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4.4.1. (1S,2R,10bS)-1,2-Dihydroxy-1,2,3,5,6,10b-hexa-
hydropyrrolo[2,1-a]isoquinoline, 2. Foam, yield 58%; IR
(CH2Cl2): 3605, 3355, 3050, 2928 cm−1; [h]D=+13 (c
(CDCl3): 170.19, 169.95, 169.83, 169.69, 169.56, 169.48,
167.82, 167.68, 137.66, 137.65, 128.76, 128.72, 128.70,
128.64, 126.85, 126.75, 83.79, 79.22, 75.92, 75.90, 70.91,
70.76, 43.52, 42.17, 33.84, 33.49, 20.77, 20.66, 20.62,
20.55, 20.51, 20.36; MS (EI, HR) m/z: (M+) calcd for
C18H21O7N: 363.1318. Found: 363.1304.
1
0.8, CH2Cl2); H NMR (CDCl3+D2O): 4.33 (m, 1H),
4.1 (t, 1H, J=6.7 Hz), 3.64 (d, 1H, J=6.7 Hz), 3.34
(dd, 1H, J=10.4, 5.6 Hz), 3.05 (m, 1H), 2.98 (m, 1H),
2.80 (m, 1H), 2.71 (m, 2H); 13C NMR (CDCl3): 136.56,
134.21, 128.52, 126.48, 126.26, 125.59, 77.20, 69.18,
66.36, 59.00, 47.95, 26.91; MS (EI, HR) m/z: (M+)
calcd for C12H15O2N: 205.1103. Found: 205.1095.
4.6. (1S,2R,10bS)-2-Benzoyloxy-1-hydroxy-
1,2,3,5,6,10b-hexahydropyrrolo[2,1-a]isoquinolin-3-one,
14
To a stirred solution of 13b (0.219 g, 1 mmol) in
pyridine (3.8 mL), cooled to −30°C, the benzoyl chlo-
ride (0.156 g, 1.1 mmol) was added dropwise. The
mixture was stirred for 1 h at −30°C and was allowed
to warm very slowly (over 3 h) to 0°C and left in
refrigerator overnight. Ethyl acetate was added (15 mL)
and the mixture was washed with 2N HCl. The organic
layer was washed additionally with brine, dried over
MgSO4 and evaporated under reduced pressure. The
residue was purified by flash column chromatography
(CH2Cl2:MeOH:NH3/aq., 20:1:0.1) to give benzoate 14
(0.259 g, 80% yield); colourless crystals, mp 153–155°C
(hexane/ethyl acetate); IR (CH2Cl2): 3364, 3062, 2934,
4.4.2. (1S,2R,10bR)-1,2-Dihydroxy-1,2,3,5,6,10b-hexa-
hydropyrrolo[2,1-a]isoquinoline, 3. Oil, yield 49%; IR
(CH2Cl2): 3601, 3361, 3052, 2927 cm−1; [h]D=−206 (c
1
1.3, CH2Cl2); H NMR (CDCl3+D2O): 4.45 (dd, 1H,
J=5.4, 3.6 Hz), 4.38 (m, 1H), 3.54 (bd, 1H, J=3.3 Hz),
3.18 (ddd, 1H, J=11.0, 6.3, 1.9 Hz), 3.08 (m, 1H), 3.03
(dd, 1H, J=11.0, 2.8 Hz), 2.73 (m, 2H), 2.53 (m, 1H);
13C NMR (CDCl3): 135.65, 131.90, 128.94, 126.94,
126.25, 126.23, 71.74, 70.40, 66.94, 60.40, 48.88, 28.17;
MS (EI, HR) m/z: (M+) calcd for C12H15O2N:
205.1103. Found: 205.1098.
4.4.3. (1S,2S,10bS)-1,2-Dihydroxy-1,2,3,5,6,10b-hexahy-
dropyrrolo[2,1-a]isoquinoline, 4. Colourless crystals,
yield 78%, mp 123–125°C (hexane/CH2Cl2); IR
(CH2Cl2): 3603, 3351, 3052, 2930, 2808 cm−1; [h]D=+55
1
1731, 1696 cm−1; [h]D=+87 (c 1.7, CH2Cl2); H NMR
(CDCl3+D2O): 5.52 (dd, 1H, J=7.0, 1.3 Hz), 4.71 (bd,
1H, J=7.0 Hz), 4.34 (ddd, 1H, J=12.9, 6.0, 2.8 Hz),
4.28 (t, 1H, J=7.0 Hz), 3.15 (m, 1H), 2.99 (m, 1H),
2.81 (m, 1H); 13C NMR (CDCl3): 168.04, 165.29,
134.45, 133.89, 132.98, 130.22, 129.03, 128.53, 128.49,
127.48, 127.16, 125.43, 80.90, 79.67, 58.86, 36.95, 28.11;
MS (LSIMS(+), HR) m/z: (M+H+) calcd for
C19H18O4N: 324.1236. Found: 324.1237. Anal. calcd for
C19H17O4N: C, 70.58; H, 5.30; N, 4.33. Found: C,
70.41; H, 5.31; N, 4.17%.
