内盐式O-2-(N~3-替加氟)乙基-O-(1-芳硫基-3-铵基)异丙基-硒代磷酯缀合物的合成

六乙基亚磷酰三胺依次与羟乙基替加氟、1-芳硫基甘油及硒反应,制备环甘油硒代磷替加氟缀合物(2);2再与三乙胺或三甲胺反应,完成亲核开环合成了内盐式O-2-(N3-替加氟)乙基-O-(1-芳硫基-3-铵基)异丙基-硒代磷酯缀合物.其结构经1H NMR, 31P NMR及元素分析确证.     

O-(1,3-二芳硒基)异丙基-O-2-(N3-替加氟)乙基硫代磷酯的合成及其抗癌活性

六乙基亚磷酰三胺依次与羟乙基替加氟、1-芳硒基甘油及硫反应,得到环甘油硫代磷脂替加氟缀合物(2a～2e);通过苯硒化钾对2进行亲核开环,得到O-(1,3-二芳硒基)异丙基-O-2-(N-替加氟)乙基硫代磷酯(3a～3e),其结构经1H NMR,31P NMR,MS及元素分析确证.3对膀胱癌细胞PGA1有一定的抑制作用.     

新型有机硫(硒)替加氟衍生物的合成及抗肿瘤活性研究

以替加氟为原料,与氯代烷基醇反应生成中间体N-羟烷基替加氟;然后与对甲苯磺酰氯反应制得替加氟烷基磺酸酯;在双核钛全氟丁基磺酸配合物/锌粉催化体系下,替加氟烷基磺酸酯与二芳基二硫(硒)醚反应,较高产率得到一系列新型芳基(N~3-替加氟烷基)硫(硒)醚衍生物.其结构通过~1H NMR, ~(13)H NMR和HRMS确认.对目标化合物进行了关于结肠癌细胞HCT116和胃癌细胞SGC-7901的体外抗肿瘤活性测试.结果表明,绝大多数目标化合物比替加氟的抗肿瘤活性高. DAPI (4',6-diamidino-2-phenylindole)对HCT116细胞染色实验及流式细胞仪定量检测实验表明,替加氟衍生物可通过诱导细胞凋亡而抑制细胞生长.此外,有机硫(硒)替加氟衍生物作用于正常人胚胎肾细胞HEK293的毒性比替加氟低.     

O-(1-芳硒基-3-叠氮基)异丙基- O-2-(N3-替加氟)烷基硫代磷酯的合成与活性

以碘作催化剂, 无水苯为溶剂, 六乙基亚磷酰三胺依次与羟乙基替加氟、1-芳硒基甘油及硫反应, 得中间体硒代环甘油磷脂替加氟缀合物2a～2f. 以无水N,N-二甲基甲酰胺(DMF)作溶剂, 室温下, 叠氮化钠中对2a～2f进行亲核开环, 得到O-(1-芳硒基-3-叠氮基)异丙基-O-2-(N3-替加氟)乙基硫代磷酯. 体外活性测试结果表明, 目标化合物3a～3f 对膀胱癌细胞PGA1抑制作用比替加氟高, 对胃癌细胞BGC-823的抑制作用与替加氟相当.     

O-(1-芳硫基-3-铵基)异丙基-O-2-(N3-替加氟)乙基硫代磷酯的合成及其抗癌活性

六乙基亚磷酰三胺与羟乙基替加氟、1-芳硫基甘油及硫一锅反应得到环甘油硫代磷脂替加氟缀合物(2),三乙胺对2进行亲核开环合成了O-(1-芳硫基-3-铵基)异丙基-O-2-(N3-替加氟)乙基硫代磷酯(3)。2和3的结构经1HNMR,31PNMR和元素分析表征。生物活性测试结果表明,3对膀胱癌细胞PGA1有一定的抑制作用。     

