C O M M U N I C A T I O N S
FEMS Microbiol. Lett. 2001, 196, 147.
(5) (a) Loomis, L. D.; Raymond, K. N. Inorg. Chem. 1991, 30, 906. (b) Harris,
W. R.; Carrano, C. J.; Raymond, K. N. J. Am. Chem. Soc. 1979, 101,
2213.
(6) (a) Karpishin, T. B.; Dewey, T. M.; Raymond, K. N. J. Am. Chem. Soc.
1993, 115, 1842. (b) Stack, D. T. P.; Hou, Z.; Raymond, K. N. J. Am.
Chem. Soc. 1993, 115, 6466.
(7) Sprencel, C.; Cao, Z.; Qi, Z.; Scott, D. C.; Montague, M. A.; Ivanoff, N.;
Xu, J.; Raymond, K. N.; Newton, S. M. C.; Klebba, P. E. J. Bacteriol.
2000, 182, 5359.
(8) Nielands, J. B.; Erikson, T. J.; Rastetter, W. H. J. Biol. Chem. 1981, 256,
3831.
(9) (a) Budzikiewicz, H.; Bo¨ssenkamp, A.; Taraz, K.; Pandey, A.; Meyer,
J.-M. Z. Naturforsch., C: Biosci. 1997, 52, 551. (b) The biosynthesis of
corynebactin (improperly renamed) has been reported: May, J. J.;
Wendrich, T. M.; Marahiel, M. A. J. Biol. Chem. 2001, 276, 7209.
(10) Meyer, M.; Telford, J. R.; Cohen, S. M.; White, D. J.; Xu, J.; Raymond,
K. N. J. Am. Chem. Soc. 1997, 119, 10093.
(11) (a) Olah, G. A.; Nojima, M.; Kerekes, I. Synthesis 1973, 487-488. (b)
Carpino, L. A.; Sadat-Aalaee, D.; Chao, H. G.; DeSelms, R. H. J. Am.
Chem. Soc. 1990, 112, 9651-9652. (c) Carpino, L. A.; Beyermann, M.;
Wenschuh, H.; Bienert, M. Acc. Chem. Res. 1996, 29, 268-274.
(12) 3: 1H NMR (CDCl3) δ 7.72-7.75 (m, 1H, NH), 7.14-7.47 (m, 13H,
Har), 5.18 (s, 2H, CH2), 5.14 (s, 2H, CH2), 4.06 (d, 2H, glycine CH2).
EI+-MS m/z 391 (M+, 20). Anal. Calcd (Found) for 3 C, 70.58 (70.90);
H, 5.41 (5.37); N 3.58 (3.22). 4: 1H NMR (CDCl3) δ 4.17 (dd, 2H, CH2),
5.17 (d, 4H, CH2), 7.13-7.71 (m, 13H, Har), 8.52 (t, 1H, NH). 19F NMR
(CDCl3) δ -16 (s). EI+-MS m/z 393 (M+, 80).
Figure 2. Circular dichroism spectra of ferric enterobactin, ferric coryne-
bactin, and ferric serine-corynebactin in water. T ) 22 °C.
Table 1. Circular Dichroism Results of Ferric Complexes
ferric complex
diastereomer
λmax [nm]
∆ꢀ [M-1 cm-1
]
(13) 6: UV-vis λ [nm] ) 215, 268, 444 (charge-transfer bands); IR ν ) 1641
(amide CO), 1750 (ester CO). 1H NMR (CDCl3) δ 3.69-3.90 (ddd, J )
5, 15, 23 Hz, 6H, CH2), 4.09 (dd, J ) 3, 11 Hz, 3H, gly-CH2), 4.82 (d,
J ) 8 Hz, 3H, CH), 4.90 (dd, J ) 3, 11 Hz, 3H, gly-CH2), 5.00-5.17 (m,
12H, benzyl-CH2), 7.09-7.72 (m, 39H, Har), 8.30 (d, J ) 8 Hz, 3H, NH),
8.64 (t, J ) 5 Hz, 3H, NH). 13C NMR (CDCl3) δ 43.4, 64.9, 71.2, 117.5,
123.0, 124.5, 126.5, 127.7, 128.3, 128.5, 128.6, 128.7, 129.1, 136.3, 147.3,
152.0, 165.7 (CO), 168.8 (CO), 169.7 (CO). FAB+-LR-MS: m/z 1381
(M+, 80), 1290 (M+ - benzyl, 5). FAB+-HR-MS m/z 1381.495410 (calcd),
found 1381.498135 for C78H73N6O18, δ ) 2.7 mDa. Anal. Calcd (Found)
for 6: C 67.82 (67.87), H 5.25 (5.23), N 6.08 (5.70); mp ) 78 °C.