1
(c 1, CH2Cl2); H NMR (CDCl3+D2O): 4.12 (m, 1H),
3.96 (dd, 1H, J=7.5, 3.3 Hz), 3.37 (d, 1H, J=7.5 Hz),
3.08 (m, 2H), 2.88 (dd, 1H, J=10.3, 3.0 Hz), 2.80 (dd,
1H, J=10.3, 6.3 Hz), 2.71 (m, 1H), 2.60 (m, 1H); 13C
NMR (CDCl3): 136.35, 133.99, 128.49, 126.62, 126.14,
125.00, 84.48, 78.21, 67.75, 59.04, 48.63, 27.37; MS (EI,
HR) m/z: (M+) calcd for C12H15O2N: 205.1103. Found:
205.1096. Anal. calcd for C12H15O2N: C, 70.22; H, 7.37;
N, 6.82. Found: C, 70.06; H, 7.31; N, 6.83%.
4.7. (1R,2R,10bS)-1-Benzoyloxy-2-hydroxy-
1,2,3,5,6,10b-hexahydropyrrolo[2,1-a]isoquinolin-3-one,
4.5. (3R,4R,5S)- and (3R,4R,5R)-1-Phenethyl-3,4,5-tri-
acetoxypyrrolidin-2-one, 12b
16
A vigorously stirred solution of compound 14 (0.646 g,
2 mmol) and pyridine (0.32 g, 0.32 mL, 4 mmol) in
CH2Cl2 (10 mL) was cooled to −30°C. To this solution
triflic anhydride (0.9 g, 0.53 mL, 3.2 mmol) was added
dropwise and the mixture was allowed to reach rt very
slowly (2 h). The mixture was stirred at rt for additional
1 h (TLC monitoring), then water (1.5 mL) was added
and the reaction mixture was left overnight with stirring
at rt. The mixture was poured into water, extracted
with CH2Cl2, extracts washed with water, saturated
solution of NaHCO3, dried over MgSO4 and evapo-
rated under reduced pressure. The residue was purified
by flash column chromatography (hexane:ethyl acetate,
1:4) to give benzoate 16 (0.486 g, 75% yield); foam; IR
(CH2Cl2): 3550, 3063, 2942, 1713 cm−1; [h]D=+239 (c
To a stirred solution of imide 11 (4.7 g, 20 mmol) in
anhydrous methanol (60 mL), the NaBH4 (0.84 g, 22
mmol) was added at −10°C. Stirring was continued at
−10°C for 2 h (TLC control). Subsequently, the satu-
rated solution of NaHCO3 (20 mL) was added, and
mixture was vigorously stirred for 20 min. The precipi-
tate was filtered off and the filtrate was evaporated
under reduced pressure. The oily residue was dissolved
in pyridine (30 mL), DMAP (0.1 g) and Ac2O (15 mL)
were added and left in the refrigerator overnight. The
solution was poured into ice–water mixture (150 mL)
and extracted with ethyl acetate (2×50 mL). The com-
bined extracts were washed with water (3×50 mL),
saturated solution of sodium bicarbonate (50 mL),
dried (MgSO4) and evaporated. The crude product was
purified by flash column chromatography (hexane:
t-BuOMe, 1:3) to give 12b (5.88 g, 81% yield calculated
for two steps); oil; IR (CH2Cl2): 3064, 3031, 2947, 1755,
1736 cm−1. Selected data for the mixture of epimers
5S:5R (1:1); 1H NMR (CDCl3): 5.99 (d, 1H, J=1.9
Hz), 5.69 (d, 1H, J=8.2 Hz), 5.24 (m, 2H), 5.13 (dd,
1H, J=3.8, 1.9 Hz), 3.83 (m, 2H), 3.36 (m, 1H), 3.22
(m, 1H), 2.95 (m, 2H), 2.83 (m, 2H); 13C NMR
1
0.5, CH2Cl2); H NMR (CDCl3+D2O): 6.23 (m, 1H),
5.12 (bd, 1H, J=3.6 Hz), 4.73 (dd, 1H, J=4.5, 1.2 Hz),
4.45 (ddd, 1H, J=12.1, 5.4, 2.3 Hz), 3.09 (ddd, 1H,
J=12.1, 3.0, 1.2 Hz), 3.01 (m, 1H), 2.82 (m, 1H); 13C
NMR (CDCl3): 171.16, 165.57, 134.70, 133.07, 129.60,
129.38, 129.24, 129.13, 128.16, 127.43, 127.00, 125.89,
72.93, 71.98, 57.46, 37.17, 28.74; MS (LSIMS(+), HR)
m/z: (M+Na+) calcd for C19H17O4NNa: 346.1055.
Found: 346.1044.