洛索洛芬钠的高效液相色谱手性拆分

使用三(对甲苯甲酸)纤维素酯手性固定相(Chiralcel OJ-R手性柱),建立了洛索洛芬钠4个手性异构体的高效液相色谱拆分方法。以甲醇与pH3．0的0．1mol／L醋酸-三乙胺或0．5mol／LHCIO4-NaClO4按80：20组成流动相,4个异构体中相邻峰的分离度均达到1．7以上。确认了4个组分的结构按出峰次序依次为：(1′R,2R)、(1′S,2R)、(1′R,2S)和(1′S,2S)。对流动相中不同的pH、缓冲溶液浓度和类型以及有机改性剂类型对分离结果的影响作了系统考察,其结果有助于更好地了解这类固定相的手性识别机理。     

1-(5-氯甲基-2-羟基-4-烷氧基)苯乙酮的合成

以2,4-二羟基苯乙酮为起始原料,经羟基烷基化和氯甲基化反应合成了3个新型查尔酮类衍生物的关键中间体——1-(5-氯甲基-2-羟基-4-烷氧基)苯乙酮,其结构经1H NMR和ESI-MS确证。     

黄酮化合物的合成新方法

黄酮类化合物具有广泛而重要的生物活性和药理作用,其化学合成研究受到普遍重视.经典的合成方法主要是查耳酮路线和β-丙二酮路线.近年来有很多新技术、新方法在黄酮化合物合成中得到了巧妙的应用.对近年来出现的新的改进的Baker-Venkataraman法、催化羰基化闭环法以及其他合成黄酮化合物的新方法作了介绍.     

新型丹皮酚衍生物的合成

根据拼合原理,将丹皮酚和非甾体抗炎药通过连接臂[(CH2)n或NCH2CH2]偶联合成了8个新型的丹皮酚衍生物,其结构经1H NMR和HR-MS表征。     

氟伐他汀钠的合成

以氟苯为起始原料,通过两步反应得N-(4-氟苯甲酰甲基)-N-(1-甲基乙基)苯胺(5);5在ZnCl2存在下环化得3-(4′-氟苯基)-1-(1′-甲基乙基)吲哚(6);6与3-N-甲基-N-苯基胺基丙烯醛发生Vilsmeier-Haauc反应得(E)-3-[3′-(4″-氟苯基)-1′-(1″-甲基乙基)吲哚-2′-基]-2-丙烯醛(8);8经缩合、还原、水解得氟伐他汀钠,总收率10.5%.     

1-(2-氯-4-吡啶基)-3-苯基脲的合成

氯氨基吡啶;氯吡啶基苯基脲;1-(2-氯-4-吡啶基)-3-苯基脲的合成     

3-(4-氨基苯基偶氮)苯磺酸钠的合成

氨基甲基苯基偶氮苯磺酸钠;3-(4-氨基苯基偶氮)苯磺酸钠的合成     

美金刚衍生物的合成

盐酸美金刚(抗老年痴呆药物)与非甾体抗炎药(NSAIDs)反应合成了含NSAIDs药效单元的新美金刚衍生物,其结构经1H NMR, IR和MS表征.     

1-(4-氯苯基)-2-环丙基酮肟醚的设计、合成及杀虫活性

采用中间体衍生化方法,以环唑醇中间体1-(4-氯苯基)-2-环丙基丙酮作为基本骨架,引入肟醚活性片段,合成了32个新的1-(4-氯苯基)-2-环丙基酮肟醚类化合物,其化学结构经核磁共振波谱和质谱等确认.单晶X衍射分析表明,化合物2n属于单斜晶系,空间群为P21/c.生物活性筛选结果表明,化合物1i在200mg/L浓度下对蚜虫的致死率为78. 57%;化合物1g在200 mg/L浓度下对红蜘蛛的致死率为69. 95%;化合物1i在200和12. 5 mg/L浓度下对黏虫的致死率分别为100%和85%.     

3-氯-2-羟基丙磺酸钠的合成工艺研究

以环氧氯丙烷（1）和NaHSO₃为原料,Na₂SO₃为引发剂,乙二胺四乙酸二钠（EDTA₂Na）为络合增效剂,经酸催化开环反应合成了磺酸型两性表面活性剂中间体--3-氯-2-羟基丙磺酸钠（2）,其结构经¹H NMR, IR和ESI-MS确证。在最佳反应条件［1 0.55 mol, n(NaHSO₃）: n（Na₂SO₃）: n（EDTA₂Na）: n（H₂O)=1.00 : 0.04 : 0.01 : 9.50, 1的滴加时间15 min,在适宜的转速（前期100 rpm, 后期300 rpm）下,于70 ℃(浴温)反应1.25 h］下合成的2,收率81.55%。并对反应机理进行了推测。     

Solubility Optimization of Loxoprofen as a Nonsteroidal Anti-Inflammatory Drug: Statistical Modeling and Optimization

