Journal
ORGANIC PROCESS RESEARCH & DEVELOPMENT
Volume -, Issue -, Pages -Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.oprd.2c00345
Keywords
continuous flow synthesis; DTT; bis-epoxide; process intensification; PCR testing kits; telescope synthesis; engineering control
Categories
Ask authors/readers for more resources
The importance of rapid access to diagnostics tools, including bioreagents, for pathogen identification has been highlighted in the COVID-19 pandemic. A telescoped continuous flow synthesis of DTT has been developed, involving a base-mediated ring closure epoxidation, a nucleophilic epoxide opening, and an acid-mediated deacetylation. This method allows in situ generation and consumption of the hazardous intermediate, minimizing the need for isolation and improving safety.
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available