W.C. Cheah et al. / Tetrahedron 67 (2011) 7603e7610
7607
205 (10,500). HRMS (ESI) m/z 343.1264 (MþNa)þ, C16H20N2O5Na
2520 cmꢀ1 Mꢀ1), 234 (15,019), 207 (7680). HRMS (ESI) m/z 375.0985
(MþNa)þ; C16H20N2O5SNa requires 375.0991.
requires: 343.1270.
4.1.3. (S)-Methyl 2-(2-(2-acetamidophenyl)-2-oxoacetamido)-3-
phenyl propanoate (2c). This compound was prepared by the
same method as compound 2a, from N-acetylisatin (0.10 g,
4.1.6. Methyl 2-(2-(2-acetamidophenyl)-N-methyl-2-oxoacetamido)
acetate (2f). This compound was prepared by the same method as
compound 2a, from N-acetylisatin (0.10 g, 0.53 mmol) and sarco-
sine methyl ester hydrochloride (0.20 g, 1.5 mmol). The title com-
pound 2f was obtained as a yellow liquid (80 mg, 52%). Rf 0.26
(EtOAc/CH2Cl2, v/v 1:9); Found: C, 57.45; H, 5.60; N, 9.57%.
C14H16N2O5 requires: C, 57.53; H, 5.52; N, 9.58%. 1H NMR (300 MHz;
0.53 mmol) and
L-phenylalanine methyl ester hydrochloride
(0.29 g, 1.3 mmol). The title compound 2c was obtained as an off-
white solid (0.18 g, 98%). Mp 116e118 ꢁC. Rf 0.45 (EtOAc/CH2Cl2, v/
v 1:9); ½a 2D6
ꢀ7.4 (c 0.02, MeOH). Found: C, 64.89; H, 5.34; N, 7.54%.
ꢂ
C20H20N2O5 requires: C, 65.21; H, 5.47; N, 7.60%. 1H NMR (300 MHz;
CDCl3): d 11.2 (1H, br s, NHCO), 11.1 (1H, br s, NHCO), 8.72 (1H, dd, J
CDCl3):
d
10.9 (1H, br s, NHCO), 8.68 (1H, dd, J 1.5, 8.7 Hz, H7), 8.17
0.8, 8.7 Hz, H7), 8.68 (1H, dd, J 0.50, 8.6 Hz, H70), 7.86 (1H, dd, J 1.5,
7.9 Hz, H4), 7.68 (1H, dd, J 1.5, 8.1 Hz, H40), 7.57 (1H, dt, J 1.1, 8.7 Hz,
H6), 7.54 (1H, dt, J 1.5, 7.9 Hz, H60), 7.13 (1H, dt, J 0.75, 7.6 Hz, H5),
(1H, dd, J 1.5, 8.3 Hz, H4), 7.60 (1H, dt, J 1.5, 7.4 Hz, H6), 7.32e7.15
(5H, m, ArH), 7.08 (1H, dt, J 1.1, 7.5 Hz, H5), 5.32 (1H, br s, CONH),
0
7.07 (1H, dt, J 1.1, 7.4 Hz, H50), 4.21 (2H, s, CH2), 4.02 (2H, s, CH2 ),
4.99 (1H, m,
a
-CH phe), 3.75 (3H, s, COOCH3), 3.31e3.08 (2H, m,
CHCH2Ar), 2.14 (3H, s, COCH3). 13C NMR (75 MHz; CDCl3)
d
191.7,
3.76 (3H, s, OCH3), 3.62 (3H, s, OCH3 ), 3.10 (3H, s, NCH03 ), 2.96 (3H,
0
0
171.0, 169.4, 162.8, 141.9, 136.4, 135.4, 134.2, 129.2, 128.6, 127.2,
122.4, 120.3, 118.1, 53.2, 52.5, 37.8, 25.3. IR (KBr): nmax 3336, 3284,
3059, 3030, 2955, 1743, 1678, 1664, 1604, 1577, 1515, 1446, 1374,
1309, 1294, 1281, 1245, 1209, 1178, 1164, 1126, 1103, 1031, 1004, 932,
908, 829, 798, 765, 701, 680, 658, 597, 549, 522, 501 cmꢀ1. UV
s, NCH3), 2.20 (3H, s, COCH3), 2.18 (3H, s, COCH3 ). 13C NMR
(75 MHz; CDCl3)
d 195.2, 194.7, 169.4, 169.3, 168.5, 168.3, 166.8,
166.3, 142.4, 142.3, 136.9, 136.8, 134.1, 133.9, 122.9, 122.5, 120.4,
120.3, 117.6, 52.41, 50.81, 47.8, 36.14, 33.51, 25.39. IR (KBr): nmax
3304, 3028, 2955, 1749, 1701, 1654, 1605, 1584, 1529, 1450, 1433,
1367, 1321, 1296, 1239, 1205, 1162, 1134, 1108, 1058, 1031, 976, 959,
(MeOH): lmax 337 (
6260 cmꢀ1 Mꢀ1), 267 (14,410), 234 (34,790),
3
205 (33,320). HRMS (ESI) m/z 391.1264 (MþNa)þ; C20H20N2O5Na
947, 899, 756, 713, 691 cmꢀ1
.
