The route from problem to solution in multistep continuous flow synthesis of pharmaceutical compounds

被引:76
作者
Bana, Peter [1 ]
Orkenyi, Robert [1 ]
Lovei, Klara [2 ]
Lako, Agnes [1 ]
Turos, Gyorgy Istvan [2 ]
Eles, Janos [2 ]
Faigl, Ferenc [1 ,3 ]
Greiner, Istvan [2 ]
机构
[1] Budapest Univ Technol & Econ, Dept Organ Chem & Technol, H-1521 Budapest, Hungary
[2] Gedeon Richter Plc, Gyomroi Ut 19-21, H-1103 Budapest, Hungary
[3] MTA BME Organ Chem Technol Res Grp, Budafoki Ut 8, H-1111 Budapest, Hungary
关键词
Continuous flow processing; Active pharmaceutical ingredient; Telescoping; Multistep flow synthesis; In-line analytics; Continuous purification; CONTINUOUS MANUFACTURING SYMPOSIUM; MOVING-BED CHROMATOGRAPHY; FINAL DOSAGE FORMATION; LINE IR-ANALYSIS; ORGANIC-SYNTHESIS; CHEMICAL-SYNTHESIS; HETEROGENEOUS CATALYSTS; ENABLING TECHNOLOGY; MICROFLUIDIC SYSTEM; REACTION SEQUENCES;
D O I
10.1016/j.bmc.2016.12.046
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Recent advances in the field of continuous flow chemistry allow the multistep preparation of complex molecules such as APIs (Active Pharmaceutical Ingredients) in a telescoped manner. Numerous examples of laboratory-scale applications are described, which are pointing towards novel manufacturing processes of pharmaceutical compounds, in accordance with recent regulatory, economical and quality guidances. The chemical and technical knowledge gained during these studies is considerable; nevertheless, connecting several individual chemical transformations and the attached analytics and purification holds hidden traps. In this review, we summarize innovative solutions for these challenges, in order to benefit chemists aiming to exploit flow chemistry systems for the synthesis of biologically active molecules. (C) 2016 Elsevier Ltd. All rights reserved.
引用
收藏
页码:6180 / 6189
页数:10
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