Racemic Resolution of Praziquantel and Praziquanamine

 

Determination of the optical rotation of the 2 enantiomers of PZQ in dependence of ee and concentration

See also: Optical rotation of S-(+)-Praziquanamine



Enantiopure samples of R-(-)-PZQ and S-(+)-PZQ donated from Intervet Innovation GmbH, Germany (Schwabenheim)

Separation method: Chiral column chromatography performed on microcrystalline cellulose triacetate [1].

R-(-)-PZQ:
m.p. 111-112°C (lit.[2] m.p. = 113-115°C).
[α]D20 = -139° (c=1, EtOH)
(lit. [2] [α]D20 = 126.9 (c = 1, EtOH 99.%) [α]D20 = 135.0 (c = 1, CHCl3)).

S-(+)-PZQ:
m.p. 110-111°C.
[α]D20 = -136.5° (c=1, EtOH).


Determination of the optical rotation in dependence of the ee (in %)
To a solution of R-(-)-PZQ (c = 1, EtOH) was added a solution of S-(+)-PZQ (c = 1, EtOH) (vol/vol) to give a total volume of 1 mL.




Chart 1: Optical rotation α as a function of the ee



Determination of the optical rotation in dependence of the concentration:
A solution of R-(-)-PZQ (c = 1, EtOH) was diluted with EtOH to the concentration given in the tables below.
4 dilution series were performed to determine the mean value of the optical rotation α (lage deviations for diluted solutions)

Series1- Series4



Chart 2: Optical rotation α as a function of the concentration c (for Series4)


Chart 3: Mean value of the optical rotation [α] in dependence of the concentration c ([α] = α / l * c, and l=1, α and c are given in tables Series1 - Series4)
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Results:
- Linear dependence of the optical rotation α of PZQ on the ee (determined for a concentration c = 1 in DCM)
- Linear dependence of the optical rotation α of R-(+)-PZQ on the concentration


References:
[1] "Taste, A New Incentive to Switch to (R)-Praziquantel in Schistosomiasis Treatment", T. Meyer, H. Sekljic, S. Fuchs, H. Bothe, D. Schollmeyer and C. Miculka, PLoS Neglected Tropical Diseases 2009, 3, 1, e357

[2] "Enantioselective synthesis of (R)-(−)-praziquantel (PZQ)", P. Roszkowski J. K. Maurin and Zbigniew Czarnocki, Tetrahedron: Asymmetry,2006, 17, 9, 15, 1415-1419. (doi:10.1016/j.tetasy.2006.04.023)