125
give Boc-G1-meta-NH2 10 (712 mg, 0.813 mmol, 97%) as an 114.4, 116.5, 124.4, 124.7, 124.9, 125.2, 128.5, 129.9, 130.5,
off-white solid. mp 175–177 ºC (CHCl3); 1H NMR (400 MHz, 132.6, 149.1, 149.4, 150.2, 153.1, 161.4, 168.3, 171.6; IR
80 ºC, DMSO-d6) δ 1.23 (s, 18H), 1.54–1.68 (m, 4 H), 1.80– (KBr) 3440, 3258, 2973, 2877, 2358, 1677, 1594, 1517, 1478,
1.87 (m, 2 H), 1.95–2.05 (m, 2 H), 3.10–3.20 (m, 4 H), 4.15 1447, 1391, 1361, 1292, 1235, 1157, 1123 cm–1; HRMS calcd
(dd, J = 8.5 Hz, 4.7 Hz, 2 H), 5.15 (brs, 2 H), 6.85–6.88 (m, for C46H53N9O9 (M+Na) 898.3864. Found 898.3859.
1 H), 7.21–7.24 (m, 2 H), 7.27–7.32 (m, 3 H), 7.58–7.62 (m,
Boc-m-[G1]-dend (13). To a solution of Boc-G1-meta-NH2
2 H), 7.79–7.82 (m, 2 H), 8.87 (s, 2 H), 9.52 (s, 2 H), 10.76 (10) (175 mg, 0.20 mmol) in dry CH2Cl2 (0.4 mL) were added
(s, 1 H), 10.82 (s, 2 H); 13C NMR (100 MHz, DMSO-d6) δ pyridine (0.4 mL). The reaction mixture was cooled to 0 ºC
23.9, 28.4, 30.9, 47.0, 61.1, 79.3, 114.0, 115.2, 115.9, 118.5, in an ice bath. To this mixture was added a solution of freshly
125.3, 125.7, 125.8, 126.1, 129.4, 130.8, 131.4, 135.2, 149.1, prepared benzene-1,3,5-tricarbonyl trichloride (18 mg, 0.066
150.1, 150.3, 154.0, 162.3, 167.8, 172.5; IR (KBr) 3474, mmol) in CH2Cl2 (0.4 mL) dropwise over 5 min. The reaction
3260, 2964, 1680, 1592, 1518, 1481, 1444, 1393, 1305, 1230, was stirred while warming to rt gradually over 12 h. The reac-
1156 cm–1; HRMS calcd for C46H53N9O9 (M+Na) 898.3864. tion was diluted with CH2Cl2 (10 mL) and washed with cold 1
Found 898.3876.
M HCl (10 mL). The aqueous layer was back-extracted with
Boc-G1-ortho-no2 (11). To a solution of Boc-G1-NH2 CHCl3 (2 ´ 10 mL). The organic layer was treated with solid
(8) (0.50 g, 0.66 mmol) in dry CH2Cl2 (3.3 mL) were added NaHCO3 until pH ~7 and dried over Na2SO4. After concentra-
DMAP (16 mg, 0.13 mmol) and pyridine (3.3 mL). The reac- tion in vacuo, the residue was purified by column chromatog-
tion mixture was cooled to 0 ºC in an ice bath. To this mixture raphy on silica gel (1–3% MeOH/CH2Cl2) to afford Boc-m-
was added a solution of 2-nitrobenzoyl chloride (122 mg, [G1]-dend 13 (125 mg, 0.0449 mmol, 67%) as an off-white
1
0.66 mmol) in CH2Cl2 (0.7 mL) dropwise over 5 min. The solid. mp (dec) 220 ºC (CHCl3); H NMR (400 MHz, 80 ºC,
reaction was stirred while warming to rt gradually over 12 h. DMSO-d6) δ 1.24 (s, 54 H), 1.55–1.70 (m, 12 H), 1.81–1.88
The reaction was diluted with CH2Cl2 (10 mL) and washed (m, 6 H), 1.96–2.05 (m, 6 H), 3.15–3.21 (m, 12 H), 4.28 (dd, J
with cold 1 M HCl (15 mL). The aqueous layer was back-ex- = 9.0 Hz, 4.7 Hz, 6 H), 7.26–7.33 (m, 12 H), 7.59–7.65 (m, 9
tracted with CHCl3 (2 ´ 10 mL). The combined organic layer H), 7.80–7.82 (m, 6 H), 7.87–7.90 (dd, J = 7.7 Hz, J = 1.6 Hz,
was treated with solid NaHCO3 until pH ~7 and dried over 3 H), 8.14–8.17 (m, 3 H), 8.48–8.49 (m, 3 H), 8.84 (s, 3 H),
Na2SO4. After concentration in vacuo, the residue was puri- 8.90 (s, 6 H), 9.53 (s, 6 H), 10.68 (s, 3 H), 10.84 (s, 6 H), 11.00
fied by column chromatography on silica gel (1–3% MeOH/ (s, 3 H); 13C NMR (100 MHz, DMSO–d6) δ 23.9, 28.4, 30.9,
CHCl3) to afford Boc-G1-ortho-NO2 11 (289 mg, 0.319 mmol, 47.0, 61.1, 79.3, 115.4, 121.0, 123.8, 125.0, 125.3, 125.7,
48%) as an off-white solid. mp 182–185 ºC (CHCl3); 1H NMR 125.9, 126.2, 129.4, 130.4, 130.8, 131.4, 135.0, 136.0, 139.9,
(400 MHz, 80 ºC, DMSO-d6) δ 1.26 (s, 18 H), 1.55–1.71 (m, 150.1, 150.2, 162.2, 165.3, 167.0, 172.5; IR (KBr) 3455,
4 H), 1.84–1.91 (m, 2 H), 1.98–2.07 (m, 2 H), 3.12–3.23 (m, 3279, 2973, 2361, 1680, 1592, 1513, 1402, 1305, 1156 cm–1;
4 H), 4.19 (dd, J = 8.7 Hz, 4.4 Hz, 2 H), 7.23–7.34 (m, 4 H), MALDI-TOF MS calcd for C147H159N27O30 (M+Na) 2805.17.
7.62–7.64 (m, 2 H), 7.82–7.84 (m, 2 H), 7.87 (td, J = 7.6 Hz, Found 2806.60.
