Molybdenum Complexation of Tripeptides
3657 3666
0.1% trifluoroacetic acid (TFA)) and water (containing 0.1% TFA).
Compound 23-H4 was obtained as a white solid (4.4 mg, 45%). 1H NMR
(CD3OD, 400 MHz): d=7.35 (dd, J=7.9, 1.6 Hz, 1H, aryl), 6.95 (dd, J=
7.9, 1.6 Hz, 1H, aryl), 6.75 (t, J=7.9 Hz, 1H, aryl), 6.69 (dd, J=7.6,
2.0 Hz, 1H, aryl), 6.66 (dd, J=7.6, 2.0 Hz, 1H, aryl), 6.61 (t, J=7.6 Hz,
1H, aryl), 4.80 (dd, J=7.6, 5.6 Hz, 1H, a-H), 4.60 (m, 1H, a-H), 4.35 (s,
2H, CH2 benzyl), 3.90 (s, 2H, CH2 Gly), 3.21 (m, 2H, CH2 Arg), 2.88
(dd, J=16.3, 5.6 Hz, 1H, CH2 Asp), 2.77 (dd, J=16.3, 7.6 Hz, 1H, CH2
Asp), 2.01 (m, 1H, CH2 Arg), 1.84 (m, 1H, CH2 Arg), 1.70 (m, 2H, CH2
Arg) ppm; 13C NMR (CD3OD, 125 MHz): d=173.7 (C), 171.9 (C), 171.5
(C), 170.6 (C), 169.8 (C), 157.6 (C), 148.2 (C), 146.2 (C), 143.5 (C), 125.1
(C), 118.9 (CH), 116.4 (C), 114.5 (CH), 53.5 (CH), 50.3 (CH), 42.6
(CH2), 41.0 (CH2), 39.1 (CH2), 35.9 (CH2), 29.0 (CH2), 25.2 (CH2) ppm;
1.5 Hz, 1H, aryl), 7.19 (s, 1H, indole H), 7.09 (m, 1H), 6.99 (m, 1H),
6.94 (dd, J=7.8, 1.5 Hz, 1H, aryl), 6.89 (m, 2H, aryl), 6.72 (m, 2H, aryl),
6.59 (m, 3H, aryl), 6.54 (d, J=14.6 Hz, 1H, aryl), 4.82 (t, J=6.5 Hz, 1H),
4.50 (t, J=7.6 Hz, 1H, a-H), 4.27 (m, 3H, a-H Lys, CH2 benzyl), 3.31 (m,
2H, CH2), 2.99 (m, 1H, CH2), 2.76 (m, 3H, CH2, e-CH2 Lys), 1.58 (m,
1H, b-CH2 Lys), 1.49 (m, 3H, b- and g-CH2 Lys), 1.13 (m, 2H, d-CH2
Lys) ppm; elemental analysis calcd (%) for C40H44N6O9¥2H2O¥2HBr: C
49.60, H 5.41, N 8.68; found: C 49.91, H 5.24, N 8.28; positive FAB-MS
(3-NBA/DMSO): m/z: 754.4 [M+H]+; negative FAB-MS(3-NBA/
DMSO): m/z: 752.3 [MÀH]À; LC-MS(ESI): m/z: 753.19 [M]+; IR (KBr):
n˜ =3364, 2943, 1641, 1534, 1252, 746 cmÀ1
.
Formation of K2[(32)MoO2]: Ligand 32-H4 (22 mg, 0.03 mmol), K2CO3
(16 mg, 0.12 mmol), and [MoO2(acac)2] (9.6 mg, 0.03 mmol) were dis-
solved in methanol (11 mL). The mixture was stirred for six days. The
solvent was distilled off under vacuum and the crude product was filtered
over Sephadex LH20 with methanol. Coordination complex
K2[(32)MoO2] was obtained as a red solid (15 mg, 0.02 mmol, 67%).
