320
Y.-G. Liu et al. / European Journal of Medicinal Chemistry 95 (2015) 313e323
residue was purified by column chromatography on silica gel
(EtOAc/petroleum ether, 1:1), affording 15 (770 mg, 99% yield) as a
0.018, CDCl3); 1H NMR (400 MHz, CDCl3)
d
7.58 (d, J ¼ 15.9 Hz, 1H),
7.36e7.31 (m,1H), 7.25e7.15 (m, 2H), 6.81 (d, J ¼ 8.2 Hz,1H), 6.75 (d,
J ¼ 1.9 Hz, 1H), 6.71 (dd, J ¼ 1.9 Hz, 8.3 Hz, 1H), 6.27 (d, J ¼ 15.9 Hz,
1H), 6.13e6.01 (m, 2H), 5.94e5.84 (m, 1H), 5.45e5.22 (m, 7H), 5.15
(t, J ¼ 9.6 Hz, 1H), 5.02 (dd, J ¼ 8.0 Hz, 9.6 Hz, 1H), 4.64e4.55 (m,
6H), 4.53 (d, J ¼ 7.9 Hz, 1H), 4.31e4.24 (m, 2H), 4.09 (dt, J ¼ 6.4 Hz,
9.5 Hz, 1H), 3.82e3.77 (m, 1H), 3.65 (dt, J ¼ 6.4 Hz, 9.5 Hz, 1H), 2.81
(t, J ¼ 6.8 Hz, 2H), 1.97 (s, 3H), 1.92 (s, 3H); 13C NMR (100 MHz,
colorless oil. [
a]
25 ꢀ12.8 (c 0.027, CDCl3); 1H NMR (400 MHz, CDCl3)
D
d
6.80 (d, J ¼ 8.1 Hz, 1H), 6.73 (d, J ¼ 1.8 Hz, 1H), 6.70 (d, J ¼ 1.8 Hz,
8.1 Hz, 1H), 6.13e6.01 (m, 2H), 5.44e5.36 (m, 2H), 5.28e5.23 (m,
2H), 4.99 (dd, J ¼ 9.5 Hz, 9.2 Hz, 1H), 4.91 (dd, J ¼ 7.8 Hz, 9.7 Hz, 1H),
4.61e4.56 (m, 4H), 4.49 (d, J ¼ 7.8 Hz, 1H), 4.06 (dt, J ¼ 6.5 Hz,
9.5 Hz, 1H), 3.92 (dd, J ¼ 3.4 Hz, 11.9 Hz, 1H), 3.82 (dd, J ¼ 4.9 Hz,
12.0 Hz, 1H), 3.75 (t, J ¼ 9.2 Hz, 1H), 3.64 (dt, J ¼ 7.3 Hz, 9.4 Hz, 1H),
3.43e3.39 (m, 1H), 2.79 (t, J ¼ 6.8 Hz, 2H), 2.08 (s, 3H), 1.91 (s, 3H);
CDCl3)
d 170.2, 169.2, 164.8, 154.6, 148.5, 147.1, 144.2, 133.7, 133.6,
131.6, 131.3, 125.1, 121.4, 119.0, 118.0, 117.8, 117.5, 117.4, 116.7, 116.5,
115.4, 114.6, 100.7, 72.5, 71.9, 71.2, 70.8, 70.2, 70.0, 69.1, 68.7, 66.0,
35.5, 20.55, 20.48; ESI-HRMS [MþNa]þ calcd for C37H40NaO13F2
753.2329, found 753.2337.
13C NMR (100 MHz, CDCl3)
d 171.8, 169.5, 148.5, 147.2, 133.7, 133.6,
131.5,121.4,117.5,117.4,115.5,114.5,100.8, 76.2, 75.5, 71.1, 70.8, 70.2,
70.0, 69.6, 62.2, 35.6, 20.8, 20.6; ESI-HRMS [MþNa]þ calcd for
C
24H32NaO10 503.1888, found 503.1890.
