K. Wright et al. / Tetrahedron 64 (2008) 4416e4426
4425
5. (a) Brasch, R.; London, D.; Wesbey, G.; Tozer, T.; Nitecki, D.; Williams,
R.; Doemeny, J.; Dallas Tuck, L.; Lallemand, D. Radiology 1983, 147,
773e779; (b) Winalski, C.; Shortkroff, S.; Mulkern, R.; Schneider, E.;
Rosen, G. Magn. Reson. Med. 2002, 48, 965e972.
(TOF ES MS) calcd for C31H38N3O6Na: 571.2658; found:
571.2665}.
6. (a) Lex, L.; Hideg, K.; Hankovszky, H. O. Can. J. Chem. 1982, 60, 1448e
1451; (b) Hideg, K.; Hankovszky, H. O. Biological Magnetic Resonance;
Berliner, L. J., Reuben, J., Eds.; Spin Labelling Theory and Applications;
Plenum: New York, NY, 1989; Vol. 8, pp 427e488; (c) Hideg, K.; CsekT,
4.17. Boc-[(1S,2S)-ACPC-(3R,4R)-POAC-(1S,2S)-ACPC]2-
OMe 12
To a solution of tetrapeptide 10 (35 mg, 0.054 mmol) in
THF (2 mL), MeOH (1 mL) and H2O (0.5 mL) was added so-
dium hydroxide (20 mg). The mixture was stirred at 50 ꢂC
overnight, then concentrated under reduced pressure, diluted
with H2O (3 mL) and neutralized by careful addition of
a 0.5 N HCl solution. The solution was extracted three times
with CH2Cl2. The combined CH2Cl2 extracts were dried
(MgSO4), filtered and evaporated in vacuo to afford
crude Boc-(1S,2S)-ACPC-(3R,4R)-POAC-[(1S,2S)-ACPC]2-OH
(34 mg; 0.054 mmol). In parallel, the dipeptide 11 (35 mg,
0.064 mmol) was dissolved in CH3CN (2 mL) and diethyl-
amine (0.2 mL) was added. The mixture was stirred at rt for
3 h, then evaporated in vacuo. The resulting crude
H-(3R,4R)-POAC-(1S,2S)-ACPC-OMe was dissolved in THF
(2 mL) and the solution added to the residue of crude
Boc-(1S,2S)-ACPC-(3R,4R)-POAC-[(1S,2S)-ACPC]2-OH. The
resulting solution was cooled to 0 ꢂC and HATU (24 mg;
0.064 mmol) was added, followed by DIEA (0.010 mL). The
mixture was stirred at 0 ꢂC for 2 h, at rt for six days, and
then evaporated in vacuo. The residue was taken up in
CH2Cl2 and the organic phase was washed successively with
a 0.5 M HCl solution, H2O, a saturated NaHCO3 solution,
then dried (MgSO4), filtered and evaporated in vacuo. The
crude product was purified by chromatography on a preparative
TLC plate of silica gel with CH2Cl2/MeOH 92.5:7.5 as eluant
to afford 26 mg (51%) of pure hexapeptide 12 as a solid {mp
196e198 ꢂC. Rf 0.42 (CH2Cl2/MeOH 97.5:7.5). [a]25859 þ128;
´
J.; Hankovszky, H. O.; Sohar, P. Can. J. Chem. 1986, 64, 1482e1490.
7. (a) Rassat, A.; Rey, P. Bull. Soc. Chim. Fr. 1967, 3, 815e817; (b) Nakaie,
C. R.; Goissis, G.; Schreier, S.; Paiva, A. C. M. Braz. J. Med. Biol. Res.
1981, 14, 173e180; (c) Seidemann, R.; Dulog, L. Makromol. Chem.
1986, 187, 2545e2551.
´
8. Balog, M.; Kalai, T.; JekT, J.; Berente, Z.; Steinhoff, H.-J.; Engelhard, M.;
Hideg, K. Tetrahedron Lett. 2003, 44, 9213e9217.
