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N. A. L. Pereira et al.
(CH2), 56.77 (CH), 40.89 (CH2–Ph), 23.02 (CH3) ppm; IR
(NaCl): m = 1,715 (C=O) cm-1; MS (ESI, CP 3.0 kV, SP
30 V): m/z calc. 279 [M]?, m/z found 280 [M?H]?; Rf
(ethyl acetate:n-hexane 1:1) = 0.77.
(CH), 39.92 (CH2–Ph), 35.05 (C-7), 32.57 (C-6) ppm; IR
(KBr): m = 1,721 (C=O) cm-1; MS (ESI, CP 3.0 kV, SP
30 V): m/z calc. 293 [M] ?, m/z found 294 [M?H]?; Rf
(ethyl acetate:n-hexane 3:7) = 0.31.
(3S,9bR)-3-Benzyl-2,3-dihydro-9b-phenyloxazolo[2,3-a]-
isoindol-5(9bH)-one (3c, C23H19NO2)
General procedure for the cyclocondensation reaction
of (R)-2-amino-3-phenylpropan-1-ol (10)
with keto-acids 2a–2c
Prepared from 100 mg of (S)-2-amino-3-phenylpropan-1-ol
in 7 cm3 of toluene. The obtained residue was purified by
column chromatography (AcOEt:n-hexane 1:9). Recrystal-
lization from diethyl ether/n-hexane afforded 193 mg
To a stirred solution of (R)-2-amino-3-phenylpropan-1-ol
in boiling toluene under inert atmosphere and a Dean–Stark
apparatus was added 1.1 eq. of the desired oxo-acid. The
mixture was refluxed until total consumption of the starting
aminoalcohol. The solvent was evaporated and the crude
residue was purified by column chromatography using
ethyl acetate/n-hexane as eluent.
1
(86 %) 3c. M.p.: 92–94 °C; H NMR (400 MHz, CDCl3):
d = 7.80–7.75 (m, 1H, H–Ar), 7.68–7.62 (m, 2H, H–Ar),
7.50–7.37 (m, 5H, H–Ar), 7.31–7.20 (m, 4H, H–Ar),
7.17–7.14 (m, 2H, H–Ar), 4.66–4.52 (m, 1H, H-3), 4.44
(dd, J = 8.6, 7.5 Hz, 1H, H-2), 3.96 (dd, J = 8.7, 6.6 Hz,
1H, H-2), 3.02 (dd, J = 13.8, 6.8 Hz, 1H, CH2–Ph), 2.51
(dd, J = 13.8, 8.7 Hz, 1H, CH2–Ph) ppm; 13C NMR
(100 MHz, CDCl3): d = 174.52 (C=O), 147.27 (Cq),
138.95 (Cq), 137.61 (Cq), 133.41 (CH–Ar), 131.10 (Cq),
130.23 (CH–Ar), 129.11 (2CH–Ar), 128.94 (2CH–Ar),
128.86 (CH–Ar), 128.64 (2CH–Ar), 126.77 (CH–Ar),
125.96 (2CH–Ar), 124.52 (CH–Ar), 123.56 (CH–Ar),
101.04 (C-9b), 75.91 (CH2), 56.80 (CH), 40.54 (CH2–Ph)
ppm; IR (KBr): m = 1,721 (C=O) cm-1; MS (ESI, CP
3.0 kV, SP 30 V): m/z calc. 341 [M]?, m/z found 342
[M?H]?; Rf (ethyl acetate:n-hexane 3:7) = 0.61.
(3R,9bS)-3-Benzyl-2,3-dihydrooxazolo[2,3-a]isoindol-
5(9bH)-one (3a0)
Prepared from 100 mg of (R)-2-amino-3-phenylpropan-1-ol
in 15 cm3 of toluene. The obtained residue was purified by
column chromatography (AcOEt:n-hexane 2:8). Recrystal-
lization from diethyl ether/n-hexane afforded 125 mg
(71 %) 3a0. The 1H NMR spectrum was found to be
identical with the one described in Ref. [11].
