Resolution of Praziquantel
Resolution of Praziquantel
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DOI：
10.1371/journal.pntd.0001260
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发表时间：
2011-09-01
影响因子：
3.8
通讯作者：
Todd, Matthew H.
中科院分区：
文献类型：
--
作者：
Woelfle, Michael;Seerden, Jean-Paul;Todd, Matthew H.
背景：吡喹酮仍然是世界范围内治疗和控制血吸虫病的首选药物。这种药物是合成的，以外消旋体形式给药。使用纯的活性对映异构体将是可取的，因为无活性的对映异构体与副作用，是负责非常苦的味道pill.Methodology/主要调查结果：我们已经确定了两个决议的方法对生产吡喹酮作为一个单一的对映异构体。一种方法从市售吡喹酮开始，涉及水解为中间体胺，用酒石酸衍生物拆分。这种方法是通过互联网上的开放合作发现的。第二种方法，确定了一个合同研究组织，采用不同的中间体，可以解决与酒石酸itself.Conclusions/意义：这两个决议程序确定显示的承诺为大规模的，经济上可行的生产吡喹酮作为一个单一的对映异构体的低价格。此外，它们可以被实验室用于生产少量的对映体纯药物，用于研究目的，例如，阐明药物的作用机制。
Background: Praziquantel remains the drug of choice for the worldwide treatment and control of schistosomiasis. The drug is synthesized and administered as a racemate. Use of the pure active enantiomer would be desirable since the inactive enantiomer is associated with side effects and is responsible for the extremely bitter taste of the pill.Methodology/Principal Findings: We have identified two resolution approaches toward the production of praziquantel as a single enantiomer. One approach starts with commercially available praziquantel and involves a hydrolysis to an intermediate amine, which is resolved with a derivative of tartaric acid. This method was discovered through an open collaboration on the internet. The second method, identified by a contract research organisation, employs a different intermediate that may be resolved with tartaric acid itself.Conclusions/Significance: Both resolution procedures identified show promise for the large-scale, economically viable production of praziquantel as a single enantiomer for a low price. Additionally, they may be employed by laboratories for the production of smaller amounts of enantiopure drug for research purposes that should be useful in, for example, elucidation of the drug's mechanism of action.