J. Sperry, C.J. Moody / Tetrahedron 66 (2010) 6483–6495
6495
3064, 2960, 2926, 2873, 2855, 1707, 1621, 1597, 1572, 1525, 1458,
1431, 1374, 1335, 1282, 1244, 1213, 1128, 1084, 1027, 977, 929, 745;
dH (300 MHz; DMSO-d6) 11.26 (2H, br s, 2 NH), 8.67 (1H, s, ArH),
8.20 (1H, d, J 8.5, NH), 8.13 (1H, d, J 8.0, ArH), 7.53 (1H, d, J 7.9, ArH),
7.35–7.17 (11H, m, ArH), 5.11–5.07 (2H, m, CH2), 4.65–4.60 (1H, m,
CH), 3.85 (3H, s, Me), 2.08–1.93 (1H, m, CHMe2), 1.01 (3H, d, J 6.3,
CHMeMe), 0.91 (3H, d, J 6.3, CHMeMe); dC (75 MHz; DMSO-d6)
163.0, 160.1, 156.9, 156.6, 154.5, 139.2, 137.2, 136.3, 130.3 (CH), 129.3
(CH), 128.7 (CH), 128.6 (CH), 128.2 (CH), 128.l (CH), 125.7 (CH),
125.0, 123.0 (CH), 122.1, 121.4 (CH), 121.1 (CH), 112.9, 112.7 (CH),
102.6, 66.0 (CH2), 55.4 (CH), 51.8 (Me), 31.3 (CH), 19.5 (Me), 19.1
(Me), 1ꢃCH and 4ꢃC not observed; m/z (FABþ) 710 (MHþ, 2%), 708
(MHþ, 1), 472 (1), 470 (3), 450 (4), 449 (11), 448 (33), 447 (16), 331
(1), 329 (2), 314 (1), 312 (5), 309 (2), 308 (7), 307 (28), 291 (3), 290
(5), 289 (14), 274 (2), 273 (3), 272 (2), 271 (1), 219 (7), 216 (4), 178
(2), 176 (6), 165 (6), 164 (2), 156 (7), 155 (27), 154 (100), 153 (7), 152
(9), 151 (3), 150 (4), 144 (6).
(CH), 103.2, 102.7, 65.6 (CH2), 56.8 (Me), 53.0 (CH), 52.3 (CH), 31.7
(CH), 19.6 (Me), 19.1 (Me), 1ꢃCH2 not observed; m/z (ESþ) 793
(3%, MHþ), 698 (3), 687 (12), 685 (39), 684 (95), 669 (11), 651 (10),
641 (10), 638 (17), 637 (31), 579 (9), 494 (9), 420 (11), 394 (10), 365
(9), 337 (9), 310 (9), 309 (10), 280 (19), 266 (23), 239 (21), 223 (29),
219 (52), 205 (50), 170 (53), 169 (80), 168 (100), 144 (20), 117 (15),
108 (58), 107 (63), 91 (30), 79 (99), 77 (98), 53 (28), 52 (81), 46 (70).
Acknowledgements
We thank the EPSRC for support of this work (Senior Research
Fellowship to CJM, DTA award to JS), and the EPSRC Mass Spec-
trometry Service Centre at Swansea for mass spectra.
References and notes
1. Lindquist, N.; Fenical, W.; VanDuyne, G. D.; Clardy, J. J. Am. Chem. Soc. 1991, 113,
2303–2304.
2. Cruz-Monserrate, Z.; Vervoort, H. C.; Bai, R. L.; Newman, D. J.; Howell, S. B.; Los,
G.; Mullaney, J. T.; Williams, M. D.; Pettit, G. R.; Fenical, W.; Hamel, E. Mol.
Pharmacol. 2003, 63, 1273–1280.
3. Li, J.; Jeong, S.; Esser, L.; Harran, P. G. Angew. Chem., Int. Ed. 2001, 40, 4765–4770.
4. Li, J.; Burgett, A. W. G.; Esser, L.; Amezcua, C.; Harran, P. G. Angew. Chem., Int. Ed.
2001, 40, 4770–4773.
5. Nicolaou, K. C.; Bella, M.; Chen, D. Y. K.; Huang, X. H.; Ling, T. T.; Snyder, S. A.
Angew. Chem., Int. Ed. 2002, 41, 3495–3499.
