E. W. Meijer et al.
1431, 1387, 1230, 1118, 698 cmÀ1; MALDI-TOF: m/z: calcd for: 771.55;
off-white solid material (0.19 g, 0.07 mmol, 59%). 1H NMR ([D6]DMSO,
T=323 K): d=9.74 (s, 3H, NH’’), 8.60 (d, 3H, J=8.0 Hz, NH), 8.24 (s,
3H, ortho-H), 8.16 (d, 3H, J=7.5 Hz, NH’), 7.3–7.0 (m, 30H, Ar), 6.87
(s, 6H, ortho-H’), 4.79 (q, 3H, Ca1H), 4.69 (q, 3H, Ca2H), 4.0–3.7 (m,
18H, OCH2), 3.1 + 2.9 (m, 12H, CH2Ar), 1.8–1.0 (m, 108H, (CH2)6),
0.84 ppm (t, 27H, CH3); 13C NMR ([D6]DMSO, T=323 K): d=170.6,
169.1, 165.2, 152.1, 137.7, 137.1, 134.2, 134.1, 133.6, 128.9, 127.8, 126.1,
125.9, 98.6, 72.3, 68.2, 54.6, 37.5, 37.0, 31.0, 31.0, 29.6, 28.6, 28.5, 28.4,
25.3, 21.8, 13.5 ppm; FT-IR (ATR): n˜ =3273, 2923, 2854, 1639, 1603, 1532,
1506, 1467, 1455, 1428, 1387, 1230, 1117, 697 cmÀ1; MALDI-TOF: m/z:
found: 771.64 [M] +; elemental analysis calcd (%) for C48H73N3O5: C
C
74.67, H 9.53, N 5.44; found: C 74.82, H 9.51, N 5.29.
Nw-(3,4,5-Trioctyloxyphenyl)-d-phenylalanyl-d-phenylalaninamide (7d):
Compound 6d (0.30 g, 0.34 mmol) was dissolved in TFA (3.5 mL). The
solution was purged with argon for 15 min, after which the mixture was
stirred for another 45 min. The reaction mixture was concentrated in
vacuo. A mixture of ethyl acetate, 1n NaOH and some ice was added.
The organic layer was washed with 1n NaOH several times and dried
over MgSO4 to give the pure title compound (0.24 g, 0.31 mmol, 91%).
1H NMR (CDCl3): d=8.08 (s, 1H, aromatic amide NH), 7.93 (d, 1H, J=
7.6, aliphatic amide NH), 7.4–7.1 (m, 10H, Ar), 6.68 (s, 2H, ortho-H),
4.70 (q, 1H, Ca2H), 4.0–3.8 (m, 6H, OCH2), 3.60 (m, 1H, Ca1H), 3.23 (m,
2H, Ca2HCH2Ar), 3.11 + 2.45 (dd + dd, 2H, Ca1HCH2Ar), 1.9–1.2 (m,
38H, (CH2)6 {36H} + NH2 {2H}), 0.88 ppm (m, 9H, CH3); 13C NMR
(CDCl3): d=175.4, 168.9, 153.2, 137.4, 137.0, 135.0, 133.3, 129.5, 129.3,
128.9, 128.8, 127.1, 99.1, 73.6, 69.2, 56.3, 55.2, 40.7, 37.5, 32.0, 32.0, 30.4,
29.7, 29.5, 29.4, 26.3, 26.2, 22.8, 22.8, 14.2 ppm; FT-IR (ATR): n˜ =3283,
2955, 2922, 2855, 1646, 1606, 1540, 1506, 1467, 1455, 1430, 1231, 1119,
calcd for: 2471.65; found: 2471.78 [M] +, 2494.75 [M+Na]+, 2511.73
C
[M+K]+; elemental analysis calcd (%) for C153H219N9O18: C 74.33, H
8.93, N 5.10; found: C 74.06, H 8.94, N 5.04.