1H NMR (CD3OD, 400 MHz): d=7.72 (d, J=7.4 Hz, 1H, aryl), 7.33 (d,
J=7.4 Hz, 1H, aryl), 7.12 (m, 3H, aryl), 6.92 (s, 1H, indole), 6.70 (dd,
J=7.6, 1.6 Hz, 3H, aryl), 6.59 (m, 4H, aryl), 6.42 (m, 2H, aryl), 5.16 (t,
J=6.7 Hz, 1H, a-H), 4.81 (d, J=13.8 Hz, 1H, CH2), 4.51 (dd, J=11.4,
3.7 Hz, 1H, a-H), 4.42 (d, J=13.8 Hz, 1H, CH2), 3.89 (t, J=6.3 Hz, 1H,
a-H), 3.21 (m, 1H), 3.08 (m, 2H), 2.73 (dd, J=15.1, 6.8 Hz, 1H, CH2),
2.48 (m, 1H, CH2), 1.51 (m, 1H, CH2), 1.32 (m, 4H, CH2), 0.71 (m,
2H) ppm and signals of CH3COCH2COCH3 at d=5.50 and 1.97 ppm; el-
emental analysis calcd (%) for C40H40K2N6O9MoO2¥(C5H8O2)¥5H2O: C
47.20, H 5.11, N 7.34; found: C 47.12, H 5.06, N 7.23; ESI-MS: m/z: 916
{K[(32)MoO2]}À, 879 {H[(32)MoO2]}À, 1000 {K(HBr)[(32)MoO2]}À; IR
high-resolution FAB-MS(3-NBA/DMOS): calcd for
C
26H34N7O10
[M+H]+: m/z: 604.2392; found: 604.2367.
Formation of K2[(23)MoO2]: Ligand 23-H4 (13.9 mg, 0.02 mmol) was dis-
solved in methanol (8 mL) and mixed with K2CO3 (12.4 mg, 0.09 mmol)
and MoO2(acac)2 (8.3 mg, 0.03 mmol). This solution was stirred for five
days. The solvent was distilled off under vacuum and the crude product
was filtered over Sephadex LH20 with methanol. K2[(23)MoO2] was ob-
1
tained as a red solid (14 mg, 0.02 mmol, quantitative). H NMR (CD3OD,
400 MHz): d=7.21 (dd, J=8.2, 1.5 Hz, 1H, benzoic acid), 6.72 (dd, J=
7.3, 1.5 Hz, 1H, benzoic acid), 6.46 (m, 1H, benzoic acid), 6.39 (m, 2H,
benzyl amine), 6.30 (m, 1H, benzyl amine), 4.90 (covered a-H Arg), 4.79
(d, J=14.0 Hz, 1H, CH2 benzyl), 4.61 (m, 1H, a-H Asp), 4.34 (d, J=
14.0 Hz, 1H, CH2 benzyl), 3.90 (d, J=17.0 Hz, 1H, CH2 Gly), 3.78 (d, J=
17.0 Hz, 1H, CH2 Gly), 3.18 (dd, J=16.7, 2.4 Hz, 1H, CH2 Asp), 2.96 (m,
1H, d-CH2 Arg), 2.88 (m, 1H, d-CH2 Arg), 2.48 (dd, J=16.7, 5.2 Hz,
CH2 Asp), 1.87 (m, 1H, b-CH2 Arg), 1.24 (m, 1H, b-CH2 Arg), 1.15 (m,
1H, g-CH2 Arg), 0.92 (m, 1H, g-CH2 Arg) ppm; ESI-MS: m/z: 807
[{K2[(23)MoO2]}ÀH]À, 769 {K[(23)MoO2]}À, 730 {H[(23)MoO2]}À, 383.5
(KBr): n˜ =3386, 2929, 1633, 1541, 1449, 1234, 896, 865, 746 cmÀ1
.
[(23)MoO2]2À
.
Preparation of WKY-bridged compounds: The same solid-phase protocol
as was described for the preparation of 16 was used.
Acknowledgement
Ligand precursor 31: This was prepared following the general method
from resin 17 (536 mg, 0.53 mmol), HBTU (398 mg, 1.12 mmol), H¸nig×s
base (360 mL, 2.24 mmol), Fmoc-Tyr(tBu)-OH (24; 487 mg, 1.12 mmol),
Fmoc-Lys(Boc)-OH (26; 497 mg, 1.12 mmol), Fmoc-Trp(Boc)-OH (28;
558 mg, 1.12 mmol), 2,3-dimethoxybenzoic acid (1; 193 mg, 1.12 mmol),
and 2,3-dimethoxybenzylamine (4; 50 mL, 5.30 mmol). The by-products
were removed by chromatography over silica gel with ethyl acetate/
hexane 2:1 and the pure product 31 was obtained as a white solid by elut-
ing with ethyl acetate (379.1 mg, 0.36 mmol, 67%). M.p. 1308C
We thank Prof. Dr. M. Kappes and the Nanotechnology Institute, For-
schungszentrum Karlsruhe, for facilitating the ESI-MS measurements,
Dr. O. Spie˚ for his orientating investigations to build up the RGD-
bridged ligand, and Prof. G. Raabe for the CD measurements.
