3946
J. Dourlat et al. / Bioorg. Med. Chem. Lett. 17 (2007) 3943–3946
8. Beaulieu, P. L.; Cameron, D. R.; Ferland, J. M.; Gauthier,
Compound 7: 1H NMR (250 MHz, CDCl3): d 1.51 (s,
18H), 3.12 (m, 2H, bCH), 4.45 (m, 4H, Fmoc CH, Fmoc
CH2, aCH), 5.18 (s, 1H), 5.26 (d, 1H, NH), 6.91 (d, 2H,
J = 7.5 Hz), 7.07 (d, 2H, J = 7.5 Hz), 7.33–7.46 (m, 4H),
7.58 (d, 2H, J = 7.5 Hz), 7.78 (d, 2H, J = 7.5 Hz). MS
(ESI) m/z calcd: 617.2 Found: 640.3 [M+Na]+.
22. Synthesis of the core peptide LPQTV was carried out by
solid phase on HMP resin on an A433 synthesizer
(Applied Biosystems) using the standard Fmoc chemistry
protocol. HBTU/HOBt/DIPEA were used as coupling
agents. Phosphotyrosine was introduced with its phos-
phate group diprotected by methyldiphenylsilyl(ethyl)
moiety. N-Fmoc or N-acetyl-protected phenylalanine
derivatives were coupled manually using either coupling
agents HBTU/HOBt/DIPEA or HATU/HOAt/DIPEA in
the case of tetrazolyl derivatives. In the case of N-Fmoc
protected peptides, final N-acetylation was achieved, after
Fmoc-deprotection, by treatment with excess acetic anhy-
dride in NMP.
J.; Ghiro, E.; Gillard, J.; Gorys, V.; Poirier, M.; Rancourt,
J.; Wernic, D.; Llinas-Brunet, M.; Betageri, R.; Cardozo,
M.; Hickey, E. R.; Ingraham, R.; Jakes, S.; Kabcenell, A.;
Kirrane, T.; Lukas, S.; Patel, U.; Proudfoot, J.; Sharma,
R.; Tong, L.; Moss, N. J. Med. Chem. 1999, 42, 1757.
9. Ren, Z.; Cabell, L. A.; Schaefer, T. S.; McMurray, J. S.
Bioorg. Med. Chem. Lett. 2003, 13, 633.
10. Turkson, J.; Kim, J. S.; Zhang, S.; Yuan, J.; Huang, M.;
Glenn, M.; Haura, E.; Sebti, S.; Hamilton, A. D.; Jove, R.
Mol. Cancer Ther. 2004, 3, 261.
11. Coleman, D. R. T.; Ren, Z.; Mandal, P. K.; Cameron, A.
G.; Dyer, G. A.; Muranjan, S.; Campbell, M.; Chen, X.;
McMurray, J. S. J. Med. Chem. 2005, 48, 6661.
12. Tilley, J. W.; Danho, W.; Lovey, K.; Wagner, R.; Swistok,
J.; Makofske, R.; Michalewsky, J.; Triscari, J.; Nelson, D.;
Weatherford, S. J. Med. Chem. 1991, 34, 1125.
13. Oppolzer, W.; Moretti, R.; Thomi, S. Tetrahedron Lett.
1989, 30, 6009.
14. McMurray, J. S.; Khabashesku, O.; Birtwistle, J. S.;
Wang, W. Tetrahedron Lett. 2000, 41, 6555.
15. Ye, B.; Akamatsu, M.; Shoelson, S. E.; Wolf, G.;
Giorgetti-Peraldi, S.; Yan, X.; Roller, P. P.; Burke, T.
R., Jr. J. Med. Chem. 1995, 38, 4270.
Resin cleavage and peptide side-chain deprotection were
achieved by treatment with TFA/TIPS/H2O 95:2.5:2.5 in
volume. Peptides were purified by reverse-phase HPLC
and gave the correct mass by electrospray mass spectrom-
etry.
16. Ledon, H. J. Org. Synth. 1988, 6, 414.
17. House, H. O.; Czuba, L. J.; Gall, M.; Olmstead, H. D.
J. Org. Chem. 1969, 34, 2324.
18. Reuss, R. H.; Hassner, A. J. Org. Chem. 1974, 39, 1785.
19. Sarges, R.; Hank, R. F.; Blake, J. F.; Bordner, J.;
Bussolotti, D. L.; Hargrove, D. M.; Treadway, J. L.;
Gibbs, E. M. J. Med. Chem. 1996, 39, 4783.
MS (ESI) m/z:
Peptide 8: calcd: 841.4 Found: 842.4 [M+H]+.
Peptide 9: calcd: 839.4 Found: 840.3 [M+H]+.
Peptide 10: calcd: 813.4 Found:812.4 [MÀH]À.
Peptide 11: calcd: 827.4 Found: 828.4 [M+H]+.
Peptide 12: calcd: 819.9 Found: 820.6[M+H]+.
Peptide 13: calcd: 863.4 Found: 864.3 [M+H]+.
23. Liu, W. Q.; Roques, B. P.; Garbay-Jaureguiberry, C.
Tetrahedron: Asym. 1995, 6, 647.
20. Larsen, S. D.; Barf, T.; Liljebris, C.; May, P. D.; Ogg, D.;
O’Sullivan, T. J.; Palazuk, B. J.; Schostarez, H. J.; Stevens,
F. C.; Bleasdale, J. E. J. Med. Chem. 2002, 45, 598.
24. Burke, T. R., Jr.; Yao, Z. J.; Zhao, H.; Milne, G. W.; Wu,
L.; Zhang, Z. Y.; Voigt, J. Tetrahedron 1998, 54, 9981.
25. Becker, S.; Groner, B.; Muller, C. W. Nature 1998, 394,
145.
26. Yao, Z. J.; King, C. R.; Cao, T.; Kelley, J.; Milne, G. W.;
Voigt, J. H.; Burke, T. R., Jr. J. Med. Chem. 1999, 42, 25.
1
21. Compound 5: H (NMR, 250 MHz, (DMSO-d6): d (ppm)
2.02 (s, 3H, CH3), 3.14 (m, 1H, bCHa), 3.26 (m, 1H,
bCHb), 4.32 (s, 2H), 4.91 (m, 1H, aCH), 6.27 (d, 1H, NH),
7.19 (d, 2H, J = 7.5 Hz), 7.27 (d, 2H, J = 7.5 Hz). MS
(ESI) m/z calcd: 289.1 Found: 312.1 [M+Na]+.