Na,Na’,Na’’-(1,3,5-Benzenetricarbonyl)-tris[Nw-(3,4,5-trioctyloxyphenyl)]-
G
d-phenylalanyl-l-phenylalaninamide (8c): A solution of 1,3,5-benzenetri-
carbonyl trichloride (30.0 mg, 0.11 mmol) in dichloromethane (1.2 mL)
was added dropwise to a solution of 7c (0.29 g, 0.37 mmol) and triethyla-
mine (0.1 mL, 0.7 mmol) in dry dichloromethane (3.5 mL). After stirring
overnight and evaporation of the dichloromethane, the compound was
separated from the crude mixture using column filtration (silica, 2%
methanol in dichloromethane). Subsequently, reflux in methanol for
30 min and filtration afforded the product as a white solid in pure form
(0.20 g, 0.08 mmol, 71%). The product was characterized using GPC
(THF, 260 nm, purity based on UV >99%). 1H NMR ([D6]DMSO, T=
373 K): d=9.43 (s, 3H, NH’’), 8.27 (d, 3H, J=8.5 Hz, NH), 8.18 (s, 3H,
ortho-H), 8.03 (d, 3H, J=7.5 Hz, NH’), 7.3–7.0 (m, 30H, Ar), 6.88 (s,
6H, ortho-H’), 4.77 (q, 3H, Ca1H), 4.69 (q, 3H, Ca2H), 4.0–3.7 (m, 18H,
OCH2), 3.1–2.9 (m, 12H, CH2Ar), 1.8–1.0 (m, 108H, (CH2)6), 0.84 ppm
(t, 27H, CH3); 13C NMR ([D6]DMSO, T=373 K): d=170.2, 168.7, 165.0,
151.9, 137.2, 136.9, 134.3, 134.1, 133.6, 128.5, 128.4, 128.1, 127.3, 125.6,
125.5, 99.5, 72.1, 68.5, 54.6, 54.2, 37.4, 37.0, 30.6, 30.5, 29.2, 28.4, 28.2,
28.0, 28.0, 28.0, 25.0, 25.0, 21.3, 21.3, 13.0 ppm; FT-IR (ATR): n˜ =3267,
2954, 2922, 2854, 1640, 1603, 1536, 1505, 1467, 1455, 1430, 1388, 1231,
1117, 697 cmÀ1; MALDI-TOF: m/z: calcd for: 2471.65; found: 2471.88
698 cmÀ1; MALDI-TOF: m/z: calcd for: 771.55; found: 771.60 [M] +; ele-
C
mental analysis calcd (%) for C48H73N3O5: C 74.67, H 9.53, N 5.44;
found: C 74.35, H 9.53, N 5.36.
Nw-(3,4,5-Trioctyloxyphenyl)-l-phenylalanyl-d-phenylalaninamide (7e):
Compound 6e (0.78 g, 0.90 mmol) was dissolved in TFA (9 mL). The so-
lution was purged with argon for 15 min, after which the mixture was
stirred for another 45 min. The reaction mixture was concentrated in
vacuo. A mixture of ethyl acetate, 1n NaOH and some ice was added.
The organic layer was washed with 1n NaOH several times and dried
over MgSO4 to give the pure title compound (0.49 g, 0.63 mmol, 71%).
1H NMR (CDCl3): d=8.13 (s, 1H, aromatic amide NH), 7.90 (d, 1H, J=
7.6, aliphatic amide NH), 7.4–7.1 (m, 10H, Ar), 6.68 (s, 2H, ortho-H),
4.70 (q, 1H, Ca2H), 4.0–3.8 (m, 6H, OCH2), 3.57 (m, 1H, Ca1H), 3.23 +
2.74 (m, 4H, CH2Ar), 1.9–1.2 (m, 38H, (CH2)6 {36H} + NH2 {2H}),
0.87 ppm (m, 9H, CH3); 13C NMR (CDCl3): d=175.6, 168.9, 153.3, 137.3,
137.0, 135.1, 133.3, 129.4, 129.4, 128.9, 128.9, 127.1, 99.1, 73.6, 69.3, 56.3,
55.5, 40.8, 37.0, 32.0, 32.0, 30.4, 29.7, 29.5, 29.4, 26.3, 26.2, 22.8, 22.8,
14.2 ppm; FT-IR (ATR): n˜ =3265, 2924, 2855, 1644, 1614, 1603, 1555,
1504, 1467, 1454, 1427, 1379, 1229, 1115, 698 cmÀ1; MALDI-TOF: m/z:
[M] +, 2494.94 [M+Na]+, 2510.92 [M+K]+; elemental analysis calcd (%)
C
for C153H219N9O18: C 74.33, H 8.93, N 5.10; found: C 74.35, H 8.87, N
4.90.
Na,Na’,Na’’-(1,3,5-Benzenetricarbonyl)-tris[Nw-(3,4,5-trioctyloxyphenyl)]-
U
calcd for: 771.55; found: 771.58 [M] +; elemental analysis calcd (%) for
C
d-phenylalanyl-d-phenylalaninamide (8d): A solution of 1,3,5-benzenetri-
carbonyl trichloride (5.8 mg, 21.8 mmol) in dichloromethane (0.2 mL) was
added dropwise to a solution of 7d (52.6 mg, 68.1 mmol) and triethyla-
mine (20 mL, 143 mmol) in dry dichloromethane (0.7 mL). After stirring
overnight the reaction mixture was filtered to yield the title compound as
an off-white solid material (20 mg, 8.09 mmol, 37%). 1H NMR
([D6]DMSO, T=323 K): d=9.75 (s, 3H, NH’’), 8.61 (d, 3H, J=8.0 Hz,
NH), 8.24 (s, 3H, ortho-H), 8.18 (d, 3H, J=8.0 Hz, NH’), 7.3–7.0 (m,
30H, Ar), 6.87 (s, 6H, ortho-H’), 4.79 (q, 3H, Ca1H), 4.69 (q, 3H, Ca2H),
4.0–3.7 (m, 18H, OCH2), 3.1–2.9 (m, 12H, CH2Ar), 1.8–1.0 (m, 108H,
(CH2)6), 0.84 ppm (t, 27H, CH3); 13C NMR ([D6]DMSO, T=323 K): d=
170.6, 169.0, 165.2, 152.1, 137.7, 137.0, 134.2, 134.1, 133.6, 128.9, 128.9,
127.8, 127.8, 126.1, 125.9, 98.6, 72.3, 68.2, 54.6, 37.6, 37.0, 31.0, 31.0, 29.5,
28.6, 28.6, 28.5, 28.4, 25.3, 25.3, 21.8, 21.8, 13.5 ppm; FT-IR (ATR): n˜ =
3275, 2923, 2855, 1639, 1603, 1532, 1506, 1467, 1455, 1428, 1387, 1230,
1116, 697 cmÀ1; MALDI-TOF: m/z: calcd for: 2471.65; found: 2471.78
C48H73N3O5: C 74.67, H 9.53, N 5.44; found: C 74.81, H 9.62, N 5.32.