[1] A. Fersht, Structure and Mechanism in Protein Science, W. H. Free-
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[2] D. P. Fairlie, M. L. West, A. K. Wong, Curr. Med. Chem. 1998, 5, 29.
[3] S. J. Lippard, J. M. Berg, Principles in Bioinorganic Chemistry, Uni-
versity Science Books, Mill Valley, 1994.
1
(decomp); H NMR (CDCl3, 400 MHz): d=8.62 (d, J=5.2 Hz, 1H, NH),
8.09 (d, J=8.6 Hz, 1H, NH), 7.60 (dd, J=7.8, 1.8 Hz, 1H, aryl), 7.54 (m,
2H), 7.31 (m, 1H, aryl), 7.21 (t, J=7.2 Hz, 1H, aryl), 7.13 (m, 1H aryl),
7.07 (dd, J=8.2, 1.6 Hz, 1H, aryl), 7.04 7.00 (m, 3H, aryl), 6.98 (m, 1H,
aryl), 6.90 (d, J=7.4 Hz, 1H, aryl), 6.80 (dd, J=8.2, 1.4 Hz, 1H, aryl),
6.74 (d, J=8.52 Hz, 2H, aryl), 6.51 (brs, 1H, NH), 4.86 (brs, 1H, NH
Boc-Lys), 4.74 (brs, 2H, a-H Trp, a-H Tyr), 4.50 (m, 2H, CH2 benzyl),
4.10 (m, 1H, a-H Lys), 3.88 (s, 3H, OMe), 3.85 (s, 3H, OMe), 3.82 (s,
3H, OMe), 3.59 (s, 3H, OMe), 3.37 (dd, J=14.1, 5.4 Hz, 1H, CH2), 3.26
(pseudo-t, J=6.3, 4.4 Hz, 2H, CH2), 2.92 (dd, J=13.9, 9.9 Hz, 1H, CH2),
2.81 (brs, 2H, e-CH2 Lys), 1.67 (s, 9H, tBu), 1.41 (s, 11H, tBu, g-CH2
Lys), 1.25 (s, 11H, tBu, b-CH2 Lys), 1.18 (quin, J=7.42 Hz, 2H, d-CH2
[4] a) N. Voyer, Top. Curr. Chem. 1997, 184, 1; b) M. R. Ghadiri, M. A.
Case, Angew. Chem. 1993, 105, 1663; Angew. Chem. Int. Ed. Engl.
1993, 32, 1594; c) M. R. Ghadiri, C. Soares, C. Choi, J. Am. Chem.
Soc. 1992, 114, 4000; d) M. R. Ghadiri, C. Soares, C. Choi, J. Am.
Chem. Soc. 1992, 114, 825; e) B. Cuenoud, A. Schepartz, Science
1993, 259, 510; f) M. Lieberman, T. Sasaki, J. Am. Chem. Soc. 1991,
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Lys) ppm; elemental analysis calcd (%) for C58H76N6O13¥1.5H2O:
C
64.85, H 7.22, N 7.82; found: C 64.75, H 7.26, N 7.82; positive FAB-MS
(3-NBA/DMSO): m/z: 967.0 [MÀBoc+H]+; negative FAB-MS(3-NBA/
DMSO): m/z: 1065.4 [M+H]À; LC-MS(EIS):
m/z: 1065.43 [M+H]+,
1087.48 [M+Na]+; IR (KBr): n˜ =3430, 1639, 1509, 1479, 1456, 1384, 1364,
1265, 1164 cmÀ1
.
WKY-bridged ligand 32-H4: At À188C, BBr3 (0.23 mL, 2.35 mmol) was
added to a solution of 31 (100 mg, 0.09 mmol) in CH2Cl2 (27 mL). The re-
action mixture was stirred for five days and then hydrolyzed by addition
of methanol (27 mL, ice-cooled). The solvent was evaporated under
vacuum and the residue was dissolved in methanol and evaporated to
dryness. This procedure was repeated several times to remove all boron
esters. The crude product was recrystallized from isopropanol and
hexane. Ligand 32-H4 was obtained as a grey solid (70.6 mg, 0.09 mmol,
quantitative). M.p. 1308C (decomp); 1H NMR (CD3OD, 400 MHz): d=
7.60 (d, J=8.0 Hz, 1H, aryl), 7.34 (d, J=8.0 Hz, 1H), 7.26 (dd, J=8.1,
[5] P. S. Eis, J. R. Lakowicz, Biochemistry 1993, 32, 7981.
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¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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