(14) 7: 1H NMR (d6-acetone) δ 4.11 (s, 6H, gly-CH2), 4.32 (d, J ) 11 Hz,
3H, CH2), 4.61 (d, J ) 11 Hz, 3H, CH2), 4.78 (s, 3H, CH), 6.68 (t, J )
8 Hz, 3H, Har), 6.93 (d, J ) 8 Hz, 3H, Har), 7.27 (d, J ) 8 Hz, 3H, Har),
7.95 (s, br, NH), 8.45 (s, br, NH). 13C NMR (d6-acetone) δ 42.9, 52.9,
65.1, 114.9, 117.6, 118.8, 119.1, 146.6, 149.9, 169.1 (CO), 169.4 (CO),
171.0 (CO). FAB+-LR-MS m/z 841 (M+, 85). FAB+-HR-MS m/z
840.210375 (calcd), found: 840.208609 for C36H36N6O18, δ ) 1.8 mDa;
mp ) 130 °C.
(15) Ligands (1, 2, and 7) were dissolved in a mixture of 2 mL water and 3
mL of methanol. The initial concentration of the complex was 0.5 mM.
Ferric ion dissolved in 10 mM HCl was added to the solution to make a
1:1 complex. A color change was observed, and the solution was
centrifuged for 10 min (14000 rpm Eppendorf) to remove solid precipitate.
Impurities were removed by preparative HPLC eluting with H2O:MeOH
(35:65), with a pressure of approximately 1000 psi and a flow rate of 10
mL/min. The intensity of the eluent was measured at 254 nm. The colored
fraction of each ligand was collected.
enterobactin (1)
corynebactin (2)
serine-corynebactin (7)
∆
553
545
520
-2.2
+1.7
+0.6
Λ
Λ (slight)
and a new serine trilactone analogue (7) have been determined.
While the chirality of ferric enterobactin is ∆, ferric corynebactin
(2) is Λ. The hybrid analogue 7 is a mixture of ∆- and Λ-isomers.
It will be interesting to see how the microbial transport properties
respond to these different chiralities.
Acknowledgment. This work was supported by a Feodor Lynen
grant for M.B. from the Alexander von Humboldt Foundation and
Grant AI11744 from the National Institutes of Health. We thank
Jasco for help in obtaining the circular dichroism spectra and Dr.
Benjamin P. Hay (Pacific Northwest National Laboratory) for the
modeling calculations.
Supporting Information Available: Detailed synthetic procedures
for 1, 2, and 7 and intermediates (PDF). This material is available at
(16) Ferric enterobactin: ESI--HR-MS m/z 721.047857 (calcd), found 721.048500
for C30H23N3O15Fe [M - H]-, δ ) 0.6 mDa, ferric corynebactin: ESI--
HR-MS m/z 934.159198 (calcd), found 934.160100 for C39H38N6O18Fe
[M - H]-, δ ) 0.9 mDa, ferric serine corynebactin: ESI--HR-MS m/z
892.112248 (calcd), found 892.112100 for C36H32N6O18Fe [M - H]-, δ
) 0.1 mDa.
(17) The pure fraction collected from HPLC was measured by UV-vis
spectrophotometry (Cary 300 Scan). The concentrations of the ferric
compounds were approximately 0.066 mM (ꢀ ) 15000 M-1 cm-1 at 330
nm). The CD spectra of the complexes were measured using a Jasco J-810
spectrometer.
References
(1) (a) Stintzi, A.; Raymond, K. N. Siderophore Chemistry. In Molecular
and Cellular Iron Transport; Marcell Dekker: New York, 2002. In press.
(b) Telford, J. R.; Raymond, K. N. Siderophores. In ComprehensiVe
Supramolecular Chemistry; Atwood, J. L., Davies, J. E. D., MacNicol,
D. D., Vo¨gtle, F., Eds.; Elsevier Science Ltd.: Oxford, 1996; Vol. 1, pp
245-266. (c) Winkelmann, G. CRC Handbook of Microbial Iron Chelates;
CRC Press: Boca Raton, FL, 1991.
(2) Raymond, K. N.; Carrano, C. J. Acc. Chem. Res. 1979, 12, 183.
(3) Stintzi, A.; Barnes, C.; Xu, J.; Raymond, K. N. Proc. Natl. Acad. Sci.
U.S.A. 2000, 97, 10691.
(18) Karpishin, T. B.; Gebhard, M. S.; Solomon, E. L.; Raymond, K. N. J.
Am. Chem. Soc. 1991, 113, 2977-2984.
(19) Bluhm, M. E.; Hay, B. P.; Kim, S. S.; Dertz, E. A.; Raymond, K. N.
Manuscript submitted for publication.
(4) (a) O’Brien, I. G.; Gibson, F. Biochim. Biophys. Acta 1970, 215, 393. (b)
Pollack, J. R.; Neilands, J. B. Biochem. Biophy. Res. Commun. 1970, 38,
989. (c) Fiedler, H. P.; Krastel, P.; Muller, J.; Gebhardt, K.; Zeeck, A.;
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