积雪草酸衍生物的合成及抗肿瘤活性研究

以天然产物积雪草酸为起始原料,对其C-2、C-3、C-23位羟基、C-11位氢、C-28位羧基进行结构改造,合成了13个新的积雪草酸衍生物,其结构经MS及1H NMR等确证。采用MTT法,选用高表达人癌细胞(He La、Hep G2和BGC-823)对它们进行初步的体外抗肿瘤活性研究,结果表明,所测化合物对He La、Hep G2和BGC-823肿瘤细胞的抑制活性均明显强于积雪草酸,其中化合物I4和II4对He La、Hep G2和BGC-823细胞表现出很强的抑制活性,明显高于已上市药物吉非替尼,值得进一步研究。     

3-芳基-4-芳胺甲基异噁唑衍生物的合成及其生物活性初探

异噁唑衍生物由于其良好的生物活性一直受到有机合成化学家的关注,例如异噁唑衍生物具有杀虫、杀菌等生物活性.以3-芳基4-异噁唑甲酸乙酯为原料,经还原、溴化、取代反应合成了一系列3-芳基-4-芳胺甲基异噁唑衍生物,目标化合物结构经过~1H NMR、~(13)C NMR、HRMS鉴定.初步的生物活性测试结果显示,部分化合物对蚜虫和粘虫具有较好的抑制率.     

积雪草酸生物活性的研究进展

积雪草酸属于五环三萜类化合物,是中药积雪草的重要组分,具有广泛的生物活性,如治疗皮肤创伤和慢性溃疡、肝保护、抗抑郁、防治心脑血管疾病、抗阿尔茨海默病等。近年来,关于积雪草酸的药理活性、临床应用及结构修饰等方面的报道越来越多。本文就积雪草酸的药理活性及构效关系等的研究进展进行综述,为今后对积雪草酸的进一步研究提供参考。     

齐墩果酸A环与C环内酯衍生物的设计合成

齐墩果酸是一个五环三萜类天然产物,具有多种生物活性和药理活性.以齐墩果酸为起始原料,采用间氯过氧苯甲酸以及过氧化脲等试剂进行其A环和C环内酯化修饰,以较高收率获得了系列齐墩果酸A/C环内酯化衍生物.所有产物均经~1H NMR、~(13)C NMR和高分辨质谱数据分析进行了结构确定,其中有12个化合物为新化合物.     

碱性离子液体中吲哚与芳基硫酚的3-芳烃硫基化反应

无金属条件下,在离子液体[Hemim]N(CN)_2中,实现了吲哚衍生物与芳基硫酚的偶联反应,以中等至优良产率(68%~90%)合成系列芳烃硫基取代的吲哚化合物.其结构均经1H NMR,13C NMR及HRMS确证.该反应具有反应条件温和、底物适用范围广、环境友好等优点.此外,生成的产物通过进一步的修饰与转化可以衍生为结构复杂的、具有潜在生物活性的有机分子骨架结构.     

对氨基苯甲酸拟二肽酯的简易合成及其抗糖尿病活性初步研究

以未保护的对氨基苯甲酸和氨基酸酯直接反应, 一步法合成了9个未见报道的氨基酸修饰的对氨基苯甲酸衍生物(对氨基苯甲酸拟二肽酯), 合成方法简捷, 产物收率较高(78%～91%). 产物的结构经IR, 1H NMR, 13C NMR, MS, HRMS表征和证实. 初步的生物活性筛选结果表明, 这些化合物抗糖尿病活性较弱.     

PDE-4抑制剂的设计、合成及生物活性研究

依据药效团原理,对已报道的磷酸二酯酶(PDE-4)抑制剂Crisaborole进行结构修饰和改造,设计并合成了7个全新的小分子化合物,其结构经~1H NMR、~(13)C NMR和HRMS确证.研究其对磷酸二酯酶-4A(PDE-4A)的抑制活性、抑制炎症因子TNF-α释放效果以及抗炎活性.结果表明,所设计的7个化合物均表现出良好生物活性,其中一个化合物活性明显优于阳性对照药.     