Na,Na’,Na’’-(1,3,5-Benzenetricarbonyl)-tris(Nw-3,4,5-trioctyloxyphenyl)-
glycyl-l-phenylalaninamide (8a): A solution of 1,3,5-benzenetricarbonyl
trichloride (45.4 mg, 0.17 mmol) in dry THF (1.7 mL) was added drop-
wise to a solution of 7a (0.39 g, 0.57 mmol) and triethylamine (0.2 mL,
1.43 mmol) in dry THF (5 mL). After stirring overnight and evaporation
of THF, the product was purified using column chromatography (silica,
THF/hexane 2:1). Subsequently, the product was recrystallized from a
mixture of THF/methanol 2:3 to yield the title compound as a white
solid material (0.12 g, 0.05 mmol, 32%). The product was characterized
using GPC (THF, 260 nm, purity based on UV ꢀ100%). 1H NMR
([D6]DMSO, T=323 K): d=9.71 (s, 3H, NH’’), 8.78 (t, 3H, NH), 8.48 (s,
3H, ortho-H), 8.18 (d, 3H, J=7.5 Hz, NH’), 7.3–7.1 (m, 15H, Ar), 6.91
(s, 6H, ortho-H’), 4.66 (q, 3H, CaH), 4.0–3.7 (m, 24H, NHCH2CO {6H}
+ OCH2 {18H}), 3.1 + 2.9 (m, 6H, CH2Ar), 1.8–1.0 (m, 108H, (CH2)6),
0.85 ppm (t, 27H, CH3); 13C NMR ([D6]DMSO, T=323 K): d=169.2,
168.4, 165.5, 152.1, 137.3, 134.3, 134.1, 133.6, 128.9, 127.8, 126.1, 98.6,
72.3, 68.2, 54.6, 42.6, 37.5, 31.0, 31.0, 29.6, 28.7, 28.6, 28.5, 28.4, 25.4, 25.3,
21.8, 21.8, 13.6 ppm; FT-IR (ATR): n˜ =3280, 2923, 2854, 1651, 1604, 1536,
1506, 1467, 1428, 1386, 1228, 1116, 699 cmÀ1; MALDI-TOF: m/z: calcd
[M] +, 2494.75 [M+Na]+; elemental analysis calcd (%) for C153H219N9O18
:
C
C 74.33, H 8.93, N 5.10; found: C 74.15, H 8.95, N 4.94.
Na,Na’,Na’’-(1,3,5-Benzenetricarbonyl)-tris[Nw-(3,4,5-trioctyloxyphenyl)]-
G
l-phenylalanyl-d-phenylalaninamide (8e): A solution of 1,3,5-benzenetri-
carbonyl trichloride (44.2 mg, 0.17 mmol) in dichloromethane (1.7 mL)
was added dropwise to a solution of 7e (0.43 g, 0.56 mmol) and triethyla-
mine (0.16 mL, 1.15 mmol) in dry dichloromethane (5 mL). After stirring
overnight and evaporation of the dichloromethane, the product was puri-
fied using column chromatography (silica, 2% methanol in dichlorome-
thane) and subsequently washed with acetonitril to yield the title com-
pound as an off-white solid material (0.23 g, 0.09 mmol, 55%). The prod-
uct was characterized using GPC (THF, 260 nm, purity based on UV
ꢀ100%). 1H NMR ([D6]DMSO, T=373 K): d=9.43 (s, 3H, NH’’), 8.27
(d, 3H, J=8.0 Hz, NH), 8.18 (s, 3H, ortho-H), 8.03 (d, 3H, J=6.5 Hz,
for: 2200.51; found: 2200.36 [M] +; 2223.38 [M+Na]+; elemental analysis
C
calcd (%) for C132H201N9O18: C 72.00, H 9.20, N 5.72; found: C 71.41, H
9.22, N 5.77.
Na,Na’,Na’’-(1,3,5-Benzenetricarbonyl)-tris[Nw-(3,4,5-trioctyloxyphenyl)]-
G
l-phenylalanyl-l-phenylalaninamide (8b): A solution of 1,3,5-benzenetri-
carbonyl trichloride (33.4 mg, 0.13 mmol) in dry THF (1.3 mL) was
added dropwise to a solution of 7b (0.30 g, 0.39 mmol) and triethylamine
(0.1 mL, 0.7 mmol) in dry dichloromethane (4 mL). After stirring over-
night the reaction mixture was filtered to yield the title compound as an
8122
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 8111 – 8123