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利用连续流动化学合成多替拉韦

Synthesis of Dolutegravir Exploiting Continuous Flow Chemistry.

作者信息

Nqeketo Sinazo, Watts Paul

机构信息

Nelson Mandela University, University Way,Port Elizabeth6031, South Africa.

出版信息

J Org Chem. 2023 Aug 18;88(16):12024-12040. doi: 10.1021/acs.joc.3c01365. Epub 2023 Aug 8.

DOI:10.1021/acs.joc.3c01365
PMID:37552841
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10442919/
Abstract

An efficient continuous flow process for the synthesis of dolutegravir, an active pharmaceutical ingredient (API) for HIV treatment, was investigated. The synthetic procedure starts from a readily available benzyl-protected pyran via six chemical transformations using continuous flow reactors. The significant advantage of this flow process includes the reduction of the overall reaction time from 34.5 h in batch to 14.5 min. The overall yield of each reaction step improved dramatically upon flow optimization. Another key feature of this synthesis is telescoping multiple steps.

摘要

研究了一种用于合成度鲁特韦（一种用于治疗HIV的活性药物成分（API））的高效连续流工艺。该合成过程从一种易于获得的苄基保护的吡喃开始，通过使用连续流反应器进行六个化学转化步骤。这种连续流工艺的显著优势包括将总反应时间从间歇反应的34.5小时缩短至14.5分钟。通过连续流优化，每个反应步骤的总产率都有显著提高。该合成的另一个关键特征是多步反应的叠加。

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