(R)-2-{[4-(3-甲氧基丙氧基)-3-甲基吡啶-2-基]甲基亚硫酰基}- 1H-苯并咪唑的合成

以2,3-二甲基吡啶为起始原料, 经过11步反应, 不对称合成了质子泵抑制剂的关键中间体: (R)-2-{[4-(3-甲氧基丙氧基)-3-甲基吡啶-2-基]甲基亚硫酰基}-1H-苯并咪唑. 研究了用手性高效液相色谱拆分对映体、测定产品光学纯度的方法, 结果表明目标产品的ee值达到99%. 通过IR, UV, MS以及1H NMR分析对重要中间体和目标产品进行了结构鉴定.     

含取代噁唑结构的新型吡唑肟衍生物的合成与生物活性

为了发现具有良好生物活性的吡唑肟化合物,以唑螨酯为先导化合物,在吡唑肟中引入取代噁唑结构,设计并制备了20个未见文献报道的新型吡唑肟衍生物,利用1H NMR,13C NMR和元素分析确证了目标产物的结构.生物活性测试结果显示,部分目标化合物在500和100μg/mL浓度下对粘虫或蚜虫表现出优良的杀虫活性,其中5-(3-氟苯氧基)-1,3-二甲基-1H-吡唑-4-甲酰基-O-{[5-(4-氯苯基)噁唑-2-基]甲基}肟(9j)、5-(4-氟苯氧基)-1,3-二甲基-1H-吡唑-4-甲酰基-O-{[5-(4-氯苯基)噁唑-2-基]甲基}肟(9k)、5-(4-叔丁基苯氧基)-1,3-二甲基-1H-吡唑-4-甲酰基-O-{[5-(4-氯苯基)噁唑-2-基]甲基}肟(9r)和5-(4-甲氧基苯氧基)-1,3-二甲基-1H-吡唑-4-甲酰基-O-{[5-(4-氯苯基)噁唑-2-基]甲基}肟(9s)在浓度为100μg/mL时对粘虫的防治效果均达100%,5-(4-溴苯氧基)-1,3-二甲基-1H-吡唑-4-甲酰基-O-{[5-(4-氟苯基)噁唑-2-基]甲基}肟(9g)和9s在浓度为100μg/mL时对蚜虫的杀灭活性均为100%.此外,化合物9s在500μg/mL时对朱砂叶螨的防治效果为70%.     

富马酸替诺福韦二吡呋酯杂质的合成

为控制富马酸替诺福韦二吡呋酯的产品质量,以腺嘌呤为起始物料,合成了5种杂质:(R)-1-(6-氨基-9H-嘌呤-9-基)丙基-2-醇,(R)-【{[1-(6-氨基-9H-嘌呤-9-基)丙基-2-基]氧基}甲基】磷酸,【【{[(R)-1-(6-氨基-9H-嘌呤-9-基)丙基-2-基]氧}甲基】(羟基)磷酸】氧】甲基异丙基碳酸酯,【【【{[(R)-1-(6-氨基-9H-嘌呤-9-基)丙基-2-基]氧}甲基】(异并氧基)磷】氧】甲基异并氧基碳酸酯和(R)-异丙基【9-【2-【【双{[(异丙氧羰基)氧]甲氧}磷】甲氧基】丙】-9H-嘌呤-6-基】氨基碳酸酯,其结构经UV-Vis,1H NMR,13C NMR,MS(ESI)和元素分析确证。     

甲磺酸达比加群酯杂质的合成

根据甲磺酸达比加群酯工艺,合成了甲磺酸达比加群酯的7个杂质：3-【【【2-｛［(4-氰基苯基)氨基］甲基｝-1-甲基-1H-苯并咪唑-5-基】羰基】(吡啶-2-基)氨基】丙酸（A）, 3-【【【2-【｛［4-(乙氧基)叔胺基］苯基｝氨基】甲基】-1-甲基-1H-苯并咪唑-5-基】羰基】(吡啶-2-基)氨基】丙酸乙酯盐酸盐(B), 3-【【【2-【｛［(4-甲脒基)苯基］氨基｝甲基】-1-甲基-1H-苯并咪唑-5-基】羰基】(吡啶-2-基)氨基】丙酸乙酯盐酸盐(C), 3-【【【2-【【【4-｛［(己氧基)羰基］氨基亚甲胺基｝苯基】氨基】甲基】-1-甲基-1H-苯并咪唑-5-基】羰基】(吡啶-2-基)氨基】丙酸甲酯盐酸盐(D), 3-【【【2-【【【4-【｛［(己氧基)羰基］氨基｝羰基】苯基】氨基】甲基】-1-甲基-1H-苯并咪唑-5-基】羰基】(吡啶-2-基)氨基】丙酸乙酯(E), 3-【【【2-【【【4-【｛［(己氧基)羰基］氨基｝亚氨甲基】苯基】氨基】甲基】-1-甲基-1H-苯并咪唑-5-基】羰基】(吡啶-2-基)氨基】丙酸(F), (Z)-3-【【【2-【【【4-【｛［(N,N′-二己氧基)羰基］脒基｝亚氨甲基】苯基】氨基】甲基】-1-甲基-1H-苯并咪唑-5-基】羰基】(吡啶-2-基)氨基】丙酸乙酯(G),其结构经¹H NMR和ESI-MS确证。     

