(2R,3S)-(+)- and (2S,3R)-(−)-Halofuginone lactate: Synthesis, absolute configuration, and activity against Cryptosporidium parvum

The trans-enantiomers of the commercially important anti-protozoal compound Halofuginone have been prepared and characterized, and the absolute configuration was assigned by X-ray crystallography. The activity of both enantiomers against Cryptosporidium parvum was determined in vitro and related to acute toxicity in vivo. It was shown that both the activity and the toxicity are properties of the (2R,3S)-enantiomer. We conclude that with respect to broadening the therapeutic window there is no advantage in application of one enantiomer over the application of the racemic mixture in the treatment of C. parvum infections.

Graphical abstractPreparation of trans-enantiomers of Halofuginone, determination of absolute configuration, activity of enantiomers against C. parvum in vitro and acute toxicity in vivo are reported.Figure optionsDownload full-size imageDownload as PowerPoint slide