2-(2-三氟苯基)-5-芳基-1,3,4-噁二唑类化合物的合成

2-三氟苯甲酰肼与芳酰氯反应制得N,N′-二酰肼(2)。2在三氯氧磷存在下脱水闭环,合成了一系列2-(2-三氟苯基)-5-芳基-1,3,4-噁二唑类化合物,其结构经1H NMR,IR,MS和元素分析表征。     

5，5—二甲基—2—氧代—2—（N，N‘—对苯二胺基—二苄基）—二—1，3，2—氧磷杂环已烷的合成及表征

以新戊二醇、三氯化磷和乙醇为原料制得中间体5,5-二甲基-1,3,2-二氧磷杂环已烷-2-氧（DPDO）,用DPDO与由芳醛和对苯二胺缩合制得的席夫碱SBⅠ-SBⅡ加成,合成了膨胀型阻燃剂5,5-二甲基-2-氧代-2-（N,N‘-对苯二胺基-二苄基）-二-1,3,2-氧磷杂环已烷（DPPOⅠ-DPPOⅡ）,通过元素分析,IR,NMR和MS对其结构进行表征,并对其在醇酸清漆中的应用进行了讨论。     

5,5-二甲基-2-氧代-2-(N,N-对苯二胺基-二苄基)-二-1,3,2-氧磷杂环己烷的合成及表征

以新戊二醇、三氯化磷和乙醇为原料制得中间体 5 ,5 -二甲基 -1 ,3,2 -二氧磷杂环己烷 -2 -氧 ( DPDO) ,用DPDO与由芳醛和对苯二胺缩合制得的席夫碱 SB ～ SB 加成 ,合成了膨胀型阻燃剂 5 ,5 -二甲基 -2 -氧代 -2 -( N,N -对苯二胺基 -二苄基 ) -二 -1 ,3,2 -氧磷杂环己烷 ( DPPO ～ DPPO ) ,通过元素分析 ,IR,NMR和 MS对其结构进行表征 ,并对其在醇酸清漆中的应用进行了讨论     

克唑替尼关键中间体(S)-1-(2,6-二氯-3-氟苯基)乙醇的不对称合成

(S)-1-(2,6-二氯-3-氟苯基)乙醇（2）是合成抗癌药物克唑替尼的关键手性前体。本文以1-(2,6-二氯-3-氟苯基)乙酮为起始原料,利用二异松莰基氯化硼［(-)-Ipc₂BCl］不对称还原制得光学纯的2;并将中间体2经Mitsunobu反应、还原、溴代、 Suzuki偶联及脱除Boc保护合成克唑替尼,其结构¹H NMR,¹³C NMR和HR-MS(ESI)确证。对关键中间体2的合成条件进行了优化,并其对反应机理进行了推测。     

5,5-二甲基-2-氧代-2-(N,N＇-对苯二胺基-二苄基)- 二-1,3,2-氧磷杂环己烷的合成及表征

以新戊二醇、三氯化磷和乙醇为原料制得中间体5,5-二甲基-1,3,2-二氧磷杂环己烷-2-氧(DPDO),用DPDO)与由芳醛和对苯二胺缩合制得的席夫碱SBⅠ～SBⅢ加成,合成了膨胀型阻燃剂5,5-二甲基-2-氧代-2-(N,N′-对苯二胺基-二苄基)-二-1,3,2-氧磷杂环己烷(DPPO Ⅰ～DPPOⅢ),通过元素分析,IR,NMR和MS对其结构进行表征,并对其在醇酸清漆中的应用进行了讨论.     

Synthesis, characterization and anti proliferative effect of [Au(en)2]Cl3 and [Au(N-propyl-en)2]Cl3 on human cancer cell lines

