The synthesis of the antimalarial compound hydroxypiperaquine (HPQ)
MetadataShow full item record
Malaria remains one of the most common causes of illness and death in developing countries.1 The development of new drugs to combat the disease is becoming one of the fastest growing research areas. Hydroxypiperaquine (HPQ) is an antimalarial bisquinoline compound related to the emerging antimalarial drug Piperaquine (PQ).2 Various research programs are being conducted internationally in efforts to prepare PQ for possible clinical use in combination with artemisinin derivatives. The hydroxy compound (HPQ) has been described in the Chinese literature but no data exists for this compound within the Western literature.3The primary aim of this research project was to synthesise Hydroxypiperaquine via alternative synthetic pathways to that briefly described by Xu et al3 by exploring various synthetic strategies based on literature synthetic procedures involving similar compounds. HPQ was synthesised through a three step synthetic process. In the first step, tertiary butoxy carbonyl (tBOC) piperazine was coupled with 4,7-dichloroquine (4,7-DCQ) to produce the intermediate 7-chloro-4-(tBOC piperazin-1-yl)quinoline. The second synthetic step involved the deprotection of 7-chloro-4-(tBOCpiperazinyl)quinoline to remove the tertiary butoxy carbonyl (tBOC) protecting group.The deprotected intermediate, 7-chloro-4-(piperazin-1-yl)quinoline, was subsequently reacted with 1,3-dichloropropanol in 1-pentanol to yield HPQ in the third step. This three step synthetic approach provides an alternative and efficient process to synthesise HPQ. The research provides important and specific details for the synthetic methodology involved in the synthesis of HPQ for future synthetic and biological research.
Showing items related by title, author, creator and subject.
Whittell, Louise Renee' (2011)This thesis investigates the potential of the alkaloid isocryptolepine 16 as a lead compound in antimalarial drug development. Fifteen derivatives of the parent alkaloid were prepared and fully characterised, twelve of ...
Moore, Brioni R. (2011)Murine malaria models have proved to be a valuable preclinical tool, particularly in the development of new concepts in the research of human malaria. Plasmodium berghei (P. berghei), is the most extensively studied and ...
Whittell, Louise; Batty, Kevin; Wong, R.; Bolitho, Erin; Fox, Simon; Davis, T.; Murray, Paul (2011)A series of mono- and di-substituted analogues of isocryptolepine have been synthesized and evaluated for in vitro antimalarial activity against chloroquine sensitive (3D7) and resistant (W2mef) Plasmodium falciparum and ...