积雪草酸衍生物的合成与表征及体外抗癌活性的研究

为了寻找新型高效、低毒、生物活性良好的积雪草酸衍生物,以具有一定生物活性的积雪草酸为先导化合物,通过对其C-2,C-3,C-11,C-23和C-28位进行结构修饰,设计合成了9种未见文献报道的积雪草酸衍生物.目标化合物的结构经1H NMR,13C NMR,IR和HRMS表征确证.采用MTT法观察其对人宫颈癌细胞(Hela)、人乳腺癌细胞(MCF-7)的抑制作用.结果表明,经修饰的积雪草酸衍生物的抗癌活性较母体化合物有不同程度的增强.     

3-[(4'-吗啉基)-羰基或乙氧羰基]-4-苯氨基喹啉化合物的合成及抗肿瘤活性

以间氯苯胺与乙氧基亚甲基丙二酸二乙酯(EMME)为原料, 经缩合、 高温环合、 水解、 氯代和亲核取代等反应设计并合成了16个3位为(4'-吗啉)-羰基或乙氧羰基的4-苯氨基喹啉化合物(Ⅰ₁~Ⅰ₁₀, Ⅱ₁~Ⅱ₆). 目标化合物结构经MS及¹H NMR确证. 以MTT法, 采用表皮生长因子受体(EGFRs)高表达的人癌细胞(HeLa, HepG2, BGC-823)对目标化合物进行活性测试, 结果表明, 该类化合物对HeLa, HepG2和BGC-823细胞增殖具有一定程度的抑制作用. 其中化合物Ⅱ₄~Ⅱ₆ 对 HepG2 细胞抑制作用较强, 化合物Ⅱ₁和Ⅱ₅对BGC-823细胞抑制作用较强. 初步探讨了化合物结构与生物活性的关系.     

3-芳基噻唑烷-4-酮-2-酰胺的合成及其抗肿瘤活性研究

合成了系列新的3-芳基噻唑烷-4-酮-2-酰胺衍生物,并测试了化合物抑制肿瘤细胞增殖活性.部分化合物对A-549和Hela肿瘤细胞有弱的细胞毒性,而对BGC-823没有抑制作用,表现出一定的选择性.其中,化合物7ad对A-549有较强的抑制活性(IC50=21.0μmol·L-1),与阳性对照顺铂的抑制活性(IC50=19.4μmol·L-1)相当.初步的构效关系表明化合物的立体结构可能对其抗肿瘤活性影响较大.     

纳米TiO2光催化氧化对胃癌细胞周期的影响

以胃癌细胞系BGC-823为研究对象,采用倒置相差显微镜观察纳米TiO2光催化氧化前后BGC-823细胞形态的变化,通过流式细胞仪考察其对BGC-823细胞凋亡率及细胞周期的影响。结果表明,纳米TiO2光催化氧化使BGC-823细胞呈受激坏死或凋亡晚期继发性坏死状态;导致BGC-823细胞周期阻滞于G2/M期并诱导细胞凋亡,从而抑制其DNA合成及增殖分化进程。当TiO2比负载量为9.8×10-7g/cm2、光照时间为40 min时,G2/M期阻滞较为显著,细胞凋亡率达24.34%。     

二萘并呋喃衍生物的合成及其抗肿瘤活性研究

为了研究二萘并呋喃衍生物的构效关系,设计合成了两个系列的二萘[2,1-b:1',2'-d]呋喃衍生物,通过1H NMR、13C NMR、HRMS和IR数据对所有目标化合物进行了结构鉴定.通过噻唑蓝(MTT)法测试了目标化合物的体外抗肿瘤活性,大多数化合物对人肝癌细胞(Hep G2和SMMC-7721)、人宫颈癌细胞(He La细胞)和急性早幼粒细胞白血病细胞(NB4细胞)显示了较强的抗肿瘤活性.其中N~3,N~(11)-二羟基二萘并[2,1-b:1',2'-d]呋喃-3,11-二甲酰胺(13k)对SMMC-7721细胞显示了很强抑制作用,其半数抑制浓度为0.57μmol·L~(-1),远低于阳性对照药5-氟脲嘧定的20.21μmol·L~(-1).     

某些B-降胆甾噻唑化合物的合成及抗肿瘤活性研究

从胆甾醇出发,合成了系列B-降胆甾烷噻唑化合物,通过IR、NMR及HRMS等现代分析方法对合成物进行了结构表征.同时,分别采用人肺癌细胞(A549)、宫颈癌细胞(He La)、肝癌细胞(HEPG2)和人正常肾上皮细胞(HEK293T)对合成产物进行体外抑制肿瘤细胞增殖活性研究,结果表明具有N-甲基噻唑结构的化合物14和17对A549和HEPG2细胞的生长增殖表现出较好的抑制活性;具有N-苯基噻唑结构的化合物20~24对He La细胞表现出选择性的增殖抑制作用,但对人正常肾上皮细胞却几乎没有作用.     

