5268
Q. Gu et al. / Tetrahedron 65 (2009) 5265–5270
column chromatography on silica gel (10:1 EA: MeOH, 0.5% Et3N) to
afford the pure desired product.
2H), 1.74 (br, 2H), 1.27–1.23 (m, 4H); 13C NMR (CDCl3, 125 MHz):
172.8, 172.5, 171.9, 171.6, 171.2, 82.5, 71.2, 70.8, 70.4, 64.2, 63.8,
62.1, 57.0, 37.9, 33.8, 26.3, 22.7, 22.5, 22.4, 22.3, 15.8; IR (film, cmꢁ1):
3359, 2934, 2854, 1747, 1547, 1371, 1231, 1055, 800; HRMS (ESI):
d
4.2.1. N-[(1S,2S)-2-Aminocyclohexyl]-N0-(2,3,4,6-tetra-O-acetyl-
D
b
-
n
-glucopyranosyl)-thiourea (1a)8
calcd for C21H34N3O9S [MþH]: 504.2016, found 504.2028.
20
White solid; 47% yield; mp 87–89 ꢀC; [
a]
ꢁ47.6 (c 0.57, CHCl3);
D
1H NMR (CDCl3, 400 MHz):
d
6.10 (br, 1H), 5.49 (br, 1H), 5.36–5.31
4.2.7. N-[(1S,2S)-2-Amino-1,2-diphenylethyl]-N0-(2,3,4,6-tetra-O-
(m, 1H), 5.10–5.03 (m, 2H), 4.31 (d, J¼12.4 Hz, 1H), 4.14–4.11 (m,
2H), 4.86 (d, J¼9.6 Hz, 1H), 2.94 (br, 1H), 2.53 (br, 1H), 2.08 (s, 3H),
2.06 (s, 3H), 2.04 (s, 3H), 2.02 (s, 3H), 2.08–2.02 (m, 2H), 1.92 (br,
2H), 1.74 (br, 2H), 1.28–1.24 (m, 4H).
acetyl-
White solid; 63% yield; mp 178 ꢀC (decomp.); [
CHCl3);. 1H NMR (DMSO-d6, 500 MHz):
8.45 (br, 1H), 8.37 (d,
b-D-glucopyranosyl)-thiourea (1g)
20
a]
ꢁ11.5 (c 1.0,
D
d
J¼8.7 Hz, 1H), 7.35–7.30 (m, 4H), 7.26–7.18 (m, 5H), 7.11 (br, 1H),
5.72 (t, J¼9.2 Hz, 1H), 5.52 (d, J¼2.8 Hz, 1H), 5.30 (t, J¼9.6 Hz,
1H), 4.91 (t, J¼9.6 Hz, 1H), 4.84 (t, J¼9.4 Hz, 1H), 4.29 (d, J¼2.8 Hz,
1H), 4.17–4.14 (m, 1H), 3.91–3.88 (m, 2H), 1.97 (s, 3H), 1.96 (s, 3H),
4.2.2. N-[(1R,2R)-2-Aminocyclohexyl]-N0-(2,3,4,6-tetra-O-acetyl-
b
-
8
D
-glucopyranosyl)-thiourea (1b)
20
White solid; 45% yield; mp 150 ꢀC (decomp.); [
a
]
þ47.0 (c 0.51,
1.94 (s, 3H),1.91 (s, 3H); 13C NMR (DMSO-d6,125 MHz):
d 183.3,17.0,
D
CHCl3); 1H NMR (CDCl3, 500 MHz):
d
6.15 (br, 1H), 5.83 (br, 1H), 5.34
169.5, 169.3, 169.2, 143.0, 141.1, 128.1, 127.7, 127.0, 126.9, 126.8, 81.4,
72.7, 72.0, 70.5, 67.9, 63.0, 61.6, 59.8, 59.4, 20.5, 20.4, 20.3; IR (film,
(t, J¼9.5 Hz, 1H), 5.10–5.03 (m, 2H), 4.33 (dd, J¼4.6, 12.5 Hz, 1H),
4.14–4.10 (m, 2H), 3.87–3.84 (m, 1H), 3.20 (br, 1H), 2.54–2.53 (m,
1H), 2.10 (s, 3H), 2.05 (s, 3H), 2.03 (s, 3H), 2.01 (s, 3H), 2.05–2.01 (m,
2H), 1.92 (m, 2H), 1.73 (br, 2H), 1.28–1.25 (m, 4H).
cmꢁ1):
n 3308, 1748, 1547, 1370, 1233, 1041; HRMS (ESI): calcd for
C29H35N3O9SNa [MþNa]: 624.1992, found 624.2007.