9. Preliminary reports of part of this work have been published: (a) Wright,
´
K.; Formaggio, F.; Toniolo, C.; Torok, R.; Peter, A.; Wakselman, M.; Ma-
¨ ¨
´
zaleyrat, J.-P. Tetrahedron Lett. 2003, 44, 4183e4186; (b) Peter, A.;
Torok, R.; Wright, K.; Wakselman, M.; Mazaleyrat, J.-P. J. Chromatogr.,
¨ ¨
A 2003, 1021, 1e10; (c) Wright, K.; De la Croix de Castries, A.; Sarciaux,
´
M.; Wakselman, M.; Mazaleyrat, J.-P.; Torok, R.; Peter, A.; Crisma, M.;
¨ ¨
Formaggio, F.; Toniolo, C. Peptides 2004; Flegel, M., Fridkin, M., Gilon,
C., Slaninova, J., Eds.; Kenes International: Geneva, Switzerland, 2005;
pp 1047e1048.
´
10. (a) Wright, K.; Crisma, M.; Toniolo, C.; Torok, R.; Peter, A.; Wakselman,
¨ ¨
M.; Mazaleyrat, J.-P. Tetrahedron Lett. 2003, 44, 3381e3384; (b) Wright,
K.; De Castries, A.; Sarciaux, M.; Formaggio, F.; Toniolo, C.; Toffoletti,
A.; Wakselman, M.; Mazaleyrat, J.-P. Tetrahedron Lett. 2005, 46, 5573e
5576; (c) Wright, K.; Sarciaux, M.; De Castries, A.; Wakselman, M.;
Mazaleyrat, J.-P.; Toffoletti, A.; Corvaja, C.; Crisma, M.; Peggion, C.;
Formaggio, F.; Toniolo, C. Eur. J. Org. Chem. 2007, 3133e3144.
´
11. Hideg, K.; Hankovszky, H. O.; Halasz, H. A.; Sohar, P. J. Chem. Soc.,
´
Perkin Trans. 1 1986, 1482e1490.
12. (a) Marchetto, R.; Schreier, S.; Nakaie, C. R. J. Am. Chem. Soc. 1993, 115,
11042e11043; (b) Toniolo, C.; Valente, E.; Formaggio, F.; Crisma, M.;
Pilloni, G.; Corvaja, C.; Toffoletti, A.; Martinez, G. V.; Hanson, M. P.;
Millhauser, G. L.; George, C.; Flippen-Anderson, J. L. J. Pept. Sci.
1995, 1, 45e47; (c) Toniolo, C.; Crisma, M.; Formaggio, F. Biopolymers
1998, 47, 153e158; (d) Martin, L.; Ivancich, A.; Vita, C.; Formaggio, F.;
Toniolo, C. J. Pept. Res. 2001, 58, 424e432.
25
25
25
13. (a) Hanson, P.; Millhauser, G.; Formaggio, F.; Crisma, M.; Toniolo, C.
J. Am. Chem. Soc. 1996, 118, 7618e7625; (b) Toniolo, C.; Formaggio,
F.; Crisma, M.; Mazaleyrat, J.-P.; Wakselman, M.; George, C.;
Deschamps, J.; Flippen-Anderson, J. L.; Pispisa, B.; Venanzi, M.;
Palleschi, A. Chem.dEur. J. 1999, 5, 2254e2264; (c) Corvaja, C.;
Sartori, E.; Toffoletti, A.; Formaggio, F.; Crisma, M.; Toniolo, C.;
Mazaleyrat, J.-P.; Wakselman, M. Chem.dEur. J. 2000, 6, 2775e2782;
(d) Pispisa, B.; Mazzuca, C.; Palleschi, A.; Stella, L.; Venanzi, M.;
Wakselman, M.; Mazaleyrat, J.-P.; Rainaldi, M.; Formaggio, F.; Toniolo,
C. Chem.dEur. J. 2003, 9, 4084e4093.
[a]
þ140; [a]
þ181; [a]
þ146; (c 0.13, CH2Cl2).
578
546
436
ESIþ MS m/z (%): 966.0 (calcd 965.6) [M, Na]þ. Anal. Calcd
for C48H78N8O11 (943.168): C, 61.12; H, 8.34. Found: C,
61.54; H, 8.71. HRMS (TOF ES MS) calcd for
C48H78N8O11Na: 965.5688; found: 965.5748}.