Two Au(III) complexes of the type [Au(en)2]Cl3 (2a) and [Au(N-pr-en)2]Cl3 (3a) were synthesized by reacting Auric acid (HAuCl(4)·3H2O) with 2 equiv. ethylenediamine (en) or N-alkyl substituted ethylenediamine ligands. This metallodrug was characterized by various analytical and spectroscopic techniques such as elemental analysis, UV-Vis, Far-IR, 1H NMR and solution 13C as well as solid 13C and 15N NMR. Potentiality of [Au(en)2]Cl3 and [Au(N-pr-en)2]Cl3 as an anti-cancer agent were investigated by measuring some relevant physicochemical and biochemical properties such as stability of Au-N bonds by vibrational stretching from Far IR as well as cytotoxicity and stomach cancer cell inhibiting effect, respectively. The solid-state 15N NMR chemical shift shows that the ligand is strongly bound to gold(III) centre via N atoms. The computational study of 2a shows that the gold coordination sphere adopts distorted square planar geometry with bidentate ethylenediamine ligands acting as a tetradentate chelate. While stable in the solution state, the in vitro biological studies performed with these compounds 2a in solution showed higher activity towards the inhibitory effects of the human cancer cell lines such as prostate cancer (PC-3) and gastric carcinoma (SGC-7901) than that of the N-substituted gold(III) complex (3a). Cytotoxicity of the new compounds has also been estimated in PC-3 and SGC-7901 cells.     

Cytotoxic triterpenoid saponins from the roots of Cephalaria gigantea

Three new oleanane-type saponins, giganteosides L (1), M (2) and N (3) along with eight known ones were isolated from the roots of Cephalaria gigantea. Their structures were established as 3-O-[beta-D-galactopyranosyl-(1-->2)-beta-D-glucuronopyranosyl]-28-O-[beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl]-oleanolic acid, 3-O-[beta-D-galactopyranosyl-(1-->2)-beta-D-glucuronopyranosyl]-28-O-[beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl]-hederagenin, 3-O-[alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucuronopyranosyl]-28-O-[beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl]-hederagenin, respectively, by means of spectroscopic methods (1D and 2D NMR, HR-ESI-MS). Cytotoxic activity of monodesmosides was investigated in vitro using three cancer cell lines, namely, human non pigmented melanoma MEL-5 and human leukemia HL-60. Giganteosides D (4) and E (5) showed antiproliferative effect on human cell lines with IC(50) values in the range 3.15-7.5 microM.     

Terpsichorean movements of pentaammineruthenium on pyrimidine and isocytosine ligands

Pentaammineruthenium moves on ambidentate nitrogen heterocycles by both rotation and linkage isomerization, which may affect the biological activity of potential ruthenium metallopharmaceuticals. The rapid rotation rates of [(NH3)5RuIII] coordinated to the exocyclic nitrogens of isocytosine (ICyt) and 6-methylisocytosine (6MeICyt) have been determined by 1H NMR. Since these rotamers can be stabilized by hydrogen bonding between the coordinated ammines and the N1 and N3 endocyclic nitrogens, rotamerization is under pH control. Spectrophotometrically (UV-vis) measured pKa values for the two endocyclic sites for the ICyt complex are 2.78 and 9.98, and for 6MeICyt are 3.06 and 10.21, which are probably weighted averages for ionization from N3 and N1, respectively. Activation parameters for the rotamerizations were determined by variable-temperature NMR at pKa1 < pH < pKa2 for the complexes with (ICyt-kappa N2)-, (6MeICyt kappa N2)-, and 2AmPym kappa N2. For [(6MeICyt kappa N2)(-)-(NH3)5RuIII]2+, delta H* = 1.6 kcal/mol, delta S* = -37 cal/mol K, and Ea = 2.2 kcal/mol. Due to strong RuIII-N pi-bonding, the activation enthalpies are approximately 10 kcal lower than the expected values for the free ligands. Rotameric structure is correlated with pKa values, pH-dependent reduction potentials, and 1H NMR parameters. Linkage isomers of [(2AmPym)(NH3)5Ru]n+ are reported in which RuII is coordinated to the endocyclic nitrogen (N1) and RuIII to the exocyclic nitrogen (N2). The rate constant for the kappa N2-->kappa N1 isomerization as part of an ECE mechanism is 3.9 s-1 at pH 3. The pH dependence of the acid-catalyzed hydrolysis of [(2AmPym kappa N1)(NH3)5Ru]2+ is determined.     

