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(m, 1H), 1.47 (d, J ¼ 7:2 Hz, 3H), 1.44 (s, 18H), 1.13 (s,
4.7. Preparation of compounds 11a–f
9H).
To compound 10a–f (0.1 mmol) dissolved in 4 mL
CH2Cl2 at about 0 °C was added TFA (2 mL), then the
mixture was stirred overnight with gradual warming to
room temperature. The solvents were removed under
vacuum. The residue was dissolved in water (5 mL) and
lyophilized to give 11a–f as a white solid.
4.6.2. (2S)-3-tert-Butoxy-2-{2-[(2S)-2-tert-butoxycarbon-
ylamino-4-methylsulfanyl-butyrylsulfanyl]-acetylamino}-
1
propionic acid tert-butyl ester (10b). Yield 76%.
H
NMR (CDCl3, 300 MHz): d 6.86 (d, J ¼ 8:1 Hz, 1H),
5.32 (d, J ¼ 8:7 Hz, 1H), 4.48 (m, 2H), 3.72 (dd of ABX
system, J ¼ 9:0, 3.0 Hz, 1H), 3.66, 3.50 (dd of AB sys-
tem, J ¼ 15:0 Hz, 2H), 3.47 (dd of ABX system, J ¼ 9:0,
3.0 Hz, 1H), 2.60 (m, 2H), 2.16 (m, 1H), 2.06 (s, 3H),
1.94 (m, 1H), 1.42 (s, 18H), 1.11 (s, 9H).
4.7.1. (2S)-2-{(2S)-2-[(2S)-2-Amino-4-methylsulfanyl-
butyrylsulfanyl]-propionylamino}-3-hydroxy-propionic acid
1
(11a). Yield 100%. H NMR (D2O, 300 MHz): d 4.47
(m, 2H), 4.38 (m, 1H), 3.93 (dd of ABX system,
J ¼ 11:7, 4.5 Hz, 1H), 3.82 (dd of ABX system,
J ¼ 11:7, 3.9 Hz, 1H), 2.59 (t, J ¼ 7:2 Hz, 2H), 2.20 (m,
2H), 2.06 (s, 3H), 1.48 (d, J ¼ 7:2 Hz, 3H).
4.6.3. (2S)-3-tert-Butoxy-2-{(2S)-2-[(2S)-2-tert-butoxy-
carbonylamino-4-methylsulfanyl-butyrylsulfanyl]-3-phenyl-
propionylamino}-propionic acid tert-butyl ester (10c).
1
Yield 99%. H NMR (CDCl3, 300 MHz): d 7.32–7.17
(m, 5H), 6.73 (d, J ¼ 7:8 Hz, 1H), 5.04 (d, J ¼ 9:3 Hz,
1H), 4.48 (m, 2H), 4.26 (m, 1H), 3.71 (dd of ABX sys-
tem, J ¼ 9:0, 2.7 Hz, 1H), 3.45 (dd of ABX system,
J ¼ 9:0, 3.0 Hz, 1H), 3.37 (dd of ABX system, J ¼ 14:1,
6.9 Hz, 1H), 2.98 (dd of ABX system, J ¼ 14:1, 8.4 Hz,
1H), 2.41 (m, 2H), 2.04 (s, 3H), 1.82 (m, 2H), 1.43 (s,
18H), 1.15 (s, 9H).
4.7.2. (2S)-2-{2-[(2S)-2-Amino-4-methylsulfanyl-butyr-
ylsulfanyl]-acetylamino}-3-hydroxy-propionic acid (11b).
Yield 89%. H NMR (D2O, 300 MHz): d 4.52 (m, 2H),
1
3.96–3.82 (m, 4H), 2.63 (t, J ¼ 6:9 Hz, 2H), 2.31–2.17
(m, 2H), 2.08 (s, 3H).
13C NMR (D2O, 75 MHz): d 196.64, 173.28, 170.11,
61.22, 58.07, 55.50, 32.71, 30.00, 28.40, 14.17.
4.6.4. (2S)-3-tert-Butoxy-2-{(2R)-2-[(2S)-2-tert-butoxy-
carbonylamino-4-methylsulfanyl-butyrylsulfanyl]-3-phenyl-
propionylamino}-propionic acid tert-butyl ester (10d).
4.7.3.
(2S)-2-{(2S)-2-[(2S)-2-Amino-4-methylsulfanyl-
butyrylsulfanyl]-3-phenyl-propionylamino}-3-hydroxy-pro-
pionic acid (11c). Yield 100%. 1H NMR (D2O,
300 MHz): d 7.39–7.28 (m, 5H), 4.64 (m, 1H), 4.46 (m,
1H), 4.40 (m, 1H), 3.83 (m, 2H), 3.17 (m, 2H), 2.62 (t,
J ¼ 6:9 Hz, 2H), 2.24 (m, 2H), 2.10 (s, 3H).
