Synthesis and Characterization of 2:1 [α/Aza]-oligomers
129.5 (CH, Ar), 129.7 (CH, Ar), 129.8 (CH, Ar), 136.3 (C, Ar),
137.1 (C Ar), 156.7 (C=O, Boc), 157.5 (O=C-NH), 171.1 (O=C-
NH), 174.7 (C=O, ester) ppm. HRMS (ESI) calculated for
C26H34N4NaO6 [M + Na]+ m/z 521.2371, found 521.2389.
Acknowledgments
The authors thank the NMR and X-ray diffraction facilities of
Institut Jean Bariol (FR-CNRS 2843) and the SCBIM NMR facili-
ties of Biopôle (IFR 111) at Université de Lorraine.
Representative Procedure for the Coupling Reaction with HBTU/
DIEA: To a stirred solution of the CF3COOH-amine partner salt
(1 equiv.) in CH2Cl2 and DMF were successively added at room
temperature pure DIEA (2.2 equiv.), a solution in CH2Cl2 of acid
partner (1.1 equiv.) and a solution in CH2Cl2 and DMF of HBTU
(1.2 equiv.). After a night to 24 h, the mixture was diluted with
aqueous HCl 1m under vigorously stirring (pH = 2). The organic
layer was washed with water, aqueous NaHCO3 0.5m, brine, dried
with MgSO4 and the solvents evaporated.
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Boc-(Phe-azaPhe-Ala)2-OMe (11a): Purified by the trituration with
Et2O then cyclohexane, yield 92%, white powder, m.p. 132 °C. IR
(CDCl ): ν
= 3438, 3401, 3351, 3259 (NH), 1741, 1700, 1665
˜
3
max
(C=O) cm–1. 1H NMR (300 MHz, CD3CN): δ = 1.17 (d, J =
7.0 Hz, 3 H, βCH3 Ala), 1.27–1.36 (m, 12 H, βCH3 Ala and Boc),
2.79 (m, 1 H, βCH2 Phe), 2.94–3.00 (m, 2 H, βCH2 Phe), 3.17–3.18
(m, 1 H, βCH2 Phe), 3.60 (s, 3 H, OCH3), 3.91 (m, 1 H, αCH Phe),
4.03–4.05 (m, 1 H, αCH Phe), 4.20–4.25 (m, 2 H, αCH Ala), 4.63
(m, 4 H, CH2, Nα-Bn), 5.61 (br. s, 1 H, NHBoc), 6.37 (br. s, 1 H,
NH Ala), 6.52 (br. s, 1 H, NH Ala), 7.17–7.28 (m, 21 H, Ar, NH
Phe), 8.99 (br. s, 2 H, 2ϫNH azaPhe) ppm. 13C NMR (75 MHz,
CD3CN): δ = 17.3 (CH3 Ala), 18.2 (CH3 Ala), 28.6 (3 CH3 Boc),
37.2 (CH2 Phe), 37.4 (CH2 Phe), 50.5 (CH Ala), 52.3 (CH2, Nα-
Bn), 52.6 (CH Ala, O-CH3), 53.3 (CH2, Nα-Bn), 81.3 (C, Boc),
127.8 (CH, Ar), 128.1 (CH, Ar), 128.2 (CH, Ar), 128.4 (CH, Ar),
129.2 (CH, Ar), 129.3 (CH, Ar), 129.5 (CH, Ar), 129.7 (CH, Ar),
129.8 (CH, Ar), 130.3 (CH, Ar), 130.4 (CH, Ar), 137.6 (C, Ar),
138.0 (C, Ar), 138.5 (C, Ar), 139.9 (C, Ar), 158.3 (O=C-NH), 159.7
(O=C-NH), 171.4 (O=C-NH), 175.3 (C=O ester) ppm. HRMS
(ESI) calculated for C46H56N8 NaO9 [M + Na]+ m/z 887.4062,
found 887.4062.
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Boc-(D-Phe-azaPhe-Ala)2-OMe (11b): Purified by the trituration
with cyclohexane, yield 95%, white powder, m.p. 172 °C. IR (ATR):
ν
˜
max = 3423, 3351, 3240 (NH), 1741, 1704, 1665, 1635 (C=O) cm–1.
1H NMR (300 MHz, CDCl3): δ = 1.30 (d, J = 6.6 Hz, 3 H, βCH3
Ala), 1.34 (s, 9 H, Boc), 1.40 (d, J = 7.0 Hz, 3 H, βCH3 Ala), 2.56–
2.60 (m, 1 H, βCH2 Phe), 2.85–2.89 (m, 1 H, βCH2 Phe), 2.98–3.01
(m, 1 H, βCH2 Phe), 3.24–3.27 (m, 1 H, βCH2 Phe), 3.32 (s, 3 H,
OCH3), 3.81 (m, 1 H, αCH Ala), 4.10 (m, 1 H, αCH Phe), 4.27–
4.34 (m, 2 H, CH2, Nα-Bn), 4.40–4.48 (m, 3 H, CH2, Nα-Bn,
NHBoc and αCH Phe), 4.67–4.68 (m, 1 H, αCH Ala), 5.27 (m, 1
H, CH2, Nα-Bn), 6.30 (br. d, J = 8.21 Hz, 1 H, NH Ala), 6.42 (br.
s, 1 H, NH Phe), 6.97–7.34 (m, 20 H, Ar), 8.88 (br. s, 1 H, NH
azaPhe), 9.48 (br. s, 1 H, NH azaPhe) ppm. 13C NMR (75 MHz,
CDCl3): δ = 16.5 (CH3 Ala), 18.9 (CH3 Ala), 29.0 (CH3 Boc), 36.2
(CH2 Phe), 37.1 (CH2 Phe), 49.5 (CH Ala), 52.3 (CH2, Nα-Bn),
56.2 (CH Ala, and O-CH3), 82.0 (C, Boc), 127.9 (CH, Ar), 128.1
(CH, Ar), 128.8 (CH, Ar), 129.0 (CH, Ar), 129.5 (CH, Ar), 129.6
(CH, Ar), 136.4 (C Ar), 137.7 (C Ar), 156.9 (O=C-NH), 157.6
(O=C-NH), 170.6 (O=C-NH), 176.4 (C=O ester) ppm. HRMS
(ESI) calculated for C46H56N8NaO9 [M + Na]+ m/z 887.4062,
found 887.4062.
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Supporting Information (see footnote on the first page of this arti-
cle): 1H and 13C NMR spectra of 5, 7, 8a, 8b, 11a, 11b, complemen-
tary information on structural data, such as chemical shift varia-
tions, NOE spectra, NOEs and dihedral angles used for structural
calculations and crystals data are available in Supporting Infor-
mation.
Eur. J. Org. Chem. 2014, 7643–7650
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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