References and notes
1. (a) Griffith, O. H.; Waggoner, A. S. Acc. Chem. Res. 1969, 2, 17e24; (b)
Keana, J. F. Chem. Rev. 1978, 78, 37e64; (c) Millhauser, G. L. Trends
Biochem. Sci. 1992, 17, 448e452; (d) Columbus, L.; Hubbell, W. L.
Trends Biochem. Sci. 2002, 27, 288e295.
14. (a) Iverson, B. L. Nature 1997, 385, 113e115; (b) Seebach, D.; Matthews,
J. L. Chem. Commun. 1997, 2015e2022; (c) Cheng, R. P.; Gellman, S. H.;
DeGrado, W. F. Chem. Rev. 2001, 101, 3219e3232; (d) Seebach, D.;
Beck, A. K.; Bierbaum, D. J. Chem. Biodivers. 2004, 1, 1111e1239; (e)
ˇ
2. (a) Beckwith, A. L. J.; Bowry, V. W.; Ingold, K. U. J. Am. Chem. Soc.
1992, 114, 4983e4992; (b) Bowry, V. W.; Ingold, K. U. J. Am. Chem.
Soc. 1992, 114, 4992e4996; (c) Hawker, C. J.; Bosman, A. W.; Harth,
E. Chem. Rev. 2001, 101, 3661e3688.
Hook, D. F.; Bindschadler, P.; Mahajan, Y. R.; Sebesta, R.; Kast, P.;
¨
Seebach, D. Chem. Biodivers. 2005, 2, 591e632; (f) Seebach, D.;
Hook, D.; Glattli, A. Biopolymers (Pept. Sci.) 2006, 84, 23e27.
¨
15. Tominaga, M.; Barbosa, S. R.; Poletti, E. F.; Zukerman-Schpector, J.;
Marchetto, R.; Schreier, S.; Paiva, A. C. M.; Nakaie, C. R. Chem. Pharm.
Bull. 2001, 49, 1027e1029.
16. Nakaie, C. R.; Silva, E. G.; Cilli, E. M.; Marchetto, R.; Schreier, S.; Paiva,
T. B.; Paiva, A. C. M. Peptides 2002, 23, 65e70.
17. (a) Mazaleyrat, J.-P.; Wright, K.; Gaucher, A.; Toulemonde, N.; Waksel-
3. (a) Adam, W.; Saha-Moller, C. R.; Ganeshpure, P. A. Chem. Rev. 2001,
¨
101, 3499e3548; (b) Sheldon, R. A.; Arends, I. W. C. E.; Ten Brink,
G.-J.; Dijksman, A. Acc. Chem. Res. 2002, 35, 774e781; (c) Naik, N.;
Braslau, R. Tetrahedron 1998, 54, 667e696; (d) Formaggio, F.; Bonchio,
M.; Crisma, M.; Peggion, C.; Mezzato, S.; Polese, A.; Barazza, A.;
Antonello, S.; Maran, F.; Broxterman, Q. B.; Kaptein, B.; Kamphuis, J.;
Vitale, R. M.; Saviano, M.; Benedetti, E.; Toniolo, C. Chem.dEur. J.
2002, 8, 84e93.
ꢀ
man, M.; Oancea, S.; Peggion, C.; Formaggio, F.; Setnicka, V.; Keiderling,
T. A.; Toniolo, C. J. Am. Chem. Soc. 2004, 126, 12874e12879; (b)
Mazaleyrat, J.-P.; Wright, K.; Gaucher, A.; Toulemonde, N.; Dutot, L.;
Wakselman, M.; Broxterman, Q. B.; Kaptein, B.; Oancea, S.; Peggion,
C.; Crisma, M.; Formaggio, F.; Toniolo, C. Chem.dEur. J. 2005, 11,
´
`
4. Krishna, M.; DeGraff, W.; Hankovszky, O.; Sar, C.; Kalai, T.; Jeko, J.;
¨
Russo, A.; Mitchell, J.; Hideg, K. J. Med. Chem. 1998, 41, 3477e3492.