伊贝沙坦的合成

以环戊酮为起始原料,与氰胺、戊酰化物反应得到N-(1-氰基环戊基)戊酰胺(2); 2经双氧水水解得到1-戊酰胺基环戊烷-1-羟酰胺(3);化合物3依次经分子内环合、酸化和缩合制得4'-[(2-丁基-4-氧-1,3-二氮杂螺环[4,4]壬-1-烯-3-基)甲基]联苯-2-甲腈(5);化合物5与叠氮钠发生叠氮化反应合成了伊贝沙坦(6),总收率40.7 %,纯度99.5 %,其结构经¹H NMR、 ¹³C NMR和HR-MS(ESI)确证。      

新型L-酪氨酸二肽衍生物的合成及其抗肿瘤活性

以L-酪氨酸甲酯盐酸盐和对羟基苯甲酸（PHBA）为原料,经缩合、水解和亲核取代反应,设计并合成了9个新型的L-酪氨酸二肽衍生物（3b和4a~4h）,其结构经¹H NMR、 ¹³C NMR和MS（ESI）表征。采用MTT法评价了化合物对白血病细胞（K562）、人肺癌细胞（A549）和人肝癌细胞（HepG2）的体外抑制活性。结果表明：N-[N-(4-苄氧基-苯甲酰基)-O-二甲氨基丙基-L-酪氨酰基]-L-苯丙氨醇(4e)对HepG2和K542细胞的抑制活性均高于阳性对照药阿霉素,IC₅₀分别为0.41和11.77 μmol·L^-1。     

N-芳基-二茂铁甲酰烯胺的合成

含二茂铁基的烯胺及其过渡金属络合物前人做过一些工作^[1-4]。但二茂铁甲酰烯胺类衍生物未见文献报道。我们考虑二茂铁甲酰烯胺及其络合物的应用前景,研究了二茂铁甲酰烯胺类化合物的合成方法及其络合性质。由二茂铁甲酰丙酮^[5]与取代苯胺缩合,得到了十种不同N-芳基-二茂铁甲酰烯胺:FcCOCH=C(CH₃)-NHC₆H₄X 其中:X=H; O-, m-, p-OH; m-, p-OCH₃; O-, p-Cl; m-, p-NO₂着重研究了取代基的种类与位置对缩合反应的影响。     

利托那韦的合成新方法

建立了利托那韦的合成新方法。N-{N-甲基-N-[(2-异丙基-4-噻唑基)甲基]氨基羰基}-L-缬氨酸(1)与(2S,3S,5S)-5-氨基-2-{N-[(5-噻唑基)-甲氧羰基]氨基}-1,6-二苯基-3-羟基己烷在3-(二乙氧基磷酰氧基)-1,2,3-苯并三嗪-4-酮催化下于室温经缩合反应合成了利托那韦,其结构经1H NMR,13C NMR,MS和元素分析确证。在最佳反应条件[1 0.2 mol,DEPBT 0.25 mmol,二氯甲烷为溶剂,三乙胺为缚酸剂,于室温反应过夜]下,收率72.6%。     

β-L-2’-脱氧胞苷的合成

β-L-2’-脱氧胞苷为重要的医药中间体。以2’-脱氧-L-核糖和胞嘧啶为起始原料，通过甲苷化、酯化、氯代、水解脱保护基等步骤，以49.7%的收率合成了β-L-2’-脱氧胞苷，HPLC纯度达99.9%。产物结构经¹H NMR, ¹³C NMR和MS确证。      

