究对象,采用再沉淀法制备其纳米晶体,通过研究溶剂、温度、搅拌速度、搅拌时间等因素对所形成的纳米粒子的形貌尺寸的影响,成功制备出了形貌较单一的纳米棒和纳米带结构并进一步考察了它们的紫外吸收和发射光谱,结果表明随着纳米粒子尺寸的增加,其吸收光谱和荧光光谱均出现红移,荧光量子效率随着粒子尺寸的增大略有增大.     

Comparative Studies on Regioselectivity of α- and β-Linked Glucan Tosylation

Alpha- and beta-linked 1,3-glucans have been subjected to conversion with p-toluenesulfonic acid (tosyl) chloride and triethylamine under homogeneous reaction conditions in N,N-dimethyl acetamide/LiCl. Samples with a degree of substitution of tosyl groups (DS_Ts) of up to 1.91 were prepared by applying 5 mol reagent per mole repeating unit. Hence, the reactivity of α-1,3-glucan is comparable with cellulose and starch, while the β-1,3-linked glucan curdlan is less reactive. The samples dissolve in aprotic dipolar media independent of the DS_Ts and possess a solubility in less polar solvents that depends on the DS_Ts. NMR studies on the tosyl glucans and of the peracylated derivatives showed a preferred tosylation of position 2 of the repeating unit. However, the selectivity is less pronounced compared with starch. It could be concluded that the α-configurated glycosidic bond directs tosyl groups towards position 2.     

Synthesis of photolabile 2-(2-nitrophenyl)propyloxycarbonyl protected amino acids

The 2-(2-nitrophenyl)propyloxycarbonyl (NPPOC) group has been introduced as a photolabile amino protecting group for amino acids to be used as building blocks in photolithographic solid-phase peptide synthesis. NPPOC-protected amino acids were found to be cleaved in the presence of UV light about twice as fast as the corresponding o-nitroveratryloxycarbonyl (NVOC)-protected amino acids.     

α-Functionally Substituted α,β-Unsaturated Aldehydes as Fine Chemicals Reagents: Synthesis and Application

α-Functionalized α,β-unsaturated aldehydes is an important class of compounds, which are widely used in fine organic synthesis, biology, medicine and pharmacology, chemical industry, and agriculture. Some of the 2-substituted 2-alkenals are found to be the key metabolites in plant and animal cells. Therefore, the development of efficient methods for their synthesis attracts the attention of organic chemists. This review focusses on the recent advances in the synthesis of 2-functionally substituted 2-alkenals. The approaches to the preparation of α-alkyl α,β-unsaturated aldehydes are not included in this review.     

Syntheses Based on 3,4α-Epoxy-1,5,7α,6β(H)-guai-10(14),11(13)-dien-6,12-olide

The sesquiterpene γ-lactone estafiatin 1, the molecule of which has a structure of 3,4α-epoxy-1,5,7α,6β(H)-guai-10(14),11(13)-dien-6,12-olide, is characteristic of plants of the genera Achillea L. and Artemisia L. of the Asteraceae family. This article presents the results of chemical modification for three reaction centers of the estafiatin molecule 1: epoxy cycle, exomethylene group conjugated with γ-lactone carbonyl, and exomethylene group in position C10=C14; and at the same time 33 new derivatives were synthesized, the structures of which were established based on physicochemical constants, spectral data (IR-, PMR-, ¹³C-NMR), and X-ray diffraction analysis. The stereo- and regiospecificity, as well as the chemoselectivity of the reaction based on estafiatin molecule 1, are discussed. The reactivity of the substrate is significantly influenced by the stereochemistry of its molecule, the nature of the reagent, and the reaction medium. Based on the results of in silico screening, derivatives of estafiatin with high binding energies for both DNA-topoisomerase I and DNA-topoisomerase II were identified. The values of the inhibitory dose of IC₅₀ for estafiatin 1 and its derivatives were determined on cell lines of eight types of tumors. in vivo experiments of the samples made it possible to establish that estafiatin 1 and its derivatives have pronounced antitumor activity against Pliss lymphosarcoma, Walker’s carcinosarcoma, sarcoma 45, sarcoma-180, alveolar liver cancer PC-1, leukemia P-388 and L-1210, and sarcoma-45 resistant to 5-fluorouracil.     

