新型1,2,3-三唑类化合物的合成及抗菌构效关系

根据活性基团拼接原理, 以4-取代-苯胺为原料, 经重氮化、 关环和缩合反应合成了17个化合物1-(4-取代苯基)-5-取代苯基亚氨基-4-取代-1,2,3-三唑(7a~7c和13a~13d)和1-(4-取代苯基)-5-取代苄基氨基-4-取代-1,2,3-三唑(5a~5c, 10a~10c和14a~14d), 其中化合物5a~5c, 7b, 7c, 10a, 10c, 13b~13d和14b~14c为新化合物, 对所制备化合物的结构进行了表征. 生物活性测试结果表明, 所有化合物均表现出一定的抑菌活性, 对大肠杆菌的抑菌活性均优于氟康唑; 化合物7a和10c对金黄色葡萄球菌的抑制活性明显优于氟康唑; 而化合物13a和13d则对白色念球菌表现出良好的抑制活性, 与三氯生相当.     

有机磷杂环化合物研究(Ⅷ)──Lawesson试剂与合两个氨基的底物的成环反应

研究Lawesson试剂与含有两个氨基的底物的成环反应,合成了N-P-N型五元、六元磷杂环3a-3b、sa－5b及8a－8b,并讨论了成环机理．初步的生测结果表明,所合成的磷杂环具有一定的除草活性,因此LR的成环反应是合成具有生物活性的磷杂环的新方法．     

The synthesis of substituted [1]benzothieno[2,3-c]quinolines and their N-methyl quaternary salts

Four substituted [1]benzothieno[2,3-c]quinolines 14a-14d were prepared by photocyclization of the appropriate carboxamides 8a-8d to the corresponding [1]benzothieno[2,3-c]quinolin-6(5H)-ones 12a-12d followed by chlorination to 6-chloro[1]benzothieno[2,3-c]quinolines 13a-13d and dechlorination resulting in the title compounds. Treatment of 14a-14d with iodomethane furnished the corresponding N-methyl quaternary salts 5a-5d .     

Furopyridines. IX. Syntheses and properties of 3-ethoxy derivatives of furo[2,3-b]-, furo[3,2-b]-, furo[2,3-c]- and furo[3,2-c]pyridine

Reaction of ethyl 3-ethoxycarbonylmethoxyfuropyridine-2-carboxylates 2a-2d with sodium ethoxide afforded 3-ethoxy derivatives 3a-3d which converted to 3-ethoxyfuropyridines 5a-5d by hydrolysis and decarboxylation of the ester group. Vilsmeier reaction of 5a and 5b gave 2-formyl-3-ethoxy derivatives 6a and 6b and 2-formyl-3-chloro derivatives 7a and 7b , while 5c and 5d did not give any formyl compound. Bromination of 3-ethoxyfuropyridines with 1 equivalent mole of bromine gave 2-bromo-3-ethoxyfuropyridines 9a-9d , whereas reaction with 3 equivalents of bromine yielded 2,2-dibromo-3,3-diethoxy-2,3-dihydrofuropyridines ( 10a and 10b ) and/or 2-bromo-3,3-diethoxy-2,3-dihydrofuropyridines 11b , 11c and 11d . Treatment of compounds 5a-5d with n-butyllithium in hexane-tetrahydrofuran at ?70° and subsequent addition of N,N-dimethylformamide yielded 2-formyl derivatives 6a-6d .     

1,7,7—三甲基双环[2,2,1]庚基环烷基(或环己基烷基)醚的合成

本文报道以缺铝氢型丝光沸石催化烯或三环烯与六种含环醇的烷氧基化反应,以较高产率生成1,7,7—三甲基双环(2,2,1)庚基环烷基醚(或苯基烷基醚)。同时生成少量的(6,7,7—三甲基双环(2,2,1)庚基环烷基醚(或苯基烷基醚)副产物。含苯环产物通过Raney镍催化剂加氢也可得到标题化合物。     

20(S)-20-O-Camptothecin β-Aminopropionate: Novel Synthesis and Antitumor Activity in vitro

To improve the biological anticancer activity of 20(S)-camptothecin, a novel class of 20(S)-20-O-camptothecin β-aminopropionates were designed and synthesized with camptothecins as the starting materials, through acylation with acryloyl chloride followed by Michael′s addition. Twelve esters, 1a-1d, 4a-4d and 5a-5d, were synthesized and evaluated by using MTT assay method. The results demonstrate that all these compounds show a potential cytotoxicity on KB, HT-29, HCT-8, and Bel7402 tumor cell lines. Some compounds, 1d, 4c, 5b, 5c and 5d, show a higher cytoto-xicity on KB and HCT-8 compared with camptothecin.     