新型酰基脲类Raf激酶抑制剂的合成及其抗肿瘤活性

以4-氯吡啶甲酸为原料,经6步反应制得两个中间体——取代基-4-【{2-[5-(三氟甲基)-1H-咪唑-2-基]吡啶-4-基}氧基】苯胺(7a和7d);7分别与取代苯甲酰基异硫氰酸酯反应,合成了6个新型的酰基脲类Raf激酶抑制剂(9a~9f),其结构经1H NMR和ESI-MS表征。用MTT法考察了9a~9f对人胃癌细胞株(BGC823)的抑制活性。结果表明:N-【3-氟-4-{2-[5-(三氟甲基)-1H-咪唑-2-基]吡啶-4-氧基}苯基】-4-氯苯甲酰硫脲(9c)和N-【4-{2-[5-(三氟甲基)-1H-咪唑-2-基]吡啶-4-氧基}苯基】-3-(吡啶-3-基)丙烯酰硫脲(9d)的抑制活性较好。在用药量为100μg时,9c和9d对BGC823的抑制率分别为66.86%和63.60%,与索拉非尼药效接近(70.97%)。     

新型含N-吡啶基吡唑结构的吡唑肟类衍生物的合成与生物活性

为了探索与发现具有优良生物活性的吡唑肟类衍生物,利用活性基团拼接法,以杀螨剂唑螨酯为先导化合物,引入N-吡啶基吡唑结构单元,设计合成了20个未见文献报道的新型吡唑肟类化合物,化合物结构均经~1H NMR, ~(13)C NMR和元素分析确认.生物活性初步测试结果表明,所有目标化合物在500μg/mL浓度下对东方粘虫均呈现出100%的杀虫活性. 5个化合物在100μg/mL下对东方粘虫的杀灭活性均达100%, 2个化合物在20μg/mL下对东方粘虫仍具有40%的杀虫效果.此外,3个化合物在500μg/mL浓度下对苜蓿蚜的致死率为40%～60%.值得注意的是,5-(2-溴苯氧基)-1,3-二甲基-1H-吡唑-4-甲醛-O-{1-(3-氯吡啶-2-基)-3-[(6-氯吡啶-3-基)甲氧基]-1H-吡唑-5-甲酰基}肟(10b)和5-(4-叔丁基苯氧基)-1,3-二甲基-1H-吡唑-4-甲醛-O-{1-(3-氯吡啶-2-基)-3-[(6-氯吡啶-3-基)甲氧基]-1H-吡唑-5-甲酰基}肟(10k)对东方粘虫的杀虫活性较为突出,可作深入的结构优化与杀虫活性探究.     

达比加群酯中间体3-【【【2-{[(4-氰基苯基)氨基]甲基}-1-甲基-1H-苯并咪唑-5-基】羰基】(吡啶-2-基)氨基】丙酸乙酯的合成

以对氨基苯腈为起始原料,经胺化反应制得N-(4-氰基苯基)甘氨酸(4);4与N-[3-氨基-4-(甲基氨基)苯甲酰基]-N-2-吡啶-β-丙氨酸乙酯(5)经酰胺化后经闭环反应,合成了达比加群酯的关键中间体——3-【【【2-{[(4-氰基苯基)氨基]甲基}-1-甲基-1H-苯并咪唑-5-基】羰基】(吡啶-2-基)氨基】丙酸乙酯,总收率79.6%,其结构经~1H NMR和ESI-MS确证。     

