Stereodynamic Investigation of Labile Stereogenic Centres in Dihydroartemisinin

Autor: Ilaria D’Acquarica, Francesco Gasparrini, Dorina Kotoni, Marco Pierini, Claudio Villani, Walter Cabri, Michela Di Mattia, Fabrizio Giorgi
Jazyk: angličtina
Rok vydání: 2010
Předmět:
Zdroj: Molecules, Vol 15, Iss 3, Pp 1309-1323 (2010)
Druh dokumentu: article
ISSN: 1420-3049
DOI: 10.3390/molecules15031309
Popis: 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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