Catalytic Enantioselective Synthesis of a Pyrrolizidine-Alkaloid-Inspired Compound Collection with Antiplasmodial Activity

J Org Chem. 2018 Jul 6;83(13):7033-7041. doi: 10.1021/acs.joc.7b03202. Epub 2018 Feb 20.

Abstract

A novel enantioselective approach to the synthesis of a compound collection inspired by natural pyrrolizidine alkaloids was developed, employing an enantioselectively catalyzed 1,3-dipolar cycloaddition as the key step. The cycloadducts were obtained with excellent enantio- and diastereoselectivity. Biological evaluation of the resulting compound collection revealed that the compound class has multiple bioactivities, including activity against Plasmodium falciparum 3D7 and inhibition of Hedgehog signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimalarials / chemical synthesis*
  • Antimalarials / pharmacology*
  • Biological Products / chemistry
  • Catalysis
  • Cell Line
  • Cycloaddition Reaction
  • Hedgehog Proteins / metabolism
  • Mice
  • Mice, Inbred C3H
  • Plasmodium falciparum / drug effects
  • Plasmodium falciparum / growth & development
  • Pyrrolizidine Alkaloids / chemical synthesis*
  • Pyrrolizidine Alkaloids / pharmacology*
  • Stereoisomerism

Substances

  • Antimalarials
  • Biological Products
  • Hedgehog Proteins
  • Pyrrolizidine Alkaloids