油溶性缓蚀剂ω,ω’-双(1-辛基苯并咪唑-2-基)烷烃的合成及缓蚀性能研究

合成了系列ω,ω’-双(1-辛基苯并咪唑-2-基)烷烃油溶性缓蚀剂,并通过红外、质谱等进行结构表征。通过恒电位极化曲线,考察了此类缓蚀剂在2×10-4mol/L H2S-乙醇溶液中对铜电极极化曲线的影响。结果表明,此系列油溶性缓蚀剂对铜电极具有明显的缓蚀作用,且对金属铜的缓蚀效率高,作为润滑油添加剂具有很好的应用前景。     

4(6)-{2-[4-(2,3,4-三甲氧基苄基)哌嗪-1-基]-2-氧代乙氧基}芳甲酰胍类化合物的合成及其Na~+/H~+交换器1抑制活性

NHE1(Na+/H+交换器1)抑制剂对于心肌缺血再灌注损伤具有较好的保护作用.以苯(或吡啶)甲酰胍为母核,利用拼合原理,在苯(或吡啶)甲酰胍母环上引入4-(2,3,4-三甲氧基苄基)哌嗪-1-甲基,设计并合成了8个未见文献报道的目标化合物.其结构经MS,IR,1H NMR和元素分析确证.体外血小板肿胀模型(PSA)试验结果表明,大部分目标化合物显示出较好的NHE1抑制活性.     

新型烟酰胺腺嘌呤二核苷酸(NAD)类似物的合成及其辅酶活性

尝试4种形成焦磷酸键的方法合成了5种结构新颖的新型烟酰胺腺嘌呤二核苷酸(NAD)类似物.初步考察了类似物的生物活性,发现苹果酸酶和醇脱氢酶以类似物3b和3d为辅酶时,活性只有以NAD为辅酶时的13%～30%;而以类似物3a,3c和3e为辅酶时,这些酶的活性均极低.     

Design,synthesis characterization and in vitro biological activity of a series of 3-aryl-6-(bromoarylmethyl)-7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives as the novel acetylcholinesterase inhibitors

Bromination is used as a strategy to improve biological activity in medicinal chemistry.In order to study on the structure-activity relationships of the novel acetylcholinesterase inhibitors with 7H-thiazolo[3,2-b]-1,2,4-triazin-7-one scaffold,based on our previous work and molecular modeling,a series of novel 3-aryl-6-(bromoarylrnethyl)-7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives were designed by molecular docking,synthesized and characterized by mass spectra,infrared spectra,proton NMR and elemental analyses.The study of AChE inhibitory activity was carried out using the Ellman colorimetric assay with huperzine-A as the positive control.Most of all target compounds exhibited more than 45%inhibition at 10μmol/L.The preliminary structureactivity relationship was the bromine atoms and the hydroxyl group at the phenyl ring at the C6 position of the parent nucleus played significant roles in the AChE inhibitory activity of the target compounds.     

The isolation, structural determination, and total synthesis of terfestatin A, a novel auxin signaling inhibitor from Streptomyces sp.

Indole 3-acetic acid, a plant hormone auxin, regulates every aspects of plant growth and development. In the screening for specific inhibitors on auxin signaling using the transgenic Arabidopsis plant harboring the auxin-responsive reporter gene, terfestain A was found to be a novel inhibitor of auxin signaling from the culture of Streptomyces sp. F40. The structure of terfestatin A was determined to be p-terphenyl β-glucoside on the basis of spectroscopic analyses, chemical degradation, and total synthesis.     

Efficient routes to optically active azido-, amino-, di-azido- and di-amino-cyclitols with chiro- and allo-configuration from myo-inositol

Efficient routes to hitherto unknown 1d-2,5-di-azido-di-deoxy-allo-inositol, 1d-2,5-di-amino-di-deoxy-allo-inositol, 1l-1-azido-1-deoxy-chiro-inositol and 1l-1-amino-1-deoxy-chiro-inositol were developed by using cheaply available myo-inositol as the starting material. Preliminary investigations on the enzyme inhibitory properties were done. The methodology reported is amenable to gram scale synthesis and thus can find application in natural product synthesis.     

