The synthesis of the antimalarial compound hydroxypiperaquine (HPQ)

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 antimalaria...

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Main Author: Mohammed, Yousuf Hussain
Format: Thesis
Language:English
Published: Curtin University 2007
Subjects:
Online Access:http://hdl.handle.net/20.500.11937/1111
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author Mohammed, Yousuf Hussain
author_facet Mohammed, Yousuf Hussain
author_sort Mohammed, Yousuf Hussain
building Curtin Institutional Repository
collection Online Access
description 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.
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spelling curtin-20.500.11937-11112017-02-20T06:39:26Z The synthesis of the antimalarial compound hydroxypiperaquine (HPQ) Mohammed, Yousuf Hussain malaria artemisinin derivatives antimalarial drug Piperaquine (PQ) antimalarial compound hydroxypiperaquine (HPQ) 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. 2007 Thesis http://hdl.handle.net/20.500.11937/1111 en Curtin University fulltext
spellingShingle malaria
artemisinin derivatives
antimalarial drug Piperaquine (PQ)
antimalarial compound hydroxypiperaquine (HPQ)
Mohammed, Yousuf Hussain
The synthesis of the antimalarial compound hydroxypiperaquine (HPQ)
title The synthesis of the antimalarial compound hydroxypiperaquine (HPQ)
title_full The synthesis of the antimalarial compound hydroxypiperaquine (HPQ)
title_fullStr The synthesis of the antimalarial compound hydroxypiperaquine (HPQ)
title_full_unstemmed The synthesis of the antimalarial compound hydroxypiperaquine (HPQ)
title_short The synthesis of the antimalarial compound hydroxypiperaquine (HPQ)
title_sort synthesis of the antimalarial compound hydroxypiperaquine (hpq)
topic malaria
artemisinin derivatives
antimalarial drug Piperaquine (PQ)
antimalarial compound hydroxypiperaquine (HPQ)
url http://hdl.handle.net/20.500.11937/1111