苯基取代的苯并噻唑胺双苯甲酰胺衍生物的合成及生物活性

以取代苯甲酸和取代邻氨基苯甲酸为起始原料,设计合成了13个含取代苯并噻唑胺邻甲酰氨基苯甲酰胺类化合物,其结构经1H NMR、13C NMR、IR及元素分析确证。 初步生物活性测试结果表明,在500 mg/L目标化合物浓度下,对黄瓜花叶病毒有一定抑制作用。 采用MTT法进行化合物抑制PC3癌细胞体外活性测试,结果表明,所合成的化合物具有不同程度的抑制PC3癌细胞活性,其中化合物4f在10 μmol/L浓度下对PC3的抑制率为74.2%。     

Multi‐Compartment Unimolecular Micelles from (ABC)n Multi‐Arm Star Triblock Terpolymers

Four linear and four star equimolar terpolymers based on non‐ionic hydrophilic methoxy hexa(ethylene glycol) methacrylate, ionizable hydrophilic 2‐(dimethylamino)ethyl methacrylate and neutral hydrophobic methyl methacrylate were synthesized using group transfer polymerization and investigated in aqueous dilute solutions. It was found that the (ABC)_n multi‐arm star terpolymers formed unimolecular micelles comprising three centrosymmetric compartments. The position of each compartment could be determined by the block sequence (ABC, ACB or BAC) at will. On the other hand, the ABC linear counterparts formed loose associates with very low aggregation numbers. It was shown that the polymer architecture (linear versus star) greatly affected the micellization phenomena of the terpolymers in selective media.

     

mPEG-PLA共聚物胶束对DHA的增溶及光保护作用

以聚乙二醇单甲醚(mPEG)和外消旋丙交酯(D,L-LA)为原料,采用开环聚合法合成聚乙二醇单甲醚-聚乳酸(mPEG-PLA)共聚物,并用溶剂挥发法制备包载双氢青蒿素(DHA)的共聚物胶束(DHA/mPEG-PLA)。利用红外光谱(FT-IR)、核磁共振氢谱(1 H-NMR)和接触角测量仪研究了共聚物的结构和性质;利用激光粒度分析仪和扫描电镜(SEM)研究了胶束的粒径和形貌。结果表明mPEG-PLA共聚物的临界胶束浓度(CMC)为7.71mg/L。DHA/mPEG-PLA共聚物胶束呈球形,平均粒径(118.1±1.9)nm,载药量和包封率分别为(2.7±0.1)%和(77.1±0.3)%。胶束对DHA的水相表观溶解度增大约1.5倍。紫外光光照39h,纯DHA在混悬液中降解率达37%且持续增长,胶束中DHA降解率达到10%后基本保持不变。     

UV resistance of encapsulated low molecular weight aromatic compounds in fluoroalkyl end‐capped trimethoxyvinylsilane oligomer/silica nanocomposites

Sol–gel reactions of fluoroalkyl end‐capped trimethoxyvinylsilane oligomer in the presence of low molecular weight aromatic compounds (ArH) such as 1,1′‐bi(2‐naphthol) (BINOL) and 2‐hydroxy‐4‐methoxy benzophenone (HMB) were found to proceed smoothly under alkaline conditions at room temperature to give the corresponding fluorinated oligomeric silica nanocomposites‐encapsulated aromatic compounds (BINOL and HMB) [R_F‐(VM‐SiO₂)_n‐R_F/ArH nanocomposites]. UV light irradiation (λ_max: 254 nm) toward R_F‐(VM‐SiO₂)_n‐R_F/ArH nanocomposites showed that photodegradation of encapsulated ArH was not observed at all in the fluorinated nanocomposites cores, although the parent ArH can exhibit an effective photodegradation behavior under similar conditions. Especially, encapsulated ArH can exhibit no weight loss corresponding to the contents of the aromatic compounds in the fluorinated nanocomposites even after calcination at 800°C. Therefore, fluoroalkyl end‐capped trimethoxyvinylsilane oligomer has high potential for not only the thermal resistance but also the UV resistance fluorinated polymeric materials. Copyright © 2014 John Wiley & Sons, Ltd.     

