2,5-二取代吲哚碳酰肼衍生物的合成及活性研究

以对硝基苯肼为起始原料,采用费舍尔吲哚合成法合成中间体5-硝基吲哚-2-羧酸酯(3),经还原合成5-氨基吲哚-2-羧酸酯(4),再与氯甲酸苯酯合成酰胺(5),5在水合肼作用下形成2,5-碳酰肼吲哚(6),化合物6和取代醛反应,合成了7个2,5-二取代吲哚碳酰肼衍生物(7a～7g)。目标化合物经~1HNMR、~(13)CNMR、HR-MS结构确证。采用MTT法研究了目标化合物的细胞毒活性。结果显示,目标化合物对所选肿瘤细胞的增殖活性具有一定抑制作用。其中7c对宫颈癌细胞(Hela)、乳腺癌细胞(MCF-7)和人肝癌细胞(HepG-2)的抑制活性与阳性药顺铂活性相近。     

2,5-二取代吲哚衍生物的合成及抗增殖活性研究

以对硝基苯肼为起始原料,采用费舍尔吲哚合成法合成中间体5-硝基吲哚-2-羧酸酯(3),经还原合成5-氨基吲哚-2-羧酸酯(4),再与4-甲氧基-2-甲苯基异氰酸酯合成脲(5),(5)在水合肼作用下5-(3-(4-甲氧基-2-甲苯基)脲基)-1H-吲哚-2-碳酰肼(6),化合物6和取代醛反应,合成了6个2,5-二取代吲哚衍生物(7a～7f),其结构经~1HNMR,~(13)CNMR和HR-MS表征。采用MTT法研究了7a～7f对人肺癌细胞(A549)和人肝癌细胞(HepG-2)的体外抗增殖活性。结果显示:7d体外抑制活性最优,其IC_(50)分别为10.35μmol·L~(-1)、12.60μmol·L~(-1)。     

新型N-甲基吲哚类衍生物的设计、合成及抗肿瘤活性研究

本文以吲哚骨架为起点,设计合成了5个含吲哚骨架的新型有机小分子(4a-4e),通过NMR,IR和MS对目标化合物进行了结构表征.采用MTS法测试了目标化合物对SMMC-7721,Hela,MCF-7和HepG2癌细胞的体外抗肿瘤活性.结果表明,部分化合物选择性地作用于一种细胞,显示出较强的抑制肿瘤细胞增殖的活性,值得进一步研究.     

N-(2-氟-4-氯-5-取代苯基)异吲哚-1,3-二酮衍生物的合成及除草活性

为了发现新的农药先导化合物,以氯酰亚酞和苯氧羧酸酯结构为基础,通过活性亚结构拼接方法,设计合成了一系列新型的N-(2-氟-4氯-5-取代苯基)异吲哚-1,3-二酮衍生物6a~6f和7a~7k.目标化合物以2-氯-4-氟-5-硝基苯酚为原料,经4步反应制得,其结构经过1H NMR,13C NMR,HRMS确证.初步生物活性测试结果表明,大部分化合物在1500 g/ha剂量下,对双子叶杂草苘麻、反枝苋具有优异的芽前芽后除草活性.进一步活性筛选发现,化合物6d在750g/ha剂量下对苘麻、反枝苋具有100%抑制活性,化合物7a,7i在22.5 g/ha剂量下对苘麻的芽后抑制率大于80%,远高于对照药剂三氟羧草醚.     

基于薯蓣皂苷元催化合成N-甲基吲哚孕烯醇酮化合物及其抗肿瘤活性

利用N-甲基吲哚对类固醇药物的前驱体16-脱氢孕烯醇酮乙酸酯(16-DPA)的D环C16位进行修饰,采用ZrCl₄-乙酸乙酯廉价催化体系,合成了16个3β-乙酰氧基-16α-3’-吲哚孕烯醇酮化合物和6个3β-羟基-16α-3’-吲哚孕烯醇酮衍生物.该方法具有收率高、立体选择性好和底物适应性强等优点.通过噻唑蓝(MTT)比色法测试了22个化合物对三阴性乳腺癌细胞(MDA-MB-231)的抗肿瘤活性.初步测试结果表明, 3β-乙酰氧基-16α-3’-吲哚孕烯醇酮化合物6h和6i对MDA-MB-231癌细胞有较好的抑制活性,其半数抑制浓度(IC₅₀)分别为18.07和23.22μmol/L;而化合物7a～7f均对MDA-MB-231癌细胞有较好的抑制活性,其中化合物7e的抗肿瘤活性最好,其IC₅₀为12.50μmol/L.目标化合物为药物筛选提供了一定的参考.     

