A. Kamal et al. / Tetrahedron Letters 44 (2003) 4783–4787
4787
1
3
5
6
7
. Wong, D. T.; Threlkeld, P. G.; Best, L. L.; Bymaster, F.
P. J. Pharmacol. Exp. Ther. 1982, 222, 61.
. Wong, D. T.; Bymaster, F. P.; Horng, J. S.; Molloy, B.
B. J. Pharmacol. Exp. Ther. 1975, 193, 804.
. (a) Fuller, R. W.; Hemrick-Luecke, S. K.; Snoddy, H. D.
J. Pharmacol. Exp. Ther. 1994, 269, 132; (b) Wong, D. T.
Eur. Pat. Appl. EP 759,299.
J=4.9 Hz); C NMR (75 MHz, CDCl ) l 28.1, 66.0,
3
+
117.0, 124.6, 125.6, 127.0, 144.4; mass (EI) 153 (M ), 127,
113, 85. 5: IR (neat) 3114, 2910, 2800, 2243, 1734, 1216
cm ; H NMR (200 MHz, CDCl ) l 2.10 (s, 3H), 2.94
(d, 2H, J=6.7 Hz), 6.20 (t, 1H, J=6.7 Hz), 6.97 (t, 1H,
J=3.8 Hz), 7.10 (d, 1H, J=3.0 Hz), 7.30 (d, 1H, J=5.9
Hz); mass (EI) 195 (M ), 154, 137, 114, 85, 43. 6: IR
neat) 3325, 3294, 2934, 2886, 2839, 1678, 1255, 1129,
066, 1012 cm ; H NMR (200 MHz, CDCl ) l 1.24 (t,
H, J=7.3 Hz), 1.88–2.02 (m, 2H), 3.13–3.32 (m, 1H),
.40–3.60 (m, 1H), 4.09 (q, 2H, J=7.32 Hz), 4.89–5.05
m, 1H), 6.85–6.96 (m, 2H), 7.13–7.20 (m, 1H); C NMR
75 MHz, CDCl ) l 14.5, 37.7, 39.2, 61.0, 67.7, 123.3,
24.3, 126.6, 148.1, 157.4; mass (EI) 229 (M ), 183, 166,
40, 113, 85. 7: IR (neat) 3325, 3196, 2949, 2910, 1553,
396, 1051 cm ; H NMR (200 MHz, CDCl ) l 2.15–
.18 (m, 2H), 2.55 (s, 3H), 3.04–3.09 (m, 2H), 5.16 (t, 1H,
J=5.95 Hz), 6.93–6.95 (m, 2H), 7.20 (dd, 1H, J=2.3 Hz,
−
1 1
3
+
8
9
. Pitsikas, N. Curr. Opin. Invest. Drug (PharmaPress Ltd.)
(
−
1 1
2
000, 116.
. Horrobin, D. R.; Lodu, C. PCT Int. Appl. WO 01
6,623.
1
3
3
3
2
1
1
0. Iyengar, S.; Muhlhauser, M. A.; Thor, K. B. PCT Int.
Appl. WO 97 33,880.
1. Heilegenstrin, J. H.; Tollenson, G. G.; Wong, D. T. PCT
Int. Appl. WO 96 12, 485.
2. James, S. P. U. S. US Pat. 5,776,969.
3. Michelson, D.; Tollefson, G. D. PCT Int. Appl. WO 99
9,593.
4. Wheeler, W. J.; Kuo, F. J. Label Compd Radiopharm.
995, 36, 213.
5. Berglund, R. A. EP 0650965, US 5362886, JP 1995
88065.
6. (a) Kamal, A.; Khanna, G. B. R.; Ramu, R. Tetrahedron:
Asymmetry 2002, 13, 2039; (b) Kamal, A.; Khanna, G. B.
