Langmuir
ARTICLE
Synthesis of Acetylated Maltose Conjugates OAc-Malt-Tz-
C16 and OAc-Malt-Tz-Phe-C16. Propargyl derivatives 6 or 7 (266
mg, 0.91 mmol), azide 1 (602 mg, 0.91 mmol), copper(I) bromide (27.7
mg, 0.19 mol) and N-pentamethyldiethylenetriamine (PMDETA) (38
μL, 0.18 mmol) were dissolved in anhydrous dimethylformamide
(6 mL) under an argon atmosphere. The mixture was stirred at room
temperature for 2 days. The reaction was monitored by TLC with
hexane/ethyl acetate 1:1 as eluent. The catalyst was removed by
filtration and the solvent was removed under reduced pressure. The
reaction was poured into 150 mL of water. The aqueous phase was
extracted three times, each with 150 mL of dichloromethane/ethyl
acetate 1:1. The organic phase was dried with anhydrous MgSO4. The
solution was filtered and the solvent was removed under reduced
pressure. The resulting white solid was purified by flash chromatography
using initially dichloromethane/ethyl acetate 1:1 and then increasing the
polarity. A white solid was obtained (756 mg, 87%).
36.5 COꢀCH2ꢀCH2, 38.2 CHꢀCH2ꢀPhe, 54.3 ꢀCOꢀCHꢀCH2,
61.5 C6, 62.5 C60, 68.0 C4, 68.8 C5, 69.3 C3, 70.0 C2, 70.9 C20, 72.5 C40,
75.2 C30, 75.5 C50, 85.0 C10, 96.0 C1, 120.8 NꢀCHdCꢀN triazole,
127.0, 128.9, 129.2 CHarom, 136.5 Carom, 144.9 CHdCꢀN triazole,
169.1 CH3ꢀCOꢀOꢀC20, 169.3 CH3ꢀCOꢀOꢀC4, 169.8 CH3ꢀ
COꢀOꢀC3, 169.9 CH3ꢀCOꢀOꢀC30, 170.4 CH3ꢀCOꢀOꢀC2,
170.5, 170.3 CH3ꢀCOꢀOꢀC6/C60, 171.0 NHꢀCOꢀCHꢀ, 173.2
NHꢀCOꢀCH2ꢀ.
MALDI-TOF MS (DCTB): 1124.4 [M + Na]+.
Anal. Calcd for C54H79N5O19: C, 58.84; H, 7.22; N, 6.35. Found: C,
58.24; H, 7.12; N, 6.28.
IR (KBr, cmꢀ1): 3306, 2923, 2852, 1753, 1640, 1546, 1370, 1234,
1037.
Synthesis of Maltose Conjugates Malt-Tz-C16 and Malt-Tz-
Phe-C16. The protected triazole-disaccharide-octaateate derivatives
(OAc-Malt-Tz-C16 and OAc-Malt-Tz-Phe-C16) (149.7 mg, 0.146
mmol) were dissolved in 7.5 mL of anhydrous methanol. Sodium
methoxide (55.3 mg, 1.023 mmol) was added. The solution was stirred
at room temperature until the reaction was complete (TLC, hexane/
ethyl acetate 1:1). Amberlyst IR 120 (H+ form) was added to exchange
sodium ions, the resin was filtered off, and the solvent was evaporated in
vacuo. A white solid was obtained (85ꢀ90%).
