4-取代-3-烷基-4,5-二氢-1-(3-氯-4-氟苯基)-1,2,4-三唑-5-酮的合成及生物活性

为寻找活性强、作用时间长的新型非肽类血管紧张素II AT₁受体拮抗剂, 从易得原料3-烷基-4,5-二氢-1-(3-氯-4-氟苯基)-1,2,4-三唑-5-酮出发, 经过N-烃化反应、1,3-偶极反应、氢解、水解和酰化等反应, 合成得到一系列4-取代-3-烷基-4,5-二氢-1-(3-氯-4-氟苯基)-1,2,4-三唑-5-酮类衍生物, 总收率为58%～87%, 其结构经IR, ¹H NMR, MS和元素分析确证. 初步药理试验结果表明: 所有目标化合物均有一定的AT₁受体拮抗活性, 其中化合物12d抑制AII诱导的兔主动脉环收缩的IC₅₀值为4.0×10^－9 mol/L, 与阳性药坎地沙坦(candesartan)相当, 具有进一步的研究意义.     

1-乙基-4-氧-7-甲基-1,8-萘啶-3-羧酸的合成

乙基氧甲基萘啶羧酸;缩合反应;成环反应;乙基化反应;水解反应;光谱特征     

2-乙氧羰基-3-溴-4-甲基-5-甲酰基-吡咯的合成

2-乙氧羰基-3-溴-4-甲基-5-甲酰基-吡咯的合成;乙氧羰基二甲基吡咯;乙氧羰基溴二甲基吡咯;乙氧羰基溴甲基甲酰基吡咯     

6-溴-7-异丙基-1,10-二甲基-1,2,3,4-四氢蒽-1-羧酸的合成

以脱氢松香酸为原料,经酯化、溴代、氧化、异构化、水解等反应,合成了一种新型的四氢蒽羧酸类衍生物———6-溴-7-异丙基-1,10-二甲基-1,2,3,4-四氢蒽-1-羧酸,其结构经1H NMR,13C NMR,MS和元素分析表征。     

17β-羟基-17α-甲基-雌甾-4-烯-3-酮的合成

分别以酸性脱羧物和碱性脱羧物为起始原料,经官能团的保护制备甲基诺龙。考察了酸性对保护3位羰基的影响,确定了无水乙醇/石油醚是目标分子重结晶的最佳溶剂体系。考擦了格氏试剂(CH3MgI)和甲基锂(CH3Li)对17位羰基的亲核加成反应,发现用甲基锂试剂反应收率可达86.7% 。     

6-溴-3-[2-(6-溴-2-甲氧基喹啉-3-基)-1,2-二苯乙基]-2-甲氧基喹啉的合成

以6-溴-3-(氯苯基甲基)-2-甲氧基喹啉(2)为起始原料,经过偶合对接反应合成了新型喹啉类抗结核药物TMC-207的衍生物6-溴-3-[2-(6-溴-2-甲氧基喹啉-3-基)-1,2-二苯乙基]-2-甲氧基喹啉,其结构经1H NMR和HR-MS确证.最佳反应条件:2 10 mmol,Et_3N 5 mL,KI 0.17 g,乙腈150 mL,于80 ℃反应6 h,收率73%.     

3-甲基-1-戊烯-4-炔-3-醇的合成

以甲基乙烯酮为原料,用乙炔基格氏试剂对其加成,然后水解得到目标物3-甲基-1-戊烯-4-炔-3-醇。研究了温度对反应的影响,发现在25℃的反应温度下,目标化合物的气相色谱产率为50%,减压蒸馏纯化后收率为30%。目标产物用1HNMR、IR进行了表征。     

