6
K.B. Mishra et al. / Carbohydrate Research 399 (2014) 2–7
Table 1 (continued)
Entrya
Azideb
Click productc
Timed
Yielde
N
OH
N
N
HO
N
OH
O
N
N3
N
O
N
H
N
N
O
OCH3
OBn
BnO
BnO
O
O
H
BnO
BnO
9
12
80
H
OBn
OCH3
4i
2i
a
b
c
Molar ratios: sugar azide (1.0 equiv), ethisterone (1.0 equiv), CuI (0.5 equiv), and DIPEA (1 equiv).
Sugar based triazolyl azido-alcohols.
Bis-triazolyl ethisterone glycoconjugate.
Time in hours.
d
e
Isolated yield.
OH
N
OH
HO
N
N
Epichlorohydrin
OH
H
H
H
H
NaN3
N
N
O
H
O
O
N
H
H
CuSO4.5H2O
NaAsc, H2O
H
H
3
6 (30%)
O
O
OH
N
O
N
N
O
OH
H
1a
OH N
N3
N
N
OH
O
O
H
O
H
N
CuI, DIPEA
DCM, 10h
H
O
N
H
N
H
4a
(82%)
2j
(45%)
Scheme 2. Synthesis of bistriazolyl ethisterone glycoconjugate 4a via ethisterone azido-alcohol 2j.
23.6, 20.5, 17.3, 14.2; HRMS: Calcd for C42H56N6O8 [M+Na]
795.4057; found 795.4052.
63.2, 55.6, 53.1, 52.9, 48.8, 44.9, 38.5, 37.6, 36.1, 35.5, 33.8, 32.7,
32.6, 31.5, 23.6, 20.5, 17.3, 14.1; HRMS: Calcd for C47H60N6O8
[M+Na] 859.4370; found 859.4369.
3.1.2.4. Bis-triazolyl ethisterone glycoconjugate (Table 1, entry
4).
Compound 2d (0.265 g, 0.7 mmol), ethisterone (0.24 g,
3.1.2.6. Bis-triazolyl ethisterone glycoconjugate (Table 1, entry
0.7 mmol), DIPEA (0.129 mL, 0.7 mmol), and CuI (0.065 g,
0.3 mmol) were reacted in dry DCM (10 mL) to afford 4d
(0.441 g, 92%) after flash column chromatography (SiO2) using
chloroform/methanol (9:1) as eluent. White solid; mp = 132–
134 °C; IR (KBr) cmÀ1: 3426, 3135, 2976, 2920, 1666, 1465, 1371,
1093; 1H NMR (300 MHz, CDCl3): d 7.73 (s, 1H), 7.59 (s, 1H), 5.67
(s, 1H), 4.94 (s, 1H), 4.64–4.48 (m, 7H), 4.36–4.26 (m, 3H), 3.60–
3.48 (m, 2H), 3.29 (s, 3H), 2.41–1.86 (m, 12H), 1.63–1.25 (m,
12H), 1.16 (s, 3H), 1.04 (s, 3H), 0.73–0.65 (m, 1H), 0.48–0.40 (m,
1H); 13C NMR (75 MHz, CDCl3): d 199.5, 171.3, 153.3, 144.7,
123.7, 112.4, 109.2, 85.0, 84.9, 81.9, 81.9, 71.6, 68.6, 64.5, 54.8,
53.1, 48.7, 46.7, 38.5, 37.6, 36.1, 35.5, 33.8, 32.7, 32.6, 31.5, 26.4,
24.9, 23.6, 20.5, 17.3, 14.2; HRMS: Calcd for C36H52N6O8 [M+Na]
719.3744; found 719.3748.
6).
