972
H. Azami et al. / Bioorg. Med. Chem. 9 (2001) 961±982
Table 8. Physical data for benzoylthio compoundsa
No.
1H NMR (200 MHz, D2O) d ppm
MS
386
IR
17a
1.82±2.02 (1H, m), 2.41 ꢃ2.72 (1H, m), 2.70±2.98 (1H, m), 3.20±3.67 (2H, m), 3.67 (3H, brs), 3.92±4.30 (3H, m),
NT
4.49±4.73 (2H, m), 5.15±5.42 (2H, m), 5.82±6.16 (1H, m), 6.82 (1H, s), 7.30±7.70 (4H, m), 7.80±8.22 (2H, m)
17b
17c
17d
2.10±2.39 (1H, m), 2.43±2.73 (1H, m), 2.92 (1H, dd, J=15.6 Hz, 10.1 Hz), 3.32 (1H, dd, J=10.8 Hz, 6.3 Hz),
3.36±3.70 (1H, m), 3.68 (3H, s), 4.03±4.38 (3H, m), 4.57±4.71 (2H, m), 5.21±5.37 (2H, m), 5.86±5.97 (1H, m),
6.81 (1H, d, J=1.2 Hz), 6.93 (1H, d, J=1.2 Hz), 7.40±7.69 (5H, m)
386
386
386
NT
1.74±1.88 (1H, m), 2.40±2.60 (1H, m), 2.79 (1H, dd, J=14.2 Hz, 8.9 Hz), 2.90±3.15 (1H, m), 3.19 (1H, dd,
J=10.8 Hz, 7.3 Hz), 3.86 (3H, s), 3.95±4.25 (3H, m), 4.58±4.74 (2H, m), 5.19±5.42 (2H, m), 5.87±6.08 (1H, m),
7.17 (1H, s), 7.31 (1H, s), 7.37±7.74 (3H, m), 7.88±7.98 (2H, m)
1680,
1655,
1400
1.80±2.00 (1H, m), 2.42±2.68 (1H, m), 2.75±3.00 (1H, m), 3.20±3.55 (2H, m), 3.75±3.98 (3H, brs),
4.00±4.30 (3H, m), 4.52±4.70 (2H, m), 5.18±5.40 (2H, m), 5.86±6.06 (1H, m), 6.04 (1H, d, J=1.8 Hz),
7.40 (1H, d, J=1.8 Hz), 7.30±8.20 (5H, m)
1680,
1650,
1390
17e
17f
17g
1.73±1.93 (1H, m), 2.48±2.70 (1H, m), 2.99 (1H, dd, J=14.7 Hz, 9.7 Hz), 3.20±3.55 (2H, m), 3.85±4.30 (6H, m),
4.55±4.70 (2H, m), 5.18±5.40 (2H, m), 5.85±6.05 (1H, m), 7.35±8.18 (6H, m)
387
387
NT
1701,
1664
2.10±2.32 (1H, m), 2.52±2.95 (1H, m), 3.08 (1H, dd, J=14.5 Hz, 9.5 Hz), 3.25±3.60 (2H, m), 3.90 (3H, brs),
4.05±4.40 (3H, m), 4.61±4.64 (2H, m), 5.22±5.36 (2H, m), 5.85±6.05 (1H, m), 7.80 (1H, s), 7.40±8.30 (5H, m)
NT
1.67±2.13 (2H, m), 2.30±2.60 (1H, m), 2.98 (1H, dd, J=13.2 Hz, 9.3 Hz), 3.15±3.35 (1H, m), 3.40±3.65 (1H, m),
4.00±4.40 (2H, m), 4.61±4.64 (2H, m), 5.20±6.03 (2H, m), 5.89±6.12 (1H, m), 7.10±7.20 (2H, m),
7.40±7.65 (4H, m), 7.90±7.95 (2H, m), 8.53±8.55 (1H, m)
1685,
1650
17h
17i
1.70±1.90 (2H, m), 2.20±2.60 (1H, m), 2.84 (1H, dd, J=13.3 Hz, 9.4 Hz), 3.20±3.40 (2H, m), 4.03±4.26 (2H, m),
4.63±4.66 (2H, m), 5.23±5.39 (2H, m), 5.88±6.07 (1H, m), 7.20±7.73 (6H, m), 7.91±7.94 (2H, m), 8.47±5.50 (4H, m)
NT
NT
NT
NT
1.65±1.85 (1H, m), 2.30±2.65 (1H, m), 2.80 (1H, dd, J=13.1 Hz, 9.6 Hz), 3.20±3.60 (2H, m), 3.90±4.35 (3H, m),
4.62±4.66 (2H, m), 5.23±5.39 (2H, m), 5.87±6.07 (1H, m), 7.14±7.73 (5H, m), 7.90±7.95 (2H, m),
8.47±8.53 (2H, m)
21
23
1.60±2.70 (3H, m), 2.90±3.55 (3H, m), 3.75±4.70 (10H, m), 5.20±5.45 (2H, m), 5.85±6.05 (1H, m),
7.35±8.10 (6H, m)
416
416
NT
NT
1.84±1.96 (1H, m), 2.50±2.63 (1H, m), 2.73 (1H, dd, J=14.2 Hz, 9.0 Hz), 3.00±3.10 (1H, m), 3.20±3.60 (2H, m),
3.90 (3H, s), 4.00±4.21 (2H, m), 4.58±4.69 (4H, m), 5.21±5.35 (2H, m), 5.85±6.15 (1H, m), 7.27 (1H, s),
7.40±8.01 (5H, m)
17j
1.70±2.00 (2H, m), 2.15 (3H, s), 2.30±2.65 (1H, m), 2.70±2.90 (1H, m), 3.20±3.60 (2H, m), 4.00±4.40 (2H, m),
4.55±4.75 (2H, m), 5.15±5.20 (2H, s), 5.85±6.15 (1H, m), 7.00±7.30 (2H, m), 7.40±8.00 (5H, m),
8.50 (1H, d, J=5.0 Hz)
NT
1747,
1701,
1662
17k
19
1.65±2.10 (2H, m), 2.35±2.65 (1H, m), 2.87 (1H, dd, J=13.1 Hz, 9.5 Hz), 3.20±3.80 (2H, m), 3.85±4.50 (2H, m),
4.62±4.66 (2H, m), 5.23±5.39 (2H, m), 5.75±6.15 (2H, m), 7.27±8.20 (5H, m), 8.08 (1H, s), 8.48 (1H, d, J=4.9 Hz)
426
NT
1693
1.85±2.05 (1H, m), 2.40±2.65 (1H, m), 2.69±2.90 (1H, m), 3.10±4.00 (3H, m), 3.70 (3H, brs), 4.00±4.30 (3H, m),
4.60±4.75 (4H, m), 5.22±5.37 (2H, m), 5.86±6.05 (1H, m), 6.68 (1H, s), 7.43±7.64 (3H, m), 7.91±7.95 (2H, m)
NT
aMS, APCI (NH+), m/z; IR, IR (neat), cmÀ1
.