一类新型大环内酯衍生物的合成及其生物活性研究

为了寻找高效、广谱的杀虫、杀菌剂,以去糖基或部分去糖基的多杀菌素为母体进行结构修饰,合成了8种大环内酯酰化衍生物,其结构经1H NMR,13C NMR和MS表征.对合成的化合物进行了生物活性测试.结果表明,这类化合物对鳞翅目、鞘翅目、双翅目、半翅目及线虫等害虫有较好的杀灭活性,其中化合物3e在100 mg/L浓度下对桃蚜的24 h杀灭率达到100%,化合物3f和3h在上药量为200μg时对假单胞菌有一定的抑制作用.     

螺环季酮酸的羧酸酯衍生物的合成及其杀螨活性

采用类同合成、活性亚结构拼接方法,对螺环季酮酸类杀虫杀螨剂Spirodiclofen进行设计修饰,合成了18种螺环季酮酸羧酸酯的新衍生物,结构经1H NMR、IR和元素分析确证,并用X射线单晶衍射测定了化合物6d的晶体结构。 通过其生物活性测试,探讨了其构效关系。     

染料木素氨基甲酸酯类衍生物的合成及生物活性研究

基于多靶点药物设计策略,以染料木素为先导化合物,对其7-位和4’-位羟基进行修饰,合成了24个染料木素氨基甲酸酯类衍生物,其化学结构经1H NMR和HRMS确证.生物活性测试结果表明,部分化合物对乙酰胆碱酯酶具有较强抑制活性,且对H2O2诱导的PC12细胞氧化损伤具有显著保护作用.     

Synthesis of Boswellic Acid Derivatives and Primary Research on their Activities

In order to search for new potent anti-cancer agents, a series of boswellic acid derivatives were designed and synthesized. Six of them were identified by IR, NMR and MS as new compounds and biologic assay of anti-cancer is underway.     

Synthesis of novel 15-membered macrolide derivatives

In order to develop new antibiotics effective against resistant bacteria,a series of novel 15-membered macrolide derivatives were designed and synthesized by the modification of hydroxyl groups at C-11,C-12 and C-4＂ positions.Their structures were confirmed by MS,IR,^1H NMR or ^13C NMR.     

13C NMR spectroscopy of some third-generation cephalosporins, their synthetic intermediaries and reaction byproducts

(13)C NMR spectroscopic data for 25 cephalosporin derivatives were assigned by combination of one- and two-dimensional experiments. The effect of the substitution at C-3, C-7 and C-4 acid group positions on the chemical shifts of the cephem nucleus is discussed.     

含哌嗪基7-溴噻吩并[3,2-d]嘧啶抗癌试剂的设计与合成

为寻找以蛋白酪氨酸激酶为靶点的新型抗癌试剂,本文设计与合成了系列含哌嗪基的7-溴噻吩并[3,2-d]嘧啶衍生物。以巯基乙酸为原料,经六步反应得4-氯-7-溴噻吩并[3,2-d]嘧啶母核,再与不同的哌嗪衍生物在添加三乙胺作碱的条件下反应,制备了五个未见报道的含哌嗪基7-溴噻吩并[3,2-d]嘧啶化合物。结构经1H NMR和HRMS表征。     

熊果酸衍生物的合成、表征及其对癌细胞的抑制活性

以熊果酸为母体化合物,对其3-OH和17-COOH进行结构修饰,设计合成了9个熊果酸衍生物,其结构经IR、¹H NMR和MS测试技术确证;噻唑蓝(MTT)比色法考察了所合成衍生物对体外人肝癌细胞HepG2培养增殖的抑制作用,结果显示受试衍生物均对细胞增殖有一定抑制作用,且呈剂量依赖性,其中衍生物9的抑制作用最强;衍生物9与细胞作用24 h后,经Hoechst 33342/PI双染色,倒置荧光显微镜下观察,出现细胞凋亡所具有的高蓝色/低红色荧光图;流式细胞术检测细胞周期发现：细胞被阻滞于S期,且阻滞作用随药物浓度的增加而增强。     

Synthesis and antibacterial activity of novel 10, 11-epoxy acylide erythromycin derivatives

A series of novel acylide derivatives have been synthesized from clarithromycin A via a facile procedure. The C-3 modifications involved replacing the natural C-3 cladinosyl group in clarithromycin core with different aryl-piperzine sidechain via chemical synthesis. Meanwhile a distinctive intermediate with 10,11-epoxy moiety was obtained. The structure and stereochemistry of this novel structure were confirmed via NMR and X-ray crystallography. Potential anti-bacterial activities against both Grampositive and Gram-negative bacteria were reported. Because of existence of C10,11-epoxide, these derivatives can be used as intermediates for further structural modification.     

