resolution of praziquantel解决吡喹酮.pdfVIP

Resolution of Praziquantel 1 2 2 2 3 Michael Woelfle , Jean-Paul Seerden , Jesse de Gooijer , Kees Pouwer , Piero Olliaro , Matthew H. Todd1* 1 School of Chemistry, The University of Sydney, Sydney, New South Wales, Australia, 2 Syncom B.V., Groningen, The Netherlands, 3 UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR), World Health Organization, Geneva, Switzerland Abstract Background: Praziquantel remains the drug of choice for the worldwide treatment and control of schistosomiasis. The drug is synthesized and administered as a racemate. Use of the pure active enantiomer would be desirable since the inactive enantiomer is associated with side effects and is responsible for the extremely bitter taste of the pill. Methodology/Principal Findings: We have identified two resolution approaches toward the production of praziquantel as a single enantiomer. One approach starts with commercially available praziquantel and involves a hydrolysis to an intermediate amine, which is resolved with a derivative of tartaric acid. This method was discovered through an open collaboration on the internet. The second method, identified by a contract research organisation, employs a different intermediate that may be resolved with tartaric acid itself. Conclusions/Significance: Both resolution procedures identified show promise for the large-scale, economically viable production of praziquantel as a single enantiomer for a low price. Additionally, they may be employed by laboratories for the production of smaller amounts of enantiopure drug for research purposes that should be useful in, for example,