Industrial-based application of supercritical CO₂ (SCCO₂) has emerged as a promising technology in numerous scientific fields due to offering brilliant advantages, such as simplicity of application, eco-friendliness, and high performance. Loxoprofen sodium (chemical formula C₁₅H₁₈O₃) is known as an efficient nonsteroidal anti-inflammatory drug (NSAID), which has been long propounded as an effective alleviator for various painful disorders like musculoskeletal conditions. Although experimental research plays an important role in obtaining drug solubility in SCCO₂, the emergence of operational disadvantages such as high cost and long-time process duration has motivated the researchers to develop mathematical models based on artificial intelligence (AI) to predict this important parameter. Three distinct models have been used on the data in this work, all of which were based on decision trees: K-nearest neighbors (KNN), NU support vector machine (NU-SVR), and Gaussian process regression (GPR). The data set has two input characteristics, P (pressure) and T (temperature), and a single output, Y = solubility. After implementing and fine-tuning to the hyperparameters of these ensemble models, their performance has been evaluated using a variety of measures. The R-squared scores of all three models are greater than 0.9, however, the RMSE error rates are 1.879 × 10⁻⁴, 7.814 × 10⁻⁵, and 1.664 × 10⁻⁴ for the KNN, NU-SVR, and GPR models, respectively. MAE metrics of 1.116 × 10⁻⁴, 6.197 × 10⁻⁵, and 8.777 × 10⁻⁵errors were also discovered for the KNN, NU-SVR, and GPR models, respectively. A study was also carried out to determine the best quantity of solubility, which can be referred to as the (x₁ = 40.0, x₂ = 338.0, Y = 1.27 × 10⁻³) vector.     

OJ手性柱分离芳基烷酸类非甾体解热镇痛药的色谱保留特性和拆分机理

使用纤维素类手性柱OJ柱, 分离布洛芬、依托度酸、非诺洛芬钙、酮洛芬、洛索洛芬等5个芳基烷酸类非甾体解热镇痛药对映体, 并通过溶质计量置换保留模型和热力学研究对OJ手性柱手性分离机理进行探讨. 结果表明, OJ手性柱可在正相条件下分离系列芳基烷酸类非甾体解热镇痛药, 对映体的色谱保留和分离度可以通过改变流动相中醇类置换剂和浓度、有机酸性改性剂和浓度、柱温等因素调节.     

丹曲林钠杂质B的合成

以5-对硝基苯胺为原料,与糠醛经重氮化反应制得5-对硝基苯基糠醛(1);1与1-氨基乙内酰脲盐酸盐经缩合、精制得丹曲林(2);2与甲醇钠成盐制得丹曲林钠(3);3在氢氧化钠水溶液中加热条件下,经开环水解制得丹曲林钠杂质B钠盐,再经盐酸酸化、精制合成了丹曲林钠杂质B,总收率16.9%,纯度99.9%,其结构经1H NMR,IR和MS(ESI)确证。     

泮托拉唑钠的合成工艺改进

以5-二氟甲氧基-2-巯基-1H-苯并咪唑和2-氯甲基-3,4-二甲氧基吡啶盐酸盐为原料,经缩合,氧化和成盐反应合成了泮托拉唑钠,其结构经1HNMR和MS表征。缩合,氧化和成盐反应的收率分别为88.8%,79.2%,89.7%。     

噁唑酮类化合物的合成及其抗炎活性

以马尿酸为原料,与取代苯甲醛经Erlenmeyer环合反应合成了8个噁唑酮类化合物（3a~3h）,其结构经¹H NMR, FT-IR和HR-MS确证。二甲苯致小鼠耳肿胀实验结果表明：3f［4,3,5-二甲氧基甲撑基）-2-苯基-4H-5-噁唑酮］抗炎活性最好,其抑制率为50.3%,优于阿司匹林（41.5%）。     

抗丙肝药物维拉帕维的合成

以7-羟甲基-1-四氢萘酮和1-溴-4-氯-苯甲醛为起始原料,经14步反应合成了抗丙肝新药维拉帕维--甲基（2S）-1-【(2S,5S)-2-【9{2［（2S,4S）-1-（2R)-2-［（甲氧基羰基）氨基］-2-苯乙酰基-4-（甲氧基甲基）吡咯烷-2-基］-1H-咪唑 5 基} 1,11-二氢异色烯［4′,3′ :6,7］萘并［1,2-d］咪唑-2-基-5-甲基吡咯烷-1-基】-3-甲基-1-氧丁烷-2-基】氨基甲酸酯,总产率10.14%,其结构经¹H NMR和ESI-MS确证。     

Synthesis and medicinal importance of oxicams and their analogues

The biological and medicinal properties of oxicams and its analogues are attracting attention of chemist aimed at developing synthetic routes to these heterocycles. This review focuses on the synthesis and medical importance of oxicams and their analogues.     

Easy Access to Supramolecular Gels of the Nonsteroidal Anti‐inflammatory Drug Diflunisal: Synthesis,Characterization, and Plausible Biomedical Applications

By exploiting salt formation, a new series of primary ammonium monocarboxylate salts of a nonsteroidal anti‐inflammatory drug, namely, diflunisal, was synthesized. The majority of the salts thus synthesized turned out to be good gelators of various solvents, including the solvents (e.g., methyl salicylate and pure water) typically used for topical gel formulation. Single‐crystal X‐ray diffraction studies of a few gelator and nongelator salts in the series revealed details of the hydrogen‐bonding networks present in the salts. Furthermore, one such gelator salt, namely, the diflunisal salt of serinol, was found to be biocompatible (MTT assay), and its anti‐inflammatory (PGE₂ assay) response turned out to be as good as that of the parent drug, which is indicative of its potential in biomedical applications.