K. Kobayashi et al. / Bioorg. Med. Chem. 20 (2012) 2651–2655
2655
powder: ½a 3D1
ꢂ
ꢀ16.8 (c 1.03, H2O); 1H NMR (500 MHz, D2O) d 1.63–
Fe standard solution [Fe(NO3)3 in 0.1 mol/L HNO3] were dissolved
in H2O; Re(CO)5Cl and ReCl5 were dissolved in DMF and methanol,
respectively. After 24 h, the mixture was analyzed by HPLC and
assessment of ESI-MS spectra. HPLC conditions: a linear gradient
of solvent B in solvent A (0–25% over 25 min); COSMOSIL 5C18-
ARII column (4.6 ꢁ 250 mm); flow rate, 1 mL/min; solvent A:
0.1% TFA–H2O; solvent B: 0.1% TFA–MeCN; detection at 220 nm.
2.03 (m, 12H), 2.12–2.19 (m, 9H), 3.60–3.75 (m, 6H), 3.85–3.98 (m,
5H), 4.08 (d, J = 16.6 Hz, 1H), 4.29–4.35 (m, 1H), 4.36–4.48 (m, 4H);
13C NMR (125 MHz, D2O, internal standard; dioxane) d ꢀ47.3 (3C),
ꢀ44.2, ꢀ44.1, ꢀ43.9, ꢀ38.8, ꢀ38.63, ꢀ38.61, ꢀ23.5, ꢀ19.4 (2C),
ꢀ19.3, ꢀ13.0, ꢀ12.4 (2C), ꢀ10.6, ꢀ10.5, ꢀ6.1, ꢀ6.0, 104.7, 105.1,
105.4, 106.9, 107.1, 107.3 (4C); HRMS (FAB), m/z calcd for
C
29H50N9O14 (MH+) 748.3472, found: 748.3479. The NMR data
was in good agreement with the literature data.4,22
Acknowledgements
4.1.8. Deferriferrichrome (2)
By use of a procedure identical with that described for the prep-
aration of the deferriferrichrysin 1, the deferriferrichrome
This work was supported by Grants-in-Aid for Scientific
Research from the Ministry of Education, Culture, Sports, Science
and Technology of Japan. K.K. is grateful for Research Fellowships
from the Japan Society for the Promotion of Science (JSPS) for
Young Scientists.
2
(4.9 mg, 0.0071 mmol, 7.1% based on H-Gly-(2-Cl)Trt resin) was
obtained as yellow freeze-dried powder: ½a D27
ꢀ2.6 (c 0.351,
ꢂ
H2O); 1H NMR (500 MHz, D2O) d 1.63–2.02 (m, 12H), 2.12–2.19
(m, 9H), 3.61–3.78 (m, 6H), 3.91 (d, J = 16.6 Hz, 1H), 3.95–4.11
(m, 4H), 4.15 (d, J = 17.2 Hz, 1H), 4.30–4.39 (m, 1H), 4.39–4.49
(m, 2H); 13C NMR (125 MHz, D2O, internal standard; dioxane) d
ꢀ47.30, ꢀ47.27 (2C), ꢀ44.5, ꢀ44.2, ꢀ44.0, ꢀ39.2, ꢀ38.4, ꢀ37.9,
ꢀ24.0, ꢀ23.9, ꢀ23.6, ꢀ19.4 (2C), ꢀ19.3, ꢀ12.8, ꢀ12.7, ꢀ12.6,
105.0, 105.4, 105.6, 107.2, 107.3 (2C), 107.4, 107.48, 107.55; HRMS
(FAB), m/z calcd for C27H46N9O12 (MH+) 688.3260, found: 688.3256.
The NMR data was in good agreement with the literature data.4,22
Supplementary data
Supplementary data associated with this article can be found, in
References and notes
1. For a review, see: Hider, R. C.; Kong, X. Nat. Prod. Rep. 2010, 27, 637.
2. Tadenuma, M.; Sato, S. Agric. Biol. Chem. 1967, 31, 1482.
3. Neilands, J. B. J. Am. Chem. Soc. 1952, 74, 4846.
4. Zähner, H.; Keller-Schierlein, W.; Hütter, R.; Hess-Leisinger, K.; Deér, A. Arch.
Für Mikrobiol. 1963, 45, 119.
