新型嘧啶单环类非经典叶酸拮抗剂的合成及抗肿瘤活性研究

以课题组前期设计合成的非经典叶酸拮抗剂6-(4'-甲基苯乙基)-N5-氯乙酰基-2,4-二氨基哌啶并[3,2-d]嘧啶(wm-8.2)为先导化合物,将wm-8.2中的哌啶并嘧啶双环结构简化为嘧啶单环结构,以提高分子柔韧性并简化分子结构,根据6-位空间占位设计6-H和6-甲基两个系列,考察了不同桥链长度和不同芳香杂环侧链对抗肿瘤活性的影响.同时对具有叶酸抑制剂分子结构特征的关键中间体进行活性对比测定,研究了N(5)位氯乙酰基对活性的影响.两个系列目标化合物和关键中间体共36个化合物的结构均经1H NMR,13C NMR和MS确证.生物活性测定表明,6位为甲基的化合物中,具有三碳桥链及对甲基苯环侧链的6-甲基-2,4-二氨基-5-(N-(4-甲基苯基)丙基-N-(2-氯乙酰基))氨基嘧啶(6b-3)具有最好的HL-60、A549和HCT116细胞增殖抑制活性,IC50分别为0.25,0.83和0.63μmol?L^-1.化合物6b-3在N(5)位氯乙酰基取代之前的关键中间体6-甲基-2,4-二氨基-5-(N-(4-甲基苯基)丙基)氨基嘧啶(5b-3)具有最优的二氢叶酸还原酶抑制活性.总结了化合物的构效关系,并用计算机模拟进行了阐释.     

利用单模光纤中的交叉相位调制产生单周期化脉冲的研究

描述了利用光纤中的交叉相位调制（XPM）效应产生单周期化脉冲的基本原理.详细分析了不同初始脉冲条件对脉冲频谱展宽的影响，然后针对具体事例用分步傅里叶方法对分析结果进行了验证.最终得到了200—1000THz的超宽带频谱，并给出了理想压缩脉冲的时域脉宽和形状. 关键词： 单周期化脉冲 交叉相位调制 超宽带频谱     

模型复合推进剂燃烧转爆轰研究

本文较详细地研究了模型推进剂(AP/wax,AP/A1/wax,AP/RDX/A1/wax)由燃烧转爆轰(DDT)的过程。分析了装药密度和铝粉含量对装药DDT的影响。结果表明:模型推进剂当其配比接近零氧平衡时较易产生DDT;含与不含铝粉的AP/粘合剂系复合推进剂药柱以及硝胺含量为20％的AP/硝胺炸药/A1粘合剂系复合推进剂药柱都不可能产生DDT。     

Distortions in nitramine substituted cubanes: The structures of N,N′-dinitro-1,4-diaminocubane,N,N′-dinitro-N,N′-(2-pyridyl)-1,4-diaminocubane,and 1,2,4,7-tetrakis(N-methoxycarbonylnitramino)cubane

The structures of three nitramine substituted cubane molecules, N,N-dinitro-1,4-diaminocubane (1), N,N-dinitro-N,N-(2-pyridyl)-1,4-diaminocubane (2), and 1,2,4,7-Tetrakis(N-methoxycarbonylnitramino)-cubane (3), have been determined.1 crystallized in the space group P2₁/a with cell dimensionsa=6.545(1),b=9.331(1),c=7.459(1) Å, =105.80(1),2 crystallized in the monoclinic space group P2₁/a with cell dimensionsa=7.545(2),b=8.697(3),c=12.406(4 Å, =96.28(3)°, while3 crystallized in the monoclinic space group P2₁/c with cell dimensionsa=10.866(3),b=6.866(2),c=16.167(6) Å, =108.79(3)°. The metrical parameters of the cubane skeleton showed no significant deviations from those found in other similarly substituted cubane molecules. For2 and3 there were considerable distortions of the nitramine moiety from planarity in contrast to1 where the nitramine moiety was almost exactly planar. The bond distances and angles for the nitramine group in1 indicates a substantial introduction of double bond character into the N–N bond in1, achieved by delocalization of the amine lone pair, compared with2 and3.     