A novel isomerization on interaction of antitumor-active azole-bridged dinuclear platinum(II) complexes with 9-ethylguanine. Platinum(II) atom migration from N2 to N3 on 1,2,3-triazole

The reactions of the dinuclear platinum(II) complexes, [[cis-Pt(NH(3))(2)](2)(mu-OH)(mu-pz)](NO(3))(2) (1, pz = pyrazolate), [[cis-Pt(NH(3))(2)](2)(mu-OH)(mu-1,2,3-ta-N1,N2)](NO(3))(2) (2, 1,2,3-ta = 1,2,3-triazolate), and a newly prepared [[cis-Pt(NH(3))(2)](2)(mu-OH)(mu-4-phe-1,2,3-ta-N1,N2)](NO(3))(2) (3, 4-phe-1,2,3-ta = 4-phenyl-1,2,3-triazolate), whose crystal structure was determined, with 9-ethylguanine (9EtG) have been monitored in aqueous solution at 310 K by means of (1)H NMR spectroscopy. The dinuclear platinum(II) complexes 1-3 each react with 9EtG in a bifunctional way to form 1:2 complexes, [[cis-Pt(NH(3))(2)(9EtG-N7)](2)(mu-pz)](3+) (4), [[cis-Pt(NH(3))(2)(9EtG-N7)](2)(mu-1,2,3-ta-N1,N3)](3+) (5), and [[cis-Pt(NH(3))(2)(9EtG-N7)](2)(mu-4-phe-1,2,3-ta-N1,N3)](3+) (6). The reactions of 2 and 3 involve a novel isomerization, in which the Pt atom, initially bound to N2 on the 1,2,3-ta, migrates to N3 after the first substitution by N7 of 9EtG. This isomerization reaction has been unambiguously characterized by 1D and 2D NMR spectroscopy and pH titration. The reactions of 2 and 3 with 9EtG show faster kinetics, and the second-order rate constants (k) for the reactions of 1-3are 1.57 x 10(-4), 2.53 x 10(-4), and 2.56 x 10(-4) M(-1) s(-1), respectively. The pK(a) values at the N1H site of 9EtG were determined for 4-6 from the pH titration curves. Cytotoxicity assays of 1-3 were performed in L1210 murine leukemia cell lines, respectively sensitive and resistant to cisplatin. In the parent cell line, 2 and 3 exhibit higher cytotoxicity compared to cisplatin, especially, 2 is 10 times as active as cisplatin. 1 was found to be less cytotoxic than cisplatin, but still in the active range and more active than cisplatin in a cisplatin-resistant cell line.     

微波辅助合成有机膦功能化离子液体及对稀土离子的萃取

用微波辐射法,合成了5个含有机膦氧基团的离子液体：1-丙基-3-(3-二苯基氧膦基)丙基咪唑双(三氟甲基磺酰基)亚胺盐([PImC3P(O)Ph2][Tf2N])、1-己基-3-(3-二苯基氧膦基)丙基咪唑双(三氟甲基磺酰基)亚胺盐([HImC3P(O)Ph2][Tf2N])、1-丙基-3-(3-苯基乙氧基氧膦基)丙基咪唑双(三氟甲基磺酰基)亚胺盐([PImC3P(O)Ph(OEt)][Tf2N])、1-己基-3-(3-苯基乙氧基氧膦基)丙基咪唑双(三氟甲基磺酰基)亚胺盐([HImC3P(O)Ph(OEt)][Tf2N])和(3-苯基乙氧基氧膦基)丙基三乙胺双(三氟甲基磺酰基)亚胺盐([TENC3P(O)Ph(OEt)][Tf2N])。 用31P NMR、1H NMR、13C NMR、MS及FT-IR对产物结构进行了表征。 研究了这类离子液体对稀土Nd(III)的萃取性能。 结果表明,这类功能化离子液体可作为单一组分萃取稀土而无需加入有机稀释剂,离子液体结构对萃取效率影响很大,相同条件下季铵盐型结构的离子液体[TENC3P(O)Ph(OEt)][Tf2N]对稀土Nd(Ⅲ)的萃取效率最高。 稀土溶液pH值对萃取效率影响显著,近中性条件下(pH=6.63),对稀土Nd(Ⅲ)的萃取率最高。 用pH=1.00的盐酸溶液可以较好的从离子液体相反萃Nd(Ⅲ),反萃率可达94%。     

