- Combining Incompatible Processes for Deracemization of a Praziquantel Derivative under Flow Conditions
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An efficient deracemization method for conversion of the racemate to the desirable (R)-enantiomer of Praziquantel has been developed by coupling incompatible racemization and crystallization processes. By a library approach, a derivative that crystallizes as a conglomerate has been identified. Racemization occurs via reversible hydrogenation over a palladium on carbon (Pd/C) packed column at 130 °C, whereas deracemization is achieved by alternating crystal growth/dissolution steps with temperature cycling between 5–15 °C. These incompatible processes are combined by means of a flow system resulting in complete deracemization of the solid phase to the desired (R)-enantiomer (98 % ee). Such an unprecedented deracemization by a decoupled crystallization/racemization approach can readily be turned into a practical process and opens new opportunities for the development of essential enantiomerically pure building blocks that require harsh methods for racemization.
- Valenti, Giulio,Tinnemans, Paul,Baglai, Iaroslav,Noorduin, Willem L.,Kaptein, Bernard,Leeman, Michel,ter Horst, Joop H.,Kellogg, Richard M.
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supporting information
p. 5279 - 5282
(2021/01/26)
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- One-pot palladium-catalyzed racemization of (S)-praziquanamine: A key intermediate for the anthelmintic agent (R)-praziquantel
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An one-pot palladium-catalyzed procedure for racemization of (S)-praziquanamine, which is the undesired enantiomer and produced during the resolution step for preparing the anthelmintic drug (R)-praziquantel, has been developed through dehydrogenation of
- Yang, Zhezhou,Guo, Xiang,Xu, Shanghu,Jiao, Huirong,Tan, Zhinmin,Zhang, Fuli
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p. 122 - 130
(2017/03/01)
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- Preparation method of (R)-praziquantel amine salt, and preparation method of levopraziquantel
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The invention relates to a preparation method of (R)-praziquantel amine salt, and a preparation method of levopraziquantel. The (R)-praziquantel amine salt is prepared through a reaction of racemic praziquantel amine and a chiral resolution reagent in a solvent, and the chiral resolution reagent is one or more of (R)-ibuprofen, (R)-naproxen and (R)-phenethylsulfonic acid. The preparation methods have the advantages of easily available raw materials, simple process, short preparation cycle, low cost, and stability, low price and easiness in recovery of the chiral resolution reagent,.
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- METHOD FOR THE PRODUCTION OF PRAZIQUANTEL AND PRECURSORS THEREOF
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The present invention relates to methods for the production of enantiopure or enantioenriched Praziquantel precursors and to methods for the production of enantiopure or enantioenriched Praziquantel comprising the methods for the production of the Praziquantel precursors. The present invention further relates to compounds or intermediates useful in such methods.
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- Optically active [...][...] and the corresponding method for the preparation of the
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The invention provides a preparation method of pyrazino amine salt with optical activity. The preparation method is characterized in that pyrazino amine salt is prepared through the reaction of racemic pyrazino amine and dibenzoyltartaric acid with optical activity in the presence of a solvent, wherein the solvent comprises more than 50% of 2-butanone in volume fraction; and dibenzoyltartaric acid with optical activity is diphenyl diketone-L-tartaric acid with optical impurity not less than 95%, or diphenyl diketone-D-tartaric acid with optical impurity not less than 95%. The invention also provides a preparation method of corresponding pyrazino amine with optical activity. The method performed for separating racemic pyrazino amine is very suitable for industrial application.
