A Concise Total Synthesis of Dehydroantofine and Its Antimalarial Activity against Chloroquine-Resistant Plasmodium falciparum

Chemistry. 2021 Mar 22;27(17):5555-5563. doi: 10.1002/chem.202100032. Epub 2021 Feb 26.

Abstract

The total synthesis of dehydroantofine was achieved by employing a novel, regioselective, azahetero Diels-Alder reaction of easily accessible 3,5-dichloro-2H-1,4-oxazin-2-one with 14 a as a key step. Furthermore, it is demonstrated that dehydroantofine is a promising candidate as a new antimalarial agent in a biological assay with chloroquine-resistant Plasmodium falciparum.

Keywords: Diels-Alder reactions; antimalarial drugs; dehydroantofine; density functional calculations; pi interactions.

MeSH terms

  • Antimalarials* / pharmacology
  • Chloroquine / pharmacology
  • Drug Resistance
  • Plasmodium falciparum

Substances

  • Antimalarials
  • Chloroquine