Multistep Continuous Flow Synthesis of Stavudine

Herein, we demonstrate an elegant multistep continuous flow synthesis for stavudine (d4T), a potent nucleoside chemotherapeutic agent for human immunodeficiency virus, acquired immunodeficiency syndrome (AIDS) and AIDS-related conditions. This was accomplished via six chemical transformations in five sequential continuous flow reactors from an affordable starting material, 5-methyluridine. In the first instance, single step continuous flow synthesis was demonstrated with an average of 97% yield, 21.4 g/h throughput per step, and a total of 15.5 min residence time. Finally, multistep continuous flow synthesis of d4T in 87% total yield with a total residence time of 19.9 min and 117 mg/h throughput without intermediate purification was demonstrated.

Automated summary

This study demonstrates an elegant multistep continuous flow synthesis for stavudine (d4T), a potent nucleoside chemotherapeutic agent for HIV, AIDS, and related conditions. The synthesis involved six chemical transformations and was achieved in five sequential continuous flow reactors starting from 5-methyluridine. The single step continuous flow synthesis showed an average yield of 97%, 21.4 g/h throughput, and a total residence time of 15.5 min, while the multistep continuous flow synthesis of d4T achieved 87% total yield with a total residence time of 19.9 min and a throughput of 117 mg/h without intermediate purification.