Resolution of praziquantel.

Abstract:

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.

journal_name

PLoS Negl Trop Dis

authors

Woelfle M,Seerden JP,de Gooijer J,Pouwer K,Olliaro P,Todd MH

doi

10.1371/journal.pntd.0001260

subject

Has Abstract

pub_date

2011-09-01 00:00:00

pages

e1260

issue

9

eissn

1935-2727

issn

1935-2735

pii

PNTD-D-11-00420

journal_volume

5

pub_type

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