新型汉防己甲素衍生物的合成及其生物活性

以汉防己甲素为原料,经溴代反应制得关键中间体5-溴汉防己甲素(2); 2与硼酸衍生物经Suzuki反应合成了6个新型的汉防己甲素衍生物(4a~4f),其结构经¹H NMR, ¹³C NMR和ESI-MS表征。采用CCK-8法初步考察了4a~4f对人早幼粒白血病细胞(HL60)和人肺癌细胞(A549)的抑制活性;并采用MTT法对活性较好的化合物进行复筛。采用酶联免疫吸附法考察4a~4f对多种受体酪氨酸激酶的抑制活性。结果表明：4b, 4c和4e对HL60和A549有一定的抑制活性; 4b和4c对受体酪氨酸激酶FGFR1的抑制活性大于50%。     

汉防己甲素全合成研究进展

汉防己甲素是防己科千金藤属植物粉防己中分离提取的双苄基异喹啉类生物碱,已作为临床药物用于抗风湿及阵痛、抗肺癌、抗矽肺。基于粉防己产量的限制及汉防己甲素的需求量增加,深入开展汉防己甲素的全合成研究势在必行。本文按照合成策略,对汉防己甲素的全合成方法进行了综述。      

雷公藤甲素及其衍生物的合成研究进展

综述了雷公藤甲素及其衍生物的化学合成与结构修饰研究进展.参考文献40篇.     

新型腔肠素衍生物的合成

以2-氨基吡嗪为原料,经5步反应(两次NBS溴代反应,两次Suzuki 交叉偶联反应和HCl作用下的缩合反应),合成了6个新型的C⁸-位芳杂环取代的腔肠素衍生物,其结构经¹H NMR和¹³C NMR表征。     

丁烷型木脂素及衍生物的合成和生物活性

报道了一条合成丁烷木脂素的新路线. 以芳香醛为起始原料, Stobbe缩合和烷基化反应为关键步骤, 构建了木脂素骨架, 再经拆分及还原, 可得到相应的苏式和赤式异构体. 经官能团转化得到5个丁烷木脂素和8个丁醚木脂素, 其中3个天然产物为首次合成. 对合成产物进行抗HIV病毒和和抗疱疹病毒活性研究, 部分化合物显示出较高的抗病毒活性, 而且骨架构型对活性影响较大.     

冬凌草甲素葡萄糖苷的合成

为研究冬凌草甲素的构效关系,合成生物活性更高的化合物,以冬凌草甲素为先导化合物,通过对其进行选择性保护,再进行糖苷化,最后脱保护,经五步反应,以23.0%的总收率,合成了冬凌草甲素-6-O-β-D-葡萄糖苷,并得到一系列冬凌草甲素衍生物,它们的结构经IR,1H NMR,MS和元素分析确证.     

邻苯二甲酰亚胺-多胺缀合物的合成及其生物活性

以邻苯二甲酰亚胺、1,3-丙二胺、1,4-丁二胺为原料,合成了5个邻苯二甲酰亚胺-多胺缀合物．所合成的目标化合物经过^1H NMR、^13C NMR、MS、元素分析确认,并评价了它们对K562（人慢性原白血病细胞）、MB231（乳腺癌细胞）、LnCap（前列腺癌细胞）的生物活性．结果表明：5个目标化合物均不具备抗肿瘤活性,提示多胺衍生化不能提高邻苯二甲酰亚胺的抗肿瘤活性．     

新型褪黑激素衍生物的合成及其抗氧化活性

以褪黑激素和取代苄溴为原料,四氢呋喃为溶剂,经亲核取代反应在N1位衍生化,合成了16个褪黑激素衍生物(3a~3p);以褪黑激素和取代苯硼酸为原料、四三苯基膦钯作为催化剂、甲苯和乙醇作为溶剂,加热回流下发生Suzuki偶联反应在C2位衍生化,合成了11个褪黑激素衍生物(7a~7k)。所有产物的结构经1H NMR、 13C NMR和LC-MS表征,其中有15个为新化合物(3a~3o)。体外抗氧化活性(ORAC法)测试结果显示：抗氧化活性最强的为7a,是阳性对照L-抗坏血酸(VC)的1.68倍[μMTE/gDW=7582.0(7a),μMTE/gDW=4507.9(VC)]。     

含三氟甲取代喹啉衍生物的合成及其抗肿瘤活性

为了寻找高效低毒的抗肿瘤活性化合物,设计并合成21个新型含三氟甲基取代喹啉酰胺类衍生物,其结构经¹H NMR、¹³C NMR及¹⁹F NMR和MS（ESI）进行了确证。用MTT法评价了所得目标化合物对乳腺癌细胞（MDA-231）、前列腺癌细胞（LNCAP）、人肺癌细胞（A549）、肾癌细胞（A498）和宫颈癌细胞（Hela）增殖的抑制活性。      

8-氯腺苷衍生物的合成及生物活性研究

N^6－甲基－8－氯腺苷的合成是以N，N－二甲基乙酰胺为溶剂由腺苷与碘甲烷反应，生成N^1-甲基－8－氯腺苷，经过Dimorth重排而得到，优化反应条件后，N^1-甲基－8－氯腺苷收率为52％。8－氯腺苷糖环羟基被酯化后失去原有的生物活性，碱基环外氨基氢被甲基取代后基本保持原有的生物活性。     

