S. A. Popo6 et al. / Tetrahedron: Asymmetry 14 (2003) 233–238
237
4.5.1. Data for (1S,5R)-2-{(E)-1-[(1R)-6-hydroxy-7-
methoxy - 1 - methyl - 3,4 - dihydro - 1H - isoquinolin - 2-
as pale yellow crystals with mp 169–172°C (lit. 171–
22
578
172°C) and [h]
+42.1 (c 3.1, H2O) (lit. [h]D +40.1).
yl]ethylidene}-6,6-dimethylbicyclo[3.1.0]hexan-3-one, 5a.
Diastereomer 5b (100 mg, 0.62 mmol) was worked up
22
578
Mp 163–165°C (MeO-t-Bu, dec.), [h]
−934 (c 0.57,
as described above for diastereomer 5a to give (−)-sal-
CHCl3). MS (m/z, %): 341.1991 (M+, 100%,
C21H27NO3 requires 341.1991), 326 (81), 313 (15), 298
(44), 286 (19), 272 (5), 256 (4), 244 (16), 230 (12), 218
(3), 192 (61), 178 (35), 150 (11), 145 (21), 121 (8), 117
(13), 105 (8), 91 (16), 77 (11), 67 (3), 55 (7), 41 (8). IR
(CHCl3) w/cm−1: 3545, 1635, 1515, 1465, 1420, 1377,
1332, 1278, 1248, 1211, 1157, 1129, 1050, 1015, 943,
877, 828. UV (EtOH) umax/nm: 288 (m 3100), 352 (m
18700). 1H NMR (CDCl3): 2.55 (s, 3H-1), 2.12 (d,
J=18.9, 1H-5a), 2.51 (dd, J=18.9, 7.6, 1H-5b), 1.13
(dd, J=7.8, 7.6, 1H-6), 1.85 (d, J=7.8, 1H-7), 1.17 (s,
3H-9), 0.86 (s, 3H-10), 5.07 (q, J=6.7, 1H-11), 4.04
(dd, J=14.3, 5.5, 1H-12a), 3.40 (ddd, J=14.3, 13.4,
3.9, 1H-12b), 2.94 (ddd, J=15.7, 13.4, 5.5, H-13a),
2.64 (dd, J=15.7, 3.9, 1H-13b), 6.63 (s, 1H-15), 6.42
(s, 1H-18), 1.55 (d, J=6.7, 3H-20), 3.83 (s, 3H-21), 6.0
soline hydrochloride (50 mg) as pale yellow crystals
25
578
with mp 168–170°C and [h] −41.9 (c 2.9, H2O).
4.7. (1S,5R)-2-{(Z)-1-[(1R,2R)-2-Hydroxy-1-hydroxy-
methyl-2-(4-nitrophenyl)ethylamino]ethylidene}-6,6-
dimethylbicyclo[3.1.0]hexan-3-one, 6a and (1S,5R)-2-
{(Z)-1-[(1S,2S)-2-hydroxy-1-hydroxymethyl-2-
(4-nitrophenyl)ethylamino]ethylidene}-6,6-dimethyl-
bicyclo[3.1.0]hexan-3-one, 6b
The crude mixture of diastereomers 6a and 6b (ca.
1:1 according to NMR data) was prepared in 81%
yield as a yellow gum from ( )-2-amino-1-(4-nitro-
phenyl)propane-1,3-diol and chlorovinylketone 2.
(br. W1/2=300 Hz, ArꢀOH6
). 13C NMR (CDCl3): 15.26
(C-1), 160.07 (C-2), 106.53 (C-3), 205.68 (C-4), 39.07
(C-5), 20.65 (C-6), 35.21 (C-7), 21.51 (C-8), 26.82 (C-
9), 14.50 (C-10), 53.35 (C-11), 39.61 (C-12), 28.98 (C-
13), 130.08 (C-14), 114.41 (C-15), 144.53 (C-16 or
C-17), 145.35 (C-17 or C-16), 108.73 (C-18), 125.38
(C-19), 23.24 (C-20), 55.91 (C-21).
4.7.1. (1S,5R)-2-{(Z)-1-[(1R,2R)-2-Hydroxy-1-hydroxy-
methyl - 2 - (4 - nitrophenyl)ethylamino]ethylidene} - 6,6-
dimethylbicyclo[3.1.0]hexan-3-one, 6a. The mixture of
diastereomers 6a,b (1.46 g, 4.1 mmol) was crystallized
from MeCN (5 ml) to give pure diastereomer 6a
(0.45 g, 63%) as yellow crystals. Reaction of 2 with
(1R,2R)-2-amino-1-(4-nitrophenyl)propane-1,3-diol
afforded 6a in 78% yield. Mp 177–183°C (MeCN,
4.5.2. Data for (1S,5R)-2-[(E)-1-((1S)-6-hydroxy-7-
methoxy - 1 - methyl - 3,4 - dihydro - 1H - isoquinolin - 2-
19
dec.). [h]
+642 (c 0.33, CHCl3). MS (m/z, %):
578
360.1701 (M+, 8%, C19H24N2O5 requires 360.1685), 345
(2), 208 (100), 165 (6), 148 (9), 121 (4), 91 (7), 84 (46),
60 (6), 42 (8). IR (KBr) w/cm−1: 3346, 3151, 1619,
1578, 1516, 1486, 1456, 1383, 1349, 13232, 1308, 1264,
1225, 1199, 1168, 1105, 1085, 1043, 1014, 969, 927,
880, 865, 814. UV (EtOH) umax/nm: 204 (m 15300), 273
yl)ethylidene]-6,6-dimethylbicyclo[3.1.0]hexan-3-one, 5b.
