A. Robert, B. Meunier, et al.
FULL PAPER
(250 MHz, CDCl3, 293 K): δ = 7.89–7.83 (m, 2 H, Haromatic), 7.77–
by column chromatography (SiO2, diethyl ether 100%). A white
7.68 (m, 2 H, Haromatic), 4.77 [t, 3J = 5.8 Hz, 1 H, CH(OMe)2], 3.83 powder was obtained (91 mg, quantitative). Rf average = 0.57 (100%
(d, 3J = 5.8 Hz, 2 H, CH2), 3.38 (s, 6 H, 2ϫOCH3) ppm. ES+-MS:
Et2O), m.p. 70–73 °C. UV/Vis (CH2Cl2): λmax, nm (ε, –1 cm–1): 262
m/z (%) = 204.2 (43) [M + H – CH3OH]+, 236.2 (6) [M + H]+, (420). MS (DCI/NH3): m/z (%) = 385 (40) [M + H]+, 402 (100) [M
258.2 (100) [M + Na]+, 274.3 (4) [M + K]+.
+ NH4]+. Compound 32 is a mixture of two diastereomeric race-
mates, each of them existing as two rotamers that were identified
at 273 K. For clarity, the NMR spectra of the diastereomers and
rotamers are described separately.
Acylpraziquanamine (30): (Ϯ)-Praziquanamine
3
(500 mg,
2.48 mmol, 1 equiv.) was dissolved in CHCl3 (5 mL), and
CH3COOH (2.3 mL, 24.8 mmol, 10 equiv.) was added. The mixture
was stirred at room temperature for 8 h. Solvents were removed
under vacuum, and the residue was purified by column chromatog-
raphy (SiO2, CH2Cl2/MeOH, from 100:0, v/v to 93:7, v/v). A pale
brown powder was obtained (675 mg, quantitative). Rf = 0.63
(CH2Cl2/MeOH 90:10, v/v). MS (DCI/NH3): m/z (%) = 245.3 (3)
Diastereomer 1-32, Major Rotamer: 1H NMR (500 MHz, CDCl3,
273 K): δ = 7.30 (m, 1 H, HC10), 7.29 (m, 1 H, HC11), 7.28 (m, 1
H, HC9), 7.22 (m, 1 H, HC8), 4.91 (m, 1 H, HC11b), 4.89 (m, 1
2
H, HC6), 4.78 (m, 1 H, HC1), 4.62 (m, 1 H, HC3Ј), 4.57 (d, J =
2
17.6 Hz, 1 H, HC3), 3.92 (d, J = 17.6 Hz, 1 H, HC3), 3.00 (m, 1
[M + H]+, 262.2 (100) [M + NH4]+, 279.3 (6) [M + NH4
+
H, HC7), 2.95 (m, 1 H, HC1), 2.91 (m, 1 H, HC6), 2.81 (m, 1 H,
HC7), 2.10 (m, 1 H, HC8Ј), 1.93 (m, 1 H, HC9Ј), 1.70 (m, 2 H,
HC5Ј, HC6Ј), 1.52 (m, 1 H, HC7Ј), 1.40 (m, 1 H, HC4Ј), 1.07 (m,
1 H, HC5Ј), 1.00 (m, 1 H, HC8Ј), 0.93 (s, 3 H, H3C12Ј), 0.92 (m,
3 H, H3C11Ј), 0.89 (m, 1 H, HC6Ј), 0.79 (d, 3J = 7.1 Hz, 3 H,
H3C10Ј) ppm. 13C NMR (126 MHz, CDCl3, 273 K): δ = 65.1 (C4),
157.4 (C1Ј), 139.9 (C7a), 132.6 (C11a), 129.4 (C8), 127.5 (C9),
127.0 (C10), 125.6 (C11), 76.2 (C3Ј), 55.3 (C11b), 47.5 (C3), 47.2
(C4Ј), 46.9 (C1), 41.3 (C8Ј), 38.8 (C6), 34.2 (C6Ј), 31.4 (C7Ј), 28.8
(C7), 26.2 (C9Ј), 23.3 (C5Ј), 22.2 (C12Ј), 21.0 (C11Ј), 16.4
(C10Ј) ppm.
NH3]+. For clarity, the NMR spectra of the two rotamers are de-
scribed separately.