UV (MeOH): lmax 341
(
3
requires 391.1270.
12,010 cmꢀ1 Mꢀ1), 268 (25,690), 236 (68,840), 204 (41,760). HRMS
(ESI) m/z 315.0959 (MþNa)þ; C14H16N2O5Na requires: 315.0957.
4.1.4. (R)-Methyl 2-(2-(2-acetamidophenyl)-2-oxoacetamido)-3-
phenyl propanoate (2d). This compound was prepared by the
same method as compound 2a, from N-acetylisatin (0.10 g,
4.1.7. (S)-Dimethyl 2-(2-(2-acetamidophenyl)-2-oxoacetamido) suc-
cinate (2g). This compound was prepared by the same method as
0.53 mmol) and
D-phenylalanine methyl ester hydrochloride
compound 2a, from N-acetylisatin (0.20 g, 1.1 mmol) and L-aspartic
(0.29 g, 1.3 mmol). The title compound 2d was obtained as an off-
acid dimethyl ester hydrochloride (0.50 g, 2.6 mmol). The title
white solid (0.18 g 98%). Mp 116e118 ꢁC; Rf 0.45 (EtOAc/CH2Cl2, v/
compound 2g was obtained as a yellow liquid (0.20 g, 54%). Rf 0.20
v 1:9); ½a 2D6
ꢂ
þ6.3 (c 0.02, MeOH). Found: C, 64.89; H, 5.34; N, 7.54%,
(EtOAc/CH2Cl2, v/v 1:9); ½a D26
ꢀ6.3 (c 0.01, MeOH). Found: C, 54.83;
ꢂ
C20H20N2O5 requires: C, 65.21; H, 5.47; N, 7.60. 1H NMR (300 MHz;
H, 5.17; N, 8.00%, C16H18N2O7 requires: C, 54.86; H, 5.18; N, 8.00%. 1H
CDCl3):
d
10.9 (1H, br s, NHCO), 8.49 (1H, dd, J 1.5, 8.7 Hz, H7), 7.84
NMR (300 MHz; CDCl3): d 10.9 (1H, br s, NHCO), 8.69 (1H, dd, J 1.5,
(1H, dd, J 1.5, 8.3 Hz, H4), 7.61 (1H, d, J 8.3 Hz, CONH), 7.44 (1H, dt, J
1.1, 8.1 Hz, H6), 7.31e7.16 (5H, m, ArH), 6.96 (1H, dt, J 1.1, 7.8 Hz, H5),
8.7 Hz, H7), 8.35 (1H, dd, J 1.5, 7.9 Hz, H4), 7.76 (1H, d, J 8.3 Hz,
CONH), 7.62 (1H, dt, J 1.1, 7.9 Hz, H6), 7.14 (1H, dt, J 1.1, 7.5 Hz, H5),
4.99e4.95 (1H, m,
a
-CH phe), 3.74 (3H, s, COOCH3), 3.29e3.06 (2H,
4.98e4.92 (1H, m,
COOCH3), 3.16 (1H, dd, J 4.5, 17.5 Hz,
4.5, 17.5 Hz,
-CHaHb Asp), 2.24 (3H, s, COCH3). 13C NMR (75 MHz;
CDCl3) 190.8, 171.1, 170.1, 169.2, 162.4, 142.3, 136.8, 134.3, 122.4,
a
-CH Asp), 3.81 (3H, s, COOCH3), 3.73 (3H, s,
m, CHCH2Ar), 2.09 (3H, s, COCH3). 13C NMR (75 MHz; CDCl3)
d
192.0,
b-CHaHb Asp), 2.94 (1H, dd, J
171.1, 169.4, 163.1, 141.9, 136.3, 135.6,134.2, 129.2, 128.6, 127.2, 122.4,
120.2, 118.0, 53.2, 52.5, 37.7, 25.2. IR (KBr): nmax 3336, 3284, 3059,
3030, 2955, 1743, 1678, 1664, 1604, 1577, 1515, 1446, 1374, 1309,
1294, 1281, 1245, 1209, 1178, 1164, 1126, 1103, 1031, 1004, 932, 908,
829, 798, 765, 701, 680, 658, 597, 549, 522, 501 cmꢀ1. UV (MeOH):
b
d
120.6, 118.2, 53.07, 52.21, 48.49, 35.60, 25.43. UV (MeOH): lmax 337
(
3
2890 cmꢀ1 Mꢀ1), 289 (2520). HRMS (ESI) m/z 373.1012 (MþNa)þ,
C16H18N2O7Na requires 373.1012.
lmax 339 (
3740 cmꢀ1 Mꢀ1), 268 (8470), 234 (20,720), 205 (18,790).
