D. Georgiou et al. / Bioorg. Med. Chem. 20 (2012) 5103–5109
5107
J2 = 7.47 Hz), 3.13 (qd, –SCH–, J1 = 13.02 Hz, J2 = 7.47 Hz), 1.40 (t,
3H, –CH3, J1 = 7.47 Hz). 13C NMR (62.9 MHz, CDCl3): dC 175.2
(C@O), 170.9 (C@N), 170.4 (C@O), 170.3 [C(@O)OR], 131.2, 129.2,
128.9, 126.4, 126.2 (aromatics), 76.8 (C5), 59.1 (C3), 53.1 (OMe),
47.9 (C4), 26.1 (–SCH2–), 13.7 (Me). FT-IR (KBr pellet): 3488,
3063, 2945, 1720 (C@O), 1573 (C@N), 1495, 1454, 1437, 1383,
1348, 1291, 1248, 1200, 1176, 1090, 1044, 943, 870, 826, 797,
732, 692, 661, 623, 545, 476, 425 cmꢂ1. UV–vis (CHCl3): kmax
238 nm. Anal. Calcd for C16H16N2SO4: N, 8.43; C, 57.82; H, 4.85;
S, 9.65. Found: N, 8.36; C, 58.07; H, 4.81; S, 9.60. MS (FAB+) m/z:
333, [M+H]+. MS (ESI+) m/z: 333.34 [M+H]+, [M]: 332.37. HRMS
calcd for C16H17N2SO4, m/z: 333.0904, [M+H]+. Found: 333.0902.
C
17H18N2SO4: N, 8.09; C, 58.94; H, 5.24; S, 9.26. Found: N, 7.92;
C, 58.64; H, 5.27; S, 9.13. MS (FAB+) m/z: 347 [M+H]+.
5.2.4.2. Compound 2d-anti.
White powder. Mp: 136–137 °C.
Rf (EtOAc/n-hexanes 1:2, v/v) 0.46. 1H NMR (250 MHz, CDCl3): dH
7.46–7.26 (m, 5H, aromatics), 5.23 (dd, 1H5, JH5,H4 = 2.21 Hz,
JH5,H3 = 2.02 Hz), 4.29 (dd, 1H3, JH3,H4 = 8.32 Hz, JH3,H5 = 2.02 Hz),
4.05 (dd, 1H4, JH4,H3 = 8.32 Hz, JH4,H5 = 2.21 Hz), 3.90 (septet, par-
tially overlapped, –SCH<, J = 6.85 Hz), 3.83 (s, 3H, OMe), 1.41 (d,
3H, CH3, J = 6.85 Hz), 1.38 (d, 3H, CH3, J = 6.85 Hz). 13C NMR
(62.9 MHz, CDCl3): dC 175.2 (C@O), 171.0 (C@N), 170.4 (C@O),
170.1 [C(@O)OR], 131.2, 129.1, 128.8, 126.2 (aromatics), 76.9 (C5),
59.3 (C3), 53.0 (OMe), 47.7 (C4), 37.2 (–SCH<), 22.7 (Me), 22.5
(Me). FT-IR (KBr pellet): 3479, 2954, 2929, 2868, 1742 (C@O),
1718 (C@O), 1595, 1564 (C@N), 1496, 1439, 1387, 1320, 1276,
1239, 1205, 1185, 1086, 1031, 1012, 980, 957, 911, 806, 787, 738,
696, 665, 647, 625, 540, 494, 459 cmꢂ1. UV–vis (CHCl3): kmax
244 nm. Anal. Calcd for C17H18N2SO4: N, 8.09; C, 58.94; H, 5.24; S,
9.26. Found: N, 7.92; C, 58.84; H, 5.27; S, 9.13. MS (FAB+) m/z:
347 [M+H]+. HRMS calcd for C17H19N2SO4, m/z: 347.1060, [M+H]+.