靶向抗肿瘤药N-(N’-苄氧羰基甘氨酰脯氨酰)丙卡巴肼(Z-GP-Pcb)的环境友好合成及其透过血脑屏障活性评价

利用靶向策略设计了抗肿瘤药物N-(N’-苄氧羰基甘氨酰脯氨酰)丙卡巴肼(Z-GP-Pcb),发展了3步法合成丙卡巴肼(Pcb).首先以4-甲基苯甲醛为原料,经二溴异氰脲酸(DBI)转化为N-异丙基-4-甲基苯酰胺.该化合物经2-碘酰基苯甲酸(IBX)直接氧化为N-异丙基-4-甲酰基苯酰胺,随后还原胺化得Pcb.最后与N-苄氧羰基甘氨酰脯氨酸缩合得Z-GP-Pcb,总收率49.9%.另外,本研究还建立了体外平行人造膜渗透测血脑屏障(PAMPA-BBB)方法评价Z-GP-Pcb透过血脑屏障(BBB)活性,发现其透膜常数(Pe)为(19.22±4.25)×10^-6cm·s^-1,大于母药Pcb[(11.14±1.34))×10^-6cm·s^-1],具有较高的透过BBB活性.     

Process Improvement on the Total Synthesis of a Low Molecular Weight MyD88 Mimic AS-l

以N-Boc-L-缬氨酸为起始原料,经四步反应(最后一步用苯丙酰氯为苯丙酰化试剂)高产率地合成了蛋白质MyD88的小分子拟似物—N-(N′-3-苯丙酰-L-缬氨酰)四氢吡咯(AS-1),其结构经1H NMR和MS确证,总收率42％,纯度高于98％.     

MyD88小分子拟似物AS-1全合成的方法改进

以N-Boc-L-缬氨酸为起始原料,经四步反应(最后一步用苯丙酰氯为苯丙酰化试剂)高产率地合成了蛋白质MyD88的小分子拟似物——N-(N’-3-苯丙酰-L-缬氨酰)四氢吡咯(AS-1),其结构经1H NMR和MS确证,总收率42%,纯度高于98%。     

含哌啶的新型1,2,4-噁二唑类衍生物的设计合成及抗真菌活性研究

为了寻找新型高效的抗菌先导化合物,采用活性亚结构拼接法,设计合成了17个含哌啶的新型1,2,4-噁二唑类衍生物4a～4b和6a～6o,其结构经¹H NMR、¹³C NMR和高分辨质谱(HRMS)表征. N-(1-苯甲酰基哌啶-4-基)-4-(5-(三氟甲基)-1,2,4-噁二唑-3-基)苯甲酰胺(6e)结构由X射线单晶衍射法加以确证.抗菌活性测试结果表明:在浓度为3.13mg/L时, N-(1-乙酰基哌啶-4-基)-4-(5-(三氟甲基)-1,2,4-噁二唑-3-基)苯甲酰胺(6a)、N-(1-(环丙甲酰基)哌啶-4-基)-4-(5-(三氟甲基)-1,2,4-噁二唑-3-基)苯甲酰胺(6c)、6e、4-((4-(5-(三氟甲基)-1,2,4-噁二唑-3-基)苯甲酰胺基)甲基)哌啶-1-甲酸叔丁酯(4b)和N-((1-(苯甲酰基)哌啶-4-基)甲基-4-(5-(三氟甲基)-1,2,4-噁二唑-3-基)苯甲酰胺(6o)对大豆锈病(Phakopsora pachyrhiz)的抑制率分别为70%、82%、95%、78%和98%,优于Flufenoxa...     

利用Reformatsky反应合成1-β-碳氢霉烯类抗生素中间体

以(2R)-3-[(3S,4R)-1-(叔丁基二甲基硅氧基)乙基]-4-乙酰氧基氮杂环丁-2-酮为母体,2-溴乙(丙)酸酯或2-溴丙酰胺为亲核试剂,通过Reformatsky反应合成了一系列新型的1-β-碳氢霉烯类抗生素中间体——3-{(2R)-2-[(3S,4R)-1-(叔丁基二甲基硅氧基)乙基]氮杂环丁-2-酮-4-基}乙(丙)酸酯(3a～3d)和3-{(2R)-2-[(3S,4R)-1-(叔丁基二甲基硅氧基)乙基]氮杂环丁-2-酮-4-基}-N,N-二取代丙酰胺(3e,3i和3k),其结构经1H NMR和13C NMR表征,其中3a～3e和3i未见文献报道。     

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。     

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.     

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.     

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。