4.1.9. Deferriferricrocin (3)
By use of a procedure identical with that described for the prep-
5. Mei, B.; Budde, A. D.; Leong, S. A. Proc. Natl. Acad. Sci. U.S.A. 1993, 90, 903.
6. Eisendle, M.; Oberegger, H.; Zadra, I.; Haas, H. Mol. Microbiol. 2003, 49, 359.
7. Ong, D. E.; Emery, T. F. Arch. Biochem. Biophys. 1972, 148, 77.
8. For a review, see: Codd, R. Coord. Chem. Rev. 2008, 252, 1387.
9. Llinás, M.; Klein, M. P.; Neilands, J. B. J. Mol. Biol. 1972, 68, 265.
10. Moberg, M.; Nilsson, E. M.; Holmström, S. J. M.; Lundström, U. S.; Pettersson, J.;
Markides, K. E. Anal. Chem. 2004, 76, 2618.
11. Leong, J.; Raymond, K. N. J. Am. Chem. Soc. 1974, 96, 6628.
12. Verel, I.; Visser, G. W. M.; Boellaard, R.; Stigter-van Walsum, M.; Snow, G. B.;
van Dongen, G. A. M. S. J. Nucl. Med. 2003, 44, 1271.
13. Schrettl, M.; Bignell, E.; Kragl, C.; Sabiha, Y.; Loss, O.; Eisendle, M.; Wallner, A.;
Arst, H. N., Jr.; Haynes, K.; Haas, H. PloS Pathog. 2007, 3, 1195.
14. Petrik, M.; Haas, H.; Dobrozemsky, G.; Lass-Flörl, C.; Helbok, A.; Blatzer, M.;
Dietrich, H.; Decristoforo, C. J. Nucl. Med. 2010, 51, 639.
15. Maurer, B.; Keller-Schierlein, W. Helv. Chim. Acta 1969, 52, 388.
16. Keller-Schierlein, W.; Maurer, B. Helv. Chim. Acta 1969, 52, 603.
17. Isowa, Y.; Ohmori, M.; Kurita, H. Bull. Chem. Soc. Jpn. 1974, 47, 215.
18. Davies, S. G.; Goodwin, C. J.; Hepworth, D.; Roberts, P. M.; Thomson, J. E. J. Org.
Chem. 2010, 75, 1214.
aration of the deferriferrichrysin 1, the deferriferricrocin
3
(16.0 mg, 0.0223 mmol, 22% based on H-Gly-(2-Cl)Trt resin) was
obtained as yellow freeze-dried powder: ½a D30
ꢀ16.0 (c 1.14,
ꢂ
H2O); 1H NMR (500 MHz, D2O) d 1.63–1.96 (m, 12H), 2.16 (s, 9H),
3.60–3.75 (m, 6H), 3.85 (d, J = 16.6 Hz, 1H), 3.90 (dd, J = 11.5,
5.2 Hz, 1H), 3.95 (dd, J = 11.5, 5.7 Hz, 1H), 3.98–4.09 (m, 2H), 4.16
(d, J = 16.6 Hz, 1H), 4.27–4.33 (m, 1H), 4.35–4.45 (m, 2H), 4.50–
4.55 (m, 1H); 13C NMR (125 MHz, D2O, internal standard; dioxane)
d ꢀ47.3 (3C), ꢀ44.4, ꢀ44.2 (2C), ꢀ39.2, ꢀ38.3, ꢀ38.0, ꢀ23.9, ꢀ23.7,
ꢀ19.4 (2C), ꢀ19.3, ꢀ12.8, ꢀ12.7, ꢀ12.6, ꢀ11.4, ꢀ6.2, 104.7, 105.0,
105.4, 106.8, 107.2, 107.27 (3C), 107.34; HRMS (FAB), m/z calcd for
C
28H48N9O13 (MH+) 718.3366, found: 718.3371. The NMR data was
in good agreement with the literature data.22,23
4.1.10. Zirconium(IV)–deferriferrichrysin complex (S1)
19. Reddy, P. A.; Schall, O. F.; Wheatley, J. R.; Rosik, L. O.; McClurg, J. P.; Marshall, G.
R.; Slomczynska, U. Synthesis 2001, 1086.
To a solution of deferriferrichrysin (14.4 mg, 0.0193 mmol) in
H2O (1 mL) was added a solution of ZrCl4 (17.4 mg, 0.0747 mmol)
in H2O (1 mL) at room temperature. The mixture was purified by
preparative HPLC to afford the titled compound S1 (8.9 mg,
20. Shioiri, T.; Ninomiya, K.; Yamada, S. J. Am. Chem. Soc. 1972, 94, 6203.
21. Brady, S. F.; Freidinger, R. M.; Paleveda, W. J.; Colton, C. D.; Homnick, C. F.;
Whitter, W. L.; Curley, P.; Nutt, R. F.; Veber, D. F. J. Org. Chem. 1987, 52, 764.