Electrooxidation of primary nitramine anions on platinum in MeCN

Oxidation of primary nitramine anions RNNO₂ ⁻Bu₄N⁺ (R=Me, Et, Pr¹, or methoxyfurazanyl) in 0.1N Bu₄NClO₄ in MeCN on a Pt anode was studied by voltammetry and controlled potential electrolysis. It was found that the first stage of oxidation affords the corresponding radicals, which are further stabilized due to hydrogen abstraction from the medium. These radicals are also involved in other reactions, including those, which yield azo derivatives. The possibility of generation of nitrene species in these reactions is discussed. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1935–1939, October, 1999.     

1H and 13C NMR assignments and X-ray structures for three monocyclic benzoannelated dilactam polyethers

Three monocyclic polyether dilactams, 17,18-dihydro-5H, 9H-dibenzo[e,n]1,4,10,7,13trioxadiazacyclopentadecine-6,10(7H,11H)-dione (1); 9,10,20,21-tetrahydro-5H, 12H-dibenzo[e,q]1,4,10,13,7,16tetraoxadiazacyclooctadecine-6, 13(7H,14H)-dione (2); and 6,7,9,10-tetrahydro-16H, 20H-dibenzo[h,q]1,4,7,13, 10,16tetraoxadiazacyclooctadecine-17, 21(18H,22H)-dione (3) were isolated during the synthesis of several benzoannelated cryptands. The complete assignments of the 1H and 13C NMR spectra of 1, 2 and 3 in CDCl3 were made using gCOSY, gHMBC, gHMQC, HMQC, HSQC, and NOESY 1D techniques. The ortho (H2) benzene protons show significant downfield shifts (1.16-1.43 ppm) that are consistent with an exodentate orientation for the amide carbonyl groups. The X-ray crystal structures of 1, 2 and 3 show that the carbonyl groups adopt an exodentate conformation in the solid state.     

某些单环非典型内酰胺抗菌活性的量子化学研究

某些单环非典型内酰胺抗菌活性的量子化学研究李英富，周爱新，郭直惟，李正化，李光平（华西医科大学药学院成都６１００４４）（四川大学化学系成都６１００６４）关键词：ＭＮＤＯ，化学活性，ＬＵＭＯ，抗菌活性，单环非典型内酰胺本文用ＭＮＤＯ方法对已合成的八个单...     

Two New Regulatory Properties Arising from the Transient Phase Kinetics of Monocyclic Enzyme Cascades

Taking as starting point a previous contribution about the kinetics of the transient phase and steady-state of monocyclic enzyme cascades, this paper suggest the definition and use of new regulatory modification properties involving the time elapses from the onset of the reaction to the attainment of the steady-state for a monocyclic enzyme cascade. A minimal set of simplifying assumptions allowing to derive analytical expressions for these properties has been used. From these general expressions we derive, as particular cases, other simpler expressions by using additional assumptions which have, therefore, a smaller range of validity. A discussion of the relationships between the kinetic parameters and concentrations needed to the additional assumption is observed is carried out. The goodness of our analysis has been tested by using numerical integration of the set of differential equation describing the kinetic behaviour of the cascade. The results obtained for a type of cascade are extrapolable to other different schemes of monocyclic enzyme cascades. Finally, a kinetic data analysis and an experimental design are suggested     

Highly Strained Metallocenophanes: Synthesis and Ring-Opening of Sulfur-, Selenium- and Boron- Bridged [1]Ferrocenophanes

Abstract

The limits of cyclopentadienyl ring-tilting in [l]ferrocenophanes are explored with the incorporation of group 16 elements and a first row element. In this paper the synthesis and ring-opening polymerisation (ROP) behaviour of highly strained chalcogen-and boron- bridged [l]ferrocenophanes will be described.     

Pulsed Plasma Polymerization of Cyclic Ethers: Production of Biologically Nonfouling Surfaces

Polymerization of low molecular weight cyclic ethers was investigated under pulsed plasma conditions. Film formation conditions were adjusted to optimize retention of ethylene oxide (EO) content of the monomers in the resultant plasma generated polymers. To a large extent this goal was achieved with the 12-crown-4 and 15-crown-5 monomers, but not with dioxane. Films obtained from the 12-crown-4 monomer under ultra low power inputs are shown to be highly resistant to protein adsorption, while exhibiting good chemical compositional stability and adhesion during prolonged immersion in aqueous solutions. The dramatic differences observed in contrasting polymer film compositions from 12-crown-4 and dioxane are believed to arise from distinctive differences in the low electron impact fragmentation patterns of these two compounds, as discussed in this report.