3,4-Bis(allyloxy)phenylethyl 2,3-di-O-acetyl-4-O-((trans)-3,4-
dimethoxycinnamoyl)-6-O-alloc-b-D-glucopyranoside (compound
4.1.7. Preparation of 3,4-bis(allyloxy)phenylethyl 2,3-di-O-acetyl-6-
O-alloc- -glucopyranoside (16)
To a solution of 15 (100 mg, 0.208 mmol, 1.0 equiv) in anhydrous
CH2Cl2 (10 mL) was added allyl 1H-benzo[d][1,2,3]triazol-1-yl
carbonate (AllocBt) (54 mg, 0.250 mmol, 1.2 equiv) and Et3N
18c) was obtained from the condensation of compounds 16 and 17b
b
-D
(commercially available) as a colorless oil (98% yield): [
a
]
25 ꢀ 9.3 (c
D
0.013, CDCl3); 1H NMR (400 MHz, CDCl3)
d
7.63 (d, J ¼ 15.9 Hz, 1H),
7.11e7.03 (m, 2H), 6.86 (d, J ¼ 8.3 Hz, 1H), 6.81 (d, J ¼ 8.2 Hz, 1H),
6.74e6.70 (m, 2H), 6.22 (d, J ¼ 15.9 Hz, 1H), 6.13e6.02 (m, 2H),
5.94e5.85 (m, 1H), 5.45e5.21 (m, 7H), 5.15 (t, J ¼ 9.6 Hz, 1H), 5.02
(dd, J ¼ 8.1 Hz, 9.5 Hz, 1H), 4.60e4.52 (m, 7H), 4.28e4.27 (m, 2H),
4.09 (dt, J ¼ 6.3 Hz, 9.4 Hz, 1H), 3.91 (s, 6H), 3.82e3.77 (m, 1H), 3.65
(dt, J ¼ 7.4 Hz, 9.4 Hz,1H), 2.81 (t, J ¼ 6.8 Hz, 2H), 1.97 (s, 3H), 1.89 (s,
(140 mL, 1 mmol). The mixture was stirred at room temperature for
8 h and then neutralized with AcOH and evaporated. The residue
was purified by column chromatography on silica gel (EtOAc/pe-
troleum ether, 1:2) to furnish 16 (114 mg, 92% yield) as a colorless
oil. [
a]
25 ꢀ 27.1 (c 0.008, CDCl3); 1H NMR (400 MHz, CDCl3)
d
6.80 (d,
3H); 13C NMR (100 MHz, CDCl3)
d 170.2, 169.2, 165.6, 154.6, 151.6,
D
J ¼ 8.1 Hz, 1H), 6.73 (d, J ¼ 1.8 Hz, 1H), 6.70 (d, J ¼ 1.8 Hz, 8.1 Hz, 1H),
6.13e6.01 (m, 2H), 5.97e5.87 (m, 1H), 5.45e5.34 (m, 3H),
5.29e5.23 (m, 3H), 4.99 (d, J ¼ 8.7 Hz,1H), 4.92 (d, J ¼ 7.8 Hz, 9.6 Hz,
1H), 4.64e4.62 (m, 2H), 4.60e4.55 (m, 4H), 4.47e4.44 (m, 3H), 4.06
(dt, J ¼ 6.5 Hz, 9.5 Hz, 1H), 3.68e3.58 (m, 2H), 3.56e3.52 (m, 1H),
2.90 (d, J ¼ 3.1 Hz, 1H), 2.79 (d, J ¼ 6.9 Hz, 2H), 2.08 (s, 3H), 1.91 (s,
149.3, 148.5, 147.1, 146.7, 133.7, 133.6, 131.6, 131.3, 126.9, 123.2, 121.4,
119.0, 117.4, 117.3, 115.4, 114.6, 113.8, 111.0, 109.7, 100.7, 72.7, 72.6,
72.1, 71.3, 70.7, 70.2, 69.9, 68.7, 66.2, 56.0, 55.9, 35.5, 20.6 20.5; ESI-
HRMS [MþNa]þ calcd for C39H46NaO15 777.2729, found 777.2764.
