计算机辅助设计的新型胰蛋白酶抑制剂的合成及其抑制活性

以6-氰基-2-萘酚为原料,经两步反应制得6-羟基-2-萘甲脒甲磺酸盐(2)。利用分子对接法辅助设计,2分别与芳酸(1a~1h)反应,合成了8个萘甲脒蛋白酶抑制剂(3a~3h);硝基化合物(4)经还原反应合成了1个嘧啶胰蛋白酶抑制剂(3i)。以邻胺基苯酚为原料,经两步反应合成了1个嘧啶胰蛋白酶抑制剂(3j)。3b~3f为新化合物,其结构经1H NMR,13C NMR和HR-ESI-MS表征。体外活性测试表明:6-甲脒基-2-萘酚4-(4-氨基丁酰胺)苯甲酸酯(3e)对胰蛋白酶有较好的抑制活性,其IC50为0.352μg·m L-1,优于奈莫司他(IC500.451μg·m L-1)。     

6,11-二氢苯并噻喃并[4,3-b]吲哚类化合物的合成及其抗肿瘤活性

以取代硫色满酮(1a~1f)和盐酸苯肼(2)为原料,经Borsche-Drechsel环化反应合成了6个6,11-二氢苯并噻喃并[4,3-b]吲哚类化合物(3a~3f);3a~3f用间氯过氧苯甲酸氧化成5,5-二氧-6,11-二氢苯并噻喃并[4,3-b]吲哚类化合物(4a~4f),其结构经1H NMR,IR和HR-ESI-MS确证。采用MTT法初步测定了1,3和4对肺癌细胞A549的抑制作用。结果表明:3a~4f的抑制活性均强于1。     

新型吡咯季铵盐的合成

以乙酰乙酸乙酯为原料,经缩合、氧化、还原和氯代等反应合成了3-甲基-5-碘甲基-1H-吡咯-2,4-二(甲酸乙酯)(5);5分别与乌洛托品,吡啶和三甲胺经取代反应合成了3个吡咯季铵盐6a~6c,其中5和6a~6c均为新化合物,其结构经1H NMR,IR和ESI-MS表征。     

可再生高价碘试剂4-二氯碘苯甲酸的合成及其氧化性能

以对碘苯甲酸为原料,采用“一锅法”合成高价碘试剂4-二氯碘苯甲酸（1）,其结构经¹H NMR和IR确证。考察了其对取代苯甲醇的氧化性能。结果表明：1对4-(二甲氨基)苄醇的氧化性能最高,收率93%。     

氟代苯基异羟肟酸钴的合成及其对乙苯氧化的催化性能

以全氟碘丁烷为原料,分别与4-碘硝基苯和4-碘苯甲酸反应合成了4-全氟丁基硝基苯（1）和4-全氟丁基苯甲酸（3）; 1经还原反应,3经酰氯化反应,后再缩合反应制得氟代苯基异羟肟酸（5）; 5经络合反应合成了氟代苯基异羟肟酸钴（6）, 其结构经 UV-Vis, ¹H NMR, FT-IR和HR-MS（EI）表征。在氟两相中考察了其对乙苯氧化的催化性能。结果表明：在全氟己烷中,6 0.04 mmol,于60 ℃反应6 h,乙苯的转化率为49.2%,苯乙酮的选择性为88.3%。6循环使用5次,选择性保持良好。     

青蒿砜—氨基二硫代甲酸酯类化合物的合成

以双氢青蒿素(DHA)为原料,与草酰氯发生酰化反应,然后经硫代吗啉取代反应、双氧水氧化反应得到青蒿砜1,由1经过烷基化反应、脱硅保护基和碘代反应得到青蒿砜-碘代物2α;以三乙胺为催化剂,2α与哌嗪类化合物、CS_2在"一锅煮"条件下得到青蒿砜-氨基二硫代甲酸酯化合物(3a~3d)。所有目标化合物的结构均经~1H NMR、~(13)C NMR、IR和HR-ESI-MS得到确证。     