6. Nicolaou, K. C.; Chen, D. Y. K.; Huang, X. H.; Ling, T. T.; Bella, M.; Snyder, S. A.
J. Am. Chem. Soc. 2004, 126, 12888–12896.
4.6.31. (S,S,S,S)-Methyl [2-{2-[2-benzyloxycarbonyamino-(2-methyl-
propyl)-4-hydroxyphenyl-propionylamino]-3-methyl-
butanoylamino]-3-(indol-3-yl)-propionylamino]-3-(indol-3-yl)pro-
panoate (Z-Tyr-Val-Trp-Trp-OMe) 37. According to general proce
dure A the title compound was obtained from Z-Tyr-OH (378 mg,
1.2 mmol) and amine 22 (503 mg, 1 mmol) as a colourless solid
30
(489 mg, 61%), mp 111–113 ꢂC (from ethyl acetate); [
a
]
þ11.3
D
(c 0.8, THF); (Found: C, 67.2; H, 6.1; N, 10.0. C45H48N6O8 requires C,
67.5; H, 6.0; N, 10.3%); (Found: MHþ, 801.3603. C45H48N6O8þH
requires 801.3606); nmax (KBr)/cmꢀ1 3418, 3061, 2980, 1700, 1638,
1532,1516,1457,1440,1365,1344,1257,1218,1139,1104,1080,1050,
817, 742, 698; dH (400 MHz; DMSO-d6); 10.87 (1H, br s, NH), 10.83
(1H, br s, NH), 9.19 (1H, s, OH), 8.33 (1H, d, J 7.1, NH), 8.09 (1H, d,
J 7.9, NH), 7.83 (1H, d, J 8.8, NH), 7.57 (1H, d, J 8.0, ArH), 7.47–7.42
(1H, m, ArH), 7.34–7.22 (8H, m, 7ꢃArH and NH), 7.13–7.04 (6H, m,
ArH), 6.97 (2H, m, ArH), 6.64 (2H, m, ArH), 4.95 (2H, s, CH2), 4.63
(1H, m, CH), 4.54–4.50 (1H, m, CH), 4.26–4.19 (2H, m, 2ꢃCH), 3.51
(3H, s, Me), 3.12–3.05 (3H, m, CH of CH2 and CH2), 3.01–2.91 (2H, m,
CH2), 2.62–2.56 (1H, m, CH of CH2), 1.95–1.90 (1H, m, CHMe2), 0.77
(6H, d, J 5.8, CHMe2); dC (100 MHz; DMSO-d6) 172.4, 172.0, 171.9,
171.8, 171.1, 156.3, 156.2, 137.5, 136.5, 136.4, 130.7 (CH), 130.6, 128.8
(CH), 128.7, 128.3 (CH), 128.1 (CH), 127.9, 127.8 (CH), 127.5, 124.0
(CH), 121.4 (CH), 118.8 (CH), 118.7 (CH), 118.3 (CH), 115.2 (CH), 111.9
(CH), 111.7 (CH), 110.2 (CH), 109.6 (CH), 65.6 (CH2), 57.9 (CH), 56.8
(Me), 53.5 (CH), 53.4 (CH), 52.2 (CH), 36.9 (CH2), 30.9 (CH), 28.2
(CH2), 27.6 (CH2), 19.6 (Me), 18.4 (Me); m/z (ESþ) 801 (MHþ, 90%),
583 (10), 405 (14), 366 (21), 365 (49), 247 (72), 225 (100), 159 (23),
143 (33), 100 (99), 83 (22), 72 (41), 61 (64), 43 (28).
7. Nicolaou, K. C.; Rao, P. B.; Hao, J. L.; Reddy, M. V.; Rassias, G.; Huang, X. H.; Chen,
D. Y. K.; Snyder, S. A. Angew. Chem., Int. Ed. 2003, 42, 1753–1758.
8. Nicolaou, K. C.; Hao, J. L.; Reddy, M. V.; Rao, P. B.; Rassias, G.; Snyder, S. A.;
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4.6.32. (S,S)-Methyl 2-{1-[2-benzyloxycarbonylamino-3-(4-hydroxy-
phenyl)propionylamino]-2-methyl-propyl}-2,40]bis-oxazoyl-4-car-
boxylate 38. According to general procedure B the title compound
was obtained from 37 (80 mg, 0.1 mmol) as an orange solid, (14 mg,
25
17%), mp 146–148 ꢂC (from ethyl acetate); [
a
]
þ40.0 (c 0.1, THF);
D
(Found: MHþ, 793.2985. C45H40N6O8þH requires 793.2980); nmax
(KBr)/cmꢀ1 3411, 2960, 2915, 1704, 1668, 1617, 1589, 1516, 1457,
1375, 1337, 1244, 1218, 1130, 1086, 1052, 745; dH (400 MHz; DMSO-
d6); 12.00 (2H, br s, 2 NH), 9.21 (1H, d, J 2.9, ArH), 9.11 (1H, s, OH),
8.82 (1H, d, J 8.7, NH), 8.72 (1H, d, J 2.9, ArH), 8.18 (1H, d, J 7.8, ArH),
8.13 (1H, d, J 7.7, ArH), 7.40–7.38 (2H, m, ArH), 7.73–7.05 (12H, m, 11
ArH and NH), 6.58–6.56 (2H, m, ArH), 5.08–5.01 (1H, m, CH), 4.93
(2H, s, CH2), 4.39 (1H, m, CH), 3.91 (3H, s, Me), 2.95 (1H, m, CH of
CH2), 2.70 (1H, m, CH of CH2), 2.46 (1H, m, CHMe2), 1.11 (3H, d, J 6.6,
CHMeMe), 1.03 (3H, d, J 6.6, CHMeMe); dC (100 MHz; DMSO-d6)
172.6,163.1,160.9, 156.4,156.2,153.9, 152.7,149.1,137.5,136.6,136.5,
130.7 (CH), 129.2 (CH), 128.8 (CH), 128.7 (CH), 128.5, 128.14 (CH),
128.09 (CH), 128.0 (CH), 127.9 (CH), 125.2, 125.0, 123.4, 123.1 (CH),
121.6 (CH), 121.4 (CH), 119.8, 115.5 (CH), 115.2 (CH), 112.8 (CH), 112.7