1
Yield 56%. H NMR (CDCl3, 300 MHz): d 7.32–7.19
(m, 5H), 6.71 (d, J ¼ 8:1 Hz, 1H), 5.23 (d, J ¼ 9:0 Hz,
1H), 4.49 (m, 1H), 4.44 (m, 1H), 4.22 (m, 1H), 3.68 (dd
of ABX system, J ¼ 8:7, 2.7 Hz, 1H), 3.40–3.29 (m, 2H),
2.95 (dd of ABX system, J ¼ 13:8, 6.6 Hz, 1H), 2.36 (m,
2H), 2.13 (m, 1H), 2.06 (s, 3H), 1.88 (m, 1H), 1.49 (s,
9H), 1.42 (s, 9H), 1.07 (s, 9H).
4.7.4.
(2S)-2-{(2R)-2-[(2S)-2-Amino-4-methylsulfanyl-
butyrylsulfanyl]-3-phenyl-propionylamino}-3-hydroxy-pro-
pionic acid (11d). Yield 100%. 1H NMR (D2O,
300 MHz): d 7.40–7.29 (m, 5H), 4.67 (m, 1H), 4.46 (m,
1H), 4.39 (m, 1H), 3.85 (dd of ABX system, J ¼ 11:4,
5.1 Hz, 1H), 3.68 (dd of ABX system, J ¼ 11:4, 7.5 Hz,
1H), 3.30 (dd of ABX system, J ¼ 13:8, 7.8 Hz, 1H), 3.11
(dd of ABX system, J ¼ 13:8, 8.7 Hz, 1H), 2.45 (m, 2H),
2.14 (m, 2H), 2.08 (s, 3H).
4.6.5. (2S)-3-tert-Butoxy-2-{(2R)-2-[(2S)-2-tert-butoxy-
carbonylamino-4-methylsulfanyl-butyrylsulfanyl]-4-methyl-
pentanoylamino}-propionic acid tert-butyl ester (10e).
Yield 49%. 1H NMR (CDCl3, 300 MHz): d 6.85 (d,
J ¼ 8:4 Hz, 1H), 5.24 (d, J ¼ 9:0 Hz, 1H), 4.56–4.46 (m,
2H), 4.05 (t, J ¼ 7:5 Hz, 1H), 3.74 (dd of ABX system,
J ¼ 9:0, 2.7 Hz, 1H), 3.51 (dd of ABX system, J ¼ 9:0,
3.0 Hz, 1H), 2.59–2.52 (m, 2H), 2.17 (m, 1H), 2.08 (s,
3H), 1.92 (m, 1H), 1.67 (m, 3H), 1.45 (s, 9H), 1.44 (s,
9H), 1.15 (s, 9H), 0.95 (d, J ¼ 6:6 Hz, 3H), 0.89 (d,
J ¼ 6:6 Hz, 3H).
4.7.5.
(2S)-2-{(2R)-2-[(2S)-2-Amino-4-methylsulfanyl-
butyrylsulfanyl]-4-methyl-pentanoylamino}-3-hydroxy-
propionic acid (11e). Yield 66%. 1H NMR (D2O,
300 MHz): d 4.51–4.39 (m, 3H), 3.89 (m, 2H), 2.67 (t,
J ¼ 7:2 Hz, 2H), 2.32–2.22 (m, 2H), 2.12 (s, 3H), 1.82
(m, 1H), 1.64 (m, 2H), 0.94 (d, J ¼ 4:5 Hz, 3H), 0.89 (d,
J ¼ 5:4 Hz, 3H).
4.6.6. (2S)-3-tert-Butoxy-2-{(2R)-2-[(2S)-2-tert-butoxy-
carbonylamino-4-methylsulfanyl-butyrylsulfanyl]-4-meth-
ylsulfanyl-butyrylamino}-propionic acid tert-butyl ester
1
(10f). Yield 31%. H NMR (CDCl3, 300 MHz): d 6.90
(d, J ¼ 8:4 Hz, 1H), 5.25 (d, J ¼ 9:3 Hz, 1H), 4.52 (m,
1H), 4.48 (ddd, J ¼ 8:4, 3.0, 3.0 Hz, 1H), 4.22 (m, 1H),
3.75 (dd of ABX system, J ¼ 9:0, 3.0 Hz, 1H), 3.51 (dd
of ABX system, J ¼ 9:0, 3.0 Hz, 1H), 2.56 (t,
J ¼ 6:0 Hz, 4H), 2.30 (m, 2H), 2.09 (s, 6H), 2.01–1.93
(m, 2H), 1.46 (s, 9H), 1.44 (s, 9H), 1.16 (s, 9H).
4.7.6. (2S)-2-{(2R)-2-[(2S)-2-Amino-4-methylsulfanyl-
butyrylsulfanyl]-4-methylsulfanyl-butyrylamino}-3-hydr-
oxy-propionic acid (11f). Yield 100%. H NMR (D2O,
300 MHz): d 4.51 (m, 2H), 4.41 (m, 1H), 3.90 (m, 2H),
2.65 (m, 4H), 2.25 (m, 4H), 2.12 (s, 3H), 2.09 (s, 3H).
1