Dicarboxylic Acid Monoesters in β- and δ-Lactam Synthesis

A N-(2-methoxy-2-oxoethyl)-N-(phenylsulfonyl)glycine monomethyl ester of the respective dicarboxylic acid was involved in a reaction with imines promoted by acetic anhydride at an elevated temperature. Instead of the initially expected δ-lactam products of the Castagnoli–Cushman-type reaction, medicinally important 3-amino-2-azetidinones were obtained as the result of cyclization, involving a methylene group adjacent to an acid moiety. In contrast, replacing alcohol residue with hexafluoroisopropyl in the same substrate made another methylene group (adjacent to the ester moiety) more reactive to furnishing the desired δ-lactam in the Castagnoli–Cushman fashion.     

Synthesis,Kinetic and Conformational Studies of 2-Substituted-5-(β-d-glucopyranosyl)-pyrimidin-4-ones as Potential Inhibitors of Glycogen Phosphorylase

Dysregulation of glycogen phosphorylase, an enzyme involved in glucose homeostasis, may lead to a number of pathological states such as type 2 diabetes and cancer, making it an important molecular target for the development of new forms of pharmaceutical intervention. Based on our previous work on the design and synthesis of 4-arylamino-1-(β-d-glucopyranosyl)pyrimidin-2-ones, which inhibit the activity of glycogen phosphorylase by binding at its catalytic site, we report herein a general synthesis of 2-substituted-5-(β-d-glucopyranosyl)pyrimidin-4-ones, a related class of metabolically stable, C-glucosyl-based, analogues. The synthetic development consists of a metallated heterocycle, produced from 5-bromo-2-methylthiouracil, in addition to protected d-gluconolactone, followed by organosilane reduction. The methylthio handle allowed derivatization through hydrolysis, ammonolysis and arylamine substitution, and the new compounds were found to be potent (μM) inhibitors of rabbit muscle glycogen phosphorylase. The results were interpreted with the help of density functional theory calculations and conformational analysis and were compared with previous findings.     

2—（芳磺酰基）—1—（2—噻吩基）乙酮的合成

２－（芳磺酰基）－１－（２－噻吩基）乙酮的合成丁言斌樊爱龙张正＊（南京大学化学系南京２１００９３）关键词氯噻吩基乙酮，芳磺酰基噻吩基乙酮，合成，相转移催化１９９６－０８－１２收稿，１９９７－０１－１３修回砜类化合物不仅是有机合成的有用中间体［１］，而...     

芳氨基代-α-呋喃葡萄糖衍生物的合成及抗肿瘤活性

分别以2-甲基-5-硝基苯甲酸、2-氯-5-硝基苯甲酸为原料,经羧基氯化、Friedel-Crafts酰基化、羰基还原、硝基还原和还原胺化反应合成了4种新型的1,2-O-异丙叉基-5-芳氨基代-α-呋喃葡萄糖衍生物。 利用IR、NMR和HRMS等技术手段对反应所及中间体及目标化合物进行了结构测定和表征,并采用MTT法将目标化合物对3种人体肿瘤细胞的抗肿瘤活性进行了初步评价。 结果表明,目标化合物1a1对肿瘤细胞的生长抑制作用优于其它3种目标化合物,特别是对A431细胞表现出更明显的生长抑制活性(IC₅₀:(6.54±1.34) μmol/L)。     

Stereoselective Synthesis of β-Glycinamide Ribonucleotide

A diastereoselective synthesis of the β-anomer of glycinamide ribonucleotide (β-GAR) has been developed. The synthesis was accomplished in nine steps from D-ribose and occurred in 5% overall yield. The route provided material on the multi-milligram scale. The synthetic β-GAR formed was remarkably resistant to anomerization both in solution and as a solid.     

1-(2-苯并呋喃酰基)愈创兰烃薁的合成

在路易斯酸作用下, 以氯乙酰氯为酰基化试剂, 对愈创兰烃薁进行了酰化反应研究, 将氯乙酰化产物与水杨醛在温和反应条件下进行缩合, 以较好的收率、高选择性地得到1-(2-苯并[b]呋喃酰基)兰烃薁类衍生物, 其结构经1H NMR, IR及元素分析等得以证实.     