4.2.8. N-[(1R,2R)-2-Amino-1,2-diphenylethyl]-N0-(2,3,4,6-tetra-O-
4.2.3. N-[(1S,2S)-2-Aminocyclohexyl]-N0-(2,3,4,6-tetra-O-acetyl-
b-
acetyl-
White solid; 59% yield; mp 176 ꢀC (decomp.); [
CHCl3); 1H NMR (DMSO-d6, 400 MHz):
(br, 1H), 7.44–7.42 (m, 2H), 7.31–7.18 (m, 8H), 5.77–5.72 (m, 1H),
5.37 (d, J¼2.4 Hz, 1H), 5.29 (t, J¼9.6 Hz, 1H), 4.91 (t, J¼9.6 Hz, 1H),
4.83 (t, J¼9.6 Hz,1H), 4.30 (d, J¼3.6 Hz,1H), 4.18–4.14 (m,1H), 4.05–
3.91 (m, 2H), 1.98 (s, 3H), 1.96 (s, 3H), 1.93 (s, 3H), 1.87 (s, 3H); 13C
b-D-glucopyranosyl)-thiourea (1h)
20
D
-galactosyl)-thiourea (1c)
a
]
D
þ19.7 (c 0.76,
20
White solid; 51% yield; mp 82–84 ꢀC; [
a]
ꢁ13.3 (c 0.75, CHCl3);
d
8.50 (d, J¼9.2 Hz, 1H), 8.49
D
1H NMR (CDCl3, 400 MHz):
d
6.21 (br, 1H), 5.51–5.49 (m, 1H), 5.44
(br, 1H), 5.22–5.14 (m, 2H), 4.19–4.04 (m, 4H), 2.97 (br, 1H), 2.56–
2.51 (m, 1H), 2.14 (s, 3H), 2.06 (s, 3H), 2.04 (s, 3H), 1.99 (s, 3H), 2.06–
1.99 (m, 2H), 1.93–1.88 (m, 2H), 1.74 (br, 2H), 1.32–1.23 (m, 4H); 13C
NMR (CDCl3, 125 MHz):
71.7, 69.2, 67.9, 61.8, 61.0, 58.0, 35.7, 32.9, 25.4, 21.6, 21.4, 21.3, 21.2,
14.8; IR (film, cmꢁ1):
3362, 2936, 2861, 1748, 1548, 1372, 1232,
d
171.8, 171.5, 171.1, 170.8, 170.4, 85.0, 72.9,
NMR (DMSO-d6, 125 MHz):
141.6, 128.0, 127.9, 127.0, 126.9, 126.6, 126.4, 81.7, 72.5, 72.1, 71.0,
67.9, 63.3, 61.6, 59.7, 59.2, 20.5, 20.4, 20.3, 20.2; IR (film, cmꢁ1):
d 183.1, 169.9, 169.4, 169.3, 169.2, 142.9,
n
n
1054; HRMS (ESI): calcd for C21H34N3O9S [MþH]: 504.2016, found
3364, 3119, 3066, 2954, 2865, 1747, 1724, 1576, 1524, 1378, 1232,
1040, 910, 783, 704, 601; HRMS (EI): calcd for C29H35N3O9S [M]:
601.2094, found 601.2094.
504.2020.
4.2.4. N-[(1R,2R)-2-Aminocyclohexyl]-N0-(2,3,4,6-tetra-O-acetyl-
b-
D
-galactosyl)-thiourea (1d)
4.3. General procedure for the Michael reaction of acetone
and b-nitrostyrene
20
White solid; 51% yield; mp 91–93 ꢀC; [
a]
þ65.5 (c 0.58, CHCl3);
D
1H NMR (CDCl3, 400 MHz):
d 6.11 (br, 1H), 5.80 (br, 1H), 5.45 (s, 1H),
5.21–5.19 (m, 2H), 4.19–4.04 (m, 4H), 3.20 (br, 1H), 2.56–2.52 (m,
1H), 2.16 (s, 3H), 2.07 (s, 3H), 2.06 (s, 3H), 1.99 (s, 3H), 2.07–1.99 (m,
2H), 1.95–1.91 (m, 2H), 1.74 (br, 2H), 1.28–1.18 (m, 4H); 13C NMR
To a solution of N-[(1R,2R)-2-aminocyclohexyl]-N0-(2,3,4,6-tetra-
O-acetyl- -glucopyranosyl)- thiourea (1b) (6.3 mg, 0.0125 mmol)
in CH2Cl2 [2 mL, containing 0.0125 mmol AcOH] was added acetone
(0.076 mL, 1.25 mmol), -nitrostyrene (0.25 mmol). After the re-
action mixture was stirred at room temperature for the appropriate
time (monitored by TLC), the solvent was removed and the residue
was purified by column chromatography on silica gel to afford the
pure desired product. The enantiomeric excesses were determined
by HPLC using chiralpak AD-H or AS-H column. The absolute con-
figuration was determined by comparing of optical rotation values
with those reported in the literatures.
b-D
(CDCl3, 125 MHz):
70.4, 69.0, 62.9, 62.1, 57.4, 36.5, 33.8, 26.3, 22.6, 22.4, 22.4, 22.2,
15.9; IR (film, cmꢁ1):
3442, 2937, 1749, 1546, 1371, 1232, 1055;
d
172.8, 172.6, 172.1, 171.8, 171.4, 85.5, 74.1, 73.0,
b
n
HRMS (ESI): calcd for C21H34N3O9S [MþH]: 504.2016, found
504.2031.
