Resolution of Praziquantel 英文参考文献.docVIP

ResolutionofPraziquantel MichaelWoelfle1,Jean-PaulSeerden2,JessedeGooijer2,KeesPouwer2,PieroOlliaro3,MatthewH. Todd1* 1School of Chemistry, The University of Sydney, Sydney, New South Wales, Australia, 2Syncom B.V., Groningen, The Netherlands, 3UNICEF/UNDP/World Bank/WHO SpecialProgrammeforResearchandTraininginTropicalDiseases(TDR),WorldHealthOrganization,Geneva,Switzerland Abstract Background:Praziquantelremainsthedrugofchoicefortheworldwidetreatmentandcontrolofschistosomiasis.Thedrug issynthesizedandadministeredasaracemate. Useofthepureactiveenantiomerwould bedesirablesincetheinactive enantiomerisassociatedwithsideeffectsandisresponsiblefortheextremelybittertasteofthepill. Methodology/PrincipalFindings:Wehaveidentifiedtworesolutionapproachestowardtheproductionofpraziquantelasa 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 intermediatethatmayberesolvedwithtartaricaciditself. Conclusions/Significance: Both resolution procedures identified show promise for the large-scale, economically viable productionofpraziquantelasasingleenantiomerforalowprice.Additionally,theymaybeemployedbylaboratoriesfor the production of smaller amounts of enantiopure drug for research purposes that should be useful in, for example, elucidationofthedrug’smechanismofaction. Citation: Woelfle M, Seerden J-P, de Gooijer J, Pouwer K, Olliaro P, et al. (2011) Resolution of Praziquantel. PLoS Negl Trop Dis 5(9): e1260. doi:10.1371/ journal.pntd.0001260 Editor:TimothyG.Geary,McGillUniversity,Canada ReceivedMay11,2011;AcceptedJune15,2011;PublishedSeptember20,2011 Copyright: ? 2011 Woelfle et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License,