新型含氮杂环酰胺类衍生物的合成

根据结构拼合原理,分别将1,2,4-三唑和嘧啶连接到酰胺骨架上,设计并合成了两个新型的含氮杂环酰胺类衍生物——3-[N-3-(3-甲基-1H-1,2,4-三唑-1-基)-5-(三氟甲基)苯基硫代乙酰胺基-N-(2-氯苯基次甲基)]-5-(2,4-二氯苯基)-4H-1,2,4-三唑-4-胺和N-【3-【5-氯-2-N-{[2-甲氧基-4-(4-甲基哌嗪-1-基)苯胺]}嘧啶-4-氧醚】】苯基-1-{2-[5-(呋喃-2-基)-1,4-戊二烯-3-酮]苯氧醚}乙酰胺,其结构经1H NMR,13C NMR,19F NMR,IR,ESI-MS和元素分析表征。     

2-氯甲基-3-甲基-4-[(3-甲氧基)丙氧基]-吡啶盐酸盐的合成

以2,3-二甲基吡啶为原料,经6步反应合成了雷贝拉唑的关键中间体--2-氯甲基-3-甲基-4-[(3-甲氧基)丙氧基]-吡啶盐酸盐,总收率14.1%.     

2,5-二甲氧基-4-[(1E)-2-(1H-苯并咪唑-2-基)乙烯基]苯甲醛的合成

以2-甲基苯并咪唑(1)和2,5-二甲氧基-1,4-对苯二甲醛(3)为原料,经缩合反应合成了新化合物——2,5-二甲氧基-4-[(1E) -2-( 1H-苯并咪唑-2-基)乙烯基]苯甲醛(4),其结构经1H NMR,IR和ESI-MS表征.较佳缩合反应条件为:1 11 mol,n(1)∶n(3)=1.1∶1.0,回流反应6h,收率75.2％.     

Less symmetrical dicopper(II) complexes as catechol oxidase models--an adjacent thioether group increases catecholase activity

Three new unsymmetrical compartmental dinucleating ligands, 4-bromo-2-(4-methylpiperazin-1-ylmethyl)-6-[{2-(1-piperidyl)ethyl}aminomethyl]phenol (HL1), 4-bromo-2-(4-methylpiperazin-1-ylmethyl)-6-[{2-(morpholin-4-yl)ethyl}aminomethyl]phenol (HL2), and 4-bromo-2-(4-methylpiperazin-1-ylmethyl)-6-[{2-(thiomorpholin-4-yl)ethyl}aminomethyl]phenol (HL3), have been synthesized in order to model the active site of type 3 copper proteins. The dicopper(II) complexes of these ligands give first hints about the influence of a thioether group close to the metal site. The bromophenol-based ligands have one piperazine arm and one other bidentate arm in positions 2 and 6 of the phenolic ring, respectively. With each ligand a dinuclear copper(II) complex was prepared and structurally characterized. The copper ions were found to have square pyramidal environments and a mixture of endogenous phenoxo and exogenous acetate bridging. The influence of a heteroatom in one arm of the ligand on catecholase activity and speciation in solution was studied by UV/Vis spectroscopy, ESI-MS experiments and, DFT calculations.     

新型哌嗪化合物的合成及其晶体结构

以2-［1,2-二(2-羟基苯甲氨基)-2-(吡啶基)乙基］苯酚和2-［1,2-二(2-羟基苯甲氨基)-4-(吡啶基)乙基］苯酚为原料,分别与乙二醛经缩合反应,合成了两个新型的哌嗪化合物--2-【{12-(2-吡啶基)-3,20-二氧-11,21-二氮杂五环［11.7.1.O^2,11.O^4,9.O^14,19］二十一-4,6,8,14,16,18-六环-21-基}甲基】苯酚(2a)和2-【{12-(4-吡啶基)-3,20-二氧-11,21-二氮杂五环［11.7.1.O^2,11.O^4,9.O^14,19］二十一-4,6,8,14,16,18-六环-21-基}甲基】苯酚(2b),其结构经¹H NMR, ¹³C NMR, FT-IR, ESI-MS和X-射线单晶衍射表征。2a(CCDC: 1 439 422)属单斜晶系,空间群P2₁/n,晶胞参数a=12.250 2(16) , b=10.299 6(13) , c=18.296(2) , β=95.798(2)°, V=2 296.6(5) ³, Dc=1.341 mg·cm^-3,Z=4, F(000)=976, μ=0.088 mm^-1。     

Design,synthesis and in vitro evaluation of tetrahydropyrimidine-isatin hybrids as potential antitubercular and antimalarial agents

A series of 5-substituted-3-[{5-(6-methyl-2-oxo/thioxo-4-phenyl-1,2,3,4-tetrahydropyrimidin-5-yl)-1,3,4-oxadiazol-2-yl}-imino] -1,3-dihydro-2H-indol-2-one were synthesized,characterized and screened for their anti-tubercular and antimalarial activity.     

