The Journal of Organic Chemistry
Article
(−CH2O−), 20.7, 20.50, 20.48, 20.1; HRMS (ESI/ICR) m/z [M +
2Na]2+ calcd for [C60H69N9O33Na2]2+/2 744.6891, found 744.6904.
Synthesis of Trimeric Triazole Linked Cluster 18. Sugar azide 1247
(189 mg, 0.495 mmol, 3.3 equiv), alkyne 3 (50 mg, 0.150 mmol, 1
equiv), CuSO4 (14 mg, 0.090 mmol, 0.6 equiv) L-ascorbic acid
sodium salt (36 mg, 0.180 mmol, 1.2 equiv), and 6 mL of solvent
mixture of t-BuOH/H2O/THF (v/v/v = 1/1/1) were used. The
reaction mixture was stirred at room temperature for 24 h. Solvent
was removed under reduced pressure, and the crude product was
purified via column chromatography using eluent from pure DCM to
7% MeOH/DCM. A white solid (184 mg, 83%) was obtained as the
desired product (Rf = 0.4 in 5% MeOH/DCM): mp 246.0−248.0 °C;
1H NMR (400 MHz, d6-DMSO) δ 8.65 (s, 3H, phenyl-H), 8.43 (s,
3H, triazole-H), 8.03 (d, J = 9.1 Hz, 3H, −NH−), 6.14 (d, J = 9.9 Hz,
3H, H-1), 5.48 (s, 6H, −CH2O−), 5.35 (t, J = 9.7 Hz, 3H, H-3), 5.09
(t, J = 9.7 Hz, 3H, H-4), 4.64−4.53 (m, 3H, H-2), 4.27−4.20 (m, 3H,
H-5), 4.18−4.11 (m, 3H, Ha-6), 4.09−4.02 (m, 3H, Hb-6), 2.01 (s,
9H), 1.99 (s, 9H), 1.94 (s, 9H), 1.55 (s, 9H, CH3 in −NHAc);
13C{1H} NMR (100 MHz, d6-DMSO) δ 170.0, 169.5, 169.4, 169.2,
163.7, 141.7, 133.8, 130.8, 124.0, 84.7 (C-1), 73.4 (C-5), 72.2 (C-3),
68.0 (C-4), 61.7 (C-6), 58.4 (−CH2O−), 52.1 (C-2), 22.2, 20.4, 20.3,
(10 mL) and DCM (10 mL × 2). The crude product was purified via
column chromatography using eluent from pure DCM to 10%
MeOH/DCM. A white solid (430 mg, 81%) was obtained as the
desired product (Rf = 0.35 in 3% MeOH/DCM): mp 165.7−166.8
1
°C; H NMR (400 MHz, CDCl3) δ 8.11−8.00 (m, 9H), 6.05−5.90
(m, 6H), 5.58 (t, J = 9.3 Hz, 6H), 5.53−5.41 (m, 6H), 5.35−5.23 (m,
6H), 4.84−4.64 (m, 6H), 4.60−4.43 (m, 6H), 4.36−4.26 (m, 6H),
4.23−4.00 (m, 12H), 2.12−1.98 (m, 54H), 1.92−1.80 (m, 18H);
13C{1H} NMR (100 MHz, CDCl3) δ 170.6, 170.1, 169.9, 169.4,
169.0, 168.9, 143.8, 143.3, 136.7, 127.5, 122.7, 122.3, 85.7, 75.1, 72.7,
70.7, 70.5, 67.9, 61.8, 43.6, 39.1, 20.7, 20.5, 20.2. HRMS (ESI/ICR)
m/z [M + 2Na]2+ calcd for [C111H135N21O57Na2]2+/2 1359.9048,
found 1359.9023.
Synthesis of Hexameric Triazole Linked Cluster 22. Alkyne 5
(65.3 mg, 0.15 mmol, 1.0 equiv), sugar azide 12 (390 mg, 10.5 mmol,
7.0 equiv), CuSO4 pentahydrate (45.0 mg, 0.18 mmol, 1.2 equiv), L-
ascorbic acid sodium salt (72 mg, 0.36 mmol, 2.4 equiv), and 6 mL of
EtOH/water (v/v = 1/1) were used. The reaction mixture was stirred
at room temperature for 24 h. Solvent was removed to give the crude
product, which was worked up by DCM (10 mL × 3) and water (3
mL). The crude product was purified by column chromatography
using eluent from pure DCM to 15% MeOH/DCM to give a white
solid (301 mg, 0.11 mmol, 75%) as the desired product (Rf = 0.2 in
20.2; HRMS (ESI/ICR) m/z [M
+
2Na]2+ calcd for
[C60H72N12O30Na2]2+/2 743.2131, found 743.2134.