Synthesis and Crystal Structure of 1-（Trifluoromethyl）-1-（propioloyl）-（E）-3-oxo-（2-thienyl）-（2-naphthylamine）

1INTRODUCTIONTheSchiffbasesderivedfromb-diketonesandaliphaticamineshavebeenshowntoexistastheketo-amines.However,ifsubstituentseitherattheketooraminogrouparearomatic,itmaybeexpectedtheenoliminewillbethefavoredtautomericform[1].Recently,someSchiffbasesderivedfromTTA(4,4,4-trifluoro-1-(2-thienyl)-1,3-butanedione)andPMBPhavebeenstudiedbyWang[2]andYu[3]etal.Inordertostudytherelationshipbetweenthestructuresandperformancesofthesecompounds,thetitlecom-poundwillbereportedherein.2EXPERIMENT…     

7β-(3-Ethyl-cis-crotonoyloxy)-1α-(2-methylbutyryloxy)-3,14-dehydro-Z Notonipetranone Attenuates Neuropathic Pain by Suppressing Oxidative Stress,Inflammatory and Pro-Apoptotic Protein Expressions

7β-(3-Ethyl-cis-crotonoyloxy)-1α-(2-methylbutyryloxy)-3,14-dehydro-Z-notonipetranone (ECN), a sesquiterpenoid obtained from a natural source has proved to be effective in minimizing various side effects associated with opioids and nonsteroidal anti-inflammatory drugs. The current study focused on investigating the effects of ECN on neuropathic pain induced by partial sciatic nerve ligation (PSNL) by mainly focusing on oxidative stress, inflammatory and apoptotic proteins expression in mice. ECN (1 and 10 mg/kg, i.p.), was administered once daily for 11 days, starting from the third day after surgery. ECN post-treatment was found to reduce hyperalgesia and allodynia in a dose-dependent manner. ECN remarkably reversed the histopathological abnormalities associated with oxidative stress, apoptosis and inflammation. Furthermore, ECN prevented the suppression of antioxidants (glutathione, glutathione-S-transferase, catalase, superoxide dismutase, NF-E2-related factor-2 (Nrf2), hemeoxygenase-1 and NAD(P)H: quinone oxidoreductase) by PSNL. Moreover, pro-inflammatory cytokines (tumor necrotic factor-alpha, interleukin 1 beta, interleukin 6, cyclooxygenase-2 and inducible nitric oxide synthase) expression was reduced by ECN administration. Treatment with ECN was successful in reducing the caspase-3 level consistent with the observed modulation of pro-apoptotic proteins. Additionally, ECN showed a protective effect on the lipid content of myelin sheath as evident from FTIR spectroscopy which showed the shift of lipid component bands to higher values. Thus, the anti-neuropathic potential of ECN might be due to the inhibition of oxidative stress, inflammatory mediators and pro-apoptotic proteins.     

Binary Effects of Gynostemma Gold Nanoparticles on Obesity and Inflammation via Downregulation of PPARγ/CEPBα and TNF-α Gene Expression

Nanoscience is a multidisciplinary skill with elucidated nanoscale particles and their advantages in applications to various fields. Owing to their economical synthesis, biocompatible nature, and widespread biomedical and environmental applications, the green synthesis of metal nanoparticles using medicinal plants has become a potential research area in biomedical research and functional food formulations. Gynostemma pentaphyllum (GP) has been extensively used in traditional Chinese medicine to cure several diseases, including diabetes mellitus (DM). This is the first study in which we examined the efficacy of G. pentaphyllum gold nanoparticles (GP-AuNPs) against obesity and related inflammation. GP extract was used as a capping agent to reduce Au²⁺ to Au⁰ to form stable gold nanoparticles. The nanoparticles were characterized by using UV–VIS spectroscopy, and TEM images were used to analyze morphology. In contrast, the existence of the functional group was measured using FTIR, and size and shape were examined using XRD analysis. In vitro analysis on GP-AuNPs was nontoxic to RAW 264.7 cells and 3T3-L1 cells up to a specific concentration. It significantly decreased lipid accumulation in 3T3-L1 obese and reduced NO production in Raw 264.7 macrophage cells. The significant adipogenic genes PPARγ and CEPBα and a major pro-inflammatory cytokine TNF-α expression were quantified using RT-PCR. The GP-AuNPs decreased the face of these genes remarkably, revealing the antiadipogenic and anti-inflammatory activity of our synthesized GP-AuNPs. This study represents thorough research on the antiobesity effect of Gynostemma pentaphyllum gold nanoparticles synthesized using a green approach and the efficacy instead of related inflammatory responses.     

