The importance of rapid access to diagnostics tools in the identification of pathogens─including their crucial component, bioreagents─was recently underscored in the COVID-19 pandemic. The currently adopted synthesis of dithiothreitol (DTT) involves four steps in batch with long reaction times and which generates a highly carcinogenic and mutagenic bis-epoxide intermediate. In this work, we have developed an intensified telescoped three-step continuous flow synthesis of DTT involving a base-mediated ring closure epoxidation, a nucleophilic epoxide opening with thioacetic acid, and an acid-mediated deacetylation. One of the key features is that the first two steps are conducted in a telescoped continuous flow fashion, allowing generation and consumption of the hazardous intermediate in situ, suppressing the need for its isolation, and improving the overall safety of the synthesis. The process is completed by an acid-catalyzed deacetylation and a subsequent recrystallization to afford the desired DTT. Flow chemistry allows here to intensify the process by using high temperatures and high pressures while minimizing the number of unit operations and improving the overall safety of the process. Our protocol permits the on-demand production of DTT in case of future outbreaks.

中文翻译：

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按需连续流动合成二硫苏糖醇的过程强化和安全性提高，二硫苏糖醇是聚合酶链反应检测试剂盒中的一个重要组分

最近在 COVID-19 大流行中强调了快速获得诊断工具在识别病原体（包括其关键成分生物试剂）中的重要性。目前采用的二硫苏糖醇 (DTT) 合成涉及分批反应时间长的四个步骤，并且会产生高度致癌和致突变的双环氧化物中间体。在这项工作中，我们开发了 DTT 的强化伸缩三步连续流动合成，包括碱基介导的环闭合环氧化、硫代乙酸打开的亲核环氧化物和酸介导的脱乙酰化。其中一个关键特征是前两个步骤以伸缩连续流方式进行，允许原位生成和消耗危险中间体，抑制其分离的需要，并提高合成的整体安全性。该过程通过酸催化脱乙酰和随后的重结晶完成，以提供所需的 DTT。流动化学在这里允许通过使用高温和高压来强化过程，同时最大限度地减少单元操作的数量并提高过程的整体安全性。我们的协议允许在未来爆发时按需生产 DTT。