STUDIES ON THE SYNTHESIS OF D-GLUCURONIC ACID DERIVATIVES OF 2-BUTOXY-5-FLUORO-3H-4-PYRIMIDONE AND THEIR ANTICANCER ACTIVITIES

2-Butoxy-5-fluoro-3H-4-pyrimidone derivatives of D-glucuronic acid having 0-glycosidic linkage or N-glycosidic linkage were synthesized and their anticancer activity tested.Their structures were confirmed by elementary analysis,IR spectra and ~1HNMR.

Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist inhibits apoptosis of retinal ganglion cells in a rabbit model of optic nerve injury

A rabbit model of traumatic optic nerve injury, established by occlusion of the optic nerve using a vascular clamp, was used to investigate the effects of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist GYKI 52466 on apoptosis of retinal ganglion cells following nerve injury. Hematoxylin-eosin staining and a terminal deoxynucleotidyl transferase dUTP nick end labeling assay showed that retinal ganglion cells gradually decreased with increasing time of optic nerve injury, while GYKI 52466 could inhibit this process. The results demonstrate that following acute optic nerve injury, apoptosis of retinal ganglion cells is a programmed process, which can be inhibited by the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist.

Use of Ultrasound and Microwave Irradiation for Clean and Efficient Synthesis of 3,3’-(Arylmethylene)bis (2-hydroxynaphthalene-1,4-dione) Derivatives

Nine 3,3’-(arylmethylene)bis(2-hydroxynaphthalene-1,4-dione) derivatives were synthesized through the reaction between 2-hydroxy-1,4-naphthalen-1,4-dione and different aromatic alde-hydes in water applying ultrasonic irradiation for 5 min at room temperature and microwave irradiation for 15 min at 70°;C. Two of the nine derivatives, compounds 3-e and 3-i, obtained from 3-bromo-hydroxybenzaldehyde and 5-methylfuran-2-carbaldehyde, respectively, are previously unpublished. The structures of all compounds were established on the basis of their spectral data and mass analysis. The attractive features of this synthesis protocol include mild conditions, high atom-economy and excellent yields with the elimination of water as the only by-product.

Role of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor regulation in stress-induced pain chronification

Persistent postsurgical pain is a serious issue in public health, which has received increased interest in recent years. Previous studies have reported that psychological factors promote the development of chronic postsurgical pain. However, it is unclear how chronification of postsurgical pain occurs. The α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor(AMPA) phosphorylation in the central nervous system plays a critical role in synaptic plasticity and contributes to central sensitization and chronic pain development. Here, we discuss the role of AMPA receptor regulation in stress-induced pain chronification after surgery.

A Facile Synthesis of 9,10-Dimethoxybenzo[6,7]- ox-epino[3,4-<i>b</i>]quinolin-13(6<i>H</i>)-one and Its Derivatives

A concise and efficient method for the synthesis of novel 9,10-imethoxybenzo[6,7]oxepino[3,4-b]quinolin13(6H)-one and its derivatives 7a-p has been developed via the intramolecular Friedel-Crafts acylation reactions of 6,7-dimethoxy-2-(phenoxymethyl)quinoline-3-carboxylic acids 6a-p with polyphosphoric acid (PPA) as catalyst and solvent under mild conditions. The key intermediates 6a-p were prepared through the in situ formation of ethyl 6,7-dimethoxy-2-(phenoxymethyl)quinoline-3-carboxylates 5a-p followed by hydrolysis with aqueous ethanolic sodium hydroxide solution. The novel synthetic method has the advantages of good yields, easy work-up, and environmentally friendly character, which may provide a novel highly efficient process for making quinoline and related azaheterocycle libraries.

Synthesis and Crystal Structure of α-(3-Phenylureido)-α-(2,4-Dichlorophenyl) Methyl Phenylphosphinic Acid

The crystal structure of a (3-phenylureido)-a (2, 4-dichlorophenyl)methyl phenylphosphinic acid, C20H17Cl2N2O3P, Mr= 435. 25,which was obtained bydesulphurisation of cis-3, 4-dipheny1-5- (2, 4-dichlorophenyl ) -1, 3, 4-diazaphospholidin2-thione-4-oxide utilizing Ag+ -H2O system in a yield of 89%, is reported. It crystallizes in orthorhombic space group Pca21 with a= 11. 286(2), b= 20. 601 (4) f c=8. 695(2)A, V= 2021 (1) A3, Z= 4, D.= 1. 430 g/cm3, p=4. 21 cm-1, F(000) =896.The final R factor is 0. 040 and Rw is 0. 045 for 946 unique observed reflections[I>3a(I)]. The result of X-ray analysis indicates that the molecules in the crystal are linkedtogether by the O(3 ) ...H (2d) - N (2d ) intermolecular hydrogen-bondings.

