646
W.-Q. Zhang et al. / European Journal of Medicinal Chemistry 121 (2016) 640e648
glucopyranoside, 19. Obtained from methyl-3, 4-O-[(2R, 3R)-2, 3-
dimethoxybutane-2, 3-diyl]- -D-glucopyranoside 15 and rhamno-
syl imidate following the general procedure described above. Col-
umn chromatography gave title compound as colorless syrup
CDCl3)
d
7.67 (s, 3H), 6.22 (s, 3H), 5.26e5.18 (m, 4H), 5.11 (dd, J ¼ 3.4,
b
1.7 Hz, 2H), 5.06 (br, 2H), 5.00 (t, J ¼ 10.0 Hz, 2H), 4.45e4.40 (m,
4H), 4.35e4.31 (m, 4H), 4.15e4.04 (m, 6H), 3.86e3.83 (m, 2H),
3.78e3.74 (m, 2H), 3.66e3.53 (m, 8H), 3.25 (s, 6H), 3.15 (s, 6H),
2.19e2.16 (m, 4H), 2.07 (s, 6H), 1.98 (s, 6H), 1.91 (s, 6H), 1.88 (s, 6H),
1.21 (s, 6H), 1.20 (s, 6H), 1.13 (d, J ¼ 6.3 Hz, 6H); 13C NMR (100 MHz,
(400 mg, 65%).1H NMR (400 MHz, CDCl3)
d
5.27 (dd, J ¼ 10.1, 3.4 Hz,
1H), 5.24e5.17 (m, 2H), 5.04e4.93 (m, 2H), 4.72 (d, J ¼ 3.6 Hz, 1H),
4.23 (dd, J ¼ 2.0, 12 Hz, 1H), 4.19 (d, J ¼ 4.8 Hz, 1H), 4.07 (t,
J ¼ 10.0 Hz, 1H), 3.96e3.80 (m, 2H), 3.70e3.56 (m, 2H), 3.33 (s, 3H),
3.26 (s, 3H), 3.15 (s, 3H), 2.06 (s, 3H), 2.01 (s, 3H), 1.99 (s, 3H), 1.91 (s,
3H), 1.23 (s, 3H), 1.21 (s, 3H), 1.13 (d, J ¼ 6.3 Hz, 3H); 13C NMR
CDCl3) d 170.64,170.10,170.05,169.93,160.21,143.64,123.45,101.81,
99.76, 99.68, 97.19, 94.92, 73.79, 73.05, 72.02, 71.23, 70.09, 68.74,
66.30, 66.15, 65.61, 62.04, 61.96, 48.18, 47.93, 47.26, 30.43, 20.89,
20.81, 20.74, 20.69, 17.59, 17.56, 17.27.
(100 MHz, CDCl3)
d 169.73, 169.00, 168.94, 168.87, 98.86, 98.69,
98.11, 98.09, 70.18, 68.86, 67.88, 67.46, 66.18, 65.69, 65.20, 61.16,
54.05, 47.10, 46.86, 19.86, 19.81, 19.78, 19.71, 16.71, 16.55, 16.49.
4.2.10.3. Tetrakis-O-{1-[2-O- (2, 3, 4-tri-O-acetyl-
anosyl)-3, 4-O-((2R, 3R)-2, 3-Dimethoxybutane-2, 3-Diyl)-6-O-
acetyl- -D-glucopyranosyloxypropyl]-1H-1, 2, 3-triazole-4-
ylmethyloxy} pentaerythritol, 25. Obtained from 3-azidopropyl-2-
O-[2, 3, 4-tri-O-acetyl- -rhamnopyranosyl]-3, 4-O-[(2R, 3R)-2, 3-
dimethoxybutane-2, 3-diyl]-6-O-acetyl- -glucopyranoside, 20
and tetrakis (2-propynyloxymethyl) methane 1H NMR (400 MHz,
CDCl3) 7.79 (s, 4H), 5.24e5.21 (m, 8H), 5.12e5.11 (m, 4H),
a-L-rhamnopyr-
b
4.2.9.3. 3-Azidopropy-2-O-[2, 3, 4-tri-O-acetyl-
anosyl]-3, 4-O-[(2R, 3R)-2, 3-dimethoxybutane-2, 3-diyl]-6-O-acetyl-
-D-glucopyranoside 20. Obtained from 3-azidopropyl-3, 4-O-[(2R,
3R)-2, 3-dimethoxybutane-2, 3-diyl]- -D-glucopyranoside 17 and
a-L-rhamnopyr-
a-L
b
b-D
b
