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R. El-Haggar et al. / Bioorg. Med. Chem. Lett. 20 (2010) 1169–1172
OH
OH
1. (EtO)2POCH2CO2Et,
WSCI, NH4OH aq.,
NaH, THF, 90%
OH
HOBT, CH2Cl2
62%
2. NaOH, MeOH, 86%
CHO
Br
19
O
Br
18
OH
OH
O
tBuO
NH2
NH2
O
Pd(PPh3)4, DMF,
Br
O
Et3N, 98%
20
tBuO
O
21
OH
OTf
Pd/C, H2, MeOH
90%
Tf2O, pry.
64%
NH2
NH2
O
O
tBuO
O
tBuO
O
22
23
BocHN
O
O
1.
B(OH)2
24
Pd(PPh3)4, MeOH, H2O, Na2CO3
2. HCl, AcOH, CH2Cl2
77%, 2 steps
Scheme 3. Synthesis of biphenyl ligand 4.
4
2. Suzuki, N.; Fujii, I. Tetrahedron Lett. 1999, 40, 6013.
Table 1
3. (a) Bazan, J. F. Science 1992, 257, 410; (b) De Vos, A. M.; Ultsch, M.; Kossiakoff,
A. A. Science 1992, 255, 306; (c) McKay, D. B. Science 1992, 257, 412; (d)
Redfield, C.; Smith, L. J.; Boyd, J.; Lawrence, G. M. P.; Edwards, R. G.; Smith, R. A.
G.; Dobson, C. M. Biochemistry 1991, 30, 11029.
4. (a) Nicola, N. A.; Metcalf, D.; Matsumoto, M.; Johnson, G. R. J. Biol. Chem.
1983, 258, 9017; (b) Souza, L. M.; Boone, T. C.; Gabriloe, J.; Lai, P. H.;
Zaebo, K. M.; Murdock, D. C.; Chazin, V. R.; Bruszewski, J.; Lu, H.; Chen, K.
K.; Barendt, J.; Platzer, E.; Moore, M. A. S.; Mertelsmann, R.; Welte, K.
Science 1986, 232, 61; (c) Clark, S. C.; Kamen, R. Science 1987, 236, 1229;
(d) Nagata, S.; Fukunaga, R. Prog. Growth Factor Res. 1991, 3, 131; (e)
Roberts, A. W. Growth Factors 2005, 23, 33; (f) Koda, M.; Nishio, Y.;
Kamada, T.; Someya, Y.; Okawa, A.; Mori, C.; Yoshinaga, K.; Okada, S.;
Moriya, H.; Yamazaki, M. Brain Res. 2007, 1149, 223.
Dissociation constants of ligands 2–5 determined by SPR
Entry
Ligand
Kd
(lM)
1
2
3
4
2
3
4
5
47
a
—
20
a
—
a
No binding affinity.
Therefore, ligands inhibiting the interaction would be of interest as
cytotoxic agents for the treatment of cancer.12 Further design of
new ligands are ongoing in an effort to delineate the activity of this
class of small compound.
5. (a) Heck, R. F. Org. React. 1982, 27, 345; (b) Beletskaya, I. P.; Cheprakov, A. V.
Chem. Rev. 2000, 100, 3009.
6. (a) Orner, B. P.; Ernst, J. T.; Hamilton, A. D. J. Am. Chem. Soc. 2001, 123, 5382; (b)
Kutzki, O.; Park, S.; Ernst, J. T.; Orner, B. P.; Yin, H.; Hamilton, A. D. J. Am. Chem.
Soc. 2002, 124, 1838; (c) Yin, H.; Lee, G. I.; Sedey, K. A.; Rodriguez, J. M.; Wang,
H. G.; Sebti, S. M.; Hamilton, A. D. J. Am. Chem. Soc. 2005, 127, 5463; (d) Yin, H.;
Sedey, K. A.; Kutzki, O.; Park, H. S.; Orner, B. P.; Ernst, J. T.; Wang, H. G.; Sebti, S.
M.; Hamilton, A. D. J. Am. Chem. Soc. 2005, 127, 10191; (e) Davis, J. M.; Truong,
A.; Hamilton, A. D. Org. Lett. 2005, 7, 5405; (f) Yin, H.; Hamilton, A. D. Angew.
Chem., Int. Ed. 2005, 44, 4130; (g) Kim, I. C.; Hamilton, A. D. Org. Lett. 2006, 7,
1751; (h) Cummings, C. G.; Ross, N. T.; Katt, W. P.; Hamilton, A. D. Org. Lett.
2009, 11, 25.
Acknowledgment
We are grateful to the Egyptian Government for the post-grad-
uate scholarship provided to R. El-H.
7. Kaiser, F.; Schwink, L.; Velder, J.; Schmalz, H. G. J. Org. Chem. 2002, 67, 9248.
8. Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457.
9. See Supplementary data for detail.
Supplementary data
10. (a) Myszka, D. G. Curr. Opin. Biotechnol. 1997, 8, 50; (b) Myszka, D. G.
Methods Enzymol. 2000, 323, 325; (c) Myszka, D. G. Anal. Biochem. 2004,
329, 316.
11. (a) Nicola, N. A.; Begley, C. G.; Metcalf, D. Nature 1985, 314, 625; (b)
Craig, L. S.; Fulu, L.; Alyssa, D. G.; Katherine, S.; Daniel, C. L. Immunity
2002, 17, 413.
Supplementary data associated with this article can be found, in
References and notes
12. Michelle, B. M.; Hong, X.; James, A. T.; Daniel, E. J. Leuk. Res. 2005, 29, 1293.
1. Fujii, I.; Takaoka, Y.; Suzuki, K.; Tanaka, T. Tetrahedron Lett. 2001, 42, 3323.