6-取代氨基-2-烷硫基腺苷化合物的合成及抗血小板凝聚活性

以鸟苷(1)为原料, 经过糖环保护得到2',3',5'-三-O-乙酰基鸟嘌呤核苷(2), 化合物2与三氯氧磷反应得到2-氨基-6-氯-9-(2',3',5'-三-O-乙酰基-β-D-呋喃核糖基)嘌呤(3), 化合物3经重氮化后再与二烷基二硫醚反应得到2-烷硫基-6-氯-9-(2',3',5'-三-O-乙酰基-β-D-呋喃核糖基)嘌呤(4a~4d), 化合物4a~4d与胺进行亲核取代反应后, 脱去糖环保护得到12个新型的6-取代氨基-2-烷硫基腺苷化合物(5a~5l). 采用¹H NMR, ¹³C NMR, IR和高分辨质谱(HRMS)对目标化合物的结构进行了确证, 并对所有化合物进行了体外抗血小板聚集活性测试. 结果表明, 当测试浓度为10 μmol/L时, 化合物5a~5l仍具有一定的抗凝活性, 其中, 6-(3-苯基丙基)氨基-2-丙硫基腺苷(5d)活性最为显著, 抑制率可达90.2%.     

Novel ion-pair receptors based on hexahomotrioxacalix[3]arene derivatives

A series of novel heteroditopic hexahomotrioxacalix[3]arene triamide receptors capable of binding an anion and cation simultaneously in a cooperative fashion has been prepared. The lower rim functionalized cone-hexahomotrioxacalix[3]arene derivatives cone-5a-5d bearing three amide groups were synthesized from cone-3 by a stepwise reaction. The crystal structures of 5c and 5d and (1)H NMR studies in nonpolar solvents strongly indicate that a number of interesting intramolecular hydrogen bonding interactions exist in these receptors. The binding abilities of these compounds towards n-butylammonium chloride and bromide salts have been investigated using (1)H NMR titration experiments in CDCl(3) solvent. Owing to the 'flattened cone' conformations and intramolecular hydrogen bonding involving the amide NH and neighbouring O atoms in cone-5a-5d, the affinities toward n-Bu(4)NX (X = Cl(-) and Br(-)) were weakened. However, it should be noted that triamides cone-5a-5d show a single selectivity for halide anions in the presence of n-BuNH(3)(+) through intermolecular hydrogen bonding with the amide NH hydrogen atoms in the receptors in CDCl(3) solution. Association constants were calculated from the chemical shift changes of the amide protons.     

ω-氯氟烷基醇,烯烃及环氧化物的合成

全氟烷基碘的加成反应一直活跃在氟化学中,即使近来也依然受到注意,这是因为由它们出发可做许多有用的中间体,其中氟烷基取代的醇可做织物表面处理剂,氟烷基取代的环氧化合物可做润滑剂。我们曾用引发剂,使ψ—碘代全氟烷基磺酰氟与多键类化合物在较温和条件下进行加成。黄维垣教授等用NaHCO_3—K_3[Fe(CN)_6]引发Cl(CF_2)_(4.6)I与烯丙醇顺利加成。     

3-取代卓酚酮5位偶联产物的溴氧化成环反应

报道了采用溴氧化3-异丙烯基卓酚酮和3-肉桂酰基卓酚酮合成杂环并卓酮化合物的新方法。3-异丙烯基卓酚酮5位偶联产物1a-1f和3-肉桂酰基卓酚酮5位偶联产物3a-3d分别在吡啶介质中与过量溴作用生成5-取代苯偶氮基-7-溴-3-甲基-8-氢环庚并呋喃-8-酮2a-2f和6-取代苯偶氮基-2-苯基-8-溴-4,9-二氢环庚并吡喃-4,9-二酮4a-4d。     

手性4-膦酸二酯基-3-卤-2(5H)-呋喃酮的合成与结构

手性呋喃酮1a-1b与亚磷酸三酯2a-2b通过串联的不对称Michael加成/分子内Michalis-Arbazov重排反应,得到了含磷官能团的新手性化合物,5-(S)-(l-孟氧基)-4-膦酸二酯基-3-卤素-2(5H)-呋喃酮4a-4d。该反应具有条件温和,产率高(86%-95%),光学纯度单一(d.e.≥98%)的特点。通过元素分析,IR,UV,^1HNMR,^1^3CNMR,MS,[α]~D^2^0波谱分析数据以及X射线四圆衍射数据确定了它们的化学结构和绝对构型。     

异维A酸糖基衍生物的合成及其细胞毒活性研究

采用两种方法合成了2类新的异维A酸糖基衍生物(5a~5d, 6a, 10a~10c, 11a), 并进行了结构表征与确认. 采用MTT法测试了它们对肺癌细胞(A549)等的细胞毒活性. 结果显示, 含有糖苷结构的异维A酸衍生物明显比含有糖酯结构的异维A酸衍生物具有更好的细胞毒活性; 将糖环上的乙酰基脱去后, 相应的化合物活性有明显提高.     