Synthesis and structures of heteroleptic silylenes

The reaction of benzamidinato silicon trichloride [{PhC(NR)2}SiCl3] [R = Bu(t) (1), SiMe3 (2)] with 2 equiv of potassium in THF afforded mononuclear chlorosilylene [{PhC(NBu(t))2}SiCl] (3) and [{PhC(NSiMe3)2}2SiCl2] (4), respectively. Compound 4 was formed by the disproportionation of unstable [{PhC(NSiMe3)2}SiCl]. The reaction of [{PhC(NBu(t))2}SiCl3] (1) with 1 equiv of LiR (R = NMe2, OBu(t), OPr(i), PPr(i)2) in THF yielded [{PhC(NBu(t))2}SiCl2R] [R = NMe2 (5), OBu(t) (6), OPr(i) (7), PPr(i)2 (8)]. Treatment of 5-8 with 2 equiv of potassium in THF resulted in the novel heteroleptic silylene [{PhC(NBu(t))2}SiR] [R = NMe2 (9), OBu(t) (10), OPr(i) (11), PPr(i)2 (12)]. Compounds 4, 9, and 12 have been analyzed by X-ray crystallography.     

4-Methoxy- and 4-cyano-substituted lithium aryloxides: electronic effects of substituents on aggregation

The para-substituted lithium aryloxides [{4-NC-C6H4OLi.(Pyr)2}2.Pyr] 1a, [{4-NC-C6H4OLi.(THF)2}2] 1b, [{4-MeO-C6H4OLi.Pyr}4] 2a, [4-MeO-C6H4OLi.(THF)n] 2b, [{4-NC-2,6-(t-Bu)2-C6H2OLi.(Pyr)2}infinity] 3a, [{4-NC-2,6-(t-Bu)2-C6H2OLi.(THF)2}infinity] 3b, [{4-MeO-2,6-(t-Bu)2-C6H2OLi.Pyr}2.(Pyr)2] 4a, and [4-MeO-2,6-(t-Bu)2-C6H2OLi.(THF)n] 4b were prepared by the direct deprotonation of the corresponding phenol with an alkyllithium base (BuLi or MeLi) in the appropriate solvent, either pyridine or THF. All compounds were characterized by 1H and 13C NMR spectroscopy, and the crystal structures of 1a, 1b, 2a, 3a, 3b and 4a were elucidated. The cyano derivatives 1a and 1b adopt discrete tetrasolvated Li2O2 ring dimers whereas the methoxy analogue 2a crystallizes as a tetrasolvated molecular tetramer with a pseudo cubic Li4O4 core. The sterically encumbered cyano derivatives 3a and 3b form isostructural 1D polymeric chains of monomers via bridging of the phenolate ligands through Li...NC and Li-O contacts. In comparison, the crystal structure of the methoxy counterpart 4a is a disolvated molecular Li2O2 ring dimer. Solution NMR spectroscopic studies of 1-4 in d5-pyridine and d8-THF indicate that the methoxy complexes are more highly aggregated than the cyano derivatives, consistent with the solid-state studies. Ab initio molecular orbital calculations at the HF/6-31G* level of theory indicate that the origin of the aggregation state variations between the cyano and methoxy complexes is due to electronic effects.     

Metal-templated diyne cyclodimerization and cyclotrimerization

Reaction of [Pt(CH3)2(COD)] (COD = 1,5-cyclooctadiene) with Ph2PCCCCPPh2 led to a mixture of [{Pt(CH3)2}2(mu-Ph2PC4PPh2)2] (1) and [{Pt(CH3)2}3(mu-Ph2PC4PPh2)3] (2). Reaction of [PtCl2(COD)] with Ph2PCCCCPPh2 led to a mixture of the thermally unstable compounds [{PtCl2}2(mu-Ph2PC4PPh2)2] (3) and [{PtCl2}3(mu-Ph2PC4PPh2)3] (4) which transform into [{PtMe2}2{mu-C8(PPh2)4}] (5) and [{PtMe2}3{mu3-C12(PPh2)6}] (6) containing 8-membered diene-diyne and 12-membered triene-triyne rings, respectively. Compound 2 can be converted to [{PtMe2}3{C12(PPh2)6}] (7) by heating with CuCl at 80 degrees C, while 1 can be heated without significant cycloaddition.     

