Details

Autor(en) / Beteiligte

• Fortunak, Joseph MD
• Byrn, Stephen R
• Dyson, Brandon
• Ekeocha, Zita
• Ellison, Tiffany
• King, Christopher L
• Kulkarni, Amol A
• Lee, Mindy
• Conrad, Chelsea
• Thompson, Keeshaloy

Titel

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

Ist Teil von

• Tropical journal of pharmaceutical research, 2013-10, Vol.12 (5)

Ort / Verlag

Nigeria: Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, Nigeria

Erscheinungsjahr

2013

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Purpose: To provide a robust, efficient synthesis of the malaria drug piperaquine for potential use in resource-poor settings. Methods: 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. Results: 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. Conclusion: 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.