Compound 2f (0.138 g, 0. 26 mmol), ethisterone (0.082 g,
0.26 mmol), DIPEA (0.044 mL, 0.26 mmol), and CuI (0.024 g,
0.13 mmol) were reacted in dry DCM (10 mL) to afford 4f
(0.180 g, 82%) after flash column chromatography (SiO2) using
chloroform/methanol (9:1) as eluent. Viscous liquid; IR (KBr)
cmÀ1: 3403, 3260, 3030, 2923, 2853, 1731, 1659, 1496, 1454,
1210, 1070; 1H NMR (300 MHz, CDCl3): d 7.68 (s, 1H), 7.53 (s,
1H), 7.30–7.25 (m, 10H), 5.66 (s, 1H), 4.94 (d, J = 4.2 Hz, 1H),
4.74–4.08 (m, 14H), 3.71–3.56 (m, 2H), 3.39 (s, 3H), 2.35–1.88
(m, 12H), 1.58–1.48 (m, 3H), 1.41–1.25 (m, 3H), 1,15 (s, 3H), 1.03
(s, 3H), 0.68 (m, 1H), 0.42 (m, 1H); 13C NMR (75 MHz, CDCl3): d
199.5, 171.2, 153.8, 144.6, 138.0, 137.9, 128.3, 127.7, 127.5,
124.7, 123.7, 100.2, 83.9, 81.3, 81.2, 75.9, 73.4, 72.6, 69.2, 68.5,
63.7, 55.2, 53.0, 52.9, 48.8, 46.7, 38.5, 37.6, 36.1, 35.5, 33.8, 32.7,
32.6, 31.4, 23.6, 20.5, 17.3, 14.1; HRMS: Calcd for C47H60N6O8
[M+Na] 859.4370; found 859.4374.
3.1.2.5. Bis-triazolyl ethisterone glycoconjugate (Table 1, entry
5).
Compound 2e (0.069 g, 0.13 mmol), ethisterone (0.041 g,
0.13 mmol), DIPEA (0.022 mL, 0.13 mmol), and CuI (0.012 g,
0.06 mmol) were reacted in dry DCM (5 mL) to afford 4e (0.093 g,
86%) after flash column chromatography (SiO2) using chloroform/
methanol (9:1) as eluent. White solid; mp = 68–70 °C; IR (KBr)
3.1.2.7. Bis-triazolyl ethisterone glycoconjugate (Table 1, entry
7).
Compound 2g (0.125 g, 0.28 mmol), ethisterone (0.80 g,
0.28 mmol), DIPEA (0.047 mL, 0.28 mmol), and CuI (0.026 g,
0.13 mmol) were reacted in dry DCM (10 mL) to afford 4g
(0.185 g, 88%) after flash column chromatography (SiO2) using
chloroform/methanol (9:1) as eluent. White solid; mp = 115–
117 °C; IR (KBr) cmÀ1: 3444, 2975, 2936, 1745, 1668, 1365, 1283,
1068; 1H NMR (300 MHz, CDCl3): d 7.77 (s, 1H), 7.62 (s, 1H), 5.60
(s, 1H), 5.08 (s, 1H),4.75–4.48 (m, 7H), 4.36 (m, 2H), 4.07–3.93
(m, 4H), 2.27–1.89 (m, 12H), 1.59–1.35 (m, 7H), 1.30–1.25 (12H),
1.16–0.87 (m, 5H), 0.68 (m, 1H), 0.48 (m, 1H); 13C NMR (75 MHz,
CDCl3): d 199.5, 171.5, 153.3, 144.0, 124.7, 123.4, 112.5, 109.0,
cmÀ1
:
3406, 2922, 2851, 1662, 1454, 1231, 1058; 1H NMR
(300 MHz, CDCl3): d 7.64 (s, 1H), 7.53 (s, 1H), 7.31–7.29 (m,
10H), 5.67 (s, 1H), 4.87 (s, 1H), 4.62–4.28 (m, 12H), 4.04–4.00 (m,
2H), 3.75–3.66 (m, 2H), 3.38 (s, 3H), 2.36–2.28 (m, 6H), 2.04–
1.1.89 (m, 6H), 1.59–1.41 (m, 3H), 1.33–1.25 (m, 3H), 1.15 (s,
3H), 1.03 (s, 3H), 0.69 (m, 1H), 0.42 (m, 1H); 13C NMR (75 MHz,
CDCl3): d 199.5, 171.2, 153.4, 144.5, 137.6, 128.4, 128.3, 127.8,
127.6, 124.5, 123.7, 107.7, 86.9, 81.2, 79.9, 73.4, 72.3, 69.6, 68.6,