Formation of gels in the presence of metal ions
617
Boc-L-Phe-D-Oxd-(S)-aMe-Phg-OBn
1d
M.p. =
CH2(C3H6CO-L-Phe-D-Oxd-(S)-b3-hPhg-OBn)2
2b
196°C; [a]2D0 = ?17.3 (c = 0.25, CH2Cl2); IR (CH2Cl2,
M.p. = 129°C; [a]D20 = ?32.0 (c = 1.0, CH2Cl2); IR
(CH2Cl2, 3 mM): m 3,435, 3,319, 1,788, 1,735, 1,675,
1,655 cm-1; IR (1% in KBr): m 3,411, 3,309, 3,088, 1,772,
3 mM): m 3,434, 3,385, 1,789, 1,737, 1,720, 1,703 cm-1
;
IR (1% in dry KBr): m 3,389, 3,309, 1,768, 1,742, 1,718,
1,701, 1,687 cm-1; NMR (400 MHz, CDCl3): d 1.26
(d, 6H, J = 6.6 Hz), 1.55 (s, 9H), 1.98 (s, 3H), 2.89
(m, 1H), 3.11 (m, 1H), 4.30 (m, 1H), 4.56 (m, 1H), 5.12
(AB, 2H, J = 12.4 Hz), 5.16 (bs, 1H), 5.71 (q, 1H,
J = 6.8 Hz), 7.16–7.42 (m, 16H); 13C NMR (75 MHz,
CDCl3): d 21. 3, 28.5, 30.2, 54.3, 63.2, 68.0, 74.5, 126.4,
127.6, 128.3, 128.6, 128.8, 129.0, 129.8, 136.4, 151.8,
166.4, 173.8, 183.2. Anal. calcd. for C35H39N3O8: C,
66.76; H, 6.24; N, 6.67; Found: C, 66.73; H, 6.19; N, 6.70.
1,732, 1,715, 1,650, 1,556, 1,531 cm-1
;
1H NMR
(400 MHz, CDCl3): d 1.08–1.52 (m, 16H), 1.92–2.15
(m, 4H), 2.81–2.99 (m, 6H), 3.18 (m, 2H), 4.12 (m, 2H),
4.39 (m, 1H), 4.58 (m, 1H), 5.05 (m, 2H), 5.13 (m 1H),
5.15 (s, 2H), 5.52 (m, 1H), 5.75 (m, 1H), 6.03 (m, 1H),
7.15–7.38 (m, 30H), 7.41 (d, 1H, J = 6 Hz), 7.85 (d, 1H,
J = 6.4 Hz); 13C NMR (50 MHz, CDCl3): d 21.0, 24.8,
28.5, 29.7, 35.3, 36.4, 40.8, 50.3, 53.2, 56.9, 62.5, 66.5,
75.2, 126.8, 127.5, 127.6, 128.2, 128.4, 128.7, 128.9,
129.2, 135.0, 135.7, 140.6, 151.0, 166.4, 170.1, 175.5,
174.3. Anal. calcd. for C69H74N6O14: C, 68.41; H, 6.16; N,
6.94. Found: C, 68.44; H, 6.17; N, 6.92.
General method for the preparation of compounds 2a–d
CH2(C3H6CO-L-Phe-D-Oxd-(R)-aMe-Phg-OBn)2 2c
M.p. = 76°C; [a]D20 = ?22.0 (c = 1.0, CHCl3); IR
(CH2Cl2, 3 mM): m 3,343, 3,374, 3,366, 3,335, 1,787,
1,771, 1,738, 1,732, 1,683, 1,674 cm-1; IR (1% in dry
KBr): m 3,392, 3,370, 1,734, 1,701, 1,653 cm-1; NMR
(400 MHz, CDCl3): d 0.98–1.44 (m, 16H), 1.88–2.05
(m, 4H), 1.96 (s, 6H), 2.92 (m, 2H), 3.17 (m, 2H), 4.24
(m, 2H), 4.41 (m, 2H), 5.12 (AB, 4H, J = 12.4 Hz), 5.28
(m, 2H), 5.78 (bs, 1H), 6.10 (bs, 1H), 7.05–7.37 (m, 29H),
7.44 (m, 2H), 7.81 (m, 1H); 13C NMR (50 MHz, CDCl3): d
21.0, 24.6, 24.7, 28.3, 28.4, 28.5, 35.3, 36.8, 53.0, 62.4,
62.7, 67.5, 74.4, 126.3, 127.3, 127.4, 128.1, 128.2, 128.4,
128.7, 129.3, 135.2, 139.4, 151.6, 166.6, 171.7, 173.0,
173.6. Anal. calcd. for C69H74N6O14: C, 68.41; H, 6.16; N,
6.94. Found: C, 68.37; H, 6.19; N, 6.99.
A solution of fully protected di- or tripeptide (2 mmol) and
TFA (36 mmol, 2.78 mL) in dry methylene chloride
(20 mL) was stirred at room temperature for 4 h, then the
volatiles were removed under reduced pressure and the
corresponding amine salt was obtained pure in quantitative
yield without further purification.
