(S,S)-TsDPEN-Ru催化不对称氢转移还原β-胺基酮及在度洛西汀合成中的应用

报道了甲酸/三乙胺体系中,(S,S) -TsDPEN-Ru络合物催化的不对称氧转移反应合成(S)-γ-胺基醇的方法.考察了不同底物的反应性能,β-单/二烷基胺基-2-噻吩酮在该还原体系中氧解得到1-(2-噻吩基)-1-丙酮;氮原子上吸电子基取代的底物以高收率、高立体选择性(＞95％e.e.)得到还原产物.将这一反应用于...     

High-performance liquid chromatographic method for the simultaneous estimation of the key intermediates of duloxetine

A simple reversed-phase high-performance liquid chromatographic method employing C-18 column has been developed for simultaneous analysis of three intermediates in the synthesis of S-duloxetine, the antidepressant drug, viz., 2-acetyl thiophene (AT), N,N-dimethyl-3-keto-(2-thienyl)-propanamine (DKTP) and (S)-N,N-dimethyl-3-hydroxy-(2-thienyl)-propanamine (DHTP). Good separations were achieved by employing an isocratic system using acetonitrile and 0.05 M phosphate buffer (pH 7.0) containing 0.02% diethylamine. The detection was carried out at 241 nm. The method was validated for linearity, range, accuracy and precision. The developed method was applied for monitoring the progress of chemical synthesis of DKTP from AT followed by the biocatalytic reduction of DKTP to DHTP as the disappearance of the substrate and formation of the product can be monitored simultaneously by the present method.     

Synthesis of antidepressant duloxetine via asymmetric transfer hydrogenation

Antidepressant duloxetine （1） was prepared via asymmetric transfer hydrogenation of 3-（dimethylamino）-1-（thiophen-2- yl）propan-1-one （3）. The Ru（Ⅱ）, Rh（Ⅲ） and Ir（Ⅲ） complexes of several chiral ligands were examined as the catalyst and （S,S）-N-tosyl-1,2-diphenyl ethylenediamine （TsDPEN）-Ru（Ⅱ） complex was found to provide good yield and excellent enantioselectivity. 2007 Ming Yan. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.     

度洛西汀的合成进展

介绍了近年来抗抑郁新药度洛西汀的各种合成方法,并评述了其优缺点。参考文献13篇。     

N-甲基-2-(4-取代哌嗪)-N-[3-(萘氧基)-3-(2-噻吩基)丙基]乙酰胺衍生物的设计与合成

以N-甲基-3-(1-萘氧基)-3-(2-噻吩基)-丙胺(度洛西汀)为原料,通过N-酰氯化反应和N-烷基化反应,合成了5个新型的N-甲基-2-(4-取代哌嗪)-N-[3-(萘氧基)-3-(2-噻吩基)丙基]酰胺衍生物,其结构经1H NMR,IR和MS表征。     

度洛西汀与文拉法辛治疗老年首发抑郁症伴疼痛的临床研究

目的比较度洛西汀与文拉法辛治疗老年首发抑郁症伴疼痛的临床疗效和不良反应。方法将80例符合ICD-10中度抑郁发作诊断标准并伴躯体疼痛的老年首发抑郁症患者按随机数字表法分为度洛西汀组和文拉法辛组，分别给予度洛西汀与文拉法辛治疗，疗程8周。采用17项汉密尔顿抑郁量表（HAMD）、视觉模拟评分量表（VAS）评定疗效，采用不良反应量表（TESS）及实验室检查评定不良反应。结果度洛西汀组总有效率为72.5%，文拉法辛组总有效率为73.7%，差异无统计学意义（P＞0.05）。度洛西汀组治疗第1周末HAMD、VAS分值低于文拉法辛组，差异有统计学意义（P＜0.05）。两组患者不良反应发生率的差异无统计学意义（P＞0.05），但度洛西汀组心血管不良事件发生率低于文拉法辛组（P＜0.05）。结论度洛西汀和文拉法辛缓释剂治疗老年首发抑郁症伴疼痛的患者均有效，度洛西汀组心血管相关不良事件发生率较少，对老年患者安全有效，耐受性好。     

度洛西汀的不对称合成研究进展

盐酸度洛西汀是5-羟色胺和去甲肾上腺素再摄取抑制剂,是第三代抗抑郁药。本文综述了近年来度洛西汀的不对称合成研究进展,评述了其优缺点。     

5-Phenylthio-1,3-oxazinan-4-ones via hetero Diels–Alder reactions: synthesis of (R)- and (S)-Duloxetines and Fluoxetines

The synthesis of 5-phenylthio-1,3-oxazinan-4-ones, through a hetero Diels–Alder strategy, is described. The cycloadducts thus prepared have been shown to be useful intermediates for the synthesis of 1,3-aminoalcohols, valuable intermediates in the preparation of biologically significant molecules, e.g., optically active Duloxetines and Fluoxetines. In the course of this elaboration a novel microwave assisted desulfurization reaction is reported.     

度洛西汀与帕罗西汀治疗首发抑 郁症疗效及对性功能影响的研究

目的 比较度洛西汀与帕罗西汀治疗首发抑郁症性功能的影响。方法 将72 例首发抑郁症患者随机分为度洛西汀组（36 例）和帕罗西汀组（36 例）,观察8周。应用亚利桑那性经验量表（ASEX）评定性功能情况,同时用汉密顿抑郁量表（17 项）（HAMD17）观察疗效和副反应量表（TESS）评定不良反应。结果 治疗第2、4、8 周ASEX 评分度洛西汀组得分显著低于帕罗西汀组,自第2周末始,两组与基线时比较ASEX 得分均有显著下降。疗效观察发现,治疗8周末度洛西汀组有效率80.0%,痊愈率51.4%,帕罗西汀组有效率76.5%,痊愈率47.1%,两组比较差异无统计学意义。治疗第1周末,度洛西汀组HAMD17评分显著低于帕罗西汀组,而第2、4、8 周末两组评分比较差异无统计学意义。治疗第2、4、8 周ASEX 评分度洛西汀组得分显著低于帕罗西汀组（均P＜0.05）,自第2 周末始,两组与基线时比较ASEX 得分均有显著下降（均P＜0.05）。度洛西汀组不良反应发生率42.9%,帕罗西汀组44.1%,两组比较差异无统计学意义。结论 度洛西汀对首次发作抑郁症的性功能的改善优于帕罗西汀,或引起性功能障碍少于帕罗西汀。两者 疗效相似,但第1周度洛西汀起效较帕罗西汀快。总体不良反应相似。     

Chiral Separation of Duloxetine and Its R-Enantiomer by LC

The direct enantioseparation of duloxetine and its R-enantiomer was achieved by HPLC using hydroxypropyl-β-cyclodextrin (HP-β-CD) as a chiral selector and a vancomycin chiral stationary phase (Chirobiotic V). Operational parameters, such as the concentration of HP-β-CD, buffer pH, organic modifiers, temperature and flow rate, were varied in order to achieve the desired retention time and resolution. These two enantioseparation methods developed gave a baseline resolution of the enantiomers. Finally, the HPLC-CSP method was selected to determine the enantiomeric purity of duloxetine drug substance due to its much shorter analysis time and better resolution. The limit of detection of this method was 0.06 μg mL⁻¹.