Multistep Continuous Flow Synthesis of Stavudine

J Org Chem. 2021 Oct 15;86(20):13934-13942. doi: 10.1021/acs.joc.1c01013. Epub 2021 Jun 1.

Abstract

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.

MeSH terms

  • Humans
  • Stavudine*

Substances

  • Stavudine