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1st March 2011 @ 00:58
Summary and collection of the analytical data of PZQ and derivatives

(rac)-PZQ
1H NMR (CDCl3, 200 MHz): d = 1.28-1.80 (m, 10H), 2.47 (m, 1H), 2.75-
2.99 (m, 4H), 4.07 (d, J=17.3 Hz, 1H), 4.47 (d, J=17.3 Hz, 1H), 4.78-4.89 (m, 2H), 5.15 (br d, J=13.5, 1H), 7.18-7.28 (m, 4H). [1,5]
Data: 1H NMR PZQ.pdf
13C NMR (CDCl3, 200 MHz): d = 25.6 (3C), 28.6, 28.9, 29.1, 38.9, 40.6, 45.0, 48.9, 54.8, 125.3, 126.9, 127.3, 129.2, 132.7, 134.7, 164.3, 174.6. Data: 13C NMR PZQ.pdf
HPLC: Chiralcel OD-H, hexane/iso-propanol/Et3N = 60/40/0.1, 0.7 ml/min flow rate, RT (R-(-)PZQ): 11.6 min, S-(+)PZQ): 13.6 min.
HPLC Data: HPLC rac-PZQ (OD-H column).jpeg
C19H24N2O2 (312.4 g/mol)


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)).
HPLC: Chiralcel OD-H, hexane/iso-propanol/Et3N = 60/40/0.1, 0.7 ml/min flow rate, RT (R-(-)PZQ): 10.9 min.

S-(+)-PZQ
m.p. 110-111°C.
[α]D20 = -136.5° (c=1, EtOH).
HPLC: Chiralcel OD-H; hexane/iso-propanol/Et3N = 60:40:0.1, 0.7 ml/min flow rate, RT (S-(+)PZQ): 12.9 min

Chromatography of PZQ (Chiral HPLC of the racemate)

"Successful" dehydrogenation (NMR data)

Optical rotation of R-(-)-PZQ and S-(+)-PZQ as a function of the ee

From R-(-)-Praziquanamine to R-(-)-Praziquantel (MW48-1): N-Cyclohexanoyl-protection of the enantiopure PZQamine (1H NMR and HPLC data)

From S-(+)-Praziquanamine to S-(+)-Praziquantel (MW48-2): N-Cyclohexanoyl-protection of the enantiopure PZQamine (1H NMR and HPLC data)

N-Cyclohexanoyl-protection of the enantiopure R-(-)-PZQamine to PZQ (MW48-5)


References:
[1] Formation of Pyrazinoisoquinoline Ring System by the Tandem Amidoalkylation and N-Acyliminium Ion Cyclization: An Efficient Synthesis of Praziquantel, J. H. Kim, Y. S. Lee, H. Park and C. S. Rim, Tetrahedron 1998, 54, 7395-7400.(DOI: doi:10.1016/S0040-4020(98)00401-3)

[2] Synthesis of “Trioxaquantel”(R) Derivatives as Potential New Antischistosomal Drugs, S. A.-L. Laurent, J. Boissier, F. Coslédan, H. Gornitzka, A. Robert and B. Meunier, Eur. J. Org. Chem. 2008, 895-913. (DOI: 10.1002/ejoc.200700975)

[3] "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)

[4] “Novel Synthesis of Praziquantel“, A. Dömling, Patent Application 2009, WO 2009/11533(A1), Language: German.

[5] "Efficient Multicomponent Reaction Synthesis of the Schistosomiasis Drug Praziquantel", H. Cao, H. Liu, A. Dömling, Chem. Eur. J. 2010, 16, (2296 – 12298. DOI: 10.1002/chem.201002046)

[6] "Polycyclic Compounds by Ugi−Pictet−Spengler Sequence", W. Wang, S. Ollio, E. Herdtweck, A. Doemling, J. Org. Chem. 2011, 76 2, 637–644. (DOI: 10.1021/jo102058)

[7] Solubility Properties of Racemic Praziquantel and Its Enantiomers, S. K. El-Arini, D. Giron and H. Leuenberger, Pharm. Devel. Technol. 1998, 3, (4), 557-564. (doi:10.3109/10837459809028638)
Attached Files
HPLC rac-PZQ (OD-H column).jpeg
1H NMR PZQ.pdf
1H NMR PZQ JCAMP-DX.dx
13C_NMR PZQ JCAMP-DX.dx
13C NMR PZQ.pdf