一些吲哚二酮类衍生物的合成及对AHAS的抑制活性

基于一些新结构特征的AHAS抑制剂, 设计并合成了一系列吲哚二酮类化合物. 初步的生物活性测试结果表明, 所合成的化合物在体内和体外均具有一定的生物活性, 其中, 化合物13在100 μg/mL浓度下对AHAS的抑制达到85%, 化合物7(平皿法)在100 μg/mL浓度条件下对油菜胚根生长抑制率可达84.7%, 是一类未见文献报道的结构新型的AHAS抑制剂, 有望为进一步设计合成更高活性的化合物提供参考.     

3位苯甲酰腙和亚氨基取代硫脲取代的吲哚满二酮衍生物的合成及对AHAS的抑制活性

基于前期生物设计AHAS抑制剂的研究,设计合成了15个吲哚满二酮类衍生物,其中9个为新化合物,其结构均经过1H NMR,MS和元素分析确证,并对所有化合物进行了离体和活体活性测试.实验结果表明,这类化合物在体内和体外均具有一定的生物活性,在离体活性测试中,所有化合物在100μg/mL浓度下对拟南芥AHAS均表现出明确的抑制活性,其中化合物4d,4e,5a和5f在10μg/mL浓度下仍然对AHAS表现出45%以上的抑制率,但此类化合物除草活性普遍较差.     

1,3-取代吲哚-2-酮衍生物的合成与肿瘤细胞毒活性研究

以苯胺为原料,通过肟化、环合生成二氢吲哚-2,3-二酮,再对其进行N-烷基化、亲核加成和磺酰化反应得到目标化合物5a～5g和7a～7e。通过¹H NMR、¹³C NMR确认其结构。采用噻唑蓝（MTT）法测试了目标化合物对乳腺癌细胞MDA-MB-231、鼠黑色素瘤细胞B16、鼠结肠癌细胞CT26三种肿瘤细胞的体外抑制活性。结果表明,化合物7d、7e具有明显的肿瘤细胞毒活性,其中化合物7d对MDA-MB-231的细胞毒活性比阳性药五氟尿嘧啶更强,IC₅₀为4.63±0.14μmol/L。本文结果可为进一步研究具有肿瘤细胞毒活性的吲哚酮类衍生物提供参考。     

吲哚丙基-1,3,4-噁二唑衍生物的合成及蛋白酪氨酸磷酸酯酶1B抑制活性研究

以吲哚丁酸为原料,通过酯化、酰肼化、环化、取代四步反应得到了一系列吲哚丙基-1,3,4-噁二唑衍生物.对所合成的目标化合物进行了抗蛋白酪氨酸磷酸酯酶1B(PTP1B)活性测试,发现其中5个化合物具有明显的体外抗PTP1B活性,其中化合物5g活性最强,其IC_(50)为6.74μg·mL~(-1).该系列化合物是首次报道的具有PTP1B抑制活性的吲哚烷基-噁二唑衍生物.     

新型吲哚咔唑化合物的合成与抗肿瘤活性

设计合成了一系列吲哚咔唑结构的抗肿瘤新化合物. 通过对反应溶剂进行选择和调整, 优化了吲哚咔唑母核合成的反应条件, 使后处理更为简便. 用溴化噻唑蓝四氮唑(MTT)法对所合成的9个目标化合物进行了体外细胞毒活性测试, 结果表明, 化合物4a, 4b, 4d, 4f和4i对人结肠癌HCT116和鼠白血病P388细胞的活性均强于阳性对照ED-571, 其中化合物4f对P388细胞的活性是阳性对照的10倍.     

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.