TMSCl促进的分子内亲核取代反应合成α-亚烷基-哌啶酮

以烯基碘代物为底物,丁基锂为锂代试剂,THF为溶剂,在TMSCl促进下通过分子内亲核取代反应合成了4个α-亚烷基-哌啶酮(2a~2d),其结构经~1H NMR,~(13)C NMR和HR-MS(ESI)确证。在最优反应条件(1 2 mmol,n-Bu Li 2.4 mmol,TMSCl 3 mmol,THF 20 m L,于170℃反应1 h)下,2a~2d收率68%~84%。     

三氟甲磺酸铜催化新型苯并恶唑烷衍生物的合成

以三氟甲磺酸铜［Cu(OTf)₂］为催化剂,取代邻氨基苯酚(1a~1g)和取代联苯甲酰(2a~2g)为原料,合成了7个苯并恶唑烷衍生物（3a~3g,其中3b~3g为新化合物）,其结构经¹H NMR, ¹³C NMR, IR和HR-MS(ESI)表征。以3a的合成为例,研究了催化剂、溶剂、催化剂用量、物料比γ［n(1) : n(2)］和反应温度对3产率的影响。结果表明：在最佳反应条件［8 mmol%Cu(OTf)₂, 1,2-二氯乙烷为溶剂,1a~1g1.5 mmol, γ=3:1,于70 ℃反应10 h］下,3a~3g产率62%~91%。     

N-[2-(4-吗啉基)乙基]苯甲酰胺类单胺氧化酶抑制剂的合成及其生物活性研究

以取代苯甲酸为原料,经缩合反应制得N-(2-溴乙基)苯甲酰胺类化合物(4a~4i);4a~4i经N-烷基化反应合成N-[2-(4-吗啉基)乙基]苯甲酰胺类化合物(1a~1i),其结构经~1H NMR,~(13)C NMR,MS和元素分析表征。并对其生物活性进行了初步实验。实验结果表明:1a~1i对单胺氧化酶(MAO-A)有良好的抑制作用,其中1a最好,当IC50=3.652μmol·L~(-1)时,SI=42.32。     

Ru(PPh3)Cl2催化的苄醇氧化反应研究

以Ru(PPh₃)Cl₂为催化剂,取代苄醇为原料,在O₂氛围中利用分子氧进行选择性氧化,合成了12个芳香醛衍生物（2a~2l）,其结构经¹H NMR, ¹³C NMR和IR确证。以4-甲氧基苯甲醛（2b）的合成为例,研究了催化剂、反应温度、溶剂和催化剂用量对2产率的影响。〖JP3〗结果表明：在最优反应条件[1 1 mmol, 5 mmol%Ru(PPh₃)Cl₂, 1,2-二氯乙烷2 mL,于90 ℃反应6 h]下,2a~2l产率75%~97%。     

利用手持技术改进测定乙醇分子结构实验

利用压强传感器代替排水集气法,改进测定乙醇分子结构实验的仪器装置,并探索最佳反应条件。另外,设计两个空白实验,结合压强变化曲线对实验误差进行相关讨论。     

光谱仪测试范围的扩展

由于石化行业的生产需要，其材质的使用具有多样性和广泛性，经常会出现顾客委托的测试样品的一个或几个元素跨越光谱仪现有测试程序测量范围的情况。本法通过对光谱仪测试原理的认识，根据光谱仪的测试能力及标样的采集，实现了一个或几个元素测量范围的扩展，并对其测量的影响因素进行了研究。     

Influence of viscosity of medium on processes of oxygen quenching of excited states of mesoporphyrin

The oxygen quenching rate constants for singlet and triplet excited states of the dimethyl ester of mesoporphyrin IX increase with decreasing viscosity of the medium and reach a maximum at a viscosity of approximately 0.4 mPa·sec, after which the rate constants begin to decrease. The drop in rate constant with increasing fluidity of the medium may be related to a nonequilibrium character of the elementary act in the interaction of the reactants in the solvent cage. In viscous media such as isopropyl alcohol, isobutyl alcohol, and isoamyl alcohol, the reaction radius is greater than the sum of the radii of the reacting particles. The long-range character of these processes is due to the relatively weak dependence of the quenching probability on distance.Translated from Teoreticheskaya i Éksperimental'naya Khimiya, Vol. 25, No. 2, pp. 161–167, March–April, 1989.     