22. Llinás, M.; Wilson, D. M.; Klein, M. P.; Neilands, J. B. J. Mol. Biol. 1976, 104, 853.
23. Keller-Schierlein, W.; Deér, A. Helv. Chim. Acta 1963, 46, 1907.
24. Excess equivalents (5.0 equiv) of metal salt was used for the formation of
metal–deferriferrichrysin complex.
25. Arceo, E.; Ellman, J. A.; Bergman, R. G. J. Am. Chem. Soc. 2010, 132, 11408.
26. Yen, P.-W.; Chou, T.-C. Appl. Catal., A 1999, 182, 217.
27. Shibahara, F.; Krische, M. J. Chem. Lett. 2008, 37, 1102.
28. Of note, production of a small amount of partially reduced deferriferrichrysin was
observed (tR = 18.3 min; m/z 732) in which one hydroxamate group was reduced.
29. Zr(IV)–deferriferrichrysin complex was stable in normal mouse serum (>70%
recovery after incubation at 37 °C for 2 h).
0.0106 mmol, 55% yield) as colorless freeze-dried powder: ½a D29
ꢂ
+89.4 (c 0.926, DMSO); 1H NMR (500 MHz, D2O) d 1.34–1.46 (m,
1H), 1.50–1.59 (m, 1H), 1.65–1.80 (m, 4H), 1.82–1.89 (m, 1H),
1.92–2.11 (m, 13H), 2.22–2.36 (m, 1H), 3.36–3.51 (m, 2H), 3.51–
3.63 (m, 1H), 3.67–3.77 (m, 2H), 3.77–3.93 (m, 5H), 4.02–4.12
(m, 1H), 4.12–4.19 (m, 2H), 4.22–4.27 (m, 1H), 4.36 (t, J = 3.4 Hz,
1H), 4.48 (dd, J = 13.2, 2.9 Hz, 1H), 4.83–4.89 (m, 1H), 6.86–6.93
(m, 1H), 8.51–8.58 (m, 1H), 9.00–9.05 (m, 1H); 13C NMR
(125 MHz, D2O, internal standard; MeOH) d 17.3, 17.5, 17.9, 22.9,
26.0, 26.4, 27.0, 27.2, 29.5, 44.1, 50.5, 50.8, 51.8, 54.1, 55.9, 56.0,
59.2, 59.9, 61.45, 61.49, 165.5, 166.1, 166.2, 171.7, 171.9, 173.2,
173.7, 174.9, 177.8; HRMS (FAB), m/z calcd for C29H46N9O14Zr
(M+) 834.2206, found: 834.2202.
30. Four possible isomers (D-fac, D-mer, K-fac, K-mer) of the Ti(VI) chelate
complex with three asymmetric bidentate ligands were reported. It was
proposed that configurational rearrangement can proceed via bond rupture
mechanisms or twisting mechanisms, see: Serpone, N.; Bickley, D. G. Prog.
Inorg. Chem. 1972, 17, 391–566.
31. For a review, see: Janas, Z. Coord. Chem. Rev. 2010, 254, 2227.
32. For a review, see: Kinoshita, S.; Kawamura, K.; Fujita, T. Chem. Asian J. 2011, 6, 284.
33. For a review, see: Nakata, N.; Toda, T.; Ishii, A. Polym. Chem. 2011, 2, 1597.
34. Katsuki, T.; Shapless, K. B. J. Am. Chem. Soc. 1980, 102, 5974.
35. Ikegami, S.; Katsuki, T.; Yamaguchi, M. Chem. Lett. 1987, 16, 83.
36. Singer, R. A.; Carreira, E. M. J. Am. Chem. Soc. 1995, 117, 12360.
37. Ishitani, H.; Yamashita, Y.; Shimizu, H.; Kobayashi, S. J. Am. Chem. Soc. 2000,
122, 5403.
4.2. Metal-chelating experiment
To a 100
lL solution of deferriferrichrysin in solvent (1.0 mM)
was added a 100
lL solution of metal salts in solvent (5.0 mM) at
38. Barbayianni, E.; Fotakopoulou, I.; Schmidt, M.; Constantinou-Kokotou, V.;
Bornscheuer, U. T.; Kokotos, G. J. Org. Chem. 2005, 70, 8730.
39. Jiang, S.; Li, P.; Lai, C. C.; Kelley, J. A.; Roller, P. P. J. Org. Chem. 2006, 71, 7307.
room temperature. Sr(NO3)2, Y standard solution [Y(NO3)3 in
1 mol/L HNO3], InCl3, Gd(NO3)3, ZrCl4, 30% Ti(SO4)2 solution and