Automated Process Research. An Example of Accelerated Optimization of the Friedel-Crafts Acylation Reaction, a Key Step for the Synthesis of Anti-HIV (+)-Calanolide A

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• 作者：Jintao Zhang ; Eric W. Kirchhoff ; David E. Zembower ; Nancy Jimenez ; Prabir Sen ; Ze-Qi Xu ; and Michael T. Flavin
• 刊名：Organic Process Research & Development
• 出版年：2000
• 出版时间：November 2000
• 年：2000
• 卷：4
• 期：6
• 页码：577 - 580
• 全文大小：94K
• 年卷期：v.4,no.6(November 2000)
• ISSN：1520-586X

文摘

An automated process research approach to reaction optimization was developed. Chemical process research can be greatlyaccelerated by coupling automated synthesis equipment withstatistical design of experiments (DoE). With the use of anautomated process approach, multiple experiments can beperformed in parallel on an automated platform, and multipleparameters that may influence process performance can beexamined within one set of experiments generated from statistical design. We have successfully applied an automated processresearch approach to optimize the Friedel-Crafts acylationreaction that was used in our total synthesis of (+)-calanolideA, a potential anti-HIV agent currently in clinical trials. Thein situ yield for a coumarin product was successfully optimized,increasing from 70% to 97% by HPLC analysis.