(3R,9bS)-3-Benzyl-2,3-dihydro-9b-methyloxazolo[2,3-a]-
isoindol-5(9bH)-one (3b0, C18H17NO2)
(3S,7aR)-3-Benzyl-tetrahydro-7a-methylpyrrolo[2,1-b]-
oxazol-5(6H)-one (3d)
Prepared from 100 mg of (R)-2-amino-3-phenylpropan-1-ol
in 15 cm3 of toluene. The obtained residue was purified by
column chromatography (AcOEt:n-hexane 2:8) affording
157 mg (85 %) of a colorless oil. 1H NMR, 13C NMR, and
IR spectra were found to be identical with the ones
described for compound 3b.
Prepared from 100 mg of (S)-2-amino-3-phenylpropan-1-ol
in 10 cm3 of toluene. The obtained residue was purified by
column chromatography (AcOEt:n-hexane 1:1) affording
111 mg (73 %) of 3d as a colorless oil. The 1H NMR
spectrum was found to be identical with the one described
in Ref. [12].
(3R,9bS)-3-Benzyl-2,3-dihydro-9b-phenyloxazolo[2,3-a]-
isoindol-5(9bH)-one (3c0, C23H19NO2)
(3S,7aS)-3-Benzyl-tetrahydro-7a-phenylpyrrolo[2,1-b]-
oxazol-5(6H)-one (3e, C19H19NO2)
Prepared from 100 mg of (R)-2-amino-3-phenylpropan-1-ol
in 15 cm3 of toluene. The obtained residue was purified by
column chromatography (AcOEt:n-hexane 2:8). Recrystal-
lization from diethyl ether/n-hexane afforded 167 mg
Prepared from 100 mg of (S)-2-amino-3-phenylpropan-1-ol
in 10 cm3 of toluene. The obtained residue was purified by
column chromatography (AcOEt:n-hexane 3:7). Recrystal-
lization from diethyl ether/n-hexane afforded 140 mg
1
(74 %) of 3c0. H NMR, 13C NMR, and IR spectra were
found to be identical with the ones described for compound
1
(72 %) 3e. M.p.: 55–56 °C; H NMR (400 MHz, CDCl3):
3c.
d = 7.51 (d, J = 7.4 Hz, 2H, H–Ar), 7.44–7.38 (m, 3H,
H–Ar), 7.28–7.21 (m, 3H, H–Ar), 7.08 (d, J = 7.3 Hz, 2H,
H–Ar), 4.50–4.35 (m, 1H, H-3), 4.13 (t, J = 8.1 Hz, 1H,
H-2), 3.65–3.49 (m, 1H, H-2), 2.94 (dd, J = 13.7, 6.2 Hz,
1H, CH2–Ph), 2.89–2.77 (m, 1H, H-6), 2.63–2.45 (m, 2H,
H-6 and H-7), 2.35–2.18 (m, 2H, CH2–Ph and H-7) ppm;
13C NMR (100 MHz, CDCl3): d = 179.87 (C=O), 142.55
(Cq), 137.26 (Cq), 128.90 (2CH–Ar), 128.70 (2CH–Ar),
128.49 (2CH–Ar), 128.31 (CH–Ar), 126.60 (CH–Ar),
125.07 (2CH–Ar), 102.27 (C-7a), 72.26 (CH2), 56.44
NMDA receptor antagonist activity
The activity of the synthesized compounds as NMDA
receptor antagonists was evaluated using primary cultures
of rat cerebellar neurons, as described previously [13].
Briefly, cultures were prepared from 7–8-day-old Wistar
rats (Charles River, France). Cerebella were dissected,
minced, and trypsinized, and after several sedimentations,
cells were plated on poly-lysinized coverslips placed in
123