G. Moroy et al. / Bioorg. Med. Chem. 15 (2007) 4753–4766
4763
J = 4.36 Hz, 1H, CH3–NH), 8.22 (d, J = 8 Hz, 1H,
NHTrp), 8.93 (br s, 1H, NH), 10.64 (br s, 1H, OH),
10.82 (s, 1H, NH). 13C NMR (DMSO-d6) d ppm; 25.9;
27.5; 29.9; 31.0; 34.5; 54.3; 110.7; 111.5; 118.4; 118.5;
121.0; 123.6; 126.1; 127.5; 128.5; 130.5; 136.2; 137.0;
141.4; 167.0; 168.2; 172.0. IR (KBr): m (cmꢀ1): 3280,
2929, 2842, 1655, 1524, 1454, 1358, 1097, 743, 695.
MS ESI(+) (m/z), 50/50 H2O/CH3CN (0.1% TFA): 449
(12) [M+H]+, 424 (39), 416 (44) [Mꢀ(NH–OH)]+, 396
(95), 368 (100), 357 (8), 287 (9).
J = 4.73 Hz, 3H, CH3–NH), 2.90–3.10 (m, 2H, CH2–
CO), 3.52–3.69 (m, 2H, CH2–CH), 5.15 (dd,
J = 7.12 Hz, J = 8.90 Hz, 1H, CH2–CH), 6.46 (q,
J = 4.66 Hz, 1H, CH3–NH), 6.68–6.73 (m, 1H, CH@),
7.00–7.16 (m, 5H, H indole), 8.60 (s, 1H, NH). 13C
NMR (CDCl3) d ppm; 13.9; 22.4; 24.6; 26.4; 27.8;
28.8; 29.7; 31.4; 31.6; 55.5; 110.5; 111.3; 118.2; 119.4;
122.0; 122.8; 124.7; 126.8; 136.1; 139.8; 169.1; 169.8;
174.0. IR (film): m (cmꢀ1): 3350, 3061, 2921, 2850,
1764, 1707, 1664, 1542, 1454, 1380, 1262, 1210, 1171,
1097, 1005, 914, 800, 739. MS ESI(+) (m/z), 50/50
H2O/CH3CN (0.1% TFA): 396 (100) [M+H]+, 365
(21), 337 (25).
4.1.7.3. (2E)-3-(N-Hydroxycarbamoyl)-2-[(2E)-but-2-
en-1-ylidene]propionyl-L-tryptophan-N-methylamide (2c).
CPC (Arizona system G, tR = 42–56 min, k = 272 nm).
The hydroxamic acid was obtained as yellow foam
(yield = 11%). 1H NMR (DMSO-d6) d ppm; 1.83
(d, J = 6.43 Hz, 3H, CH3–CH@), 2.59 (d, J = 4.41 Hz,
3H, CH3–NH), 2.94–3.24 (m, 4H, CH2–CO, CH2–
CH), 4.44–4.52 (m, 1H, CH2–CH), 6.03 (dq,
J = 7.07 Hz, J = 21.8 Hz, 1H, CH3–CH@), 6.45 (dd,
J = 13.62 Hz, 1H, @CH–CH@CH@), 6.76 (d, J =
11.2 Hz, 1H, @CH–CH@CH@), 6.98 (t, J = 7.50 Hz,
1H, H indole), 7.06 (t, J = 7.01 Hz, 1H, H indole),
7.16 (s, 1H, H indole), 7.33 (d, J = 8.00 Hz, 1H, H in-
dole), 7.60 (d, J = 7.72 Hz, 1H, H indole), 7.97 (q,
J = 4.51 Hz, 1H, CH3–NH), 8.39 (d, J = 7.67 Hz, 1H,
NHTrp), 8.98 (s, 1H, NH), 10.83 (s, 2H, NH, OH).
13C NMR (DMSO-d6) d ppm; 18.8; 25.9; 27.6; 31.1;
34.5; 54.5; 110.9; 111.5; 118.4; 118.5; 121.0; 123.6;
127.1; 127.2; 127.5; 135.3; 136.2; 136.8; 166.9; 168.2;
172.1. IR (KBr): m (cmꢀ1): 3271, 2921, 1646, 1533,
1354, 1258, 1166, 1088, 970, 743. MS ESI(+) (m/z),
50/50 H2O/CH3CN (0.1% TFA): 385 (60) [M+H]+,
352 (100) [Mꢀ(NH–OH)]+, 293 (19).
4.1.8.2. (S,E)-2-(2,5-Dioxo-3-(3-phenylpropylidene)pyrr-
olidin-1-yl)-3-(1H-indol-3-yl)-N-methylpropanamide (12b).
CPC (Arizona system K, tR = 12 min, k = 280 nm).
The cyclic compound was obtained as yellow foam
1
(yield = 7%). Mp 67–68 ꢂC. H NMR (CDCl3) d ppm;
2.29–2.41 (m, 2H, CH2), 2.69–2.85 (m, 7H, CH2–CO,
CH2, CH3–NH (d, J = 4.80 Hz)), 3.51–3.67 (m, 2H,
CH2–CH), 5.13 (dd, J = 7.10 Hz, J = 9.00 Hz, 1H,
CH2–CH), 6.36 (q, J = 4.27 Hz, 1H, CH3–NH), 6.71–
6.76 (m, 1H, CH@), 6.71–7.69 (m, 10H, H aromatic),
8.40 (s, 1H, NH). 13C NMR (CDCl3) d ppm; 24.5;
26.4; 31.6; 31.6; 34.0; 55.5; 110.7; 111.2; 118.4; 119.5;
122.1; 122.7; 125.6; 126.3; 126.9; 128.2; 128.4; 128.5;
136.1; 138.0; 140.2; 169.0; 169.6; 173.8. IR (film): m
(cmꢀ1): 3342, 3061, 2921, 2850, 1768, 1703, 1672,
1546, 1494, 1380, 1258, 1162, 1114, 905, 735, 695. MS
ESI(+) (m/z), 50/50 H2O/CH3CN (0.1% TFA): 416
(61) [M+H]+, 357 (24), 279 (100).