OAc-Malt-Tz-C16. 1H NMR (400 MHz, CDCl3): 0.87 (t, 3H, J = 6.2
Hz) ꢀ(CH2)12ꢀCH3, 1.16ꢀ1.35 (m, 24H) ꢀ(CH2)12ꢀ, 1.55ꢀ1.66
(m, 2H) ꢀCH2ꢀ(CH2)12, 1.84 (s, 3H) CH3ꢀCOꢀOꢀC20, 2.00 (s,
3H), 2.02 (s, 6H), 2.06 (s, 3H), 2.10 (s, 3H), 2.13 (s, 3H),
CH3ꢀCOꢀO, 2.17 (t, 2H, J = 7.7 Hz) COꢀCH2ꢀCH2, 3.96ꢀ3.98
(m, 2H) H5/H50, 4.05 (dd, 1H, J6b‑5 = 1.5 Hz, J6a‑6b = 1.6 Hz) H6b, 4.13
(dd, 1H, J3 ‑4 = 9.3 Hz, J4 ‑5 = 9.3 Hz) H40, 4.23ꢀ4.27 (m, 2H) H6a/
Malt-Tz-C16. 1H NMR (400 MHz, MeOD, 55 °C): 0.90 (t, 3H, J =
6.9 Hz) ꢀ(CH2)12ꢀCH3, 1.20ꢀ1.36 (m, 24H), ꢀ(CH2)12ꢀCH3,
1.56ꢀ1.60 (m, 2H) CH2ꢀCH2ꢀ(CH2)12, 2.21 (t, 2H, J = 7.4 Hz)
COꢀCH2ꢀCH2, 3.28 (dd, 1H, J3ꢀ4 = 9.6 Hz, J4ꢀ5 = 9.5 Hz) H4, 3.47
(dd, 1H, J1ꢀ2 = 3.8 Hz, J2ꢀ3 = 9.7 Hz) H2, 3.64 (dd, 1H, J2ꢀ3 = 9.7 Hz,
J3ꢀ4 = 9.6 Hz) H3, 3.65ꢀ3.90 (m, 8H) H5, H6a, H6b, H30, H40, H50,
0
0
0
0
H60a, 4.44ꢀ4.54 (m, 3H) C = CꢀCH2ꢀNH, H60b, 4.87 (dd, 1H, J1ꢀ2
=
3.9 Hz, J2ꢀ3 = 10.7 Hz) H2, 5.07 (dd, 1H, J3ꢀ4 = 10.0 Hz, J4ꢀ5 = 9.8 Hz)
0
0
0
0
0
H4, 5.31 (dd, 1H, J1 ‑2 = 9.1 Hz, J2 ‑3 = 8.8 Hz) H2 , 5.37 (dd, 1H, J2ꢀ3
=
0
0
0
0
10.7 Hz, J3ꢀ4 = 10.0 Hz) H3, 5.43 (dd, 1H, J2 ‑3 = 8.8 Hz, J3 ‑4 = 9.3 Hz)
H30, 5.44 (d, 1H, J1ꢀ2 = 3.9 Hz) H1, 5.84 (d, 1H, J1 ‑2 = 9.1 Hz) H10,
6.06 (t, 1H, J = 4.7 Hz) ꢀCH2ꢀNHꢀCO, 7.69 (s, 1H) NꢀCH =
CꢀCH2 triazole.
0
0
0
0
H60a, H60b, 3.93 (dd, 1H, J1 ‑2 = 9.1 Hz, J2 ‑3 = 9.0 Hz) H20, 4.34 (s,
0
0
0
0
2H) CꢀCH2ꢀNH, 5.13 (d, 1H, J1ꢀ2 = 3.8 Hz) H1, 5.50 (d, 1H, J1 ‑2
=
13C NMR (100 MHz, CDCl3): 14.1 ꢀ(CH2)12ꢀCH3, 20.2, 20.6,
20.7, 20.8, 20.8 (CH3ꢀCOꢀO)7, 25.6 CH2ꢀCH2ꢀ(CH2)12ꢀ, 22.7,
29.3, 29.4, 29.4, 29.5, 29.6, 29.7, 29.7, 31.9, 35.6, ꢀ(CH2)12ꢀ, COꢀ
CH2ꢀCH2, 34.8 CꢀCH2ꢀNH, 61.5 C6, 62.5 C60, 67.9 C4, 68.8 C5,
69.2 C3, 70.0 C20, 70.9 C2, 72.4 C40, 75.1 C30, 75.4 C50, 85.3 C10, 95.9
C1, 120.8 NꢀCHdCꢀN triazole, 145.3 CH = CꢀN triazole, 169.1,
169.4, 169.9 CH3ꢀCOꢀOꢀC2/C6/C60, 169.9, 170.3 CH3ꢀCOꢀOꢀ
C3/30, 170.5 CH3ꢀCOꢀOꢀC4, 170.6 CH3ꢀCOꢀOꢀC20, 173.2
NHꢀCOꢀCH2.