Found: 347.1056.
5.2.3. Methyl 4,6-dioxo-5-phenyl-3-(propylthio)-1,3a,4,5,6,6a-
hexahydropyrrolo[3,4-c]pyrrole-1-carboxylate, 2c
5.2.3.1. Compound 2c-syn.
White powder. Mp: 145–146 °C.
Rf (EtOAc/n-hexanes 1:2, v/v) 0.35. 1H NMR (250 MHz, CDCl3): dH
7.49–7.23 (m, 5H, aromatics), 5.17 (dd, 1H5, JH5,H4 = 9.50 Hz,
JH5,H3 = 0.89 Hz), 4.23 (dd, 1H3, JH3,H4 = 9.16 Hz, JH3,H5 = 0.89 Hz),
3.95 (dd, 1H4, JH4,H3 = 9.16 Hz, JH4,H5 = 9.50 Hz), 3.76 (s, 3H, OMe),
3.13 (td, 1H, –SCH–, J1 = 12.76 Hz, J2=7.31 Hz), 3.06 (td, 1H, –SCH–
,J1 = 12.76 Hz, J2=7.31 Hz), 1.73 (sextet, 2H, –CH2–, J = 7.31 Hz),
1.01 (t, 3H, Me, J = 7.34 Hz). 13C NMR (62.9 MHz, CDCl3): dC 174.2
(C@O), 170.6 (C@N), 170.4 (C@O), 169.9 [C(@O)OR], 131.4, 129.1,
128.8, 126.5 (aromatics), 76.0 (C5), 59.7 (C3), 52.7 (OMe), 47.0
(C4), 33.6 (–S–CH2–), 21.9 (–CH2–), 13.4 (Me). FT-IR (KBr pellet):
3487, 2946, 2875, 1721 (C@O), 1575 (C@N), 1496, 1439, 1381,
1352, 1291, 1199, 1088, 1040, 944, 827, 768, 734, 691, 636, 544,
5.2.5. Methyl 3-(butylthio)-4,6-dioxo-5-phenyl-1,3a,4,5,6,6a-
hexahydropyrrolo[3,4-c]pyrrole-1-carboxylate, 2e
5.2.5.1. Compound 2e-syn.
White powder. Mp: 102–103 °C.
Rf (EtOAc/n-hexanes 1:2, v/v) 0.41. 1H NMR (250 MHz, CDCl3): dH
7.50–7.23 (m, 5H, aromatics), 5.17 (dd, 1H5, JH5,H4=9.51 Hz,
JH5,H3 = 0.86 Hz), 4.22 (dd, 1H3, JH3,H4 = 9.20 Hz, JH3,H5 = 0.86 Hz),
3.95 (dd, 1H4, JH4,H3 = 9.20 Hz, JH4,H5 = 9.51 Hz), 3.76 (s, 3H, OMe),
3.16 (td, 1H, –SCH–, J1 = 12.54 Hz, J2 = 7.35 Hz), 3.09 (td, 1H, –
SCH–, J1 = 12.54 Hz, J2=7.35 Hz), 1.68 (quintet, 2H, –CH2–,
J = 7.35 Hz), 1.43 (sextet, 2H, –CH2–, J = 7.31 Hz), 0.93 (t, 3H, Me,
J = 7.31 Hz). 13C NMR (62.9 MHz, CDCl3): dC 174.2 (C@O), 170.6
(C@N), 170.4 (C@O), 169.9 [C(@O)OR], 131.3, 129.1, 128.8, 126.4
(aromatics), 75.9 (C5), 59.7 (C3), 52.6 (OMe), 46.9 (C4), 31.4 (–S–
CH2–), 30.3 (–CH2–), 21.8 (–CH2–), 13.5 (Me). FT-IR (KBr pellet):
3490, 2937, 2841, 1784, 1722 (C@O), 1578 (C@N), 1438, 1384,
1352, 1291, 1244, 1198, 1085, 1038, 945, 889, 825, 797, 748,
734, 691, 638, 619, 545, 481, 442, 414 cmꢂ1. UV–vis (CHCl3): kmax
242 nm. Anal. Calcd for C18H20N2SO4: N, 7.77; C, 59.98; H, 5.59;
S, 8.90. Found: N, 7.81; C, 59.73; H, 5.57; S, 8.93. MS (FAB+) m/z:
361, [M+H]+. MS (ESI+) m/z: 361.41 [M+H]+, [M]: 360.43.