新型齐墩果酸衍生物的合成及其抗肿瘤活性

以齐墩果酸(1)为原料,经3-羟基乙酰化,17-位羧基甲酯化,11-位碳羰基化及光照反应,首次实现了1的10-位角甲基的活化,合成了新型的齐墩果酸衍生物———3β-乙酰氧基-11α-羟基-11,25-环-齐墩果-12-烯-28-酸甲酯(4),其结构经1H NMR,13C NMR,IR和MS表征。采用SRB法测试了1～4及1的衍生物7～9对N-04,Bre-04和Lu-04细胞株的体外抑制活性,结果表明,4,8和9具有明显的抑制肿瘤细胞生长的能力。     

Synthesis and evaluation of novel 1,2,4-triazolo-[3,4-b]-1,3,4-thiadiazole tethered chalcone hybrids as potential anticancer agents

A series of novel 1,2,4-triazolo-[3,4-b]-1,3,4-thiadiazole tethered chalcone derivatives were designed synthesized by using conventional as well as microwave assisted methods and characterized by ¹H NMR, ¹³C NMR and mass spectral analysis. Microwave assisted synthesis caused an improvement in yield and significant reduction in the reaction time of all the derivatives. All the new synthesized derivatives were further evaluated for their anti-cancer activity against selected four human cancer cell lines; A549 (Lung), MCF-7 (Breast), Colo-205 (Colon) and A2780 (Ovarian). Among the synthesized compounds, 7b , 7c , 7d , 7e , 7g and 7h exhibited potent anticancer activity compared to control drug (etoposide).     

Synthesis and Anti-tumor Activity of Novel Amide Derivatives of Ursolic Acid

Ursolic acid was modified at C3 and C28 position to obtain fourteen derivatives including twelve novel compounds, and their chemical structures were characterized by IR, ^1H NMR and MS. Cell growth inhibitory effects of the derivatives against Hela cell were evaluated by MTT assay. All these derivatives were found to have stronger cell growth inhibitory than their parent compound, ursolic acid. The derivatives with a substituted acetyl group at C3 hydroxyl group show better activities than those with an unsubstituted hydroxyl group.     

Versatile routes to C-2- and C-6-functionalized glucose derivatives of iminodiacetic acid

A series of novel d-glucose derivatives, functionalized at the C-2 or the C-6 position with an iminodiacetic acid moiety for transition-metal complexation, has been prepared. The sugar and the metal-chelating parts are separated by either propyl or octyl chains and were introduced by the reaction of bromoalkylamine. Either N-1-Boc-3-bromopropylamine (17) or N-(8-bromooctyl)phthalimide (19) reacted with methyl 3,5,6-tri-O-benzyl-alpha-beta-d-glucofuranoside (4) (C-2 position) and 1,2:3,5-(O-methylene)-alpha-d-glucose (11) (C-6 position), respectively, in the presence of sodium hydride in DMF at room temperature, affording the desired intermediates. For aminopropyl derivatives, yields varied between 57% and 65%, and for aminooctyl derivatives, yields varied between 40% and 71%. After deprotection of the amine functionality, the metal chelate was built up by dialkylation (6a-c and 13a,b) with methyl bromoacetate in the presence of triethylamine under reflux in THF. Yields varied between 56% and 69% for the glucose modified at the C-2 position and between 58% and 62% for the one modified at the C-6 position. All compounds were characterized by 1H or 13C NMR or both, IR, and mass spectroscopy. Final products were isolated as a mixture of alpha and beta anomers.