Absolute stereochemistries and total synthesis of (+)-arisugacins A and B, potent, orally bioactive and selective inhibitors of acetylcholinesterase

In the current studies, we used the Kakisawa-Kashman modification of the Mosher NMR method to determine the complete absolute stereochemistry of arisugacins. We also report the convergent total synthesis of (+)-arisugacins A and B by a sequence including (i) ruthenium complex-catalyzed asymmetric reduction of the cyclohexenone derivative; (ii) stereoselective construction of the arisugacin skeleton by a Knoevenagel-type reaction of an α,β-unsaturated aldehyde derivative with production of a 4-hydroxy-2-pyrone derivative as a key reaction; and (iii) stereoselective dihydroxylation to give the diol derivative, followed by deoxygenation. Accordingly, we defined the absolute structures of arisugacins A and B as 4a-(R),6a-(R),12a-(R), and 12b-(S). Finally, we characterized the bioactivities of the synthetic intermediates to understand the structure-activity relationships of the arisugacins.     

The Electrochemical Behavior of α‐Ketoglutarate at the Hanging Mercury Drop Electrode in Acidic Aqueous Solution and Its Practical Application in Environmental and Biological Samples

The voltammetric behavior of α‐ketoglutarate (α‐KG) at the hanging mercury drop electrode (HMDE) has been investigated in acetate buffer solution. Under the optimum experimental conditions (pH 4.5, 0.2 M NaAc‐HAc buffer solution), a sensitive reductive wave of α‐KG was obtained by linear scan voltammetry (LSV) and the peak potential was ?1.18 V (vs. SCE), which was an irreversible adsorption wave. The kinetic parameters of the electrode process were α=0.3 and k_s=0.72 1/s. There was a linear relationship between peak current i_{p, α‐KG} and α‐KG concentration in the range of 2×10^?6–8×10^?4 M α‐KG. The detection limit was 8×10^?7 M and the relative standard deviation was 2.0% (C_α‐KG=8×10^?4 M, n=10). Applications of the reductive wave of α‐KG for practical analysis were addressed as follows: (1) It can be used for the quantitative analysis of α‐KG in biological samples and the results agree well with those obtained from the established ultraviolet spectrophotometric method. (2) Utilizing the complexing effect between α‐KG and aluminum, a linear relationship holds between the decrease of peak current of α‐KG Δi_p and the added Al concentration Cequation/tex2gif-inf-5.gif in the range of 5.0×10^?6–2.5×10^?4 M. The detection limit was 2.2×10^?6 M and the relative standard deviation was 3.1% (Cequation/tex2gif-inf-6.gif=4×10^?5 M, n=10). It was successfully applied to the detection of aluminum in water and synthetic biological samples with satisfactory results, which were consistent with those of ICP‐AES. (3) It was also applied to study the effect of Al^III on the glutamate dehydrogenase (GDH) activity in the catalytically reaction of α‐KG+NH +NADH?L ‐glutamate+NAD⁺+H₂O by differential pulse polarography (DPP) technique. By monitoring DPP reductive currents of NAD⁺ and α‐KG, an elementary important result was found that Al could greatly affect the activity of GDH. This study could be attributed to intrinsic understanding of the aluminum's toxicity in enzyme reaction processes.     

Synthesis of an iminosugar based peptidomimetic analogue

The synthesis of an 1-deoxymannojirimycin based analogue of a known HIV-protease inhibitor is described. The strategies employed for introduction of the pharmacophore groups onto the azasugar scaffold were based on regioselective reactions of the hydroxyl groups of the natural product and of d-fructopyranoside derivatives.     

Stereoselective synthesis of procyanidin B3-3-O-gallate and 3,3″-di-O-gallate, and their abilities as antioxidant and DNA polymerase inhibitor

A simple method for the synthesis of procyanidin B3 substituted with a galloyl group at the 3 and 3″ position is described. Condensation of a benzylated catechin-3-O-gallate electrophile with a nucleophile, catechin and catechin-3-O-gallate, proceeded smoothly and stereoselectively to afford the corresponding dimer gallates, procyanidin B3-3-O-gallate and procyanidin B3-3,3″-di-O-gallate, in good yields. Further, their antioxidant activities on UV-induced lipid peroxide formation, DPPH radical scavenging activity and inhibitory activity of DNA polymerase were also investigated. Among three procyanidin B3 congeners (procyanidin B3, 3-O-gallate and 3,3″-di-O-gallate), the 3,3″-di-O-gallate derivative showed the strongest antioxidant and radical scavenging activity. Interestingly, the 3-O-gallate derivative was the strongest inhibitor of mammalian DNA polymerase with IC₅₀ value of 0.26 μM, although it showed the weakest antioxidant and radical scavenging activity. It became apparent that the presence of a galloyl group at the C-3 position in the proanthocyanidin oligomer was very important for biological activity, however, the antioxidant activity of these compounds was not parallel to the DNA polymerase inhibitory activity.