Synthesis of Trimeric Triazole Linked Cluster 19.56 Sugar azide 11
(191 mg, 0.513 mmol, 3.3 equiv), alkyne 4 (50 mg, 0.157 mmol, 1
equiv), CuSO4 (14 mg, 0.094 mmol, 0.6 equiv), L-ascorbic acid
sodium salt (36 mg, 0.188 mmol, 1.2 equiv), and 6 mL of a solvent
mixture of t-BuOH/H2O/THF (v/v/v = 1/1/1) were used. The
reaction mixture was stirred at room temperature for 24 h. An off-
white solid (178 mg, 79%) was obtained as the desired product (Rf =
0.4 in 5% MeOH/DCM): mp 165.0−167.0 °C; 1H NMR (400 MHz,
CDCl3) δ 8.34 (t, J = 5.4 Hz, 3H, −NH−), 8.12 (s, 3H, triazole-H),
8.09 (s, 3H, phenyl-H), 5.94 (d, J = 9.4 Hz, 3H, H-1), 5.75 (t, J = 9.4
Hz, 3H, H-2), 5.43 (t, J = 9.4 Hz, 3H, H-3), 5.31 (t, J = 9.4 Hz, 3H,
H-4), 4.84−4.70 (m, 6H, −CH2NH−), 4.31 (dd, J = 12.7, 5.1 Hz,
3H, Ha-6), 4.13 (dd, J = 12.7, 1.9 Hz, 3H, Hb-6), 4.10−4.04 (m, 3H,
H-5), 2.05 (s, 9H), 2.01 (s, 9H), 1.98 (s, 9H), 1.76 (s, 9H); 13C{1H}
NMR (100 MHz, CDCl3) δ 170.5, 170.0, 169.44, 169.36, 166.1,
146.0, 134.5, 128.5, 121.5, 85.8 (C-1), 75.0 (C-5), 72.9 (C-3), 70.5
(C-2), 67.8 (C-4), 61.8 (C-6), 35.8 (−CH2NH−), 20.60, 20.55, 20.1;
1
10% MeOH/DCM): mp 210.0−213.2 °C; H NMR (400 MHz, d6-
DMSO) δ 8.33 (s, 6H), 8.06 (d, J = 8.4 Hz, 6H), 7.79 (s, 3H), 6.17−
6.00 (m, 6H), 5.43−5.32 (m, 6H), 5.12 (t, J = 8.8 Hz, 6H), 4.84−
4.43 (m, 12H), 4.41−4.00 (m, 24H), 2.06−1.88 (m, 54H), 1.64−1.54
(m, 18H); 13C{1H} NMR (100 MHz, d6-DMSO) δ 170.0, 169.6,
169.2, 136.4, 143.3, 85.0, 79.2, 78.9, 78.6, 73.4, 72.1, 68.0, 61.8, 52.2,
43.6, 22.2, 20.3, 20.2. HRMS (ESI/ICR) m/z [M + 2Na]2+ calcd for
[C111H141N27O51Na2]2+/2 calcd for 1356.9527, found 1356.9533.
Synthesis of Trimeric Triazole Linked Cluster 23. Alkyne 6 (50
mg, 0.214 mmol, 1.0 equiv), sugar azide 11 (318 mg, 0.854 mmol, 4.0
equiv), CuSO4 pentahydrate (32 mg, 0.128 mmol, 0.6 equiv), L-
ascorbic acid sodium salt (51.4 mg, 0.257 mmol, 1.2 equiv), and 6 mL
of EtOH/water (v/v = 1/1) were used. The reaction mixture was
stirred at room temperature for 17 h. Solvent was removed to give the
crude product, which was worked up by DCM (10 mL × 3) and water
(3 mL). The crude product was purified by column chromatography
using eluent from 1% MeOH/DCM to 5% MeOH/DCM to afford a
white solid (255 mg, 0.188 mmol, 88%) as the desired product (Rf =
0.18 in 2% MeOH/DCM): mp 121.0−122.5 °C; 1H NMR (400
MHz, CDCl3) δ 7.90 (s, 3H), 5.99 (d, J = 9.3 Hz, 3H), 5.53 (t, J = 9.4
Hz, 3H), 5.44 (t, J = 9.4 Hz, 3H), 5.37−5.28 (m, 3H), 4.67−4.55 (m,
6H), 4.32 (dd, J = 12.6, 5.0 Hz, 3H), 4.17 (dd, J = 12.6, 2.0 Hz, 3H),
4.11−4.04 (m, 3H), 3.42−3.30 (m, 6H), 2.08 (s, 9H), 2.04 (s, 9H),
2.03 (s, 9H), 1.81 (s, 9H), 0.92 (s, 3H). 13C{1H} NMR (100 MHz,
CDCl3) δ 170.5, 170.0, 169.4, 168.8, 146.2, 121.2, 85.6, 75.0, 73.0,
72.9, 70.3, 67.9, 64.8, 61.6, 40.7, 20.63, 20.57, 20.5, 20.1, 17.5; HRMS
(ESI/ICR) m/z [M + 2Na]2+ calcd for [C56H75N9O30Na2]2+/2 calcd
for 699.7202, found 699.7196.
