Exploring ultrafast flow chemistry by autonomous self-optimizing platform

被引：23

作者：

Ahn, Gwang-Noh ^{[1
]}

Kang, Ji-Ho ^{[1
]}

Lee, Hyune-Jea ^{[2
]}

Park, Byung Eon ^{[1
]}

Kwon, Minjun ^{[3
]}

Na, Gi-Su ^{[1
]}

Kim, Heejin ^{[2
]}

Seo, Dong-Hwa ^{[3
]}

Kim, Dong-Pyo ^{[1
]}

机构：

[1] Pohang Univ Sci & Technol POSTECH, Ctr Intelligent Microproc Pharmaceut Synth, Dept Chem Engn, Pohang 37673, South Korea

[2] Korea Univ, Coll Sci, Dept Chem, Seoul 02841, South Korea

[3] Ulsan Natl Inst Sci & Technol UNIST, Sch Energy & Chem Engn, Ulsan 44919, South Korea

来源：

CHEMICAL ENGINEERING JOURNAL | 2022年 / 453卷

基金：

新加坡国家研究基金会;

关键词：

Automated microreactor; Bayesian optimization; Ultrafast chemistry; Self-optimization; In-line analysis; BAYESIAN OPTIMIZATION; FLASH CHEMISTRY; AUTOMATED OPTIMIZATION; EXPERIMENTAL-DESIGN; ORGANIC-SYNTHESIS; TECHNOLOGY;

D O I：

10.1016/j.cej.2022.139707

中图分类号：

X [环境科学、安全科学];

学科分类号：

08 ; 0830 ;

摘要：

The rapid development of novel synthetic routes for pharmaceutical compounds is highly attractive for overcoming pandemic and epidemic-prone diseases like COVID-19. Herein, we report an automated microreactor platform (AMP) with Bayesian optimization (BO) that can autonomously explore the optimal conditions for ultrafast synthesis of biologically active thioquinazolinone. First, AMP operation is successfully demonstrated with full control of quantitative variables, specifically reaction volume, temperature, and flow rate, allowing to sequentially conduct a total of 80 experiments planned by the user. Next, BO enables the AMP to autonomously self-optimize the reaction conditions, demonstrating the high efficiency of the fully automated AMP. The fully automated approach is extended to optimize more complex variables including a categorical variable (i.e. the type of organolithium for synthesis), revealing that phenyllithium (PhLi) gives superior yield for synthesizing thioquinazolinone. In addition, the autonomous AMP is utilized for combinatorial chemistry to sequentially synthesize a library composed of nine types of S-benzylic thioquinazolinone under autonomously optimized conditions within only 20 min.

引用

页数：8

共 39 条

[1] On-demand continuous-flow production of pharmaceuticals in a compact, reconfigurable system [J].