M. Zheng et al. / Bioorg. Med. Chem. 16 (2008) 9574–9587
9581
J = 8.8 Hz, 2H), 4.80 (d, J = 8.4 Hz, 1H), 4.51 (m, 3H), 3.63 (s, 3H),
3.10 (m, 2H), 1.78 (m, 3H), 1.41 (s, 9H), 1.01 (d, J = 7.4 Hz, 6H);
13C NMR (75 MHz, CDCl3) d/ppm = 171.6, 170.1, 155.8, 135.9,
134.2, 128.4, 127.2, 126.6, 79.5, 55.8, 52.0, 50.7, 44.6, 41.6, 28.4,
27.0, 22.3. Anal. Calcd for C22H32N2O5: C, 65.32; H, 7.97; N, 6.93.
Found: C, 65.53; H, 7.84; N, 6.70.
d/ppm = 8.00 (d, J = 7.6 Hz, 1H), 7.02 (m, J = 8.2 Hz, 2H), 6.98 (d,
J = 8.8 Hz, 2H), 6.95 (d, J = 8.8 Hz, 2H), 6.72 (d, J = 5.5 Hz, 2H),
5.20 (s, 1H), 4.92 (m, 1H), 4.80 (t, J = 6.4 Hz, 1H), 4.51 (d,
J = 7.6 Hz, 1H), 4.41 (d, J = 5.4 Hz, 1H), 3.63 (d, J = 7.5 Hz, 3H),
3.29 (d, J = 6.8 Hz, 1H), 3.05 (d, J = 8.3 Hz, 1H), 2.92 (m, 2H),
1.41 (s, 9H); 13C NMR (75 MHz, CDCl3) d/ppm = 171.6, 170.1,
157.9, 155.8, 141.2, 136.5, 134.9, 131.2, 129.0, 128.4, 127.2,
126.6, 114.2, 79.5, 70.9, 55.8, 52.9, 52.0, 44.6, 37.8, 28.4, 27.0.
Anal. Calcd for C25H30N2O6: C, 66.06; H, 6.65; N, 6.16. Found: C,
66.27; H, 6.78; N, 6.38.
4.3.6. (3S)-N-(Boc-L-Isoleucinyl)-1,2,3,4-
tetrahydroisoquinoline-3-carboxylic acid methylester (3f)
Yield: 89%. Syrupy. ESI-MS (m/e) 405 [M+H]+; IR (cmꢁ1) 2969,
1734, 1648, 1497, 1457, 1395, 1380, 1365, 1198, 1111, 750, 599;
½
a 2D0
ꢂ
ꢁ13.4 (c 1.0, CH3OH); 1H NMR (300 MHz, CDCl3) d/ppm = 8.00
4.3.11. (3S)-N-(Boc-L-Prolinyl)-1,2,3,4-tetrahydroisoquinoline-
(d, J = 7.6 Hz, 1H), 7.02 (m, J = 8.2 Hz, 2H), 6.95 (d, J = 8.8 Hz, 2H),
4.80 (d, J = 5.4 Hz, 1H), 4.51 (m, 3H), 3.63 (s, 3H), 3.10 (m, 2H), 2.5
(m, 1H), 1.41 (s, 9H), 1.29 (m, 2H), 1.06 (d, J = 6.5 Hz, 3H), 0.96 (d,
J = 8.1 Hz, 3H); 13C NMR (75 MHz, CDCl3) d/ppm = 171.6, 170.1,
155.8, 135.9, 134.2, 128.4, 127.2, 126.6, 79.5, 55.8, 52.0, 44.6, 28.4,
27.0, 24.3, 14.6, 10.9. Anal. Calcd for C22H32N2O5: C, 65.32; H, 7.97;
N, 6.93. Found: C, 65.14; H, 7.85; N, 6.70.
3- carboxylic acid methylester (3k)
Yield: 92%. Syrupy. ESI-MS (m/e) 389[M+H]+; IR (cmꢁ1) 3410,
2969, 1734, 1648, 1497, 1457, 1395, 1365, 1360, 1198, 1111, 750,
599; ½a 2D0
ꢂ
ꢁ54.6 (c 1.0, CH3OH); 1H NMR (300 MHz, CDCl3) d/
ppm = 7.02 (m, J = 8.2 Hz, 2H), 6.95 (d, J = 8.8 Hz, 2H), 4.80 (t,
J = 8.4 Hz, 1H), 4.51 (m, 2H), 4.29 (t, J = 7.6 Hz, 1H), 3.63 (s, 3H),
3.20 (m, 4H), 1.71 (m, 2H), 1.60 (m, 2H), 1.41 (s, 9H); 13C NMR
(75 MHz, CDCl3) d/ppm = 171.6, 170.1, 155.8, 135.9, 134.2, 128.4,
127.2, 126.6, 79.5, 55.8, 52.0, 47.1, 44.6, 29.7, 28.4, 27.0, 22.1. Anal.
Calcd for C21H28N2O5: C, 64.93; H, 7.27; N, 7.21. Found: C, 64.74; H,
7.15; N, 7.00.