9.1 Hz) H10, 7.95 (s, 1H) NꢀCHꢀC-triazole.
13C NMR (100 MHz, MeOD, 55 °C):13.0 ꢀ(CH2)12ꢀCH3, 22.3,
25.4, 28.9, 29.2, 31.6 ꢀCH2ꢀ(CH2)12ꢀ, 34.1 CꢀCH2ꢀNHꢀ, 35.5
COꢀCH2ꢀCH2, 60.4, 61.3, 73.7, 76.8, 78.2, C6, C30,C40, C50,C60, 70.1
C4, 72.2 C20, 72.8 C2, 73.5 C3, 78.9 C5, 88.0 C10, 101.5 C1, 120.0
NꢀCHdC triazole, 145.0 CHdCꢀCH2 triazole, 174.9 NHꢀCOꢀCH2.
MicroTOF MS: 683.383 [M+ Na]+, calcd: 683.384.
IR (KBr, cmꢀ1): 3313 (broad), 2917, 2849, 1643, 1543, 1464, 1429,
1241, 1050, 719.
MALDI-TOF MS (DCTB+NaTFA): 977.5 [M + Na]+.
Anal. Calcd for C45H70N4O18: C, 56.59; H, 7.39; N, 5.87. Found: C,
56.25; H, 7.28; N, 5.80.
Malt-Tz-Phe-C16. 1H NMR (400 MHz, MeOD, 55 °C): 0.86 (t, 3H,
J = 6.8 Hz) ꢀ(CH2)12ꢀCH3, 1.10ꢀ1.32 (m, 24H), CH2ꢀCH2ꢀ
(CH2)12, 1.38ꢀ1.48 (m, 2H) CH2ꢀCH2ꢀ(CH2)12‑, 2.15 (t, 2H,
J = 7.5 Hz) COꢀCH2ꢀCH2, 2.89 (dd, 1H, JCHꢀCH2a = 8.9 Hz,
IR (KBr, cmꢀ1): 3303, 2925, 2854, 1754, 1645, 1552, 1369, 1233,
1036.
JCH2a‑CH2b = 13.9 Hz) CHꢀ(CH2)a-Phe, 3.11 (dd, 1H, JCHꢀCH2b
6.4 Hz, JCH2a‑CH2b = 13.9 Hz) CHꢀ(CH2)b-Phe, 3.34 (dd, 1H, J3ꢀ4
=
=
OAc-Malt-Tz-Phe-C16. 1H NMR (400 MHz, CDCl3): 0.87 (t, 3H, J =
6.8 Hz) ꢀ(CH2)12ꢀCH3, 1.14ꢀ1.40 (m, 24H) -(CH2)12ꢀ, 1.47ꢀ1.58
(m, 2H) ꢀCH2ꢀ(CH2)12ꢀ, 1.83 (s, 3H) CH3ꢀCOꢀOꢀC20, 2.01 (s,
3H), 2.03 (s, 6H), 2.07 (s, 3H), 2.10 (s, 3H), 2.12 (s, 3H),
CH3ꢀCOꢀO, 2.10ꢀ2.17 (m, 2H) COꢀCH2ꢀCH2, 2.98ꢀ3.10 (m,
2H) ꢀCHꢀCH2ꢀPhe, 3.94ꢀ4.01 (m, 2H) H5/H50, 4.07 (dd, 1H,
8.8 Hz, J4ꢀ5 = 9.0 Hz) H4, 3.52 (dd, 1H, J1ꢀ2 = 3.8 Hz, J2ꢀ3 = 9.6 Hz)
H2, 3.67 (dd, 1H, J2ꢀ3 = 9.6 Hz, J3ꢀ4 = 8.8 Hz) H3, 3.70ꢀ3.93 (m,
9H) H5, H6a, H6b, H20, H30,H40,H50,H60a, H60b, 4.42 (s, 2H)
CꢀCH2ꢀNH, 4.61 (dd, 1H, JCHꢀCH2a = 8.9 Hz, JCHꢀCH2b = 6.4
Hz) COꢀCHꢀNH, 5.29 (d, 1H, J1ꢀ2 = 3.8 Hz) H1, 5.59 (d, 1H,
0
J1 ‑2 = 8.8 Hz) H10, 7.16ꢀ7.29 (m, 5H) Harom, 7.88 (s, 1H)
0
0
0
0
J5ꢀ6b = 1.8 Hz, J6a‑6b = 12.4 Hz) H6b, 4.16 (dd, 1H, J3 ‑4 = 9.4 Hz, J4 ‑5
=
0
9.4 Hz) H40, 4.23ꢀ4.28 (m, 2H) H6a/H60a, 4.42 (d, 2H, J = 5.8 Hz)
NꢀCHdC-triazole.