478 cmꢂ1
.
UV–vis (CHCl3): kmax 241 nm. Anal. Calcd for
C
17H18N2SO4: N, 8.09; C, 58.94; H, 5.24; S, 9.26. Found: N, 7.99; C,
58.75; H, 5.26; S, 9.22. MS (FAB+) m/z: 347 [M+H]+. HRMS calcd
for C17H19N2SO4, m/z: 347.1060, [M+H]+. Found: 347.1056.
5.2.3.2. Compound 2c-anti.
White powder. Mp: 151–152 °C.
Rf (EtOAc/n-hexanes 1:2, v/v) 0.47. 1H NMR (250 MHz, CDCl3): dH
7.50–7.25 (m, 5H, aromatics), 5.20 (dd, 1H5, JH5,H4=2.21 Hz,
JH5,H3 = 2.02 Hz), 4.32 (dd, 1H3, JH3,H4 = 8.38 Hz, JH3,H5 = 2.02 Hz),
4.08 (dd, 1H4, JH4,H3 = 8.38 Hz, JH4,H5 = 2.21 Hz), 3.83 (s, 3H, OMe),
3.17 (td, 1H, –SCH-, J1 = 12.80 Hz, J2 = 7.27 Hz), 3.05 (td, 1H, –SCH–
, J1=12.80 Hz, J2 = 7.27 Hz), 1.72 (sextet, 2H, –CH2–, J = 7.27 Hz)
1.01 (t, 3H, Me, J = 7.27 Hz). 13C NMR (62.9 MHz, CDCl3): dC 175.2
(C@O), 171.0 (C@N), 170.6 (C@O), 170.4 [C(@O)OR], 147.1, 129.2,
128.9, 126.2 (aromatics), 76.8 (C5), 59.2 (C3), 53.1 (OMe), 48.0 (C4),
33.7 (–S–CH2–), 21.9 (–CH2–), 13.4 (Me). FT-IR (KBr pellet): 3478,
3059, 2963, 2934, 2873, 1968, 1748, 1712 (C@O), 1578 (C@N),
1502, 1455, 1436, 1390, 1342, 1291, 1264, 1241, 1196, 1087,
1044, 1007, 990, 957, 941, 914, 807, 784, 756, 733, 694, 665, 618,
577, 541, 506, 480, 432 cmꢂ1. UV–vis (CHCl3): kmax 243 nm. Anal.
Calcd for C17H18N2SO4: N, 8.09; C, 58.94; H, 5.24; S, 9.26. Found:
N, 7.97; C, 58.846; H, 5.26; S, 9.15. MS (FAB+) m/z: 347 [M+H]+. HRMS
calcd for C17H19N2SO4, m/z: 347.1060, [M+H]+. Found: 347.1059.