2-(2,4-二氟苯基)-1-(4-烃基派嗪-1-基)-3-(1,2,4-三唑-1-基)-2-丙醇类化合物的合成及抗真菌活性

近20年来,真菌感染特别是深部真菌感染日益引起人们的广泛关注[1]。三唑类抗真菌药物对真菌的选择性较高,代谢稳定,体内动态、安全性都较好,已成为目前抗真菌药物研究开发的重点[2]。三唑类抗真菌药物是细胞色素P450 14α 去甲基酶的抑制剂,可影响该酶所催化的真菌麦角甾醇的生物合成,导致真菌细胞膜破损而死亡[3,4]。1998年,SynPhar实验室及Taiho制药公司[5]研制开发的化合物Syn 2869采用了取代哌嗪作为侧链。体外实验表明,该化合物抗菌谱广,对多种念珠菌、隐球菌及曲莓菌均有效,体内实验中,与目前临床上治疗真菌感染的主要用药伊曲…     

The Effect of α-, β- and γ-Cyclodextrin on Wheat Dough and Bread Properties

Cyclodextrins (CDs) are cyclic oligosaccharides that have found widespread application in numerous fields. CDs have revealed a number of various health benefits, making them potentially useful food supplements and nutraceuticals. In this study, the impact of α-, β-, and γ-CD at different concentrations (up to 8% of the flour weight) on the wheat dough and bread properties were investigated. The impact on dough properties was assessed by alveograph analysis, and it was found that especially β-CD affected the viscoelastic properties. This behavior correlates well with a direct interaction of the CDs with the proteins of the gluten network. The impact on bread volume and bread staling was also assessed. The bread volume was in general not significantly affected by the addition of up to 4% CD, except for 4% α-CD, which slightly increased the bread volume. Larger concentrations of CDs lead to decreasing bread volumes. Bread staling was investigated by texture analysis and low field nuclear magnetic resonance spectroscopy (LF-NMR) measurements, and no effect of the addition of CDs on the staling was observed. Up to 4% CD can, therefore, be added to wheat bread with only minor effects on the dough and bread properties.     

(Z)-2-(1H-咪唑-1-基)-1-(2,3,4-三甲氧基)苯乙酮肟酯的设计与合成

三甲基苯乙酮肟;立体异构体;(Z)-2-(1H-咪唑-1-基)-1-(2;3;4-三甲氧基)苯乙酮肟酯的设计与合成     

3-S-(β-D-吡喃葡萄糖基)-1,2,4-三唑的合成及抗菌活性

以自制的5-取代芳基-4-氨基-3-巯基-1,2,4三唑为底物, 经糖基修饰后, 在甲醇钠/甲醇/二氯甲烷体系中经水解脱除糖环上的乙酰基, 得到9个新化合物5-取代苯基-4-氨基-3-S-(β-D-吡喃葡萄糖基)-1,2,4-三唑(6a~6i), 其结构经核磁共振波谱(¹H NMR, ¹³C NMR), 红外光谱(IR)和高分辨质谱(HRMS)确认. 生物活性测试结果表明, 目标化合物对大肠杆菌、 金黄色葡萄球菌、 枯草芽孢杆菌和白色念珠菌均显示出良好的抑菌活性. 化合物6g对大肠杆菌、 金黄色葡萄球菌、 枯草芽孢杆菌和白色念珠菌的最小抑菌浓度分别达到2, 8, 32和8 μg/mL, 抑菌效果接近或优于对照药物三氯生和氟康唑. 利用Autodock程序研究了目标化合物(6a~6i)与大肠杆菌烯脂酰还原酶(FabⅠ)受体蛋白分子的相互作用和结合自由能变化规律.     

镍催化α,β-不饱和醛的选择性α,β-双芳基化反应

三组分双官能化反应是一种高效、简便构建C―C键、C―X键的方式. 双键广泛存在于众多有机化合物中, 对双键的双官能化反应研究有巨大的应用潜力. 本工作以Ni(COD)₂为催化剂, 以芳基溴化镁、芳基溴化物为芳基化试剂, 实现了3-芳基-2-丙烯醛亚胺中碳碳双键的双芳基化反应. 该反应建立了一个新的镍催化α,β-不饱和醛的α,β-双芳基化方法, 可以高度区域选择性地向底物分子中引入两个不同取代的芳环, 得到多种2,3,3-三芳基丙醛骨架的产物. 利用这一反应作为核心步骤实现了天然产物Quebecol的简便合成. 机理研究表明, 该反应可能经历了亲核加成、金属交换、还原消除的历程.