Dichroism of absorption and polarization of phosphorescence of molecules of the closed form of nitrobenzospirothiopyran

The spectral-polarization characteristics of absorption and phosphorescence of molecules of the initial form of nitro-substituted indolinospirobenzothiopyran were studied in oriented polyethylene films and in solutions with different polarity. An oscillator model of the electron transitions responsible for the formation of absorption and luminescence spectra was suggested. It was established that the principal differences in the spectral and photophysical properties of the compound studied and its oxygen-containing analog are associated with the fact that the electronegativity of the S atom is lower than that of the O atom. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1143–1146, June, 1997.     

Neutral diterpenoids of oleoresins of five species of conifers of Transcarpathia

The compositions of the neutral diterpenoids of the oleoresins of five species of conifers growing in the Transcarpathia have been studied. It has been found that the oleoresins ofAbies alba M.,Larix decidua M., andPicea excelsa L. contain more than 50% of neutral diterpenoids. The group and qualitative compositions of the oxygen-containing diterpenoids have been determined. In the oleoresins ofAbies alba,Picea excelsa, andPicea abies tertiary alcohols — cis-abienol and isocembrol — predominate, while inLarix decidua the main component is the hydroxy ester larixyl acetate. Primary alcohols related to the resin acids have been found in all the oleoresins investigated. Features of the distribution of diterpenoids according to the species of conifers have been revealed. The results obtained are necessary for the chemotaxonomy of conifers of the family Pinceae.Novosibirsk Institute of Organic Chemistry, Siberian Branch, Academy of Sciences of the USSR. Translated from Khimiya Prirodynkh Soedinenii, No. 6, pp. 812–816, November–December, 1988.     

Determination of heats of detonation and influence of components of composite explosives on heats of detonation of high explosives

The heats of detonation of 20 simple high explosives and explosive mixtures were determined by means of an adiabatic detonation calorimeter designed by the authors. The results indicated that the performance of the instrument was reliable and the experimental data were very accurate. For explosive mixtures, there was a linear accumulative relationship between the heats of detonation of the explosive mixture and its components. Accordingly, the heats of detonation of explosive mixtures could be calculated directly from the heats of detonation of simple explosives and the characteristic heats of other components. The experiments showed that the gold or brass shell of the cylindrical charge could be substituted by a thick-walled porcelain shell, which had the advantage of cheapness.

     

物质分配系数的测定实验改进

实验教学目的是从解决实际问题出发,以实验技术训练和实验设计思想培养为目标。介绍了将单一的物质分配系数测定实验改进为综合实验,提高了实验效果及实验资源利用率。     

Calculation of enthalpies of hydrogenation of hydrocarbons

Sets of hydrogen molecule equivalents have been developed which permit the calculation of hydrogenation of different types of carbon-carbon bonds from ab initio total energies (3-21G and 6-31G* basis sets, and, to a more limited extent, for MP2/6-31G* data) of reactants and products. The calculated enthalpies of hydrogenation are in good agreement with experiment for unstrained molecules, with average errors on the order of 2 kcal/mol. The 6-31G* equivalents allow the enthalpies for strained molecules to be calculated accurately, but the 3-21G equivalents do not. The equivalents for both basis sets have been tested by calculating the enthalpies of hydrogenation of carbon-carbon bonds in nitrogen- and oxygen-containing organic molecules, free radicals, and classical carbocations. The results are in good agreement with experiment in most cases.     

非那雄胺合成工艺改进

非那雄胺能抑制5α-还原酶的活性,明显降低二氢睾酮水平,是一种治疗良性前列腺增生的有效药品。该合成工艺以甾烯酮酸为原料,将其与氯化亚砜反应,无须分离即与叔丁胺反应得17β-酰胺化合物,再氧化开环,环合,氢化,脱氢合成了非那雄胺。经元素分析、IR、1HNMR、13CNMR、MS分析表征了其结构。该法无须使用昂贵的2,2-二吡啶二硫化物和剧毒药品苯亚硒酸酐,且以乙酸铵代替氨气,降低了对设备的要求和腐蚀,更适用于工业生产。