rhamnosyl imidate following the general procedure described
above. Column chromatography gave title compound as colorless
d
5.02e4.97 (m, 4H), 4.66e4.30 (m, 24H), 4.15e4.09 (m, 8H),
3.88e3.73 (m, 8H), 3.64e3.57 (m, 17H), 3.40 (br, 8H), 3.29 (s, 12H),
3.15 (s, 12H), 2.16 (br, 9H), 2.07 (s, 12H), 2.00 (s, 12H), 1.92 (s, 12H),
syrup (400 mg, 65%).1H NMR (400 MHz, CDCl3)
d 5.24e5.20 (m,
2H), 5.11e5.10 (m, 1H), 5.03e5.01 (t, J ¼ 8 Hz, 1H),4.33e4.29 (m,
2H), 4.13e4.09 (m, 2H), 3.90e3.88 (m, 1H), 3.75e3.73 (m, 1H),
3.63e3.53 (m, 4H), 3.36 (t, J ¼ 8 Hz, 2H), 3.18 (s, 3H), 3.14 (s, 3H),
2.07 (s, 3H), 2.00 (s, 3H),1.99 (s, 3H), 1.93 (s, 3H),1.82 (t, J ¼ 6.5 Hz,
2H), 1.21,1.20 (2s, 2 ꢁ 3H), 1.10 (d, J ¼ 6.3 Hz, 3H); 13C NMR
1.89 (s, 12H), 1.22 (s, 12H), 1.20 (s, 12H), 1.12 (d, J ¼ 6.2 Hz, 12H); 13
C
NMR (100 MHz, CDCl3)
d 170.66, 170.08, 169.98, 145.03, 123.11,
101.86, 99.76, 99.68, 97.27, 73.97, 73.02, 71.95, 71.23, 70.07, 68.81,
66.46, 66.29, 65.61, 64.87, 62.07, 48.18, 47.93, 47.31, 30.54, 20.89,
20.83, 20.75, 20.72, 17.60, 17.57, 17.28.
(100 MHz, CDCl3) d 170.07, 170.00, 101.82, 99.72, 99.64, 97.12, 77.37,
77.06, 76.74, 73.69, 73.13, 71.85, 71.24, 70.07, 68.85, 66.67, 66.16,
65.67, 62.21, 49.70, 48.28, 48.14, 47.88, 29.19, 20.85, 20.79, 20.72,
17.57, 17.54, 17.16.
4.2.10.4. 1,2,3,4,6-Penta-O-{1-[2-O- (2, 3, 4-tri-O-acetyl-
nopyranosyl)-3, 4-O-((2R, 3R)-2, 3-dimethoxybutane-2, 3-diyl)-6-O-
acetyl- -D-glucopyranosyloxypropyl]-1H-1, 2, 3-triazole-4-
ylmethyloxy}- -D-galactopyranose, 26. Obtained from 3-
azidopropyl-2-O-[2, 3, 4-tri-O-acetyl- -rhamnopyranosyl]-3, 4-
O-[(2R, 3R)-2, 3-dimethoxybutane-2, 3-diyl]-6-O-acetyl- -glu-
copyranoside, Obtained from 3-azidopropyl-3, 4-O-[(2R, 3R)-2, 3-
dimethoxybutane-2, 3-diyl]- -D-glucopyranoside 20 and 1, 2, 3,
4, 6-penta-O-propyl -D- galactopyranoside following the general
a-L-rham-
b
4.2.10. General procedure for click chemistry reaction
b
The azide (1.0 equiv.), CuSO4$5H2O (1.0 equiv.) and sodium
a-L
ascorbate (1.0 equiv.) were added to
a
solution of alkynyl
b-D
(1.0 equiv.) in mixture solvant of THF/H2O (1:1). The mixture was
stirred at room temperature overnight and monitored by TLC. The
organic phase was extracted with CH2Cl2, dried over sodium sulfate
and concentrated under reduced pressure. The obtained residue
was purified by column chromatography on a silica gel using a
gradient mixture of petroleum DCM/MeOH with increasing polarity
as an eluent.
