20(S)-O-取代苯甲酸-7-乙基喜树碱酯类化合物的合成及其抗肿瘤活性

在AcOH/98％ H2S04体系中,喜树碱和正丙醛经烷基化反应制得7-乙基喜树碱(2);以1-乙基-3-(3-二甲基氨基丙基)碳二亚胺盐酸盐为脱水剂,4-二甲氨基吡啶为催化剂,2与取代苯甲酸直接酯化合成了一系列新型的20(S)-O-取代苯甲酸-7-乙基喜树碱酯类化合物(4a -4k),其结构经1H NMR,IR和MS表征.采用MTT法初步考察了4a～4k对人肺癌细胞(LLC-E9FP),人肺腺癌细胞(95D),人胃癌细胞(BGC-803),人胃癌细胞( HGC-27)和人肝癌细胞(7721)的抑制活性.结果表明,4b和4e对LLC-E9FP具有明显强于喜树碱的抑制活性;4h～4k对HGC-27,95D,7721也有明显的抑制活性.     

手征性硫代磷酸及其衍生物的研究(Ⅱ)——旋光活性的O-乙基O-苯基硫代磷酸及其硫(醇)代酯的绝对构型

O一乙基-O-苯基硫代磷酸(1)及其硫(醇)代酯(2)的绝对构型可由以下两步反应确定(见图1)。即,(-)-(2)的氯化和(-)-O-乙基-O-苯基磷酰氯(3)的酯化反应。由(-)-(2)→(-)-(3)氯化反应的立体化学过程已a.R′=CH_3b.R′=n-prc.R′=CH_2CH_2OC_2H_5经证明,不管是使用氯气还是使用SO_2Cl_2为氯化剂,均为磷原子构型保留,由(-)-(3)生成(-)-O-乙基-O-甲基O-苯基磷酸酯(4)的反应则使构型翻转。同时(-)-(4)构型已知为(R)-(+)-(4)、(S)-(-)-(4),所以(+)-(1)和(-)-(2)的绝对构型可确定为:(R)-(+)-(1)和(R)-(-)-(2)。这一结果与X-射线衍射法所得结果完全一致。     

20(S)-O-喜树碱肉桂酸酯衍生物的合成及其抗肿瘤活性研究

为了提高喜树碱内酯环的稳定性降低其毒性, 增加其抗肿瘤效能, 以喜树碱为先导化合物, 通过酯化反应直接合成了17个20(S)-喜树碱肉桂酸酯衍生物, 并采用MTT法测定了对于人胃癌细胞SGC-7901的体外抗肿瘤活性, 活性测试结果表明有些化合物的抑制活性明显高于母体化合物喜树碱.     

含全氟壬烯基磷酸酯型表面活性剂的合成

以N-羟乙基-p-全氟壬烯氧基苯甲酰胺(I)为原料与三氯氧磷(POCl3)反应制备p-全氟壬烯氧基苯甲酰胺基乙基磷酰氯,反应结束后在常温下进行水解生成p-全氟壬烯氧基苯甲酰胺基乙基磷酸单酯(Ⅱ)。采用红外光谱(FTIR)、1HNMR、质谱(MS-ESI)对其结构进行了表征。考察了酯化反应时间、酯化反应温度、原料配比和缚酸剂对产物收率的影响。通过单因素实验和正交试验对反应进行优化,确定了最佳合成工艺条件为:n(I):n(POCl3)=1:1.6,反应温度70℃,反应时间7h,三乙胺做为缚酸剂,在此条件下Ⅱ的收率为84.3%。     

几种生物活性diphyllin天然糖苷的合成

本文以全乙酰溴代糖为糖基供体,应用相转移催化法进行糖苷化合成了7-O-b-D-喹诺糖基diphyllin苷(patentiflorin A)和7-O-b-L-岩藻糖基diphyllin苷(patentiflorin B)两种糖苷,然后将patentiflorin B糖环的3’和 4’位羟基进行原酸酯化和酸催化重排反应,得到了天然产物4’-O-乙酰7-O-b-L-岩藻糖基diphyllin苷。三个目标化合物的氢谱、碳谱和高分辨质谱数据与文献报道的天然产物一致。     

天然黄酮香叶木素类及其衍生物的合成与生物活性研究

以橙皮苷为原料,经脱氢、选择性甲基化、糖苷水解、相转移催化下的糖苷化反应、异戊烯基化和法呢烯基化等反应步骤,分别合成了3’-O-甲基香叶木素(1),香叶木素-7-O-β-D-葡萄糖苷(2),香叶木素-7-O-β-D-半乳糖苷(3),3’-O-甲基香叶木素-7-O-β-D-葡萄糖苷(4)4种天然产物及3’-O-甲基香叶木素-7-O-β-D-半乳糖苷(5),香叶木素-7-O-β-D-乙酰葡萄糖苷(6)、香叶木素-7-O-β-D-乙酰半乳糖苷(7),3’-O-甲基香叶木素-7-O-β-D-乙酰葡萄糖苷(8),3’-O-甲基香叶木素-7-O-β-D-乙酰半乳糖苷(9),7-O-异戊基香叶木素(10),7-O-异戊烯基-3’-O-甲基香叶木素(11)和7-O-法呢烯基-3’-O-甲基香叶木素(12)8种新的香叶木素衍生物.所合成化合物的结构已由核磁共振谱、红外光谱和质谱所证实,并用比色法MTT[3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐]蛋白染色法对所合成的目标化合物进行了体外抗肿瘤细胞生物活性测试,发现化合物6,10和11对肝癌细胞(SMMC-7721)、乳腺癌细胞(MCF-7)和结肠癌细胞(SW480)有一定的抑制活性.     

