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Alternatives to PZQ

Published by MatTodd on 1 April 2010 - 12:07am

A hub for alternative drugs to the currently used PZQ

31 Mar

Derivatives of PZQ: 9,10-dimethoxy-4-oxo-1,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1-a] isoquinoline

Published by Michael Wolfle

 
reaction
 
In a 3-step-sequence 3,4-dimethoxyphenethylamine 8 was converted to the tetrahydroisoquinoline derivative 9. Chloroacetyl chloride was added to 8 in the first step, some starting material was present in the product but could purified by an acidic wash.

27 Mar

Pictet-Spengler approach to PZQ: Cyclisation to Praziquanamin

Published by Michael Wolfle

 
Reaction 1
 
The Pictet-Spengler cyclisation of the acetal 4 to the tetrahydroisoquinoline substructure 5 was conducted in concentrated sulfuric acid. The reaction showed a complete conversion to the tricycle in a very good yield and with high purity. The product was isolated by extraction from the basic aqueous solution, no further purification was needed. No side products were observed in the 1H NMR spectrum.

19 Feb

Pictet-Spengler approach to PZQ: 2-chloro-N-phenethylacetamide

Published by Michael Wolfle

 
Reaction
 
Here we started another synthetic approach to PZQ. The Pictet-Spengler route, used for the industrial synthesis of (rac)-PZQ, offers a straightforward way to this anthelmetic drug in 5 steps.[1]
Starting from inexpensive 2-phenylethylamine and chloroacetyl chloride the amide 2 can be obtained in a short reaction time with high yield. 
 
Procedure:

15 Feb

Cleavage experiment with PZQ using 50 vol% TFA

Published by Michael Wolfle

 
Reaction
 
This experiment was conducted in order to examine whether the cyclohexanoyl amid bond could be cleaved under mild acidic conditions by using a 50 vol% TFA solution in DCM. After 48 h under refluxing temperature 99% of the starting material could be recovered.
As a result, this procedure can be used for the scission of acid-labile protecting groups of prospective derivatives of PZQ without touching the cyclohexanoyl group.
 
Procedure

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