3-取代-4-氧-3H-咪唑并[5,1-d][1,2,3,5]四嗪-8-羧酸衍生物抗癌活性的构效关系

采用量子化学和分子力学方法研究3-取代-4-氧-3H-咪唑并[5,1-d][1,2,3,5]四嗪-8-羧酸衍生物分子结构与抗癌活性的关系.结果表明,3-取代-4-氧-3H-咪唑并[5,1-d][1,2,3,5]四嗪-8-羧酸衍生物抗癌活性与分子疏水性参数logP、8位取代基R1上的净电荷等因素有关,可通过向8位引入带正电荷取代基的办法来提高先导化合物的抗癌活性.

4-羟基-3-甲氧基肉桂酸衍生物除草活性研究

为了寻找新的除草活性化合物,利用茎叶处理、叶绿体光密度测定及相对电导率测定等方法对天然产物4-羟基-3-甲氧基肉桂酸及其3个衍生物进行了除草活性研究。结果表明:4-羟基-3-甲氧基肉桂酸、4-羟基-3-甲氧基肉桂酸酰肼、4-乙酰氧基-3-甲氧基肉桂酸和4-羟基-3-甲氧基肉桂酸乙酯在光照条件下对马唐的抑制中浓度(IC50)分别为4.31,1.97,4.26和0.67mg/mL;黑暗条件下分别为2.65,0.83,2.54和0.36mg/mL;4-乙酰氧基-3-甲氧基肉桂酸对马唐叶绿体光密度的影响呈上升趋势;4-羟基-3-甲氧基肉桂酸酰肼、4-乙酰氧基-3-甲氧基肉桂酸和4-羟基-3-甲氧基肉桂酸乙酯处理后,马唐的相对电导率分别增加了19.24%,11.96%和18.33%。可见这3个衍生物的除草活性均高于母体化合物。

(+)-1,2,3,4-四氢罂粟碱的合成

以Merrified树脂固载的BINOL衍生磷酸催化3,4-二氢罂粟碱不对称转移氢化反应制备了(+)-1,2,3,4-四氢罂粟碱。对催化剂进行了筛选并将最优催化剂在Merrified树脂上进行了负载。考察了溶剂、反应温度、Hantzsch酯结构等对产物收率和对映选择性的影响。以甲苯作为溶剂,温度40℃,2,6-二甲基-1,4-二氢吡啶-3,5-二羧酸甲酯为氢源时,产物的收率达95%,e.e.值达98%。负载手性磷酸催化剂可以方便的分离和回收利用。催化剂反复利用7次后,催化活性略有降低,活性降低的催化剂可以经氯化氢-乙酸乙酯溶液简单洗涤再生。

3-[(3-甲氧基-4-乙酰氧基-5-溴)苯基]丙烯酸的合成

目的:合成3-[(3-甲氧基-4-乙酰氧基-5-溴)苯基]丙烯酸。方法:以香草醛为原料,经溴代、Knoevenagel反应、乙酰化得到目标化合物。结果与结论:目标化合物结构经元素分析、IR的验证,其未见文献报道。

聚乙二醇负载苯磺酸催化Biginelli反应合成3,4-二氢嘧啶-2-酮衍生物的研究

在聚乙二醇负载的苯磺酸催化作用下,由醛、乙酰乙酸乙酯(或乙酰丙酮)、脲(或硫脲)3组份经Biginelli反应"一锅法"合成了系列3,4-二氢嘧啶-2-酮衍生物.该方法反应条件温和、反应时间短、产率高,并且催化剂具有可重复使用的优点.

A new pyrrolidone derivative from Pistacia chinensis

A new N-phenyl-pyrrolidone derivative had been isolated from Pistacia chinesis Bunge. Its structure was elucidated as 4-hydroxy-5-（2-oxo-1-pyrrolidinyl）-benzoic acid, named pistaciamide on the basis of the 1D-NMR, DEPT, HMQC and HMBC spectroscopic techniques. 2007 Xi Kui Liu. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

Drug discovery based on the structure of FKBP12: Design, synthesis and evaluation of L-1,4-thiazane-3-carboxylic acid derivatives as neuroimmunophilin ligands

By choosing neuroimmunophilin FKBP12 as a therapeutical target, we have attempted to discover a new structural drug for treating neurodegenerative disease. This drug should possess neurotrophic activity and not affect the immune system. Based on the crystal structure of FKBP12, FK506 and Calcineurin complex, a series of small organic molecules were designed. These molecules were to have the ability of binding to FKBP12 in a virtual screening. By using a solution parallel synthetic method, these compounds were synthesized. The neuroprotective and neuroregenerative activities of these compounds were evaluated by binding assays, PC12 cells survival and neurite outgrowth model, chick dorsal root ganglion cultures (DRG) and 6-OHDA lesioned mice sympathetic nerve endings model. The evaluation results of these compounds showed that compound N308 has great promise as a candidate for a neuroprotective and neuroregenerative agent.