N9位芳基取代嘌呤-8-酮类衍生物的合成及抗肿瘤活性

合成了一系列N9位芳基取代嘌呤-8-酮类衍生物, 利用核磁共振氢谱(¹H NMR)、 核磁共振碳谱(¹³C NMR)和高分辨质谱(HRMS)进行了结构确证. 采用四甲基偶氮唑盐(MTT)法测定了目标化合物的体外抗肿瘤细胞增殖活性. 结果表明, 嘌呤酮环的C2位及N9位的取代对活性有较大影响, C2位引入对位由含氮六元环取代的苯胺, N9位引入对三氟甲基苯均有利于提高抗肿瘤活性. 化合物12c对人白血病细胞(K562)、 人前列腺癌细胞(PC-3)、 人乳腺癌细胞(MDA-MB-231)及人结肠癌细胞(HCT116)的抑制效果明显优于阳性对照药R-Roscovitine.     

2,5-二酮哌嗪衍生物的一锅法合成及其细胞毒活性

以DMF为溶剂,Cs₂CO₃为碱, N,N-二乙酰基-2,5-二酮哌嗪,芳醛和卤代烷经一锅法合成了１10个2,5-二酮哌嗪类衍生物（4a~4j,其中4c, 4f和4i为新化合物）,收率54.2％～75.7％,其结构经¹H NMR, ¹³C NMR和ESI-MS确证。生物活性研究结果表明：（Z）-1-乙酰基-3-（1-亚甲基萘）-4-烯丙基-2,5-二酮哌嗪（4c）对U937, Hela和Du145等细胞具有一定的细胞毒活性。     

Probing platinum azido complexes by 14N and 15N NMR spectroscopy

Metal azido complexes are of general interest due to their high energetic properties, and platinum azido complexes in particular because of their potential as photoactivatable anticancer prodrugs. However, azido ligands are difficult to probe by NMR spectroscopy due to the quadrupolar nature of (14)N and the lack of scalar (1)H coupling to enhance the sensitivity of the less abundant (15)N by using polarisation transfer. In this work, we report (14)N and (15)N NMR spectroscopic studies of cis,trans,cis-[Pt(N(3))(2)(OH)(2)(NH(3))] (1) and trans,trans,trans-[Pt(N(3))(2)(OH)(2)(X)(Y)], where X=Y=NH(3) (2); X=NH(3), Y=py (3) (py=pyridine); X=Y=py (4); and selected Pt(II) precursors. These studies provide the first (15)N NMR data for azido groups in coordination complexes. We discuss one- and three-bond J((15)N,(195)Pt) couplings for azido and am(m)ine ligands. The (14)N(α) (coordinated azido nitrogen) signal in the Pt(IV) azido complexes is extremely broad (W(1/2)≈2124 Hz for 4) in comparison to other metal azido complexes, attributable to a highly asymmetrical electric field gradient at the (14)N(α) atom. Through the use of anti-ringing pulse sequences, the (14)N NMR spectra, which show resolution of the broad (14)N(α) peak, were obtained rapidly (e.g., 1.5 h for 10 mM 4). The linewidths of the (14)N(α) signals correlate with the viscosity of the solvent. For (15) N-enriched samples, it is possible to detect azido (15)N resonances directly, which will allow photoreactions to be followed by 1D (15)N NMR spectroscopy. The T(1) relaxation times for 3 and 4 were in the range 5.7-120 s for (15)N, and 0.9-11.3 ms for (14)N. Analysis of the (1)J((15)N,(195)Pt) coupling constants suggests that an azido ligand has a moderately strong trans influence in octahedral Pt(IV) complexes, within the series 2-pic相似文献