3,3-二甲基-9-(5,5-二甲基-3-羟基-2-环己烯-1-酮-2-基)-1-氧代-2,3,4,9-四氢化氧杂蒽的合成和晶体结构

标题化合物C23H26O4是由水杨醛与5，5-二甲基-1，3-环己二酮在N，N-二甲基甲酰胺中反应而得．结构通过单晶X-射线行射法确定，其晶体属于单料晶系，空间群P21/c，a=7．056（7），b=20.263（3），c=13．665（2）A，β＝93．32（1）°，V=1950．7（4）A3，Mr=366．46，Dc=1.248g／cm3，Z=4，μ（MoKa）=0．84cm－1，F（000）=784。晶体结构用直接法解出，经全矩阵最小二乘法对原子参数进行修正，最后的偏离因子R=0．068，Rw=0．075。晶体结构分析结果表明，分子中存在一个共轭的烯醇式结构。     

2-氨基-6,7-二甲氧基-喹啉-3-甲酸甲酯的合成

以3,4-二甲氧基苯甲醛为起始原料,经硝化、缩合和还原反应合成了2-氨基-6,7-二甲氧基-喹啉-3-甲酸甲酯,其结构经UV,1HNMR,IR和MS表征。     

1-芳基-2-苯基-3-甲基-3-异丙基-2-氧代-1,4,2-二氮磷杂环戊-5-酮的合成及除草活性

利用取代苯基脲与苯基二氯化膦和3-甲基-2-丁酮进行的类Mannich反应合成了15种新的1,4,2-二氮磷杂环戊-5-酮类化合物(2a_2o), 其结构经     

POLYMERIC SURFACTANTS BASED ON OLEIC ACID III. Copolymerization of Sodium Acrylamidostearate and Oleic Acid in a Lamellar Liquid Crystal

Copolymerization of sodium acrylamidostearate (NaAAS) and oleic acid was performed in the lamellar liquid crystal (LLC) formed by NaAAS, oleic acid and water, in the absence of N.N’-methylenebisacrylamide (MBAA) and in the presence of MBAA, respectively. In the absence of MBAA, after the polymerization the lamellar structure remained, and the disorder of the lamellar liquid crystal was, to some extent, enhanced. Surface tension, small-angle X-ray diffraction, viscosity, and fluorescence methods were used to study the properties of the linear copolymer. The linear polymeric surfactant behaves like     

辛烷基苯酚聚氧乙烯醚与正癸醇层状液晶的有序性及层状结构

Order character and lamellar structure of TritonX 100/n C10H21OH/H2O lamellar liquid crystal were investigated. Partial phase diagram of TritonX 100/C10H21OH/H2O was measured at 25℃ by the polarizing microscope, and lamellar structure of the lamellar liquid crystal was verified by the 2H NMR spectra. The ESR spin probe method was used to detect the changes in the lamellar liquid crystal. A stearic acid, 5 doxylstearic acid, was used as the spin probe. The values of hyperfine coupling constant and order parameter of lamellar liquid crystal in the phase diagram were calculated. The values of the hyperfine coupling constant with different composition were almost unchanged. It indicates that the micropolarity of the lamellar liquid crystal is very similar. The order parameter decreases with the increasing water content in lamellar liquid crystal. It can be explained by considering that: First, though the penetration is determined at the given weight ratio of C10H21OH to TritonX 100, the absolute water content penetrated into the amphiphile bilayer increases with the increasing of the water content. Second, the thickness of the solvent also increases, which makes the force between layers weaker. The results also showed that order parameter of lamellar liquid crystal increased with TritonX 100 content, which may be explained from the fact that the water content penetrated into the amphiphile bilayer decreases relatively and the molecules in the amphiphile bilayer are made tighten. The interlayer spacing of lamellar liquid crystal was determined by small angle X ray diffraction. The penetration ratio of water in the lamellar liquid crystal was calculated. It was about 50%.     