The antioxidant profile of 2,3-dihydrobenzo[b]furan-5-ol and its 1-thio, 1-seleno, and 1-telluro analogues

A novel synthesis of 2,3-dihydrobenzo[b]thiophene-5-ol based on intramolecular homolytic substitution on sulfur was reported. The "antioxidant profile" of the series of 2,3-dihydrobenzo[b]furan-5-ol (2a) its 1-thio (2b), 1-seleno (2c) and 1-telluro (2d) analogues was determined by studies of redox properties, the capacity to inhibit stimulated lipid peroxidation, the reactivity toward tert-butoxyl radicals, the ability to catalyze decomposition of hydrogen peroxide in the presence of glutathione, and the inhibiting effect on stimulated peroxidation in liver microsomes. The one-electron reduction potentials of the aroxyl radicals corresponding to compounds 2a-2d, E degrees (ArO(*)/ArO(-)) were 0.49, 0.49, 0.49, and 0.52 V vs NHE, respectively, as determined by pulse radiolysis. With increasing chalcogen substitution the compounds become slightly more acidic (pK(a) = 10.6, 10.0, 9.9, and 9.5, respectively, for compounds 2a-2d). By using Hess' law, the homolytic O-H bond dissociation enthalpies of compounds 2a-2d (340, 337, 336, and 337 kJ mol(-)(1), respectively) were calculated. The reduction potentials for the proton coupled oxidation of compounds 2a-2d (ArOH --> ArO(*) + H(+)) as determined by cyclic voltammetry in acetonitrile were 1.35 (irreversible), 1.35 (quasireversible) 1.13 (reversible), and 0.74 (reversible) V vs NHE, respectively. As judged by the inhibited rates of peroxidation, R(inh), in a water/chlorobenzene two-phase lipid peroxidation system containing N-acetylcysteine as a thiol-reducing agent in the aqueous phase, the antioxidant capacity increases (2d > 2c = 2b > 2a) as one traverses the group of chalcogens. Whereas the times of inhibition, T(inh), were slightly reduced for the oxygen (2a) and sulfur (2b) derivatives in the absence of the thiol-reducing agent, they were drastically reduced for the selenium (2c) and tellurium (2d) derivatives. This seems to indicate that the organochalcogen compounds are continuously regenerated at the lipid aqueous interphase and that regeneration is much more efficient for the selenium and tellurium compounds. The absolute rate constants for the oxidation of compounds 2a-2b by the tert-butoxyl radical in acetonitrile/di-tert-butyl peroxide (10/1) were the same-2 x 10(8) M(-)(1) s(-)(1). Whereas the oxygen, sulfur, and selenium derivatives 2a-2c were essentially void of any glutathione peroxidase-like activity, the organotellurium compound 2d accelerated the initial reduction of hydrogen peroxide, tert-butyl hydroperoxide, and cumene hydroperoxide in the presence of glutathione 100, 333, and 213 times, respectively, as compared to the spontaneous reaction. Compounds 2a-2d were assessed for their capacity to inhibit lipid peroxidation in liver microsomes stimulated by Fe(II)/ADP/ascorbate. Whereas the oxygen, sulfur, and selenium compounds showed weak inhibiting activity (IC(50) values of approximately 250, 25, and 13 microM, respectively), the organotellurium compound 2d was a potent inhibitor with an IC(50) value of 0.13 microM.     

Synthesis and antibacterial activity of Schiff bases of 5-substituted isatins

Based on the existing reports on the bioactive isatin derivatives, a number of Schiff bases were synthesized by reacting 5-substituted isatins with bioactive amines/hydrazides and their structures were confirmed using spectroscopic methods such as NMR, IR and mass spectrometry. Furthermore, Nbenzylation of isatin followed by the Schiff base formation furnished a new series of compounds(11a–13c) which allowed the analysis of the effect of isatin N-substitution on the bioactivity of the resulting compounds. The antibacterial activity of the synthesized derivatives was evaluated using a microtiter plate method on a series of gram positive and gram negative bacterial strains. Compounds 2d, 3b, 5c and 6a were among the most potent derivatives against Pseudomonas aeruginosa(MIC = 6.25 μg/m L).Analysis of the structure–activity relationship showed that the incorporation of(thio)urea-based Schiff bases lead to more potent derivatives with a broader spectrum of antibacterial activity. In addition,highly lipophilic compounds such as 11a–12c did not show any measurable antibacterial activity, which implies that an optimal lipophilicity might be an important requirement for the antibacterial activity of the studied isatins. Finally, the finding that hydantoin derivatives of N-benzylisatins(13a–13c) still exhibit some antibacterial activity prompted us to consider exploring the bioactivity of more diverse derivatives of isatin-aminohydantoin Schiff bases(compounds 1a–1d) in our future studies.     