Ring-opening polymerisation of coordination compounds: a silver(I) network with both ring and polymer components

The terpyridyl ligand 2,6-C5H3N{C(=O)N(Me)-4-C5H4N}2, 1, combined with silver(I) salts to give the complexes [Ag2(1)2][BF4]2, 2, and [{Ag3(1)2}n][CF3SO3]3n, 3; the network structure of complex contains both macrocyclic units [Ag2(mu-1)2]2+ and ring-opened polymeric units [{Ag(mu-1)}n]n+.     

Cluster core controlled reactions of substitution of terminal bromide ligands by triphenylphosphine in octahedral rhenium chalcobromide complexes

Reactions of rhenium chalcobromides Cs4[{Re6(mu3-S)8}Br6].2H2O, Cs3[{Re6(mu3-Se)8}Br6].2H2O, Cs3[{Re6(mu3-Q)7(mu3-Br)}Br6].H2O (Q = S, Se), and K2[{Re6(mu3-S)6(mu3-Br)2}Br6] with molten triphenylphosphine (PPh3) have resulted in a family of novel molecular hybrid inorganic-organic cluster compounds. Six octahedral rhenium cluster complexes containing PPh3 ligands with general formula [{Re6(mu3-Q)8-n(mu3-Br)n}(PPh3)4-nBrn+2] (Q = S, n = 0, 1, 2; Q = Se, n = 0, 1) have been synthesized and characterized by X-ray single-crystal diffraction and elemental analyses, 31P{1H} NMR, luminescent measurements, and quantum-chemical calculations. It was found that the number of terminal PPh3 ligands in the complexes is controlled by the composition and consequently by the charge of the cluster core {Re6Q8-nBrn}n+2. In crystal structures of the complexes with mixed chalcogen/bromine ligands in the cluster core all positions of a cube [Q8-nBrn] are ordered and occupied exclusively by Q or Br atoms. Luminescence characteristics of the compounds trans-[{Re6Q8}(PPh3)4Br2] and fac-[{Re6Se7Br}(PPh3)3Br3] (Q = S, Se) have been investigated in CH2Cl2 solution and the broad emission spectra in the range of 600-850 nm were observed.     

Alkoxo-bridged copperII complexes as nodes in designing solid-state architectures. The interplay of coordinative and d10-d10 metal-metal interactions in sustaining supramolecular solid-state architectures

Four novel polymeric coordination networks have been obtained through self-assembly processes involving alkoxo-bridged copperII species as nodes, and anionic cyano-complexes as linkers: infinity2[{Cu2(pa)2}{M(CN)2}2](M=Ag, 1; Au, 2), (infinity)3[{Cu4(mea)4}{Au(CN)2}4.H2O]3, and (infinity)3[{Cu2(pa)2}{Ni(CN)4}](pa = deprotonated propanolamine; mea = deprotonated monoethanolamine). The supramolecular architectures of compounds 1, and 2 are sustained by argentophilic or strong aurophilic interactions. The solid-state architectures of 1 and 2, which are isomorphous, consist of infinite layers, constructed from binuclear alkoxo-bridged nodes and [M(CN)2]- spacers. The layers are stacked in an offset parallel mode, and are further interconnected through Ag...Ag or Au...Au contacts (1: Ag...Ag 3.015 A; 2: Au....Au 3.069 A). Compound 3 consists of unique fourfold interpenetrating diamondoid nets. The diamondoid topology is built of heterocubane {Cu4O4} nodes, which are connected by [Au(CN)2]- rods. The Cu-O distances within the {Cu4O4} node vary between 1.927(2) and 2.679(1) A, showing unsymmetric bridging of the copper atoms. Aurophilic interactions are established between the bridging and terminal [Au(CN)2]- metalloligands, and connect the interpenetrating nets, resulting in infinite chains of gold atoms (the Au...Au distances vary between 3.253 and 3.305 [Angstrom]). Compound 4 exhibits a 3-D network constructed from {Cu2(pa)2]2+ nodes connected by square-planar [Ni(CN)4]2- ions. Compounds 1, 2 and 4 are weakly paramagnetic. The cryomagnetic investigation of reveals a gradual increase, followed by a decrease of the chiMT product, as the temperature is lowered. A superposition of ferro- (J1=+20.8 cm(-1)) and antiferromagnetic (J2=-6.4) interactions within the tetranuclear node was found. Antiferromagnetic interactions are established between the tetranuclear nodes (theta=-2.99 K).