4.3.7. (3S)-N-(Boc-L-Tryptophanyl)-1,2,3,4-
tetrahydroisoquinoline-3-carboxylic acid methylester (3g)
Yield: 84%. Syrupy. ESI-MS (m/e) 478 [M+H]+; IR (cmꢁ1) 2968,
1734, 1648, 1497, 1457, 1395, 1380, 1365, 1198, 1111, 750, 599;
½
a 2D0
ꢂ
ꢁ6.38 (c 1.0, CH3OH); 1H NMR (300 MHz, CDCl3) d/
4.3.12. (3S)-N-(Boc-L-Methioninyl)-1,2,3,4-
ppm = 10.10 (s, 1H), 8.00 (d, J = 7.6 Hz, 1H), 7.18 (m, J = 6.4 Hz,
4H), 7.02 (m, J = 8.2 Hz, 2H), 6.95 (d, J = 8.8 Hz, 2H), 6.80 (d,
J = 6.4 Hz, 1H), 4.90 (d, J = 8.0 Hz, 1H), 4.81 (d, J = 5.4 Hz, 1H),
4.51 (m, 2H), 3.63 (s, 3H), 3.10 (m, 4H), 1.41 (s, 9H); 13C NMR
(75 MHz, CDCl3) d/ppm = 171.6, 170.1, 155.8, 135.9, 134.2, 128.4,
127.2, 126.6, 122.9, 119.0, 110.9, 79.5, 55.8, 52.0, 31.5, 44.6, 28.4,
27.0. Anal. Calcd for C27H31N3O5: C, 67.91; H, 6.54; N, 8.80. Found:
C, 67.72; H, 6.43; N, 8.61.
tetrahydroisoquinoline-3-carboxylic acid methylester (3l)
Yield: 87%. Syrupy. ESI-MS (m/e) 423[M+H]+; IR (cmꢁ1) 3411,
2969, 1734, 1648, 1497, 1457, 1395, 1380, 1365, 1198, 1111,
750, 599; ½a 2D0
ꢂ
ꢁ17.7 (c 1.0, CH3OH); 1H NMR (300 MHz, CDCl3)
d/ppm = 8.00 (d, J = 7.6 Hz, 1H), 7.02 (m, J = 8.2 Hz, 2H), 6.95 (d,
J = 8.8 Hz, 2H), 4.80 (t, J = 6.4 Hz, 1H), 4.51 (m, 3H), 3.63 (s, 3H),
3.29 (d, J = 5.3 Hz, 1H), 3.05 (d, J = 7.6 Hz, 1H), 2.44 (m, 2H), 2.16
(t, J = 6.6 Hz, 2H), 2.09 (s, 3H), 1.41 (s, 9H); 13C NMR (75 MHz,
CDCl3) d/ppm = 171.6, 170.1, 155.8, 135.9, 134.2, 128.4, 127.2,
126.6, 79.5, 55.8, 52.0, 51.6, 44.6, 31.9, 29.3, 28.4, 27.0, 17.4. Anal.
Calcd for C21H30N2O5S: C, 59.69; H, 7.16; N, 6.63. Found: C, 59.49;
H, 7.04; N, 6.84.
4.3.8. (3S)-N-(Boc-L-Serinyl)-1,2,3,4-tetrahydroisoquinoline-3-
carboxylic acid methylester (3h)
Yield: 80%. Syrupy. ESI-MS (m/e) 469 [M+H]+; IR (cmꢁ1) 3411,
2969, 1734, 1648, 1497, 1457, 1395, 1365, 1198, 1111, 750, 599;