Synthesis of compounds of interest in proton transfer spectroscopy

A new series of compounds has been prepared for use in proton transfer spectroscopy. The complexes 6a-6d have been converted into the fully characterised perchlorates 7a-7d and the corresponding anhydro bases 8a-8d.     

3-(2-羟基-4,6-二甲氧基苯基)-5-芳基异噁唑啉的合成及抑菌活性

以查尔酮衍生物为前体, 与盐酸羟胺在碱性条件下反应制得7个3-(2-羟基-4,6-二甲氧基苯基)-5-芳基异噁唑啉化合物(2a~2g), 产物经红外光谱、核磁共振谱、质谱和元素分析表征. 抑菌活性研究结果表明, 化合物2d和2e对大肠杆菌、金黄色葡萄球菌、枯草杆菌和绿脓杆菌均有一定抑制作用, 其中化合物2e对大肠杆菌、金黄色葡萄球菌表现出极好的抑菌活性.     

含噻二唑基的对叔丁基杯[4]芳烃衍生物的合成及表征

以对叔丁基杯[4]芳烃(1)为原料, 分别与1,2-二溴乙烷、1,3-二溴丙烷在碳酸钾的存在下进行选择性烷基化反应, 生成杯[4]芳烃衍生物2和3. 在氢氧化钠存在下, 化合物2和3与过量的含不同官能团的2-巯基噻二唑反应, 生成下缘含噻二唑基的杯芳烃衍生物4a～4c, 5a～5c, 其结构经¹H NMR, ¹³C NMR, IR, MS和元素分析确证.     

Design,synthesis and biological evaluation of new rhodacyanine analogues as potential antitumor agents

In an attempt to develop potent antitumor agents,new rhodacyanine analogues containing the pyridinium ring（5a-5h）,the isoquinolinium ring（6a-6c） and the quinolinium ring（7a-7e） linked to the rhodanine ring via N-N covalent bond were designed, synthesized and evaluated for antitumor activity against human lung cancer cell line（H460） by MTT assay in vitro.Most of the tested compounds showed enhanced antitumor activity with IC₅₀ values ranging from 0.006 to 9.2 u,mol/L as compared to the lead compound MKT-077.Among them,the most promising compound 7d(IC₅₀ = 0.006μmol/L) was 216.7 times more active than MKT-077(IC₅₀ = 1.3μmol/L).The preliminary structure-activity relationship of the target compounds was discussed.     

Preparation of twelve 1-methyl-2-formyl-5-substituted pyrroles and their hydrazones

Preparation of twelve 1-methyl-2-formyl-5-substituted pyrroles (2a-1), with five of them as new compounds, is described. Their derivatives, i.e., 1-methyl-2-formyl-5-substituted pyrrole phenyl hydrazones (3a-1) and 1-methyl-2-formyl-5-substituted pyrrole (4-nitrophenyl) hydrazones (4a-1) are all new compounds. They have also been prepared and further identified.     

Syntheses and structures of isomeric diaminotriazinyl-substituted 2,2'-bipyridines and 1,10-phenanthrolines

Isomeric 2,2'-bipyridines 4a-6a and 1,10-phenanthrolines 7a-9a with two diaminotriazinyl (DAT) substituents were synthesized to explore their dual ability to direct association by the chelation of metals and the characteristic hydrogen bonding of DAT groups. Crystals of compounds 4a-6a and 7a-9a were grown under diverse conditions, and their structures were solved by X-ray crystallography. Analysis revealed multiple shared features analogous to those observed in the structures of simpler DAT-substituted pyridines 1-3. For example, the bipyridines and phenanthrolines favor flattened conformations except in the cases of compounds 8a and 9a, where the patterns of substitution prevent the DAT groups from lying in the plane of the phenanthroline core. As expected, the DAT groups form approximately coplanar hydrogen bonds according to standard motifs I-III, which play a key role in directing molecular organization. However, the structures of simple pyridines 1-3, which favor efficiently packed chains and sheets, differ predictably from those of bipyridines 4a-6a and phenanthrolines 7a-9a in two ways: (1) The larger number of DAT groups in compounds 4a-9a typically leads to complex three-dimensional networks held together by a larger number of hydrogen bonds per molecule, and (2) the need to respect multiple directional interactions prevents compounds 4a-9a from forming closely packed structures, and significant quantities of guests are included. Together, these observations confirm the effectiveness of incorporating special groups such as DAT within more complex molecular structures to control association according to reliable patterns. Bipyridines 4a-6a and phenanthrolines 7a-9a promise to be particularly rich sources of new supramolecular chemistry because they have well-defined molecular topologies and a dual ability to direct association by chelating metals and by engaging in multiple hydrogen bonds according to reliable patterns.