Microstructure and rheological properties of liquid crystallines formed in Brij 97/water/IPM system

The phase diagram of Brij 97/water/IPM systems was determined at 25 degrees C. Rich liquid crystalline phases including Lalpha, H1, and cubic Fd3m phases were identified by means of small angle X-ray scattering (SAXS). Microstructure transitions of liquid crystals with changes in surfactant concentration and oil content are explained qualitatively by the surfactant packing parameter (vL/aSlc). Dynamic rheological results indicate that all three kinds of liquid crystals investigated show high elasticity. The lamellar, Lalpha, phases formed in Brij 97/water with two different oils, oleic acid and geraniol, were also studied in comparison with those of Brij 97/water/IPM systems. The strength of the network of lamellar phases formed in Brij 97/water/oleic acid and Brij 97/water/geraniol systems are appreciably stronger than for Brij 97/water/IPM systems, indicated by the smaller area of surfactant molecules at the interface and the higher moduli (G' and G').     

Lamellar liquid crystals made of anionic surfactant,oleic acid,diethyleneglycol monoethyl ether and water

Lamellar liquid crystal formulation, with very low surfactant content, was optimized for the system made of phosphated oleyl ether 3 mol ethylene oxide as anionic surfactant, oleic acid as hydrophobic ingredient, diethyleneglycol monoethyl ether as cosolvent and water. The appropriate relationships between surfactant, fatty acid and glycol to promote the lamellar liquid crystal structure through further water dilution, were established. The physical appearance of these liquid crystals corresponded to viscous transparent gels. The realms of existence of the gels were stated in terms of minimum–maximum percentage of water incorporated. The main goal of this research was to decrease the surfactant content (in the range of 2–5%) needed to form liquid crystals, when usually high percentages are necessary. The study was completed with the rheological behaviour and structural parameters of some of these transparent gels. The attractive aspect of the samples, the perfect transparency and compactness, as well as the similarity to the lamellar liquid crystal structure of the intercellular lipids in the stratum corneum, permit consideration of such gels as adequate topical formulations both in cosmetics and pharmaceuticals.     

Studies on the phase properties of lyotropic liquid crystals of Brij35/sodium oleate/oleic acid/water system:By means of polarizing microscope,SAXS,~2H-NMR and rheological methods

The pseudo-quaternary phase diagram of Brij35/sodium oleate/oleic acid/water systems has been investigated, and the liquid crystal area has been identified, which covers about two thirds of the whole phase diagram. The liquid crystal structure and behavior have been also studied by using polarizing texture, small angle X-ray scattering, 2H-NMR and rheometer etc. The result shows that when the composition of the system changes along the line of AA′ in this large liquid crystal region, the structural change is cubic→cubic/lamellar→lamellar→lamellar/hexagonal→hexagonal. Meanwhile, we made the first attempt of systematic study of the rheological properties of the above system. The lattice constants of cubic and hexagonal liquid crystals are 10.53 and 5.68 nm, respectively.     

Igepal CO系列表面活性剂溶致液晶的结构特性

对壬基酚聚氧乙烯醚（IgepalCO）系列表面活性剂,生成何种溶致液晶与其EO基团数n有关,而在何浓度范围内生成溶致液晶则与生成溶致液晶的最低水含量及最大水增溶量有关．EO基团数n小于10时,生成层状液晶,n大于10时则生成六角状液晶,层状液晶两亲双层内,水与表面活性剂的最低摩尔比rmin和最高摩尔比rmax随EO基团数n增加分别是非线型增加与线型增加,在IgepalCO520（n＝5）中加入IgepalCO710（n＝10．5）,对层状液晶的生成无显著影响,在IgepalCO710中加入IgepalCO520,则对六角状液晶的生成产生显著影响,出现了六角状液晶向层状液晶的转变。     