链烷烃类白杨素衍生物的合成及其脂溶性

白杨素为一种常见的黄酮类化合物,其药理作用广泛,但其溶解性和生物利用度低,限制了其临床应用。因此,为了提高白杨素的溶解性,本文通过酯化反应,在白杨素骨架上引入链烷烃,合成了链烷烃类白杨素衍生物,通过~1H NMR、~(13)C NMR和MS-EI进行结构表征和测定,得到乙酸-7-O-白杨素酯(1)、正丁酸-7-O-白杨素酯(2)、正己酸-7-O-白杨素酯(3)、正辛酸-7-O-白杨素酯(4)和正癸酸-7-O-白杨素酯(5)。通过观察白杨素及其衍生物在氯仿中的溶解情况,检测它们的脂溶性,实验结果发现,白杨素衍生物的脂溶性明显大于白杨素本身。     

高效液相色谱法测定防晒化妆品中水杨酸酯类紫外线吸收剂的含量

采用高效液相色谱法同时测定防晒化妆品中8种水杨酸酯类紫外线吸收剂(水杨酸乙基己酯、水杨酸三甲环己酯、水杨酸辛酯、水杨酸苯酯、水杨酸异十六酯、水杨酸己酯、水杨酸乙二醇酯和水杨酸苄酯)的含量。1.000 0g样品经5mL乙酸乙酯于20℃超声萃取10min,萃取液在Agilent ZORBAX Eclipse XDB-C_(18)色谱柱上分离,以甲醇-四氢呋喃-0.1%(质量分数)甲酸溶液为流动相进行梯度洗脱,紫外检测波长为340nm。8种水杨酸酯类紫外线吸收剂质量浓度在5.0~100.0mg·L~(-1)内与峰面积呈线性关系,检出限(3S/N)在0.5~2.5mg·kg~(-1)之间;加标回收率在90.6%~98.8%之间,测定值的相对标准偏差(n=6)在1.4%~3.6%之间。     

新型1,3,4-噁二唑-2-硫酮衍生物的合成及其抗肿瘤活性

以手性氨基酸和间甲基苯甲酸(或苯乙酸)为原料,经酯化、缩合、肼解和环合反应合成了12个新型的1,3,4-噁二唑-2-硫酮衍生物(6a~6f或7a~7f),其结构经1H NMR,FT-IR和ESI-MS表征。用MTT法研究了6和7的抗肿瘤活性。结果表明:(2S)-5-(3-甲基苯甲酰胺基)苯乙基-1,3,4-噁二唑-2-硫酮(6f)和(2S)-5-(2-羟基-苯乙酰胺基)乙基-1,3,4-噁二唑-2-硫酮(7b)对红白血病细胞(K562)抑制活性较好。     

二-(氨基葡萄糖)磷酸酯的合成研究

用2-乙酰胺-3,4,6-三-O-乙酰-2-脱氧-a-D-葡萄吡喃糖-1-磷酸吡啶盐(3)和2-乙酰胺-1,3,4-三-O-乙酰-2-脱氧-β-D-葡萄吡喃糖(4)进行缩合,没有得到6-O-(2-乙酰胺-3,4,6-三-O-乙酰-2-脱氧-D-葡萄吡哺糖-1-磷酰)-2-乙酰胺-1,3,4-三-O-乙酰-2-脱氧-β-D-葡萄吡喃糖(7),而分离到了6-O-(2-乙酰胺-3,4,6-三-O-乙酰-2-脱氧-β-D-葡萄吡喃糖基)-2-乙酰胺-1,3,4-三-O-乙酰-2-脱氧-β-D-葡萄吡喃糖(9)和二-(2-乙酰胺-1,3,4-三-O-乙酰-2-脱氧-β-D-葡萄吡喃糖-6)-磷酸酯(10)。它们是由7的二个分解产物再次与4反应生成的。用1-溴-2-N-DNP-3,4,6-三-O-乙酰-1,2-二-脱氧-α-D-葡萄吡喃糖(13)和2-乙酰胺-1,3,4-三-O-乙酰-2-脱氧-β-D-葡萄吡喃糖-6-磷酸三乙胺盐(8)反应,得到了6-O-(2-N-DNP-3,4,6-三-O-乙酰-2-脱氧-β-D-葡萄吡喃糖-1-磷酰)-2-乙酰胺-1,3,4-三-O-乙酰-2-脱氧-β-D-葡萄吡喃糖(16)。16性质稳定,说明氨基葡萄糖的2-位乙酰基的存在使其1-位磷酸基团较易离去,而2-位 DNP 基则没有这种影响。     

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.     

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。     

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.     

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。