3
HRMS (ESI) m/z 391.1264 (MþNa)þ; C20H20N2O5Na requires
4.1.8. (S)-Methyl 2-((S)-2-(2-(2-acetamidophenyl)-2-oxoaceta-
mido)-3-methylbutanamido)-3-phenylpropanoate (5a). This com-
pound was prepared by the same method as compound 2a, from N-
391.1270.
4.1.5. (S)-Methyl 2-(2-(2-acetamidophenyl)-2-oxoacetamido)-4-(me-
thylthio)-butanoate (2e). This compound was prepared by the same
method as compound 2a, from N-acetylisatin (0.10 g, 0.53 mmol) and
acetylisatin (0.50 g, 2.6 mmol) and L-valine-L-phenylalanine methyl
ester hydrochloride (1.1 g, 8.9 mmol). The title compound 5a was
obtained as a pale yellow solid (0.50 g, 40%). Mp 178e180 ꢁC; Rf 0.10
L-methionine methyl ester hydrochloride (0.27 g, 1.3 mmol). The title
(EtOAc/CH2Cl2, v/v 1:9); ½a D26
þ4.3 (c 0.01, MeOH); Found: C, 64.31;
ꢂ
compound 2e was obtained as a yellow liquid (0.17 g, 85%). Rf 0.36
H, 6.39; N, 8.96%, C25H29N3O6 requires: C, 64.23; H, 6.25; N, 8.99%.
(EtOAc/CH2Cl2, v/v 1:9); ½a D26
ꢂ
ꢀ6.9 (c 0.07, MeOH). Found: C, 54.20; H,
1H NMR (300 MHz; CDCl3):
d 10.9 (1H, br s, NHCO), 8.62 (1H, dd, J
5.70; N, 7.76%, C16H20N2O5S requires: C, 54.53; H, 5.72; N, 7.95%. 1H
1.1, 8.3 Hz, H7), 8.25 (1H, dd, J 1.1, 8.1 Hz, H4), 7.59 (1H, dt, J 1.1,
7.9 Hz, H6), 7.46 (1H, d, J 8.7 Hz, CONH), 7.24e7.15 (5H, m, ArH), 7.12
(1H, dt, J 1.1, 7.7 Hz, H5), 6.41 (1H, d, J 7.9 Hz, CONH), 4.92e4.83 (1H,
NMR (300 MHz; CDCl3):
d 10.9 (1H, br s, NHCO), 8.66 (1H, dd, J 1.1,
8.3 Hz, H7), 8.35 (1H, dd, J 1.5, 8.3 Hz, H4), 7.61 (1H, dt, J 1.5, 7.9 Hz,
H6), 7.51 (1H, d, J 7.9 Hz, CONH), 7.12 (1H, dt, J 1.1, 7.7 Hz, H5), 4.82
m, a-CH Phe), 4.34 (1H, dd, J 6.8, 8.9 Hz, a-CH Val), 3.73 (3H, s,
(1H, m,
Met), 2.34e2.22 (1H, m,
(1H, m,
-CHaHb Met), 2.12 (3H, s, COCH3). 13C NMR (75 MHz; CDCl3)
190.9, 171.3, 169.2, 162.4,142.2, 136.7, 134.3, 122.5,120.6, 118.3, 52.74,
a
-CH Met), 3.81 (3H, s, COOCH3), 2.59 (2H, t, J 7.1 Hz,
g
-CH
COOCH3), 3.20e3.05 (2H, m, CHCH2Ar), 2.22 (3H, s, COCH3), 1.99
(1H, m, CHCH(CH3)2), 0.99 (3H, d, J 6.8 Hz, CH3), 0.95 (3H, d, J 6.8 Hz,
b-CHaHb Met), 2.23 (3H, s, SCH3), 2.18e2.09
b
CH3). 13C NMR (75 MHz; CDCl3)
d 191.3, 171.5, 169.7, 169.3, 162.8,
d
142.1, 136.5, 135.4, 134.1, 129.1, 128.6, 127.2, 122.4, 120.6, 118.4, 58.5,
53.1, 52.3, 37.7, 31.2, 25.3, 19.0, 17.8. IR (KBr): nmax 3301, 3066, 2963,
2869, 1744, 1650, 1585, 1530, 1451, 1370, 1297, 1212, 1164, 1032, 990,
875, 753, 700, 678, 599, 551 cmꢀ1. UV (MeOH/TFA v/v 9.5:0.5): lmax
51.63, 31.20, 29.88, 25.38, 15.4. IR (KBr): nmax 3293, 3072, 2953, 2918,
2847, 1745, 1647, 1607, 1548, 1528, 1450, 1368, 1299, 1209, 1165, 1130,
1004, 877, 758, 682, 600, 551, 521 cmꢀ1. UV (MeOH): lmax 338 (
3