½
a 2D0
ꢂ
ꢁ7.61 (c 1.0, CH3OH); 1H NMR (300 MHz, CDCl3) d/ppm = 8.00
4.3.13. (3S)-N-(Boc-L-Asparaginyl)-1,2,3,4-tetrahydroisoquino
(d, J = 5.6 Hz, 1H), 7.02 (m, J = 8.2 Hz, 2H), 6.95 (d, J = 8.8 Hz, 2H),
4.83 (m, J = 8.2 Hz, 1H), 4.63 (s, 2H), 4.51 (m, 2H), 3.86 (m, 2H),
3.63 (s, 3H), 3.29 (d, J = 6.5 Hz, 1H), 3.05 (d, J = 8.6 Hz, 1H), 1.41 (s,
9H); 13C NMR (75 MHz, CDCl3) d/ppm = 171.6, 170.1, 155.8, 137.2,
135.9, 134.2, 128.4, 127.2, 125.6, 79.5, 74.3, 70.2, 55.8, 52.0, 50.7,
44.6, 28.4, 27.0. Anal. Calcd for C19H26N2O6: C, 60.30; H, 6.93; N,
7.40. Found: C, 60.11; H, 6.81; N, 7.59.
line-3-carboxylic acid methylester (3m)
Yield: 55%. Syrupy. ESI-MS (m/e) 406[M+1]+; IR (cmꢁ1) 3411,
2969, 1734, 1648, 1497, 1457, 1395, 1380, 1365, 1198, 1111, 750,
599; ½a 2D0
ꢂ
ꢁ10.4 (c 1.0, CH3OH); 1H NMR (300 MHz, CDCl3) d/
ppm = 8.00 (d, J = 5.6 Hz, 1H), 7.02 (m, J = 8.2 Hz, 2H), 6.95 (d,
J = 8.8 Hz, 2H), 6.0 (s, 2H), 4.78 (m, 2H), 4.51 (d, J = 6.4 Hz, 1H), 4.41
(d, J = 5.4 Hz, 1H), 3.63 (s, 3H), 3.29 (d, J = 7.2 Hz, 1H), 3.05 (d,
J = 8.6 Hz, 1H), 2.68 (m, 2H), 1.41 (s, 9H); 13C NMR (75 MHz, CDCl3)
d/ppm = 174.5, 171.6, 170.1, 155.8, 135.9, 134.2, 128.4, 127.2,
126.6, 79.5, 55.8, 52.0, 51.6, 44.6, 37.9, 28.4, 27.0. Anal. Calcd for
C20H26N2O7: C, 59.10; H, 6.45; N, 6.89. Found: C, 59.31; H, 6.58; N,
6.69.
4.3.9. (3S)-N-(Boc-L-Threoninyl)-1,2,3,4-
tetrahydroisoquinoline-3-carboxylic acid methylester (3i)
Yield: 89%. Syrupy, ESI-MS (m/e) 393 [M+1]+; IR (cmꢁ1) 3411,
2969, 1734, 1648, 1497, 1457, 1395, 1380, 1365, 1198, 1111,
750; ½a 2D0
ꢂ
ꢁ20.1 (c 1.0, CH3OH); 1H NMR (300 MHz, CDCl3)
d/ppm = 8.00 (d, J = 6.6 Hz, 1H), 7.02 (m, J = 8.2 Hz, 2H), 6.95 (d,
J = 8.8 Hz, 2H), 4.80 (t, J = 7.1 Hz, 1H), 4.61 (d, J = 8.2 Hz, 1H), 4.46
(m, 2H), 4.24 (m, 1H), 3.63 (s, 3H), 3.29 (d, J = 5.4 Hz, 1H), 3.05
(d, J = 6.4 Hz, 1H), 2.0 (s, 1H), 1.48 (s, 9H), 1.21 (d, J = 7.1 Hz, 3H);
13C NMR (75 MHz, CDCl3)/ppm = 171.6, 170.1, 155.8, 135.9,
134.2, 128.4, 127.2, 126.6, 79.5, 67.8, 58.8, 55.0, 51.7, 44.6, 28.4,
27.0, 10.9. Anal. Calcd for C20H28N2O6: C, 61.21; H, 7.19; N, 7.14.
Found: C, 61.40; H, 7.07; N, 7.36.
4.3.14. (3S)-N-(Boc-L-Glutaminyl)-1,2,3,4-tetrahydroisoquino
line-3-carboxylic acid methylesters (3n)
Yield: 45%. Syrupy. ESI-MS (m/e) 420[M+1]+; IR (cmꢁ1) 3411,
2969, 1734, 1648, 1497, 1457, 1395, 1380, 1365, 1198, 1111, 750,
599; ½a 2D0
ꢂ
ꢁ14.7 (c 1.0, CH3OH); 1H NMR (300 MHz, CDCl3)
d/ppm = 8.00 (d, J = 5.6 Hz, 1H), 7.02 (m, J = 8.2 Hz, 2H), 6.95 (d,
J = 8.8 Hz, 2H), 4.78 (t, J = 6.4 Hz, 1H), 4.48 (m, 3H), 3.63 (s, 3H),
3.29 (d, J = 7.2 Hz, 1H), 3.05 (d, J = 6.6 Hz, 1H), 2.18 (t, J = 8.5 Hz,
2H), 2.07 (m, 2H), 1.41 (s, 9H); 13C NMR (75 MHz, CDCl3)
d/ppm = 174.5, 171.6, 170.1, 155.8, 135.9, 134.2, 128.4, 127.2,
126.6, 79.5, 55.8, 52.0, 51.6, 44.6, 32.6, 28.4, 27.6, 27.0. Anal. Calcd
for C21H28N2O7: C, 59.99; H, 6.71; N, 6.66. Found: C, 59.78; H, 6.60;
N, 6.85.
4.3.10. (3S)-N-(Boc-L-Tyrocinyl)-1,2,3,4-tetrahydroisoquinoline-
3-carboxylic acid methylester (3j)
Yield: 82%. Syrupy. ESI-MS (m/e) 545[M+H]+; IR (cmꢁ1) 3411,
2969, 1734, 1648, 1497, 1457, 1395, 1380, 1365, 1198, 1111,
750, 599; ½a 2D0
ꢂ
ꢁ6.86 (c 1.0, CH3OH); 1H NMR (300 MHz, CDCl3)