4.1.8.3.
(S)-2-((E)-2,5-Dioxo-3-((E)-pent-2-enylid-
ene)pyrrolidin-1-yl)-3-(1H-indol-3-yl)-N-methylpropan-
amide (12c). CPC (Arizona system G, tR = 12 min,
k = 272 nm). The cyclic compound was obtained as yel-
low foam (yield = 22%). Mp 72–75 ꢂC. 1H NMR
(CDCl3) d ppm; 1.86 (d, J = 6.90 Hz, 3H, CH3), 2.74
(d, J = 5.10 Hz, 3H, CH3–NH), 2.98–3.15 (m, 2H,
CH2–CO), 3.53–3.69 (m, 2H, CH2–CH), 5.16 (dd,
J = 7.24 Hz, J = 8.46 Hz, 1H, CH2–CH), 5.98 (dd,
J = 12.65 Hz, J = 15.1 Hz, 1H, CH@CH–CH@), 6.13–
6.25 (m, 1H, CH3–CH@), 6.51 (q, J = 4.57 Hz, 1H,
CH3–NH), 6.98–7.68 (m, 6H, H aromatic, CH@), 8.59
(s, 1H, NH). 13C NMR (CDCl3) d ppm; 19.0; 24.6;
26.4; 31.9; 55.5; 110.6; 111.2; 118.3; 119.4; 121.2;
122.0; 122.8; 126.6; 126.8; 134.5; 136.1; 142.3; 169.1;
170.5; 173.9. IR (film): m (cmꢀ1): 3342, 3052, 2921,
1764, 1699, 1651, 1542, 1433, 1380, 1280, 1175, 1114,
970, 918, 796, 735, 691. MS ESI(+) (m/z), 50/50 H2O/
CH3CN (0.1% TFA): 352 (100) [M+H]+, 321 (27), 293
(81), 279 (94), 227 (19).
4.1.7.4. (2E)-3-(N-Hydroxycarbamoyl)-2-[(2E)-3-phe-
nylprop-2-en-1-ylidene]propionyl-L-tryptophan-N-meth-
ylamide (2d). CPC (Arizona system K, tR = 27–42 min,
k = 290 nm). The hydroxamic acid was obtained as
white foam (yield = 8%). 1H NMR (DMSO-d6) d
ppm; 2.61 (d, J = 4.37 Hz, 3H, CH3–NH), 2.99–3.30
(m, 4H, CH2–CO, CH2–CH), 4.56–4.87 (m, 1H,
CH2–CH), 6.84–7.64 (m, 13H, H aromatic), 8.00 (q,
J = 4.61 Hz, 1H, CH3–NH), 8.45 (d, J = 7.92 Hz, 1H,
NHTrp), 9.01 (s, 1H, NH), 10.79 (s, 1H, OH), 10.83
(s, 1H, NH). 13C NMR (DMSO-d6) d ppm; 25.9;
27.6; 31.5; 54.5; 110.8; 111.5; 118.4; 118.6; 121.0;
123.7; 124.1; 126.6; 127.3; 127.5; 127.5; 128.9; 128.9;
129.9; 135.4; 136.2; 136.6; 138.2; 166.9; 168.0; 172.1.
IR (KBr): m (cmꢀ1): 3228, 2929, 1655, 1620, 1546,
1485, 1376, 1284, 1249, 1188, 1153, 1097, 1040, 975,
739, 687. MS ESI(+) (m/z), 50/50 H2O/CH3CN (0.1%
TFA): 447 (75) [M+H]+, 414 (100) [Mꢀ(NH–OH)]+,
159 (12), 120 (34).
4.1.8.4. (S)-2-((E)-2,5-Dioxo-3-((E)-3-phenylallylidene)-
pyrrolidin-1-yl)-3-(1H-indol-3-yl)-N-methylpropanamide
(12d). CPC (Arizona system K, tR = 12 min,
k = 290 nm). The cyclic compound was obtained as yel-
low foam (yield = 22%). Mp 62–64 ꢂC. 1H NMR
(CDCl3) d ppm; 2.75 (d, J = 4.75 Hz, 3H, CH3–NH),
3.10–3.28 (m, 2H, CH2–CO, CH2–CH), 3.57–3.72 (m,
2H, CH2–CO, CH2–CH), 5.18 (dd, J = 7.04 Hz,
J = 9.08 Hz, 1H, CH2–CH), 6.59–6.88 (m, 2H, CH@),
4.1.8. Cyclic compounds (12a–d)
4.1.8.1. (S,E)-2-(3-Heptylidene-2,5-dioxopyrrolidin-1-
yl)-3-(1H-indol-3-yl)-N-methylpropanamide (12a). CPC
(Arizona system L, tR = 12 min, k = 272 nm). The cyc-
lic compound was obtained as yellow foam
(yield = 23%). Mp 52–55 ꢂC. 1H NMR (CDCl3) d
ppm; 0.87 (t, J = 6.33 Hz, 3H, CH3–CH2), 1.20–1.41
(m, 8H, CH2), 2.00–2.07 (m, 2H, CH2), 2.75 (d,