5.2.5.2. Compound 2e-anti.
Oil. Rf (EtOAc/n-hexanes 1:2, v/v)
0.53. 1H NMR (250 MHz, CDCl3): dH 7.50–7.24 (m, 5H, aromatics),
5.20 (dd, 1H5, JH5,H4 = 2.14 Hz, JH5,H3 = 1.99 Hz), 4.32 (dd, 1H3,
JH3,H4 = 8.34 Hz, JH3,H5 = 1.99 Hz), 4.09 (dd, 1H4, JH4,H3 = 8.34 Hz,
JH4,H5 = 2.14 Hz), 3.83 (s, 3H, OMe), 3.18 (td, 1H, –SCH–,
J1 = 12.72 Hz, J2 = 7.28 Hz), 3.08 (td, 1H, –SCH–, J1 = 12.72 Hz,
J2 = 7.28 Hz), 1.67 (quintent, 2H, –CH2–, J = 7.28 Hz), 1.42 (sextet,
2H, –CH2–, J = 7.30 Hz), 0.92 (t, 3H, Me, J = 7.30 Hz). 13C NMR
(62.9 MHz, CDCl3): dC 175.2 (C@O), 171.0 (C@N), 170.7 (C@O),
170.4 [C(@O)OR], 131.2, 129.2, 128.9, 126.3 (aromatics), 76.8
(C5), 59.2 (C3), 53.1 (OMe), 48.0 (C4), 31.5 (–S–CH2–), 30.4 (–CH2–
), 21.9 (–CH2–), 13.6 (Me). FT-IR (KBr pellet): 3437, 2954, 2915,
2856, 1742, 1721 (C@O), 1571 (C@N), 1491, 1386, 1207, 1191,
1086, 794, 735, 694, 464 cmꢂ1. UV–vis (CHCl3): kmax 244 nm. Anal.
Calcd for C18H20N2SO4: N, 7.77; C, 59.98; H, 5.59; S, 8.90. Found: N,
7.80; C, 59.81; H, 5.57; S, 8.96. MS (FAB+) m/z: 361, [M+H]+. MS
(ESI+) m/z: 361.40 [M+H]+, [M]: 360.43.
5.2.4. Methyl 3-(isopropylthio)-4,6-dioxo-5-phenyl-
1,3a,4,5,6,6a-hexahydropyrrolo[3,4-c]pyrrole-1-carboxylate, 2d
5.2.4.1. Compound 2d-syn.
Oil. Rf (EtOAc/n-hexanes 1:2, v/v)
0.34. 1H NMR (250 MHz, CDCl3): dH 7.44–7.24 (m, 5H, aromatics),
5.21 (dd, 1H5, JH5,H4 = 9.53 Hz, JH5,H3 = 0.98 Hz), 4.23 (dd, 1H3,
JH3,H4 = 9.20 Hz, JH3,H5 = 0.98 Hz), 3.94 (dd, 1H4, JH4,H3 = 9.20 Hz,
JH4,H5 = 9.53 Hz), 3.86 (septet, 1H, –SCH<, J = 6.81 Hz), 3.77 (s, 3H,
OMe), 1.39 (d, 6H, 2-CH3, J = 6.81 Hz). 13C NMR (62.9 MHz, CDCl3):
dC 174.2 (C@O), 170.6 (C@N), 170.0 (C@O), 169.9 [C(@O)OR], 131.4,
129.1, 128.9, 126.5 (aromatics), 76.3 (C5), 60.0 (C3), 52.7 (OMe),
46.7 (C4), 37.3 (–SCH<), 22.7 (Me), 22.6 (Me). FT-IR (KBr pellet):
3340, 2959, 1718 (C@O), 1581 (C@N), 1498, 1383, 1187, 740,
5.2.6. Methyl 3-(benzylthio)-4,6-dioxo-5-phenyl-1,3a,4,5,6,6a-
hexahydropyrrolo[3,4-c]pyrrole-1-carboxylate, 2f
5.2.6.1. Compound 2f-syn.
Oil. Rf (EtOAc/n-hexanes 1:2, v/v)
0.33. 1H NMR (250 MHz, CDCl3): dH 7.46–7.24 (m, 10H, aromatics),
5.21 (dd, 1H5, JH5,H4 = 9.51 Hz, JH5,H3 = 0.98 Hz), 4.42 (d, 1H,
692 cmꢂ1
.
UV–vis (CHCl3): kmax 242 nm. Anal. Calcd for