4.2.5. N-[(1S,2S)-2-Aminocyclohexyl]-N0-(2,3,4,6-tetra-O-acetyl-
a-
D
-mannopyranosyl)-thiourea (1e)
20
White solid; 64% yield; mp 84–85 ꢀC; [
a
]
D
ꢁ5.0 (c 1.0, CHCl3). 1H
NMR (CDCl3, 500 MHz):
d
7.02 (br, 1H), 6.13–6.02 (m, 1H), 5.29–5.24
4.3.1. (4S)-5-Nitro-4-(4-nitrophenyl)-pentan-2-one (3a)10
20
(m, 3H), 4.40–4.22 (m,1H), 4.20–4.01 (m, 2H), 3.95 (br,1H), 3.20 (br,
1H), 2.61 (br, 1H), 2.17 (s, 3H), 2.11 (s, 3H), 2.07(s, 3H), 2.01(s, 3H),
2.11–2.01 (m, 4H), 1.71 (br, 2H), 1.29–1.25 (m, 4H); 13C NMR (CDCl3,
Yield 94%; [
a]
þ9.8 (c 0.56, CHCl3); 90% ee, Chiralpak AD-H,
D
hexane/i-PrOH¼80/20, UV 254 nm, flow rate 1.0 mL/min,
tR¼20.8 min (major), tR¼29.2 min (minor). 1H NMR (CDCl3,
125 MHz):
63.7, 63.0, 61.1, 56.9, 35.7, 33.0, 25.3, 21.7, 21.5, 21.4, 21.3, 14.8; IR
(film, cmꢁ1):
3357, 2935, 1748, 1548, 1371, 1231, 1055, 800; HRMS
(ESI): calcd for C21H34N3O9S [MþH]: 504.2016, found 504.2025.
d
186.5, 171.5, 171.2, 170.6, 170.1, 82.3, 70.5, 69.6, 66.7,
500 MHz):
d
8.22–8.20 (m, 2H), 7.44–7.42 (m, 2H), 4.75 (dd, J¼6.3,
12.8 Hz, 1H), 4.65 (dd, J¼8.2, 12.8 Hz, 1H), 4.17–4.12 (m, 1H), 2.96
n
(dd, J¼6.8, 5.7 Hz, 2H), 2.16 (s, 3H).
4.3.2. (4S)-5-Nitro-4-(2-nitrophenyl)-pentan-2-one (3b)
20
4.2.6. N-[(1R,2R)-2-Aminocyclohexyl]-N0-(2,3,4,6-tetra-O-acetyl-
a-
Yield 92%; [
a
]
ꢁ31.0 (c 0.39, CHCl3); 92% ee, Chiralpak AD-H,
D
D
-mannopyranosyl)-thiourea (1f)
hexane/i-PrOH¼85/15, UV 254 nm, flow rate 1.0 mL/min,
20
White solid; 68% yield; mp 82–83 ꢀC; [
a
]
þ42.5 (c 1.0, CHCl3);
tR¼25.5 min (major), tR¼27.9 min (minor). 1H NMR (CDCl3,
D
1H NMR (CDCl3, 500 MHz):
d
7.32 (br, 1H), 6.23–5.70 (m, 1H), 5.31–
500 MHz): d 7.91–7.89 (m, 1H), 7.61–7.57 (m, 1H), 7.47–7.43 (m, 1H),
5.27 (m, 3H), 4.33–4.29 (m, 1H), 4.19 (d, J¼11.0 Hz, 1H), 4.13–4.01
(m, 1H), 3.94–3.79 (m, 1H), 3.14 (br, 1H), 2.59 (br, 2H), 2.30–2.20 (m
1H), 2.16 (s, 3H), 2.09 (s, 3H), 2.04 (s, 3H), 2.02 (s, 3H), 2.09–2.02 (m,
7.39–7.37 (m, 1H), 4.88–4.81 (m, 2H), 4.54–4.50 (m, 1H), 3. 06–3.04
(m, 2H), 2.17(s, 3H); 13C NMR (CDCl3, 125 MHz,):
205.5, 150.5,
134.2, 133.9, 129.3,129.1, 125.7, 78.5, 45.9, 34.4, 30.6; IR (film, cmꢁ1):
d