1-甲基-4-苯基-2(1H)喹啉酮衍生物的合成及表征

以苯丙炔酸与氮甲基苯胺合成的N-甲基-N-苯基-3-丙炔酸胺为原料,通过铁催化氧化、重氮化水解合成了一系列1-甲基-4-苯基-2(1H)喹啉酮衍生物。并对喹啉酮衍生物产物进行质谱、核磁共振氢谱和碳谱的定性及结构表征。此方法路线简单,反应条件温和,合成的各种目标产物产率和纯度较高,实验结果令人满意。

QSAR and Docking Studies of Thiazolidine-4-carboxylic Acid Derivatives as Neuraminidase Inhibitors

In order to understand the chemical-biological interactions governing their activities toward neuraminidase(NA),QSAR models of 28 thiazolidine-4-carboxylic acid derivatives with inhibitory influenza A virus were developed.Here a quantitative structure activity relationship(QSAR)model was built by three-dimensional holographic atomic vector field(3D-HoVAIF)and multiple linear regression(MLR).The estimation stability and prediction ability of the model were strictly analyzed by both internal and external validations.The correlation coefficient(R2)of established MLR model was 0.984,and the cross-validated correlation coefficient(Q2)of MLR model was 0.947.Furthermore,the cross-validated correlation coefficient for the test set(Qext 2)was 0.967.The binding mode pattern of the compounds to the binding site of integrase enzyme was confirmed by docking studies.The results of present study indicated that this model can aid in designing more potent neuraminidase inhibitors.

A New Sesquiterpene-substituted Benzoic Acid from the Brown Alga Dictyopteris divaricata

A new sesquiterpene-substituted benzoic acid has been isolated from the brown Alga Dictyopteris divaricata Okam.. Its structure was elucidated as 3-[(2-hydroxy-2,5,5,8a-tetra- methyldecahydro-1-naphthalenyl)methyl]-4-hydroxybenzoic acid, named dictyvaric acid on the basis of spectroscopic methods including IR, HRFABMS, 1D and 2D NMR techniques.

新型香豆素酰胺类化合物的合成及光学性能

以水杨醛、氰基乙酸乙酯、3-氨基-4-羟基苯甲酸为原料,合成2-（2-羰基-2H-1-苯并吡喃-3-基）苯并口恶唑-5-羧酸,再经酰氯化和N-酰化反应合成8个新型香豆素酰胺类化合物,收率为41%~65%。用核磁共振谱、质谱和红外光谱对其结构进行了表征,并用UV-Vis和荧光光谱研究了其光学性能。结果表明：其π-π＊跃迁特征峰在250~255 nm;其最大吸收波长在345~360 nm;最大发射波长λem约为440 nm,Stokes位移约为90 nm,荧光量子产率约为0.05。其摩尔吸光系数达到了10^5L/（mol·cm）的数量级,是一类潜在的荧光材料。

3-取代4-氧-3H-咪唑并[5,1-d][1,2,3,5]四嗪-8-羧酸衍生物抗肿瘤活性的定量构效关系研究

目的:研究3-取代-4-氧-3H-咪唑并[5,1-d][1,2,3,5]四嗪-8-羧酸衍生物分子结构与抗肿瘤活性的关系。方法:采用量子化学和分子力学方法计算分子结构参数,利用Gram-Schmidt正交化法筛选参数,利用偏最小二乘法建立QSAR模型。结果:建立合理的3-取代-4-氧-3H-咪唑并[5,l-d][1,2,3,5]四嗪-8-羧酸衍生物抗肿瘤活性模型。结论:3-取代-4-氧-3H-咪唑并[5,1-d][1,2,3,5]四嗪-8-羧酸衍生物抗肿瘤活性与分子油水分配系数LogP和8位取代基R_1上的非氢原子净电荷Q_1相关,研究结果可为同类抗肿瘤药物的分子设计提供参考。

△~1-哌啶酸(P2C)及其衍生物的合成综述

△~1-哌啶酸(P2C)是一种特殊的六元环席夫碱,是合成L-哌啶酸必需的前体分子。P2C和L-哌啶酸是赖氨酸在生物体内重要的代谢产物,更是化学合成中重要的手性构建模块和多种生物活性分子的关键组成片段。特别是,P2C及其衍生物可通过与生物体内乙酰胆碱受体、FKBP12结合蛋白、NO合酶等多种底物相互作用而介导特定的生理过程,对生命活动的正常进行和一些疾病的防治具有重要意义。因此,P2C片段及其衍生物的合成具有重要研究意义。通常以L-赖氨酸为原料制备P2C,但是,赖氨酸难以氧化脱氨,以及P2C的固有不稳定性,一直是干扰P2C稳定获取的关键问题。目前,在赖氨酸氧化脱氨和酶催化合成P2C方面已经有了一些成功的尝试。本文首次对有关△~1-哌啶酸及其衍生物的合成研究进行总结,以期为△~1-哌啶酸这一特殊席夫碱的研究和应用提供参考。