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- Method for preparing (R)-praziquantel
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The invention relates to a new method for preparing (R)-praziquantel. In the invention, by taking advantage of the high stereo selectivity, site selectivity and region selectivity of an enzyme, an intermediate of a pure optical and chiral (R)-praziquantel
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- Methods of use comprising deuterated pyrazino[2,1-a]isoquinolines
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This invention in one embodiment is directed to a compound of Formula Ia; where the designation (R) indicates that the designated carbon has the (R) stereochemistry; and wherein Z1 is hydrogen or fluorine; Z2 is hydrogen, deuterium,
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Page/Page column 33; 34
(2015/12/27)
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- Development and validation of process for resolution of praziquantel amine for preparation of chiral praziquantel
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Investigation of the viability of scale up preparation for chiral praziquantel was included in WHO/TDR business plan. Resolution is the major strategy for preparation of single enantiomer. In this study, a stable and effective resolution approach toward the important intermediate praziquantel amine for preparation of chiral praziquantel was developed and the process was optimized to afford high ee value and good yield. The suitable HPLC method was validated for the determination of ee value of chiral praziquantel amine.
- Hu, Changyan,Wang, Dongling,Chen, Kunquan,Liu,Chen, Qichao,Sun, Dequn
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p. 8158 - 8162
(2015/02/02)
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- Development of chiral praziquantel analogues as potential drug candidates with activity to juvenile Schistosoma japonicum
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A series of chiral praziquantel analogues were synthesized and evaluated against Schistosoma japonicum both in vitro and in vivo. All compounds exhibited low to considerable good activity in vivo. Remarkably, worm reduction rate of R-3 was 60.0% at a sing
- Zheng, Yang,Dong, Lanlan,Hu, Changyan,Zhao, Bo,Yang, Chunhua,Xia, Chaoming,Sun, Dequn
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supporting information
p. 4223 - 4226
(2014/11/07)
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- Design and synthesis of molecular probes for the determination of the target of the anthelmintic drug praziquantel
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Schistosomiasis is a highly prevalent neglected tropical disease caused by blood-dwelling helminths of the genus Schistosoma. Praziquantel (PZQ) is the only drug available widely for the treatment of this disease and is administered in racemic form, even
- Sharma, Lalit Kumar,Cupit, Pauline M.,Goronga, Tino,Webb, Thomas R.,Cunningham, Charles
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p. 2469 - 2472
(2014/05/20)
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- A straightforward and efficient synthesis of praziquantel enantiomers and their 4′-hydroxy derivatives
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A new method for the synthesis of praziquantel enantiomers via resolution of praziquanamine with (S)-(+)-naproxen was developed. The four 4′-hydroxy derivatives were obtained through each single praziquanamine enantiomer, coupling with cis- and trans-4-(benzyloxy)cyclohexanecarboxylic acids and subsequent hydrogenolysis for the deprotection of the 4′-OH cyclohexane residue. Additionally, the in vitro cysticidal activity of the compounds was tested, finding that (R)-(-)-praziquantel is the eutomer.
- Cedillo-Cruz, Alberto,Aguilar, Maria Isabel,Flores-Alamo, Marcos,Palomares-Alonso, Francisca,Jung-Cook, Helgi
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p. 133 - 140
(2014/02/14)
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- Synthesis of "Trioxaquantel" derivatives as potential new antischistosomal drugs
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Over the past 20 years, praziquantel, a pyrazinoisoquinoline derivative, has become the mainstay for morbidity control of human and animal schistosomiasis. From early in their lives in vertebrate hosts, schistosomes ingest hemoglobin and aggregate the released heme as a dark pigment very similar to the hemozoin produced by Plasmodium in malaria infection. The antimalarial artemisinin derivatives have real, though low, schistosomicide activity. Because of the complementarity of the two drug classes - praziquantel and artemisinin derivatives - we designed new molecules, named trioxaquantels, that combine the 1,2,4-trioxane unit responsible for the activity of artemisinin, and the pyrazinoisoquinoline moiety of praziquantel within a single drug. The synthesis of these new drugs and their preliminary evaluation in mice infected with Schistosoma mansoni is reported here. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
- Laurent, Sophie A.-L.,Boissier, Jerome,Cosledan, Frederic,Gornitzka, Heinz,Robert, Anne,Meunier, Bernard
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experimental part
p. 895 - 913
(2009/04/08)
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