22
578
Mp 158–165°C (MeO-t-Bu, dec.), [h]
−725 (c 0.26,
CHCl3). MS, IR and UV spectra of the compound are
identical to those of diastereomer 5a. 1H NMR
(CDCl3): 2.47 (s, 3H-1), 2.14 (d, J=18.9, 1H-5a), 2.51
(dd, J=18.9, 7.4, 1H-5b), 1.11 (dd, J=7.8, 7.4, 1H-6),
1.61 (d, J=7.8, 1H-7), 1.14 (s, 3H-9), 0.94 (s, 3H-10),
5.29 (q, J=6.5, 1H-11), 3.98 (dd, J=12.6, 5.5, 1H-
12a), 3.43 (ddd, J=12.6, 12.6, 3.7, 1H-12b), 2.77 (ddd,
J=15.7, 12.6, 5.5, H-13a), 2.60 (dm, J=15.7, W1/2=8
Hz, 1H-13b), 6.62 (s, 1H-15), 6.48 (s, 1H-18), 1.39 (d,
J=6.7, 3H-20), 3.83 (s, 3H-21), 5.7 (br. W1/2=340 Hz,
1
(m 9600), 346 (m 15000). H NMR (DMSO-d6–CDCl3):
1.60 (s, 3H-1), 0.99 (s, 3H-9), 1.96 (d, J=18.5, 1H-5a),
2.41 (dd, J=18.5, 7.7, 1H-5b), 0.94 (dd, J=7.9, 7.7,
1H-6), 1.47 (d, J=7.9, 1H-7), 0.94 (s, 3H-9), 0.66 (s,
3H-10), 3.57 (m, W1/2=22 Hz, H-11), 3.61 (m, W1/2
=
32 Hz, H-12a), 3.42 (ddd, J=10.0, 4.8, 4.4, H-12b),
5.02 (dd, J=2.4, 2.4, H-13), 7.52 (d, J=8.7, 2H-15),
ArꢀOH6
). 13C NMR (CDCl3): 15.98 (C-1), 158.83 (C-
2), 110.62 (C-3), 206.45 (C-4), 39.07 (C-5), 21.25 (C-6),
35.60 (C-7), 21.81 (C-8), 26.54 (C-9), 14.48 (C-10),
52.56 (C-11), 40.30 (C-12), 28.99 (C-13), 129.76 (C-14),
114.27 (C-15), 144.37 (C-16 or C-17), 145.29 (C-17 or
C-16), 108.71 (C-18), 126.37 (C-19), 22.62 (C-20),
55.90 (C-21).
8.06 (d, J=8.7, 2H-16), 10.13 (d, J=9.7, NH
6
), 4.47
(dd, J=4.4, 4.4, CH2ꢀOH
6
), 5.61 (d, J=2.4, CHꢀOH).
6
13C NMR (DMSO-d6–CDCl3): 15.78 (C-1), 157.46 (C-
2), 103.83 (C-3), 201.47 (C-4), 37.57 (C-5), 20.28 (C-6),
30.26 (C-7), 20.89 (C-8), 25.87 (C-9), 13.69 (C-10),
59.90 (C-11), 61.71 (C-12), 69.85 (C-13), 150.91 (C-14),
126.73 (2C-15), 122.43 (2C-16), 146.26 (C-17).
4.6. Salsoline recovery
Acknowledgements
To an ice-cooled solution of diastereomer 5a (200 mg,
0.59 mmol) in MeOH (5 ml) a solution of concen-
trated aqueous HCl in MeOH (ca. 15% w/w, 5 ml)
was added. The mixture was left at room temperature
for 14 h and concentrated under reduced pressure at
the bath temperature 40°C. The residue was stirred
with MeO-t-Bu (5 ml), the crystals were filtered,
washed with MeO-t-Bu (2×2 ml) and dried in vacuum
to afford 123 mg (92%) of (+)-salsoline hydrochloride
The authors thank the Russian Foundation for Basic
Research (Grant No. 01-03-32369) and INTAS (Grant
No. 97-0217) for the financial support of this work.
The samples of natural alkaloids salsoline (D/L ca.
2:1), cytisine and anabasine were provided by Inter-
BioScreen Ltd. (Moscow).