CꢀCH2ꢀNH, 4.51 (dd, 1H, J5 ‑6 b = 2.2 Hz, J6 a‑6 b = 12.4 Hz) H60b,
4.60ꢀ4.66 (m, 1H) ꢀCOꢀCHꢀNHꢀ, 4.88 (dd, 1H, J1ꢀ2 = 3.9 Hz,
J2ꢀ3 = 10.5 Hz) H2, 5.07 (dd, 1H, J3ꢀ4 = 9.7 Hz, J4ꢀ5 = 10.0 Hz) H4,
13C NMR (100 MHz, MeOD, 55 °C): 13.0 ꢀ(CH2)12ꢀCH3, 25.3
CH2ꢀCH2ꢀ(CH2)12ꢀ, 22.1, 28.5 28.7, 28.8, 28.9, 31.4 ꢀ(CH2)12ꢀ,
34.4 CꢀCH2ꢀNHꢀ, 35.6 COꢀCH2ꢀCH2, 37.5 CHꢀCH2-arom,
54.7 COꢀCHꢀNHꢀ, 60.6, 61.3, 73.3, 76.8, 78.2, 78.3 C5, C6, C30,
C40, C50, C60, 70.2 C4, 72.3 C20, 72.6 C2, 73.7 C3, 87.9 C10, 101.1 C1,
122.4 NꢀCHdC triazole, 126.5 Carom, 128.2, 128.9, 136.9 CHarom,
0
0
0
0
5.32 (dd, 1H, J1 ‑2 = 9.4 Hz, J2 ‑3 = 9.2 Hz) H20, 5.38 (dd, 1H, J2ꢀ3
=
0
0
0
0
0
0
0
0
10.5 Hz, J3ꢀ4 = 9.7 Hz) H3, 5.45 (dd, 1H, J2 ‑3 = 9.2 Hz, J3 ‑4 = 9.4 Hz)
H30, 5.46 (d, 1H, J1ꢀ2 = 3.9 Hz) H1, 5.83 (d, 1H, J1 ‑2 = 9.4 Hz) H10,
6.04 (d, 1H, J = 7.6 Hz) CHꢀNHꢀCO, 6.36 (t, 1H, J = 5.7 Hz)
CH2ꢀNHꢀCO, 7.12ꢀ7.13 (m, 2H) Harom, 7.27ꢀ7.22 (m, 3H)
Harom, 7.54 (s, 1H) NꢀCHdC.
0
0
144.8 CH
=
CꢀCH2 triazole, 175.6 NHꢀCOꢀCH, 175.2
NHꢀCOꢀCH2ꢀ.
Micro-TOF MS: 808.4666 [M + H]+ calcd: 808.4702; 830.4495 [M +
13C NMR (100 MHz, CDCl3): 14.1 ꢀ(CH2)12ꢀCH3, 20.5, 20.6,
20.7, 20.8, (CH3ꢀCOꢀO)7, 22.7 ꢀ(CH2)12ꢀ, 25.5 ꢀCH2ꢀ(CH2)12,
29.2, 29.3, 29.3, 29.4, 29.6, 29.7, 32.0 ꢀ(CH2)12ꢀ, 34.9 CꢀCH2ꢀNH,
Na]+, calcd: 830.4521.
IR (KBr, cmꢀ1): 3297 (broad), 2919, 2850, 1638, 1543, 1456, 1377,
1036, 699.
15245
dx.doi.org/10.1021/la203447e |Langmuir 2011, 27, 15236–15247