新型吡咯类氨基酸缀合物的合成与抗肿瘤活性测定

以苯甲醛或3,4-二甲氧基苯甲醛为原料经Wittig-Horner反应、Van Leusen吡咯合成法、水解等多步反应,设计并合成了16个未见文献报道的吡咯类氨基酸缀合物7a~7p.其结构经1H NMR,13C NMR及HRMS确证.采用噻唑蓝(MTT)法测试了目标化合物对MCF-7,MGC80-3,Hep G2,CT-26及HUVEC细胞的增殖抑制作用.结果表明,几乎所有化合物对人体正常细胞HUVEC无明显抑制作用,化合物7a~7h对Hep G2细胞株有一定的抑制活性,化合物7i~7p对MCF-7及MGC80-3较强的抑制活性.其中化合物7o~7p对MCF-7细胞株的抑制活性最强.     

去氢表雄酮噻唑衍生物的合成及抗肿瘤活性评估

以去氢表雄酮为原料,通过微波一步合成法及常规2步合成方法合成得到16个新的具有不同结构特征的去氢表雄酮噻唑衍生物.所有合成物都通过了IR、NMR及HRMS的结构表征.另外,分别选用人宫颈癌细胞(He La)、人肝癌细胞(Hep G)、人肺癌细胞(A549)和人正常肾上皮细胞(HEK-293T)对合成物的抗肿瘤活性进行了研究,结果表明4-(4'-三氟甲基)苯基噻唑-2-去氢表雄酮腙(4)对所测试的肿瘤细胞株具有很好的生长增殖抑制活性,对上述肿瘤细胞的IC_(50)值分别为13.2、11.3和8.3μmol·L~(-1),对人肾上皮正常细胞HEK-293T却没有表现出明显的抑制作用(IC_(50)值100μmol·L~(-1)).但是,其它合成物对所测试的细胞株没有表现出明显的抑制活性.     

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。     

1,2,7,9-四取代去氢骆驼蓬碱衍生物的合成及体外抗肿瘤活性

为了寻找高效低毒的抗肿瘤候选化合物, 以去氢骆驼蓬碱为原料, 对β-咔啉环的2-,7-和9-位3个结构位点进行了结构改造, 合成了11个去氢骆驼蓬碱衍生物, 化合物的结构经核磁共振、 红外光谱、 质谱及元素分析确证. 采用四甲基偶氮唑盐(MTT)法初步测试了目标化合物体外抗肿瘤(Bel-7402, 786-0, BGC-823, A375, 769-P和MCF7)活性, 结果表明化合物4a, 4b, 8a和8b具有显著的体外抗肿瘤活性.     

二氧化碳和丙烯直接合成甲基丙烯酸的NiPMo/TiO2催化剂的研究

用溶胶-凝胶法以磷钼酸(MPA)的镍盐溶液水解钛酸四丁酯制备了NiPMo/TiO2催化剂.使用ICP、 XRD、 TG-DTA、 IR、 TPD-MS和微反应技术研究了催化剂的化学组成、热稳定性、化学吸附性质和催化反应性能.杂多钼酸盐与TiO2通过O2-在TiO2表面发生了键合.在623 K下,杂多阴离子仍保持原有的Keggin结构.CO2在Lewis酸位Ni(Ⅱ)和Lewis碱位Ni-O-Mo的桥氧协同作用下生成CO2卧式吸附态Ni(Ⅱ)←O-(CO)←(O--Ni).丙烯有多种吸附态在催化剂上吸附.在563 K、 1 MPa和空速1500 h-1的反应条件下,丙烯的摩尔转化率为3.2%,产物MAA选择性为95%.     

Synthesis of 1-benzyloxypyrazin-2(1H)-one derivatives

Different approaches for the synthesis of 1-benzyloxypyrazin-2(1H)-one derivatives from simple amino acids have been investigated. A library of 33 precursors for the preparation of N-hydroxy pyrazinones was obtained in moderate to good yields.     

A general and convenient synthesis of 4-(tosylmethyl)semicarbazones and their use in amidoalkylation of hydrogen,heteroatom, and carbon nucleophiles

A general synthesis of previously unknown semicarbazone-based α-amidoalkylating reagents, 4-(tosylmethyl)semicarbazones, has been developed. The synthesis involved three-component condensation of semicarbazones of aliphatic or aromatic aldehydes with the same or other aldehydes and p-toluenesulfinic acid. The scope and limitations of this reaction were investigated. The compounds obtained were demonstrated to be an efficient α-(4-semicarbazono)alkylating agents. They were reacted with H- (sodium borohydride), O- (sodium methylate), S- (sodium phenylthiolate), N- (pyrrolidine, sodium succinimide), P- (trialkyl phosphites), and C-nucleophiles (sodium diethyl malonate) to give the corresponding products of the tosyl group substitution, 4-substituted semicarbazones, including analogues of nitrofurazone. Among the prepared compounds tested in vitro for antibacterial and antifungal activity, three nitrofuryl-containing semicarbazones exhibited high biological activities with minimum inhibitory concentration (MIC) values of 8–32 μg/mL.     

