Stereodynamic Investigation of Labile Stereogenic Centres in Dihydroartemisinin

Molecules

Ilaria D’Acquarica¹  Francesco Gasparrini¹  Dorina Kotoni¹  Marco Pierini¹  Claudio Villani¹  Walter Cabri¹  Michela Di Mattia¹ 

[1] ¹Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Università di Roma, P. le Aldo Moro 5, 00185 Roma, Italy ²Analytical Development, R&D Department, sigma-tau S.p.A., Via Pontina km 30,400, 00040 Pomezia, Italy

关键词: Dihydroartemisinin (DHA);    on-column epimerization;    cryo-HPLC;    dynamic HPLC (DHPLC);    computer simulation;   

DOI  :  10.3390/molecules15031309

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.