Timo Nuijens et al.
COMMUNICATIONS
MS: m/z=381.1666, calcd. for C18H25N2O7 [M+H]+:
381.1656.
Curr. Pharm. Des. 2007, 13, 829–843; e) M. B. Roberf-
roid, J. Nutr. 2007, 137, 2493–2502.
Cbz-Val-Glu
(OMe)-NH2 (5): White solid; Rt (HPLC):
[2] F. Guzmꢃn, S. Barberis, A. Illanes, Electron. J. Biotech-
1
14.52 min; H NMR (DMSO-d6, 300 MHz): d=0.86 (dd, J=
7.8 Hz, 6H, CH3 2ꢂ), 1.76–2.33 (m, 5H, CH, CH2 2ꢂ), 3.57
(s, 3H, COOCH3) 3.84–3.89 (m, 1H, CH), 4.19–4.27 (m, 1H,
CH), 5.03 (s, 2H, CH2), 7.08 (s, 1H, NH), 7.30–7.49 (m, 7H,
Ph and NH 2ꢂ), 8.01 (d, J=7.8 Hz, 1H, NH); 13C NMR
(DMSO-d6, 75 MHz): d=18.0, 19.1, 27.2, 30.0, 51.2, 60.2,
65.3, 127.5, 127.6, 136.9, 156.1, 170.9, 172.7; FIA-ESI(+)-
TOF-MS: m/z=394.1998, calcd. for C19H28N3O6 [M+H]+:
394.1973.
Boc-Met-Leu-NH2 (7): White solid; Rt (HPLC):
16.07 min; 1H NMR (CDCl3, 300 MHz): d=0.86 (dd, J=
6.3 Hz, 6H, CH3 2ꢂ), 1.38 (s, 9H, CH3 3ꢂ), 1.38–1.47 (m,
3H, CH and CH2), 1.73–1.83 (m, 2H, CH2), 1.96–2.04 (m,
3H, SCH3), 2.51 (dd, J=7.2 Hz, 2H, CH2), 4.11–4.17 (m,
1H, CH), 4.38–4.45 (m, 1H, CH), 5.23 (d, J=3.9 Hz, 1H,
NH), 5.53 (s, 1H, NH), 6.39 (s, 1H, NH), 6.65 (d, J=6.9 Hz,
1H, NH); 13C NMR (CDCl3, 75 MHz): d=15.4, 21.7, 23.0,
24.8, 28.3, 30.3, 40.5, 51.3, 54.1, 80.7, 171.7, 174.2; FIA-
ESI(+)-TOF-MS: m/z= calcd. for C16H32N3O4S [M+H]+:
362.2108; found: 362.2112.
nol. 2007, 10, 279–314.
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b) D. Hans, P. R. Young, D. D. P. Fairlie, Med. Chem.
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tides and Peptidomimetics, 4th edn., Houben-Weyl –
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Stuttgart, New York, 2004.
[5] a) M. Schultz, P. Hermann, H. Kunz, Synlett 1992, 37–
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Eggen, C. G. Boeriu, U.S. Patent Application No.
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Moody, R. Merkx, J. A. W. Kruijtzer, D. T. S. Rijkers,
R. M. J. Liskamp, P. J. L. M. Quaedflieg, Adv. Syn.
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1990, 29, 1139–1140.
Boc-Met-Leu-OMe (8): White solid; Rt (HPLC):
18.63 min; 1H NMR (CDCl3, 300 MHz): d=0.86 (d, J=
5.7 Hz, 6H, CH3 2ꢂ), 1.38 (s, 9H, CH3 3ꢂ), 1.40–1.64 (m,
3H, CH and CH2), 1.81–2.06 (m, 5H, CH2 and SCH3), 2.54
(dd, J=6.9 Hz, 2H, CH2), 3.66 (s, 3H, COOCH3), 4.15–4.30
(m, 1H, CH), 4.50–4.57 (m, 1H, CH), 5.08 (d, J=7.5 Hz,
1H, NH), 6.65 (d, J=8.4 Hz, 1H, NH); 13C NMR (CDCl3,
75 MHz): d=15.5, 22.2, 23.2, 25.1, 28.7, 30.5, 31.7, 41.8, 51.1,
52.7, 80.7, 171.6, 173.4; FIA-ESI(+)-TOF-MS: m/z=
377.2099, calcd. for C17H33N3O5S [M+H]+: 377.2105.
Boc-Met-Leu-Phe-NH2 (9): White solid; Rt (HPLC):
[8] P. J. L. M. Quaedflieg, T. Sonke, G. K. M. Verzijl, R. W.
Wiertz, WO Patent Application No. 20090298118, 2009.
[9] C. G. Boeriu, A. E. Frissen, E. Boer, K. van Kekem,
D.-J. van Zoelen, I. F. Eggen, J. Mol. Cat. B: Enzymatic
2010, 66, 33–42.
[10] R. A. Sheldon, Biochem. Soc. Trans. 2007, 35, 1583.
[11] T. Nuijens, J. A. W. Kruijtzer, C. Cusan, D. T. S. Rijkers,
R. M. J. Liskamp, P. J. L. M. Quaedflieg, Tetrahedron
Lett. 2009, 50, 2719–2721.
[12] R. J. Freer, in: Peptides, Structure and Biological Func-
tion, Proceedings of the 6th American Peptide Symposi-
um, 1979, 749.
1
20.14 min; H NMR (DMSO-d6, 300 MHz): d=0.82 (dd, J=
14.1 and 5.4 Hz, 6H, CH3 2ꢂ), 1.38–1.79 (m, 15H, CH, CH2
2ꢂ and CH3 3ꢂ), 2.02 (s, 3H, SCH3), 2.41–2.50 (m, 2H,
CH2), 2.79–3.02 (m, 2H, CH2), 3.80–4.15 (m, 1H, CH), 4.21–
4.30 (m, 1H, CH), 4.38–4.54 (m, 1H, CH), 7.00–7.23 (m,
2H, NH 2ꢂ), 7.26–7.34 (m, 6H, NH and Ph), 7.80–7.88 (m,
2H, NH 2ꢂ); 13C NMR (DMSO-d6, 75 MHz): d=14.5, 21.5,
22.9, 23.8, 28.0, 29.6, 31.3, 51.0, 53.3, 53.4, 78.0, 126.1, 127.9,
129.0, 137.6, 155.2, 171.4 (2ꢂ), 172.4; FIA-ESI(+)-TOF-MS:
m/z=509.2820, calcd. for C25H41N4O5S [M+H]+: 509.2792.
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Acknowledgements
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We thank Mr. Math Boesten for his analytical support and
Dr. Theo Sonke and Dr. Claudia Cusan for fruitful discus-
sions.
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Adv. Synth. Catal. 2011, 353, 1039 – 1044