Toward new camptothecins. Part 6: Synthesis of crucial ketones and their use in Friedländer reaction

In the context of the preparation of camptothecin and luotonin A analogs, the synthesis of some key keto-precursors and their use in Friedländer condensation are described. This paper also focuses on the stability of these keto intermediates and emphasizes the major differences between indolizinones and pyrroloquinazolinones series. Noteworthy is also the report of some original structures isolated as by-products of some experiments.     

Synthesis of novel chiral bidentate hydroxyalkyl-N-heterocyclic carbene ligands and their application in palladium-catalyzed Mizoroki–Heck couplings and asymmetric addition of diethylzinc to benzaldehyde

A small library of new chiral bidentate hydroxyalkyl-imidazolium salts 1 is conveniently synthesized on multi-gram scale from inexpensive and commercially available chiral pool amino acids. The corresponding carbenes, generated by deprotonation of imidazolium salts 1, in combination with palladium(II) chloride were tested in the Mizoroki–Heck coupling reaction. The most significant results in terms of yields and reactivities were achieved with low catalyst loading. The catalytic activities of these imidazolium salts were also investigated in the asymmetric addition of diethylzinc to benzaldehyde. The use of MgO nanoparticles as an additive in conjunction with these ligands played a crucial role in increasing the efficiency of these reactions.     

α-Amino acid derived enaminones and their application in the synthesis of N-protected methyl 5-substituted-4-hydroxypyrrole-3-carboxylates and other heterocycles

A new and simple synthesis of novel N-protected methyl 5-substituted-4-hydroxypyrrole-3-carboxylates, which exist in equilibrium with their 4-oxo tautomers, has been developed in two steps starting from N-protected α-amino acids. The key intermediates are enaminones, which can also be isolated, characterized, and used for the construction of other functionalized heterocycles, before they spontaneously decompose to pyrrole products. 4-Hydroxypyrroles are prone to partial aerial oxidation but can be efficiently alkylated or reduced to stable polysubstituted pyrrolidine derivatives.     

Specific intramolecular aromatic CH insertion of diazosulfonamides

The chemoselectivity in the intramolecular CH insertion of various diazosulfonamides has been experimentally studied. The results reveal that the aliphatic 1,4-, 1,5-, or 1,6-C(sp³)?H insertions of diazosulfonamides are not accessible, while the aromatic 1,5-C(sp²)?H insertion can be realized specifically by adjusting the diazo-adjacent group. In addition, the general chemoselectivities in the intramolecular CH insertions of diazosulfonyl compounds are summarized. Generally, diazosulfones undergo both aromatic 1,5-C(sp²)?H and aliphatic 1,5- and 1,6-C(sp³)?H insertions, while diazosulfonates undergo aliphatic 1,5- and 1,6-C(sp³)?H insertions. However, diazosulfonamides only undergo aromatic 1,5-C(sp²)?H insertion.     

CoFe2O4自形成磁性液体场致结构化对磁化的影响

The Langevin paramagnetic theory can’t describe the relation between magnetization of ferrofluids and applied magnetic field. The structuralization of ferrofluids, which is considered the main influence factor of the magnetization, is regarded. The part of magnetization works is deposited when the structure is forming. This action influences the magnetization of ferrofluids directly or indirectly. On the base of the “compressing” model, the Langevin function that usually describes the magnetization of ferrofluid is modified, and a well-fitted curve is obtained. An equation of the relation between the equivalent volume fraction after being “compressed” and the intensity of magnetic field is discovered, which approximately describes the process of magnetization. The relation between the approximate initial susceptibility and the volume fraction can be obtained from modified formula.     

Microwave-assisted copper-catalyzed stereoselective ring expansion of three-membered heterocycles with α-diazo-β-dicarbonyl compounds

Microwave-assisted copper-catalyzed ring expansions of three-membered heterocycles with α-diazo-β-dicarbonyl compounds were investigated. Thiiranes generated 3-acyl-5,6-dihydro-1,4-oxathiines in the presence of copper sulfate and trans-3-acyl-5,6-dihydro-1,4-oxathiines as stereospecific products for 1,2-disubstituted cis-thiiranes through an intramolecular S_N2 process. Oxiranes gave rise to 2-acyl-5,6-dihydro-1,4-dioxines under the catalysis of copper hexafluoroacetylacetonate and cis-3-acyl-5,6-dihydro-1,4-dioxines as stereospecific products for 1,2-disubstituted cis-oxiranes via an intimate ion-pair mechanism. The current method provides a direct and simple strategy in efficient preparation of 3-acyl-5,6-dihydro-1,4-oxathiines and 2-acyl-5,6-dihydro-1,4-dioxines, important agents in medicinal and agricultural chemistry, from readily available thiiranes and oxiranes, respectively.     

KMnO4-mediated oxidative CN bond cleavage of tertiary amines: Synthesis of amides and sulfonamides

KMnO₄-mediated oxidative CN bond cleavage of tertiary amines producing secondary amine was introduced, which was trapped by electrophiles (acyl chloride and sulfonyl chloride) to form amides and sulfonamides. The reaction could take place at mild condition, tolerating a wide range of function groups and affording products in moderate to excellent yields.