Two New Limonoids from the Root Bark of Chinese Medicinal Plant Dictamnus dasycarpus

Two new limonoids, kihadanin C ( 1 ) and 23‐methoxydasylactone A ( 2 ), together with seven related known ones, 3 – 9 , were isolated from the root bark of the plant Dictamnus dasycarpus. The structures of the new compounds were elucidated on the basis of extensive analyses of their spectroscopic data (1D‐ and 2D‐NMR, MS) and by comparison of their NMR data with those reported in the literature. To the best of our knowledge, 1 presents the first example of A,D‐seco limonoid with an unusual 3,4‐dihydroxy‐2,5‐dimethoxytetrahydrofuran moiety as ring E. In the bioassay in vitro, 7 showed moderate antibacterial activity against Staphylococcus aureus, while 8 and 9 displayed neuroprotective activities against H₂O₂‐induced injury in SH‐SY5Y cells.     

Reactions of allyloxy(methoxy)carbene in solution. Carbene rearrangement and Claisen rearrangement of the carbene dimer

Allyloxy(methoxy)carbene, with and without deuterium in the α-position of the allyloxy group, was generated in benzene at 50 and at 110 °C. At the higher temperature, the carbene fragmented to allyl and methoxycarbonyl radicals that subsequently coupled. At the lower temperature, most of the carbene dimerised. The structure of the major product and the distribution of deuterium indicated that the dimer underwent Claisen rearrangement at 50 °C to methyl 2-allyloxy-2-methoxy-4-pentenoate. Facile rearrangement of the dimer was supported by the results of a computation which placed the barrier at about 18 kcal mol⁻¹.     

Chemical Constituents of Two Liverworts Metacalypogeia Alternifolia and Chandonanthus Hirtellus

A novel linear dihydrodichromene derivative, metacalypogin, was identified from the Taiwanese liverwort Metacalypogeia alternifolia. Together with data from M. cordifolia, the chemical marker of the genus Metacalypogeia is obvious chroman derivatives, which is far different from that of Calypogeia, the other genus in the same family. In addition, two isomeric diterpenoids of cembrane‐type were identified from the Chinese liverwort Chandonanthus hirtellus. The relative stereostructures of the latter two isomers were proved by X‐ray crystallography. Both compounds were unstable in chloroform solution and further oxidized to the corresponding peroxy hemiacetal derivatives.     

High-throughput LC-MS/MS assay for 6-methoxy-2-naphthylacetic acid, an active metabolite of nabumetone in human plasma and its application to bioequivalence study

A simple, precise and accurate assay for the determination of 6-methoxy-2-naphthylacetic acid (6-MNA), an active metabolite of nabumetone in human plasma, was developed and validated using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The analyte (6-MNA) and propranolol (internal standard, IS) were extracted from 200 microL aliquot of human plasma via solid-phase extraction employing HLB Oasis cartridges and separated on a Discovery HS C18 (50 x 4.6 mm, 5 microm) column. Detection of analyte and IS was done by tandem mass spectrometry with a turbo ion spray interface operating in positive ion and multiple reaction monitoring acquisition mode. The total chromatographic runtime was 3.0 min with retention time for 6-MNA and IS at 1.97 and 1.26 min, respectively. The method was validated over a dynamic linear range of 0.20-60.00 microg/mL for 6-MNA with mean correlation coefficient r > or = 0.9986. The intra-batch and inter-batch precision (%CV) across five validation runs (lower limit of quantiation, low-, medium- and high-quality controls and upper limit of quantitation) was less than 7.5%. The accuracy determined at these levels was within -5.8 to +0.2% in terms of percentage bias. The method was successfully applied for a bioequivalence study of 750 mg nabumetone tablet formulation in 12 healthy Indian male subjects under fasted condition.     

固相β-环糊精包结物诱导7-羟基-2-甲氧基-2-甲基色满的不对称合成

研究了室温下间苯二酚和甲基乙烯基酮分别与β-环糊精（ β-CD）形成包结物后的几种不同固相反应,结果表明包结物A（间苯二酚/β-CD）与包结物B（甲基乙烯基酮/β-CD）反应能够很好地得到目的产物,产率及ee值分别为82.8%和78.4%;间苯二酚与包结物B反应仅得到低光学活性产物（ee值为19.5%）;包结物A与甲基乙烯基酮反应却没有得到手性目的产物。以熔点、X-粉末衍射、固相核磁碳谱及ROESY多种方法对所形成的包结物进行了表征,包结物中主客体的比例（1：1）通过¹H NMR (400 MHz)得以确定,文章对固相环加成反应的机制也进行了初步探讨。