Molecules (Mar 2010)

Stereodynamic Investigation of Labile Stereogenic Centres in Dihydroartemisinin

  • Ilaria D’Acquarica,
  • Francesco Gasparrini,
  • Dorina Kotoni,
  • Marco Pierini,
  • Claudio Villani,
  • Walter Cabri,
  • Michela Di Mattia,
  • Fabrizio Giorgi

DOI
https://doi.org/10.3390/molecules15031309
Journal volume & issue
Vol. 15, no. 3
pp. 1309 – 1323

Abstract

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Since its identification in the early 1970s, artemisinin, as well as semi-synthetic derivatives and synthetic trioxanes, have been used in malaria therapy. Reduction of artemisinin by NaBH4 produced dihydroartemisinin (DHA), and yielded a new stereochemically labile centre at C-10, which, in turn, provided two interconverting lactol hemiacetal epimers (namely a and b), whose rate of interconversion depends on buffer, pH, and solvent polarity. Since interconversion of the two epimers occurred on a chromatographic time-scale, this prompted a thorough investigation of the phenomenon as a crucial requisite of any analytical method aimed at quantitating this family of drugs. In this critical review we discuss the current importance of the on-column epimerization of DHA in the development of analytical methods aimed at quantifying the drug, with the purpose of identifying the optimal conditions to minimize on-column epimerization while achieving the best selectivity and efficiency of the overall separation.

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