stereodynamic investigation of labile stereogenic centres in dihydroartemisininstereodynamic不稳定双氢青蒿素含量测定手性中心的调查.pdfVIP

Molecules 2010, 15, 1309-1323; doi:10.3390/molecule OPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Review Stereodynamic Investigation of Labile Stereogenic Centres in Dihydroartemisinin Ilaria D’Acquarica 1,*, Francesco Gasparrini 1,*, Dorina Kotoni 1, Marco Pierini 1, 1 2 2 2 Claudio Villani , Walter Cabri , Michela Di Mattia and Fabrizio Giorgi 1 Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Università di Roma, P. le Aldo Moro 5, 00185 Roma, Italy 2 Analytical Development, RD Department, sigma-tau S.p.A., Via Pontina km 30,400, 00040 Pomezia, Italy; E-Mail: walter.cabri@sigma-tau.it (W.C.) * Authors to whom correspondence should be addressed; E-Mails: ilaria.dacquarica@uniroma1.it (I.D.); francesco.gasparrini@uniroma1.it (F.G.); Tel.: +390649912776 (F.G.); Fax: +390649912780 (F.G.). Received: 1 January 2010; in revised form: 25 January 2010 / Accepted: 4 March 2010 / Published: 5 March 2010 Abstract: 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 α and β), whose rate of interconversion depends on buffer, pH, and solvent polarity.