A solution of azelaic acid (0.98 g, 0.52 mmol) and
HBTU (0.4 mg, 1.04 mmol) in dry acetonitrile (22 mL)
was stirred under inert atmosphere for 10 min at room
temperature. Then a mixture of the previously obtained
amine salt (1.04 mmol) and Et3N (3.2 mmol, 0.47 mL)
in dry acetonitrile (15 mL) was added dropwise at room
temperature. The solution was stirred for 40 min under
inert atmosphere, then acetonitrile was removed under
reduced pressure and replaced with ethyl acetate. The
mixture was washed with brine, 1 N aqueous HCl (3 9
30 mL) and with 5% aqueous NaHCO3 (1 9 30 mL),
dried over sodium sulphate and concentrated in vacuo.
The product was obtained pure after silica gel chroma-
tography (DCM 100% ? DCM/acetato di etile 80:20 as
eluant).
CH2(C3H6CO-L-Phe-D-Oxd-(S)-aMe-Phg-OBn)2 2d
M.p. = 150°C; [a]D20 = ?92.0 (c = 1, CHCl3); IR
(CH2Cl2, 3 mM): m 3,433, 3,385, 3,323, 3,304, 1,787,
1,737, 1,714, 1,677 cm-1; IR (1% in KBr): m 3,422, 3,327,
1
3,284, 1,781, 1,749, 1,706, 1,684, 1653, 1642 cm-1; H
NMR (400 MHz, CDCl3):
d 0.88–1.41 (m, 16H),
1.65–2.02 (m, 4H), 1.96 (s, 6H), 2.94 (m, 2H), 3.18 (m,
2H), 4.24 (m, 2H), 4.42 (m, 2H), 5.08 (AB, 4H,
J = 12.0 Hz), 5.28 (m, 2H), 5.71 (bs, 2H), 6.05 (bs, 2H),
7.05–7.35 (m, 30H), 7.40 (bs, 1H), 7.78 (s, 1H); 13C NMR
(100 MHz, CDCl3): d 14.1, 20.8, 21.0, 21.8, 24.5, 28.5,
29.6, 35.2, 36.7, 53.0, 53.4, 60.3, 62.2, 63.0, 67.3, 74.6,
81.4, 126.1, 127.3, 127.9, 128.0, 128.1, 128.3, 128.7,
129.2, 135.4, 151.6, 166.9, 171.6, 173.4. Anal. calcd. for
C69H74N6O14: C, 68.41; H, 6.16; N, 6.94. Found: C, 68.45;
H, 6.20; N, 6.91.
CH2(C3H6CO-L-Phe-D-Oxd-(R)-b3-hPhg-OBn)2
2a
M.p. = 179°C; [a]D20 = ?44.0 (c = 1.1, CHCl3); IR
(CH2Cl2, 3 mM): m 3,433, 3,323, 1,785, 1,735, 1,719,
1,672, 1,658 cm-1; IR (1% in dry KBr): m 3,310, 3,298,
1,773, 1,734, 1,718, 1,653 cm-1 1H NMR (400 MHz,
;
CDCl3): d 1.09–1.58 (m, 16H), 1.85–2.05 (m, 4H),
2.85–3.21 (m, 8H), 4.11 (m, 2H), 4.39 (m, 1H), 4.62 (m,
1H), 5.05 (m, 2H), 5.13 (m 1H), 5.17 (s, 2H), 5.42 (m, 1H),
5.65 (m, 1H), 6.12 (m, 1H), 7.05–7.41 (m, 31H), 7.96 (m,
1H); 13C NMR (50 MHz, CDCl3): d 20.8, 24.7, 28.3, 35.2,
36.5, 40.5, 41.1, 50.6, 53.3, 62.5, 66.5, 75.3, 82.1, 126.4,
127.4, 128.1, 128.5, 128.8, 129.2, 135.1, 135.6, 140.6,
143.5, 151.7, 167.1, 170.5, 172.9, 174.3. Anal. calcd. for
C69H74N6O14: C, 68.41; H, 6.16; N, 6.94. Found: C, 68.47;
H, 6.19; N, 6.91.
General method for the preparation of compounds 3a–d
Compound 1a–e (1 mmol) was dissolved in MeOH
(35 mL) under nitrogen. C/Pd (50 mg, 10% w/w) was
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