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24. All new compounds exhibited satisfactory spectroscopic
1
and/or analytical properties. Selected data: Data for 19: H
NMR(400 MHz, DMSO) (3:1 mixture of diastereomers) 7.77
(0.25H, d, J=8.9 Hz), 7.72 (0.75H, d, J=8.9 Hz), 7.58 (1H, d,
J=9.0 Hz), 7.42 (1H, s), 7.03 (1H, s), 6.37–6.22 (1H, m), 4.6–
4.5 (2H, m), 4.23–4.14 (2H, m), 3.72–3.56 (1H, m), 3.2–3.1
(2H, m), 2.03–1.97 (1H, m), 1.67–0.74 (33H, m). HPLC reten-
tion time: 3.737 min (minor peak), 3.867 min (major peak)
65% mobile phase: MeCN–pH 3.0 phosphate buffer (65%/
35%), stationary phase: ACE 3C8-A1645; 1.0 mL/min; 210
1
2. Beher, D.; Wrigley, J. D. J.; Nadin, A.; Evin, G.; Masters,
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18736.
14. A similar approach, but based on the substantially less
1
potent difluoroketone/alcohol isostere motif, has been repor-
nm detection. Data for 18: H NMR(360 MHz, DMSO) 7.82
7
aꢀc
ted by Wolfe and co-workers.
5. Nadin, A.; Sanchez Lopez, J. M.; Neduvelil, J. G.; Thomas,
S. R. Tetrahedron 2001, 57, 1861.
(1H, d, J=8.2 Hz), 7.57 (1H, d, J=9.0 Hz), 7.22 (1H, s), 7.02
(1H, s), 6.32 (1H, d, J=8.0 Hz), 4.83 (1H, d, J=5.2 Hz), 4.48
(1H, d, J=5.1 Hz), 4.15–4.08 (2H, m), 3.75–3.63 (1H, m),
3.44–3.32 (2H, m), 2.41–2.36 (1H, m), 2.12–2.07 (1H, m),
1.73–1.68 (1H, m), 1.6–1.5 (2H, m), 1.37 (9H, s), 1.08 (3H, d,
J=6.2 Hz), 0.96 (3H, d, J=6.4 Hz), 0.87–0.78 (14H, m).
HPLC retention time: 5.087 min (conditions as for 19). Data
1
´
´
1
7
1
6. Kowalski, C. J.; Reddy, R. E. J. Org. Chem. 1992, 57,
194.
7. FG isostere was readily prepared from [1S-(5-oxo-tetra-
hydrofuran-2-yl)-2R-phenylethyl]-carbamic acid, tert-butyl
ester (Litera, J.; Budesinsky, M.; Urban, J.; Soucek, M. Col-
lect. Czech. Chem. Commun. 1998, 63, 231) by the procedure
described in ref 15.
1
for 20: H NMR(400 MHz, DMSO) 7.80 (1H, d), 7.62 (1H,
d), 7.27 (1H, s), 7.01 (1H, s), 6.29 (1H, d), 4.74 (1H, d), 4.49
(1H, d), 4.18–4.07 (2H, m), 3.69–3.58 (1H, m), 3.5–3.35 (2H,
m), 2.41–2.35 (1H, m), 2.04–1.96 (1H, m), 1.77–1.5 (3H, m),
1.37 (9H, m), 1.02–0.80 (20H, m). HPLC retention time: 3.824
min (conditions as for 19).
1
Wolfe and co-workers
8. These observations are similar to those disclosed by
7
b
for a series of substrate-based
difluoroketone isosteres, where it was found that a change