Bile Acid-Based 1,2,4-Trioxanes: Synthesis and Antimalarial Assessment(1)

  • 10.1021/jm301323k
  • Journal of Medicinal Chemistry
  • p 10662-10673, Volume 55, Issue 23,
  • journal-article
A new series of bile acid-based trioxanes 23a–d, 24a–d, 25a–d, 26a, 26b, and 26d have been synthesized and assessed for their antimalarial activity against multidrug-resistant Plasmodium yoelii in Swiss mice by oral route. The antimalarial activity of these trioxanes showed a strong dependence on the side-chain length; shortening side-chain length lead to increase in activity. The antimalarial activity also showed even stronger dependence on the stereochemistry at C3 and C6 (C21 in Figure 5) of the trioxane moiety. Of the two diastereomers isolated of each of the trioxanes, more polar one was significantly more active than the less polar one. The more polar diastereomer of the trioxanes 26a, 26b, and 26d, were the most active compounds of the series. All these three trioxanes provided 100% protection at 24 mg/kg × 4 days. In this model β-arteether provided 100% and 20% protection at 48 mg/kg × 4 days and 24 mg/kg × 4 days, respectively.

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Decarboxylative oxidation of lithocholic acid

Summary:

A new series of bile acid-based trioxanes have been synthesized and assessed for their antimalarial activity against multidrug-resistant Plasmodium yoelii in Swiss mice by oral route.

The Reaction of Interest:

Decarboxylative oxidation of the O-acylated...

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