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An Efficient, Green Chemical Synthesis of the Malaria Drug, Piperaquine

Fortunak, J. M. , Byrn, S. R. , Dyson, B. , Ekeocha, Z. , Ellison, T. , King, C. L. , Kulkarni, A. A. , Lee, M. , Conrad, C. and Thompson, K. (2013) An Efficient, Green Chemical Synthesis of the Malaria Drug, Piperaquine. Tropical Journal of Pharmaceutical Research , 12 (5). pp. 791-798. ISSN 1596-5996

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To provide a robust, efficient synthesis of the malaria drug piperaquine for potential use in resource-poor settings. We used in-process analytical technologies (IPAT; HPLC) and a program of experiments to develop a synthesis of piperaquine that avoids the presence of a toxic impurity in the API and is optimized for overall yield and operational simplicity. A green-chemical synthesis of piperaquine is described that proceeds in 92 – 93 % overall yield. The chemistry is robust and provides very pure piperaquine tetraphosphate salt (> 99.5 %). The overall process utilizes modest amounts (about 8 kg/kg) of 2-propanol and ethyl acetate as the only organic materials not incorporated into the API; roughly 60 % of this waste can be recycled into the production process. This process also completely avoids the formation of a toxic impurity commonly seen in piperaquine that is otherwise difficult to remove. An efficient synthesis of piperaquine is described that may be useful for application in resource-poor settings as a means of expanding access to and reducing the cost of ACTs.

Item Type: Article
Keywords: ACTs, Dihydroartemisinin Piperaquine, Dihydroartemisinin, Green Chemistry, Malaria, Piperaquine, Drug, Toxic, Chemicals
Subjects: Malaria > Diagnosis & treatment
Divisions: Other
Depositing User: Mr Joseph Madata
Date Deposited: 08 Jan 2014 07:33
Last Modified: 08 Jan 2014 07:33

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