1.7 Hz, 2 H), 7.94 (td, J = 7.5 Hz, 1.1 Hz, 1 H), 8.22 (dd, J =
m-[G1]-dend (3). To a solution of Boc-m-[G1]-dend 13 (55
8.2 Hz, 1.0 Hz, 1 H), 8.72 (s, 2 H), 9.56 (s, 2 H), 10.87 (s, 2 H), mg, 0.0197 mmol) in CH2Cl2 (2 mL) was added anisole (2 mL)
11.38 (s, 1 H); 13C NMR (100 MHz, DMSO–d6) δ 23.0, 27.5, at rt. The mixture was cooled to 0 ºC and TFA (2 mL) was
30.0, 46.1, 60.3, 78.4, 114.0, 123.9, 124.4, 124.8, 125.0, 125.3, added dropwise over 2 min. The reaction was stirred while
128.8, 129.8, 130.6, 131.1, 131.2, 133.8, 146.0, 148.6, 149.5, warming to rt gradually over 12 h. The volatiles were removed
153.1, 161.2, 165.0, 171.6; IR (KBr) 3447, 3355, 3086, 2978, in vacuo. To the residue was added diethyl ether (5 mL) and
2931, 2347, 1681, 1596, 1531, 1481, 1393, 1367, 1349, 1296, the solid precipitate was isolated by filtration. The precipi-
1256, 1160, 1128 cm–1; HRMS calcd for C46H51N9O11 (M+Na) tate was redissolved in a mixture of H2O (2 mL) and CH3CN
928.3600. Found 928.3609.
(2 mL). To this mixture was added solid NaHCO3 with stir-
Boc-G1-ortho-nH2 (12). Boc-G1-ortho-NO2 (11) (289 ring until pH ~8. The white solid precipitate was isolated by
mg, 0.320 mmol) was dissolved in anhydrous EtOH (6 mL). filteration and dried in vacuo over P2O5 to give m-[G1]-dend 3
10% Pd/C (29 mg) was added to this mixture and the reaction (42 mg, 0.0192 mmol, 98%) as a white solid. mp 260-263 ºC
was hydrogenated under H2 at atmospheric pressure for 12 h. (CH3CN); 1H NMR (400 MHz, 80 ºC, DMSO-d6) δ 1.74–1.80
The catalyst was removed by filtration through a pad of Celite. (m, 12 H), 2.00–2.07 (m, 6 H), 2.21–2.30 (m, 6 H), 3.11–3.15
The solvent was removed in vacuo and the residue was puri- (m, 12 H), 4.37 (dd, J = 8.8 Hz, 4.1 Hz, 6 H), 7.32–7.36 (m,
fied by column chromatography on silica gel (1–3% MeOH/ 12 H), 7.60–7.64 (m, 3 H), 7.68–7.78 (m, 12 H), 7.89 (d, J =
CHCl3) to give Boc-G1-ortho-NH2 12 (237 mg, 0.271 mmol, 9.0 Hz, 3 H), 8.15 (d, J = 9.8 Hz, 3 H), 8.56 (s, 3 H), 8.89 (s,
85%) as an off-white solid. mp 174–178 ºC (CHCl3); 1H NMR 9 H), 10.74 (s, 6 H), 10.78 (s, 3 H), 10.98 (s, 3 H); 13C NMR
(400 MHz, 80 ºC, DMSO–d6) δ 1.24 (s, 18 H), 1.54–1.70 (m, (100 MHz, DMSO–d6) δ 24.0, 29.9, 46.3, 60.4, 115.6, 121.1,
4 H), 1.79–1.88 (m, 2 H), 1.95–2.05 (m, 2 H), 3.10–3.20 (m, 123.8, 125.1, 125.8, 126.4, 126.5, 126.8, 129.3, 130.4, 131.1,
4 H), 4.16 (dd, J = 9.0 Hz, 4.4 Hz, 2 H), 6.42 (brs, 2 H), 6.65 131.6, 135.1, 136.0, 140.0, 149.8, 150.7, 162.8, 165.3, 167.1;
(td, 7.0 Hz, 1.4 Hz, 1 H), 6.84 (dd, J = 8.4 Hz, 1.1 Hz, 1 H), IR (KBr) 3247, 3070, 1682, 1591, 1519, 1454, 1304, 1203,
7.23–7.34 (m, 5 H), 7.59–7.61 (m, 2 H), 7.78–7.82 (m, 3 H), 1134 cm–1; MALDI-TOF MS calcd for C117H111N27O18 (M+H)
8.84 (s, 2 H), 9.53 (s, 2 H), 10.82 (s, 2 H); 13C NMR (100 MHz, 2182.86. Found 2183.07.
DMSO–d6) δ 23.0, 27.5, 30.0, 46.1, 60.2, 69.5, 78.3, 113.3,
Boc-o-[G1]-dend (14). To a solution of Boc-G1-ortho-
Mitsui and Parquette / Dendritic Amplification of Stereoselectivity