LCMS (ESI/Quadrupole) m/z [M
+
H]+ calcd for
C60H73N12O301440.4, found 1441.4.
Synthesis of Trimeric Triazole Linked Cluster 20. Sugar azide 12
(286 mg, 0.769 mmol, 3.3 equiv), alkyne 4 (75 mg, 0.233 mmol, 1
equiv), CuSO4 pentahydrate (35 mg, 0.140 mmol, 0.6 equiv), L-
ascorbic acid sodium salt (55.4 mg, 0.280 mmol, 1.2 equiv), and 6 mL
of solvent mixture of t-BuOH/H2O/THF (v/v/v = 1/1/1) were used.
The reaction mixture was stirred at room temperature for 24 h. A
green precipitate was observed in the reaction mixture. The reaction
mixture was filtered, and the precipitate was washed with DI water
(10 mL) and DCM (10 mL). Light green solid (226 mg, 67%) was
obtained as the desired product: mp 259.0−261.0 °C (sample turned
1
Synthesis of Trimeric Triazole Linked Cluster 24. Alkyne 6 (50
mg, 0.214 mmol, 1.0 equiv), sugar azide 12 (318 mg, 0.854 mmol, 4.0
equiv), CuSO4 pentahydrate (32 mg, 0.128 mmol, 0.6 equiv), L-
ascorbic acid sodium salt (51.4 mg, 0.257 mmol, 1.2 equiv), and 6 mL
of EtOH/water (v/v = 1/1) were used. The reaction mixture was
stirred at room temperature for 17 h. Solvent was removed to give the
crude product, which was worked up by DCM (10 mL × 3) and water
(3 mL). The crude product was purified by column chromatography
using eluent from 1% MeOH/DCM to 5% MeOH/DCM to afford a
white solid (245 mg, 0.180 mmol, 85%) as the desired product (Rf =
0.18 in 5% MeOH/DCM): mp 150.0−152.5 °C; 1H NMR (400
MHz, CDCl3) δ 7.92 (s, 3H), 6.92 (d, J = 8.9 Hz, 3H), 6.18 (d, J =
9.8 Hz, 3H), 5.51 (t, J = 9.9 Hz, 3H), 5.32 (t, J = 9.7 Hz, 3H), 4.70−
4.59 (m, 3H), 4.57−4.47 (m, 6H), 4.33 (dd, J = 12.7, 4.7 Hz, 3H),
4.23−4.16 (m, 3H), 4.14−4.07 (m, 3H), 3.27 (s, 6H), 2.10−2.00 (m,
27H), 1.72 (s, 9H), 0.87 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3)
δ 171.0, 170.7, 170.6, 169.4, 145.5, 122.2, 85.6, 75.0, 72.6, 72.5, 68.1,
64.2, 61.8, 53.5, 40.6, 22.7, 20.7, 20.64, 20.60, 17.5; HRMS (ESI/
brown at 180 °C and started melting at 259.0 °C); H NMR (400
MHz, d6-DMSO) δ 9.35−9.14 (m, 3H, -NH-CH2), 8.48 (s, 3H,
phenyl-H), 8.16 (s, 3H, triazole-H), 8.05 (d, J = 8.8 Hz, 3H, −NH−),
6.10 (d, J = 9.7 Hz, 3H, H-1), 5.34 (t, J = 9.7 Hz, 3H, H-3), 5.07 (t, J
= 9.7 Hz, 3H, H-4), 4.65−4.43 (m, 9H, H-2, −NHCH2), 4.28−3.94
(m, 9H, H-5, Ha-6, Hb-6), 2.00 (s, 9H), 1.97 (s, 9H), 1.93 (s, 9H),
1.58 (s, 9H, CH3 in −NHAc); 13C{1H} NMR (100 MHz, d6-DMSO)
δ 169.9, 169.5, 169.4, 169.2, 165.3, 134.5, 128.8, 121.9, 84.5 (C-1),
73.3 (C-5), 72.3 (C-3), 67.9 (C-4), 61.7 (C-6), 52.0 (C-2), 34.8
(−NH-CH2), 22.2, 20.4, 20.3, 20.1; HRMS (ESI/ICR) m/z [M +
2Na]2+ calcd for [C60H75N15O27Na2]2+/2 741.7371, found 741.7379.
Synthesis of Hexameric Triazole Linked Cluster 21. Alkyne 5 (87
mg, 0.2 mmol, 1 equiv), sugar azide 11 (491.2 mg, 1.32 mmol, 6.6
equiv), CuSO4 pentahydrate (60 mg, 0.24 mmol, 1.2 equiv, L-ascorbic
acid sodium salt (95 mg, 0.48 mmol, 2.4 equiv), and 3 mL of ethanol/
water mixture (v/v = 1/1) were used. The reaction mixture was
stirred at room temperature for 30 h. The reaction mixture was then
diluted with DCM (10 mL) and underwent a workup using DI water
P
J. Org. Chem. XXXX, XXX, XXX−XXX