1
Major Rotamer of 30: H NMR (500 MHz, [D6]DMSO, 293 K): δ
3
= 7.46 (d, J = 5 Hz, 1 H, HC11), 7.31–7.20 (m, 3 H, HC8, HC9,
3
3
HC10), 5.00 (dd, J = 10.0, J = 5.0 Hz, 1 H, HC11b), 4.56 (m, 1
2
2
3
H, HC6), 4.44 (d, J = 20.0 Hz, 1 H, HC3), 4.42 (dd, J = 16.5, J
2
= 5.0 Hz, 1 H, HC1), 3.75 (d, J = 20.0 Hz, 1 H, HC3), 3.30 (dd,
2J = 16.5, 3J = 10.0 Hz, 1 H, HC1), 2.87–2.80 (m, 2 H, H2C7), 2.85
(m, 1 H, HC6), 2.17 (s, 3 H, CH3).
1
Minor Rotamer of 30: H NMR (500 MHz, [D6]DMSO, 293 K): δ
Diastereomer 2-32, Major Rotamer: 1H NMR (500 MHz, CDCl3,
273 K): δ = 7.30 (m, 1 H, HC10), 7.29 (m, 1 H, HC11), 7.28 (m, 1
H, HC9), 7.22 (m, 1 H, HC8), 4.91 (m, 1 H, HC11b), 4.89 (m, 1
= 7.28 (m, 1 H, HC11), 7.31–7.20 (m, 3 H, HC8, HC9, HC10),
4.81 (m, 1 H, HC1), 4.80 (m, 1 H, HC11b), 4.56 (m, 1 H, HC6),
4.33 (d, 2J = 18.5 Hz, 1 H, HC3), 4.07 (d, 2J = 18.5 Hz, 1 H, HC3),
2.89 (m, 1 H, HC1), 2.87–2.80 (m, 2 H, H2C7), 2.85 (m, 1 H, HC6),
2.06 (s, 3 H, CH3).
2
H, HC6), 4.78 (m, 1 H, HC1), 4.62 (m, 1 H, HC3Ј), 4.58 (d, J =
2
17.6 Hz, 1 H, HC3), 3.93 (d, J = 17.6 Hz, 1 H, HC3), 3.00 (m, 1
H, HC7), 2.95 (m, 1 H, HC1), 2.91 (m, 1 H, HC6), 2.81 (m, 1 H,
HC7), 2.10 (m, 1 H, HC8Ј), 1.93 (m, 1 H, HC9Ј), 1.70 (m, 2 H,
HC5Ј, HC6Ј), 1.52 (m, 1 H, HC7Ј), 1.40 (m, 1 H, HC4Ј), 1.07 (m,
1 H, HC5Ј), 1.00 (m, 1 H, HC8Ј), 0.93 (s, 3 H, H3C12Ј), 0.91 (m,
3 H, H3C11Ј), 0.89 (m, 1 H, HC6Ј), 0.78 (d, 3J = 7.1 Hz, 3 H,
H3C10Ј) ppm. 13C NMR (126 MHz, CDCl3, 273 K): δ = 165.1
(C4), 154.6 (C1Ј), 134.9 (C7a), 132.6 (C11a), 129.4 (C8), 127.5 (C9),
127.0 (C10), 125.6 (C11), 76.1 (C3Ј), 55.3 (C11b), 47.4 (C3), 47.2
(C4Ј), 46.8 (C1), 41.3 (C8Ј), 38.8 (C6), 34.1 (C6Ј), 31.4 (C7Ј), 28.8
(C7), 26.2 (C9Ј), 23.1 (C5Ј), 22.2 (C12Ј), 20.9 (C11Ј), 16.3
(C10Ј) ppm.