(RS)-[(2S,4R)-1-Benzyl-4-tert-butyldimethylsilyloxypyrro-
lidin-2-yl]-(1-methylimidazol-2-yl)methanol (4b). The iso-
mer A of 4b was isolated by precipitation with hexane
from crude oil (48 g, 14.7%). The ®ltrate was evapor-
ated and puri®ed with column chromatography (SiO2
5200 mL, EtOAc/hexane (3:2±1:0)) to give the isomer B
of 4b (147.4 g, 45%) containing 17% of isomer A, as a
(RS)-[(2S,4R)-1-Benzyl-4-tert-butyldimethylsilyloxypyrro-
lidin-2-yl]-(1-methylpyrazol-4-yl)methanol (4c). Oil (65%
as a mixture of diastereoisomers): H NMR (CDCl3) d
1
0.01 (s) and 0.02 (s) and 0.04 (s) total 6H, 0.85 (s) and
0.89 (s) total 9H, 1.46±1.62 (m) and 1.80±2.13 (m) total
2H, 2.41 (dd, J=9.7 Hz, 5.6 Hz) and 2.52 (dd,
J=10.2 Hz, 3.5 Hz) total 1H, 3.00 (dd, J=11.0 Hz,
4.7 Hz) and 3.12±3.25 (m) and 3.27±3.38 (m) total 2H,
3.54 (d, J=13.0 Hz) and 3.72 (d, J=13.1 Hz) and 3.91
(d, J=13.1 Hz) and 4.11 (d, J=13.0 Hz) total 2H, 3.88 (s)
and 3.95 (s) total 3H, 4.15±4.35 (1H, m), 4.41 (d, J=5.4 Hz)
and 4.85 (d, J=2.7 Hz) total 1H, 7.23±7.40 (6H, m), 7.41 (s)
and 7.45 (s) total 1H; MS (APCI+) 402 (MH+).
1
solid. Isomer B: brown oil; H NMR (CDCl3) d 0.00
(6H, s), 0.86 (9H, s), 1.84±2.04 (2H, m), 2.57 (1H, dd,
J=11.1 Hz, 3.3 Hz), 2.97 (1H, dd, J=11.1 Hz, 4.7 Hz),
3.66 (3H, s), 3.80 (1H, d, J=13.0 Hz), 3.81±3.91 (1H,
m), 4.10 (1H, d, J=13.0 Hz), 4.18±4.25 (1H, m), 4.41
(1H, d, J=5.6 Hz), 6.79 (1H, d, J=1.2 Hz), 6.93 (1H, d,
J=1.2 Hz), 7.20±7.30 (5H, m); MS (APCI+) 402
(MH+). Isomer A: amorphous solid; 1H NMR (CDCl3)
d 0.02 (6H, s), 0.85 (9H, s), 1.89±2.03 (1H, m), 2.17±2.31
(1H, m), 2.42 (1H, dd, J=9.6 Hz, 6.3 Hz), 3.13 (1H, dd,
J=9.6 Hz, 5.4 Hz), 3.44±3.51 (2H, m), 3.57 (1H, d,
J=13.1 Hz), 3.67 (3H, s), 3.88 (1H, d, J=13.1 Hz),
4.22±4.34 (1H, m), 4.70 (1H, d, J=3.6 Hz), 6.79 (1H, d,
J=1.2 Hz), 6.96 (1H, d, J=1.2 Hz), 7.22±7.37 (5H, m);
MS (APCI+) 402 (MH+).
(RS)-[(2S,4R)-1-Benzyl-4-tert-butyldimethylsilyloxypyrro-
lidin-2-yl]-(1-methyl-1,2,4-triazol-5-yl)methanol (4f). Oil
1
(75% as 1.6:1 mixture of diastereoisomers): H NMR
(CDCl3) d 0.00±0.04 (6H, m), 0.85±0.88 (9H, m), 1.70±2.20
(2H, m), 2.49 (dd, J=9.9 Hz, 5.6 Hz) and 2.63 (dd,
J=11.3 Hz, 3.8 Hz) total 1H, 3.02 (dd, J=11.3 Hz,
4.6 Hz) and 3.17 (dd, J=9.9 Hz, 5.2 Hz) total 1H, 3.40±
4.01 (6H, m), 4.20±4.35 (1H, m), 4.53 (d, J=4.7 Hz) and