溶剂性质对DBS/C~1~0H~2~1OH/溶剂体系的相行为 与结构的影响

在DBS/C~1~0H~2~1OH/溶剂体系中,以甲酰胺、水或甘油为溶剂时,在一定浓度范围内能生成O/W,W/O微乳液和层状液晶。C~1~0H~2~1OH在各种溶剂的DBS胶束中的分配系数K均很高。以甲酰胺、水为溶剂时,DBS能在一定浓度范围内生成层状液晶,但以甘油为溶剂时,则不能生成层状液晶。C~1~0H~2~1OH的加入有助于层状液晶的生成,但过量的C~1~0H~2~1OH却使层状液晶失稳。在相同质量比C~1~0H~2~1OH/DBS下,按顺序H~2O,FA,Gly,层状液晶中溶剂的渗透率α降低,d~0值亦降低;以FA为溶剂时,表示其表观有序度的Δν值却较高;以水为溶剂时,Δν值却较低;以Gly为溶剂时,Δν具有中等值。不同溶剂层状液晶两亲双层内的分子取向与溶剂性质对层状液晶稳定性的影响相一致。     

Interlamellar forces and the thermodynamic characterization of lamellar phospholipid systems

In this review, we summarize a series of experimental studies of the swelling of zwitterionic lamellar phospholipid and phospholipid-cholesterol systems using a novel double twin calorimeter. With this method, one can obtain simultaneous measures of the partial molar free energy and the partial molar enthalpy, and the experimental studies thus provide a complete thermodynamic characterization of the isothermal swelling process. A major finding is that the swelling of lamellar zwitterionic phospholipid systems at higher water contents (> 4 water molecules per lipid) is endothermic. The enthalpy has the opposite sign relative to the free energy, thus demonstrating that the swelling process is entropy driven. The water uptake also triggers a transition from a gel to a liquid crystalline state showing that, at given water content, the swelling pressure is much higher in the liquid crystal than in the gel. When cholesterol is added to the system the liquid ordered phase is formed at all available water contents. In this phase the swelling pressure varies smoothly and takes relatively low values at water contents below two per phospholipid, while it is substantially higher than in the gel phase at higher water contents. Together, these data demonstrate that the swelling pressure is sensitive to the phase state of the lipids. We also describe a series of studies that demonstrate that the addition of a second polar solute to the phospholipid–water system has a remarkably small effect on the swelling behavior when analyzed with respect to solvent volume. The reviewed experimental studies provide a thermodynamic characterization of the swelling of lamellar zwitterionic phospholipid systems that should be encompassed in the mechanistic molecular interpretation of the “hydration force.”     

POLYMERIC SURFACTANTS BASED ON OLEIC ACID IV. Lamellar Liquid Crystal Polymerization of Sodium Oleate/Oleic Acid/Aliphatic Diene/Water System

The lamellar liquid crystalline phase in the system consisting of sodium oleate (NaOL), oleic acid (OLA), and water was determined. The interlayer spacing (d) of the lamellar liquid crystal was measured through small angle X-ray diffraction, which indicated that oleic acid molecules were solubilized between the end methyl groups at low concentrations, and then were located within the hydrocarbon chain layer with further increase of its concentration. Cross-linking agents were added to the system, which were found being located partly in between the end methyl groups and partly within the hydrocarbon chain layers. The liquid crystal phase of NaOL/OLA/H₂O system with the cross-linking agent was polymerized at 60 °C, which turned out to be a mixture of liquid crystals and solids. Interlayer spacing decreased by about 10 Å, indicating a disruption of the ordered structure by the polymerization. The polymerization took place not only within the hydrocarbon layer, but also in between the layers separated by the end methyl groups. The resulting polymer lowered the surface tension of water to below 30 mN/m, with a critical micellization concentration of about O.25g/L.     

亚甲蓝在分子有序组合体中的聚集行为

研究了生物染色剂亚甲蓝(MB)在分子有序组合体(胶束、O/W微乳液和层状液晶)介质中的聚集行为。根据MB特征峰处的吸收光谱值,计算了MB的二聚平衡常数和相应单体、二聚体的摩尔消光系数。并用稳态荧光法和无外加探针的循环伏安法进一步论证了计算结果。研究发现,当MB总浓度一定时,在胶束体系中MB单体量较少,在层状液晶体系中单体量较多,在O/W微乳液体系中则介于胶束和层状液晶之间。表明层状液晶体系是获取更多MB单体的理想介质。