b
b
procedure described above. Column chromatography gave title
compound as colorless syrup (400 mg, 65%). 1H NMR (400 MHz,
CD3OD)
d 7.85 (br, 5H), 5.20e4.99 (m, 30H), 4.45e4.36 (m, 30H),
4.10 (br, 14H), 3.75e3.59 (m, 50H), 3.25 (s, 15H), 3.16 (s, 15H), 2.17
(br, 12H), 2.07e1.92 (m, 60H), 1.22 (s, 15H), 1.21 (s, 15H), 1.12 (br,
4.2.10.1. 1, 2-Di-{1-[2-O- (2, 3, 4-tri-O-acetyl-
anosyl)-3, 4-O-((2R, 3R)-2, 3-dimethoxybutane-2, 3-Diyl)-6-O-
acetyl- -D-glucopyranosyloxypropyl]-1H-1, 2, 3-triazole-4-
ylmethyloxy} ethane, 23. Obtained from 3-azidopropyl-2-O-[2, 3,
4-tri-O-acetyl- -rhamnopyranosyl]-3, 4-O-[(2R, 3R)-2, 3-
dimethoxybutane-2, 3-diyl]-6-O-acetyl- -glucopyranoside, 20
a
-L-rhamnopyr-
15H); 13C NMR (100 MHz, CD3OD)
d 169.04, 100.81, 98.68, 96.33,
71.94, 71.04, 70.18, 69.06, 67.77, 65.35, 64.52, 60.93, 47.19, 46.94,
19.90, 16.59.
b
a
-L
4.2.10.5. 1, 2, 3, 6, 20, 30, 40, 60-Octa-O-{1-[2-O- (2, 3, 4-tri-O-acetyl-
L-rhamnopyranosyl)-3, 4-O-((2R, 3R)-2, 3-dimethoxybutane-2, 3-
a-
b-D
and 1, 2-Bis(2-propynyloxy) ethane following the general proce-
dure described above. Column chromatography gave title com-
pound as colorless syrup (400 mg, 65%).1H NMR (400 MHz, CDCl3)
diyl)-6-O-acetyl-
4-ylmethyloxy} -
[2, 3, 4-tri-O-acetyl-
dimethoxybutane-2, 3-diyl]-6-O-acetyl-
and 1, 2, 3, 6, 20, 30, 40, 60-Octa-O-propyl-
b
-D-glucopyranosyloxypropyl]-1H-1, 2, 3-triazole-
b
-D-lactose, 27. Obtained from 3-azidopropyl-2-O-
a
-L
-rhamnopyranosyl]-3, 4-O-[(2R, 3R)-2, 3-
-glucopyranoside, 20
-D- lactopyranoside
d
7.68 (br, 2H), 5.23 (s, 6H), 5.19 (br, 2H), 5.10 (br, 2H), 4.99 (br, 2H),
b-D
4.63 (br, 4H), 4.43e4.33 (m, 7H), 4.15e4.06 (m, 4H), 3.89e3.46 (m,
4H), 3.25 (s, 6H), 3.15 (s, 6H), 2.07 (br, 6H), 2.00 (br, 6H), 1.80e1.77
(m, 12H), 1.85e1.71 (m, 12H), 1.14e1.12 (m, 6H).
b
following the general procedure described above. Column chro-
matography gave title compound as colorless syrup (400 mg, 65%).
1H NMR (400 MHz, CDCl3)
d 7.79 (br, 8H), 5.24e4.99 (m, 20H),
4.2.10.2. 1, 3, 5-tri-{1-[2-O-(2, 3, 4-tri-O-acetyl-
anosyl)-3, 4-O-((2R, 3R)-2, 3-dimethoxybutane-2, 3-diyl)-6-O-acetyl-
-D-glucopyranosyloxypropyl] -1H-1, 2, 3-triazole-4-ylmethyloxy}
benzene, 24. Obtained from 3-azidopropyl-2-O-[2, 3, 4-tri-O-
acetyl- -rhamnopyranosyl]-3, 4-O-[(2R, 3R)-2, 3-
dimethoxybutane-2, 3-diyl]-6-O-acetyl- -glucopyranoside 20
a
-L-rhamnopyr-
4.44e4.04 (m, 34H), 3.68e3.60 (m, 57H), 3.25 (s, 24H), 3.16 (s, 24H),
2.07e1.78 (m, 96H), 1.21e1.13 (m, 72H); 13C NMR (100 MHz, CDCl3)
b
d 170.14, 169.05, 100.81, 98.75, 98.67, 96.27, 73.06, 71.96, 70.99,
70.18, 69.05, 67.76, 66.94, 65.30, 64.51, 60.96, 59.38, 47.17, 46.93,
28.68, 24.59, 20.03, 19.89, 19.77, 16.59, 16.30, 13.18.
a-L
b-D
and 1, 3, 5-tris (2-propynyloxy) benzene following the general
procedure described above. Column chromatography gave title
compound as colorless syrup (400 mg, 65%).1H NMR (400 MHz,
4.2.10.6. Poly-1, PoD. Poly (methyl vinyl ether-alt-maleic anhy-
dride) (MW~130,000) 300 mg was dissolved in DMF, then prop-
argylamine (0.5 mL) was added dropwise under 0 ꢀC and the