(R)-Sulfinate of (؎)-Praziquanamine 31: (Ϯ)-Praziquanamine 3
(100 mg, 0.5 mmol, 1 equiv.) was dissolved under argon in freshly
distilled THF (5 mL). The solution was cooled to –78 °C, and a
solution of n-butyllithium (1.6 in hexane, 344 µL, 0.55 mmol,
1.1 equiv.) was added. The mixture was warmed to room tempera-
ture and was added to a solution of (1S,2R,5S)-menthyl (5R)-p-
toluenesulfinate (147 mg, 0.5 mmol, 1 equiv.) in freshly distilled
THF (0.5 mL). The mixture was stirred at room temperature for
3 h. The reaction was quenched by the addition of an aqueous solu-
tion of Na2HPO4 (1 , 15 mL), and then diluted with water
(15 mL) and CH2Cl2 (15 mL). The aqueous layer was extracted
with CH2Cl2 (3ϫ15 mL). The organic layers were combined, dried
with MgSO4, filtered, and concentrated. The residue was purified
by column chromatography (SiO2, hexane/ethyl acetate from
100:0, v/v to 50:50, v/v). A yellow glassy compound was obtained
(15 mg, 10% yield, two diastereomers). Rf = 0.53 (hexane/AcOEt,
50:50, v/v). [α]D = –16 (c = 2.5.10–3, CH2Cl2). 1H NMR (250 MHz,
Diastereomer 1-32, Minor Rotamer: 1H NMR (500 MHz, CDCl3,
273 K): δ = 7.32 (m, 1 H, HC10), 7.27 (m, 1 H, HC9), 7.22 (m, 2
H, HC8, HC11), 4.83 (m, 1 H, HC11b), 4.89 (m, 1 H, HC6), 4.85
2
(m, 1 H, HC1), 4.62 (m, 1 H, HC3Ј), 4.58 (d, J = 17.6 Hz, 1 H,
2
HC3), 3.94 (d, J = 17.6 Hz, 1 H, HC3), 3.07 (m, 1 H, HC1), 3.00
(m, 1 H, HC7), 2.91 (m, 1 H, HC6), 2.81 (m, 1 H, HC7), 2.11 (m,
1 H, HC8Ј), 1.98 (m, 1 H, HC9Ј), 1.72 (m, 1 H, HC5Ј), 1.70 (m, 1
H, HC6Ј), 1.52 (m, 1 H, HC7Ј), 1.49 (m, 1 H, HC4Ј), 1.12 (m, 1
H, HC5Ј), 1.03 (m, 1 H, HC8Ј), 0.97 (d, 3J = 7.0 Hz, 3 H, H3C11Ј),
2
CDCl3, 293 K): δ = 7.43 (d, J = 8.1 Hz, 2 H, =CH–CSO2), 7.25–
7.04 [m, 6 H, Hphenyl + 2ϫ= CH–C(CH3)], 4.96 (dd, J = 10.2, J =
4.4 Hz, 1 H), 4.80 (m, 1 H), 3.91–3.75 (m, 1 H), 3.83 (AB, 2J =
16.6 Hz, 1 H, HC3), 3.43 (AB, 2J = 16.6 Hz, 1 H, HC3), 2.86–2.67
(m, 4 H), 2.34 (s, 3 H, CH3 tolyl) ppm. MS (DCI/NH3): m/z (%) =
325 (100) [M – O + H]+, 342 (38) [M – O + NH4]+, 358 (7) [M +
H]+.
3
0.93 (s, 3 H, H3C12Ј), 0.89 (m, 1 H, HC6Ј), 0.86 (d, J = 7.0 Hz, 3
H, H3C10Ј) ppm. 13C NMR (126 MHz, CDCl3, 273 K): δ = 165.5
(C4), 154.4 (C1Ј), 135.3 (C7a), 132.5 (C11a), 129.6 (C8), 127.5 (C9),
126.9 (C10), 125.4 (C11), 76.2 (C3Ј), 55.6 (C11b), 47.7 (C3), 47.6
(C1), 47.3 (C4Ј), 41.6 (C8Ј), 38.8 (C6), 34.2 (C6Ј), 31.4 (C7Ј), 28.8
(C7), 27.0 (C9Ј), 23.8 (C5Ј), 22.2 (C12Ј), 20.8 (C11Ј), 17.0
(C10Ј) ppm.
Menthyl Carbamate of (؎)-Praziquanamine 32: (Ϯ)-Praziquan-
amine 3 (50 mg, 248 µmol, 1 equiv.) and triethylamine (38 µL, 495
µmol, 2 equiv.) were dissolved under argon in THF (1.3 mL). The
solution was cooled to 0 °C, and (–)-menthyl chloroformate
(105 µL, 495 µmol, 2 equiv.) was added. The slurry mixture was
stirred at room temperature for 1 h and then diluted with water
(10 mL) and CH2Cl2 (10 mL). The aqueous layer was extracted
with CH2Cl2 (3ϫ20 mL). The organic layers were combined, dried
with MgSO4, filtered, and concentrated. The residue was purified
Diastereomer 2-32, Major Rotamer: 1H NMR (500 MHz,CDCl3,
273 K): δ = 7.32 (m, 1 H, HC10), 7.27 (m, 1 H, HC9), 7.22 (m, 1
H, HC8), 7.17 (m, 1 H, HC11), 4.83 (m, 1 H, HC11b), 4.89 (m, 1
2
H, HC6), 4.85 (m, 1 H, HC1), 4.62 (m, 1 H, HC3Ј), 4.58 (d, J =
2
17.6 Hz, 1 H, HC3), 3.94 (d, J = 17.6 Hz, 1 H, HC3), 3.07 (m, 1
H, HC1), 3.00 (m, 1 H, HC7), 2.91 (m, 1 H, HC6), 2.81 (m, 1 H,
910
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Eur. J. Org. Chem. 2008, 895–913