R. Tetrahedron: Asymmetry 2001, 12, 405; (c) Kamal, A.;
Sandbhor, M.; Ramana, K. V. Tetrahedron: Asymmetry
13
(
(
3
+
1
1
1
2
1
1
−1 1
3
5
1
1
1
+
J=4.5 Hz); mass (EI) 171 (M ), 128, 110, 85, 44. R-8: mp
0–83°C H NMR (200 MHz, CDCl ) l 1.47 (s, 9H),
.78–2.12 (m, 2H), 2.88 (s, 3H), 3.02–3.10 (m, 1H),
.85–3.89 (m, 1H), 4.79–4.83 (br d, 1H, J=7.3 Hz),
.90–6.92 (m, 2H), 7.18–7.26 (m, 1H); C NMR (50
1
1
8
1
3
6
3
1
13
MHz, CDCl ) l 28.4, 34.4, 37.1, 45.2, 66.6, 80.1, 123.0,
3
1
1
24.1, 126.5, 148.2. S-9: H NMR (300 MHz, CDCl ) l
.33 (s, 9H), 2.25–2.34 (m, 1H), 2.40–2.45 (m, 1H), 2.85
s, 3H), 3.42–3.53 (m, 2H), 5.63–5.65 (m, 1H), 6.76 (d,
H, J=7.5 Hz), 6.90 (dd, 1H, J=3.4, J=5 Hz), 7.03–7.04
m, 1H), 7.17–7.19 (m, 1H), 7.23 (d, 1H, J= 8.3 Hz), 7.35
d, 1H, J=8.2 Hz), 7.42–7.47 (m, 2H), 7.73 (dd, 1H,
J=3.1, J=6.2 Hz), 8.30 (dd, 1H, J=3.4, J=6.3 Hz);
NMR (50 MHz, CDCl ) l 28.4, 34.7, 37.3, 45.8, 74.0,
9.5, 106.9, 120.7, 122.0, 124.7, 125.2, 125.6, 126.3, 126.4,
26.6, 127.5, 128.8, 134.6, 144.8, 153.2, 155.7. S-10: IR
neat) 3404, 3059, 2965, 2925, 2855, 2785, 1567, 1396,
263, 1247, 1082 cm ; H NMR (300 MHz, CDCl ) l
.18–2.42 (m, 1H), 2.52 (s, 3H), 2.57–2.59 (m, 1H), 3.02
t, 2H, J=7.0 Hz) 5.81 (m, 1H), 6.83 (d, 1H, J=7.5 Hz),
.88–6.91 (m, 1H), 7.05 (d, 1H, J=3 Hz), 7.18 (d, 1H,
J=4.9 Hz), 7.22–7.27 (m, 1H), 7.37–7.40 (m, 1H), 7.46–
.49 (m, 2H), 7.75–7.78 (m, 1H), 8.27–8.31 (m, 1H).
3
1
(
1
(
2
002, 13, 815; (d) Kamal, A.; Sandbhor, M. Bioorg. Med.
Chem. Lett. 2002, 12, 1735; (e) Kamal, A.; Damayanthi,
Y.; Reddy, B. S. N.; Laxminarayana, B.; Reddy, B. S. P.
Chem. Commun. 1997, 1015; (f) Kamal, A.; Khanna, G.
B. R.; Ramu, R.; Rao, M. V. US Patent Appl. No.
(
13
C
1
0/393,406.
3
1
7. (a) Thiophene was slowly added to an equimolar solution
of AlCl3 and chloroacetyl chloride in CS2 at 0°C and
allowed to warm to room temperature over a period of
7
1
(
1
2
1
2 h; (b) NaBH in methanol at room temperature for 30
4
−
1 1
min gave the corresponding alcohol; (c) 2 equiv. of
NaCN was added to a solution of chlorohydrin in
3
(
6
MeOH/H O (3:1) at room temperature and stirred for 4
2
h.
−
1 1
1
8. 4: IR (neat) 3475, 3075, 2878, 2251, 1105, 698 cm ; H
7
NMR (400 MHz, CDCl ) l 2.82 (dd, 2H, J=3.0 Hz,
3
J=6.6 Hz), 3.00 (s, 1H), 5.25 (t, 1H, J=5.5 Hz), 6.98 (t,
19. Brown, H. C.; Choi, Y. M.; Narasimhan, S. J. Org.
Chem. 1982, 47, 3153.
1
H, J=4.9 Hz), 7.05 (d, 1H, J=3.7 Hz), 7.28 (d, 1H,