含二茂铁基的咪唑啉酮类化合物的合成与生物活性

含二茂铁基的咪唑啉酮类化合物的合成与生物活性     

Synthesis,Characterization, and Biological Activity of Substituted Thiazole-5-carboxaldehydes and Their Ylidenenitriles Derivatives

The Vilsmeier–Haack reaction of 2-amino -4-(4-substituted phenyl)-thiazoles 1, in the presence of micellar media, gives formylated derivatives 2, which upon hydrolysis afforded thiazole-5-carboxaldehydes 3. Microwave-assisted Knoevenagel condensation of 3 with active methylene compounds, in the presence of piperidine as catalyst, gives excellent yields of ylidenenitrile compounds 4. The structures of the newly synthesized compounds were established on the basis of elemental analysis, IR, ¹H NMR, and ¹³C NMR spectral analysis. All newly synthesized compounds were screened for antibacterial activity using two Gram-positive and one Gram-negative bacterial species and their antifungal activity was screened using two fungal species.     

新型苯并噻吩七元稠环芳烃衍生物的合成

以2,3,4,5-四碘代噻吩为起始原料,经Suzuki偶联反应和三氯化铁氧化成环反应,合成了三个新型的苯并噻吩七元稠环芳烃衍生物,其结构经1H NMR,13C NMR,MS,IR和元素分析表征。     

Design,Synthesis, and Biological Evaluation of N14-Amino Acid-Substituted Tetrandrine Derivatives as Potential Antitumor Agents against Human Colorectal Cancer

As a typical dibenzylisoquinoline alkaloid, tetrandrine (TET) is clinically used for the treatment of silicosis, inflammatory pulmonary, and cardiovascular diseases in China. Recent investigations have demonstrated the outstanding anticancer activity of this structure, but its poor aqueous solubility severely restricts its further development. Herein, a series of its 14-N-amino acid-substituted derivatives with improved anticancer effects and aqueous solubility were designed and synthesized. Among them, compound 16 displayed the best antiproliferative activity against human colorectal cancer (HCT-15) cells, with an IC₅₀ value of 0.57 μM. Compared with TET, 16 was markedly improved in terms of aqueous solubility (by 5-fold). Compound 16 significantly suppressed the colony formation, migration, and invasion of HCT-15 cells in a concentration-dependent manner, with it being more potent in this respect than TET. Additionally, compound 16 markedly impaired the morphology and motility of HCT-15 cells and induced the death of colorectal cancer cells in double-staining and flow cytometry assays. Western blot results revealed that 16 could induce the autophagy of HCT-15 cells by significantly decreasing the content of p62/SQSTM1 and enhancing the Beclin-1 level and the ratio of LC3-II to LC3-I. Further study showed that 16 effectively inhibited the proliferation, migration, and tube formation of umbilical vein endothelial cells, manifesting in a potent anti-angiogenesis effect. Overall, these results revealed the potential of 16 as a promising candidate for further preclinical studies.     

取代嘧啶化合物的合成和生物活性研究

合成了14个新型取代嘧啶类化合物,结构经质谱、红外光谱、氢核磁共振光谱和元素分析确证.杀虫、杀菌和除草活性测定结果表明,部分化合物具有良好的杀菌活性.在嘧啶环的2-位上导入二甲氨基时表现出杀菌活性,但在嘧啶环的5-位上有甲基取代基时,杀菌活性下降.在嘧啶的4-位导入苯氧基时,显示出良好的杀菌活性,如化合物3b,3c和3e,苯环上的最优取代基是2-硝基-4-三氟甲基.     

吡唑衍生物的合成及生物活性

以５－吡唑甲酰肼（７，８）为原料合成了４类共３０种新化合物，这些化合物的结构均经＾１Ｈ ＮＭＲ，元素分析证实，部分化合物还经过了ＭＳ、ＩＲ确证，对大部分化合物做了生物活性测试，结果表明均具有一定的杀菌和除草活性。     

One-Pot Synthesis of Phosphinylphosphonate Derivatives and Their Anti-Tumor Evaluations

This paper reports on the synthesis of new hydroxymethylene-(phosphinyl)phosphonates (HMPPs). A methodology has been developed to propose an optimized one-pot procedure without any intermediate purifications. Various aliphatic and (hetero)aromatic HMPPs were synthesized in good to excellent yields (53–98%) and the influence of electron withdrawing/donating group substitution on aromatic substrates was studied. In addition, the one-pot synthesis of HMPP was monitored by ³¹P NMR spectroscopy, allowing effective control of the end of the reaction and identification of all phosphorylated intermediate species, which enabled us to propose a reaction mechanism. Optimized experimental conditions were applied to the preparation of biological relevant aminoalkyl-HMPPs. A preliminary study of the complexation to hydroxyapatite (bone matrix) was carried out in order to verify its lower affinity towards bone compared to bisphosphonate molecules. Moreover, in vitro anti-tumor activity study revealed encouraging antiproliferative activities on three human cancer cell lines (breast, pancreas and lung).