7382
T. N. Lambert et al. / Tetrahedron Letters 43 (2002) 7379–7383
(3)
In conclusion, the mesylate salt 5 is a convenient
reagent for the incorporation of the 3,2-HOPO moiety
onto a variety of amine platforms. This methodology
leads to HOPO derivatives without concomitant forma-
tion of an amide linkage and hence leads to chelators
with better aqueous solubility. It is clear that the elec-
tronic and steric nature of the primary amine determine
the site of the reaction of 5 (path A versus path B),
while secondary amines react predictably via path A
leading to the desired HOPO derivatives. The commer-
cial availability of a number of aromatic polyamines
and secondary polyamines should allow access to a
structurally diverse group of HOPO chelators using this
strategy. The preparation of two new dihydroxypyridi-
none analogs 19 and 21 clearly demonstrates the poten-
tial of this methodology.
Houpert, P.; Durbin, P. W.; Raymond, K. N. Int. J.
Radiat. Biol. 2000, 76, 113; (f) Xu, J.; Radkov, W.;
Ziegler, M.; Raymond, K. N. Inorg. Chem. 2000, 39,
4156; (g) Stradling, G. N.; Henge´-Napoli, M.-H.; Paquet,
F.; Poncy, J.-L.; Fritsch, P.; Taylor, D. M. Radiation
Protection Dosimetry 2000, 87, 19.
4. Lambert, T. N.; Dasaradhi, L.; Huber, V. J.; Gopalan, A.
S. J. Org. Chem. 1999, 64, 6097.
5. (a) Zhao, P.; Romanovski, V. V.; Whisenhunt, D. W., Jr.;
Hoffman, D. C.; Mohs, T. R.; Xu, J.; Raymond, K. N.
Solvent Extraction and Ion Exchange 1999, 17, 1327; (b)
Feng, M.; van der Does, L.; Bantjes, A. J. Appl. Polym.
Sci. 1995, 56, 1231.
6. (a) Rai, B. L.; Khodr, H.; Hider, R. C. Tetrahedron 1999,
55, 1129; (b) Meyer, M.; Telford, J. R.; Cohen, S. M.;
White, D. J.; Xu, J.; Raymond, K. N. J. Am. Chem. Soc.
1997, 119, 10093.
7. Sun, Y.; Motekaitis, R. J.; Martell, A. E. Inorg. Chim.
Acta 1998, 281, 60.
Acknowledgements
8. (a) Gopalan, A.; Huber, V.; Koshti, N.; Jacobs, H.;
Zincircioglu, O.; Jarvinen, G.; Smith, P. In Separations of
f Elements; Nash, K. L.; Choppin, G.R., Eds. Synthesis
and Evaluation of Polyhydroxamate Chelators for the
Selective Actinide Ion Sequestration. Plenum: New York,
1995; pp.77–98; (b) Koshti, N.; Huber, V.; Smith, P.;
Gopalan, A. S. Tetrahedron 1994, 50, 2657; (c) Koshti, N.
M.; Jacobs, H. K.; Martin, P. A.; Smith, P. H.; Gopalan,
A. S. Tetrahedron Lett. 1994, 35, 5157.
This work was supported in part by a grant from the
National Institutes of Health under PHS Grant no. S06
GM08136-27 and also by the Waste-Management Edu-
cation and Research Consortium of New Mexico. We
would like to thank Mr. Alan Olague and Ms. Gloria
Martinez for assistance in the preparation of some
starting materials.
9. Clark, J. H. Chem. Rev. 1980, 80, 429.
10. Methanesulfonic anhydride (2.5 g, 14.4 mmol) was added
portionwise to a solution of HOPO alcohol 3 (2.5 g, 9.6
mmol) in dry CH2Cl2 (10 mL) and triethylamine (1.95 g,
19.3 mmol) at 0°C under N2. The reaction was stirred at
0°C for 1 h and then at rt for 1 h. The CH2Cl2 was
removed under reduced pressure. The residue was dis-
solved in CHCl3 and stirred overnight at rt. The solvent
was removed in vacuo and the residue was triturated with
hot ethyl acetate (4×25 mL). The resulting solid was dried
in vacuo to give 5 as a pale white solid (3.0 g, 92%): mp
References
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Inorg. Chem. 2000, 39, 2652; (b) Hajela, S.; Botta, M.;
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(b) Bailly, T.; Burgada, R. C. R. Acad. Sci. Paris 1998,
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108–110°C; IR (neat) 3436, 1639 cm−1 1H NMR (200
;
MHz, CDCl3) l 2.52 (m, 2H), 2.69 (s, 3H), 4.87 (t, J=5.5
Hz, 2H), 4.98 (t, J=6.0 Hz, 2H), 5.21 (s, 2H), 7.28 (t,
J=7.4 Hz, 1H), 7.37–7.44 (m, 5H), 7.62 (dd, J=8.3 and
1.2 Hz, 1H), 8.22 (dd, J=6.6 and 1.3 Hz, 1H). Anal.
calcd for C16H19NO5S: C, 56.96; H, 5.68; N, 4.15; found:
C, 56.63; H, 5.56; N, 4.19%.
11. An authentic sample of 6 was prepared by conversion of
the alcohol 3 to the corresponding chloride (PPh3, CCl4)
followed by its reaction with neat amylamine at rt. Spec-
tral data for 6: 1H NMR (200 MHz, CDCl3) l 0.89 (t,
J=6.7 Hz, 3H), 1.22–1.39 (m, 4H), 1.42–1.58 (m, 2H),
1.90–2.04 (m, 2H), 2.39 (br s, 1H), 2.61 (unres q, 4H),
4.07 (t, J=6.8 Hz, 2H), 5.11 (s, 2H), 6.02 (t, J=7.2 Hz,
1H), 6.64 (dd, J=7.4 and 1.6 Hz, 1H), 6.95 (dd, J=6.9
and 1.7 Hz, 1H), 7.29–7.46 (m, 5H).