3,4-Bis(allyloxy)phenylethyl
chlorocinnamoyl)-6-O-alloc-
2,3-di-O-acetyl-4-O-((trans)-p-
-glucopyranoside (compound 18d)
b-
D
3H); 13C NMR (100 MHz, CDCl3)
d
171.6, 169.4, 155.3, 148.4, 147.1,
was obtained from the condensation of compounds 16 and 12a [19]
133.7, 133.6, 131.6, 131.3, 121.4, 119.2, 117.5, 117.4, 115.4, 114.5, 100.7,
75.8, 74.0, 71.0, 70.7, 70.2, 70.0, 69.1, 68.9, 66.3, 35.5, 20.8, 20.6; ESI-
HRMS [MþNa]þ calcd for C28H36NaO12 587.2103, found 587.2104.
as a colorless oil (87% yield): [
(400 MHz, CDCl3)
a
]
25 ꢀ 22.6 (c 0.019, CDCl3); 1H NMR
D
d
7.62 (d, J ¼ 15.9 Hz, 1H), 7.44 (d, J ¼ 8.5 Hz, 2H),
7.36 (d, J ¼ 8.5 Hz, 2H), 6.81 (d, J ¼ 8.4 Hz, 1H), 6.74 (d, J ¼ 1.9 Hz,
1H), 6.71 (d, J ¼ 1.9 Hz, 8.2 Hz, 1H), 6.33 (d, J ¼ 15.9 Hz, 1H),
6.12e6.02 (m, 2H), 5.94e5.84 (m, 1H), 5.45e5.36 (m, 2H),
5.34e5.21 (m, 5H), 5.15 (t, J ¼ 9.6 Hz, 1H), 5.01 (dd, J ¼ 8.0 Hz,
9.6 Hz, 1H), 4.62e4.55 (m, 6H), 4.53 (d, J ¼ 7.9 Hz, 1H), 4.27e4.25
(m, 2H), 4.08 (dt, J ¼ 6.4 Hz, 9.5 Hz, 1H), 3.80 (m, 1H), 3.65 (ddd,
J ¼ 7.3 Hz, 7.5 Hz, 9.5 Hz, 1H), 2.80 (d, J ¼ 6.8 Hz, 2H), 1.96 (s, 3H),
4.1.8. General procedure for the preparation of 18aee
To a stirred and cooled (0 ꢁC) solution of 16 (1.0 equiv) and
corresponding acid (1.5 equiv) in CH2Cl2 was added DCC (1.5 equiv)
and DMAP (1.5 equiv), and the mixture was stirred for 1 h at 0 ꢁC.
The mixture was allowed to be gradually warmed to room tem-
perature, and stirred overnight. The solvent was removed and the
residue was purified by column chromatography on silica gel
(EtOAc/petroleum ether, 1:4 to 1:3) to give the coupling product.
3,4-Bis(allyloxy)phenylethyl 2,3-di-O-acetyl-4-O-((trans)-3,4-
1.91 (s, 3H); 13C NMR (100 MHz, CDCl3)
d 170.2, 169.3, 165.1, 154.6,
147.1, 145.2, 136.8, 133.7, 133.6, 132.4, 131.5, 131.3, 129.5, 129.2, 121.4,
119.0, 117.5, 117.45, 117.4, 116.8, 115.3, 114.5, 100.7, 72.5, 71.9, 71.2,
70.8, 70.2, 69.9, 69.0, 68.8, 66.1, 35.5, 20.6, 20.5; ESI-HRMS
[MþNH4]þ calcd for C37H45NO13Cl 746.2574, found 746.2564.
3,4-Bis(allyloxy)phenylethyl 2,3-di-O-acetyl-4-O-((trans)-3,4-
bis(allyloxy)cinnamoyl)-6-O-alloc-
b
-D
-glucopyranoside
(com-
pound 18a) was obtained from the condensation of compounds 16
and 9a as a colorless oil (85% yield): [
NMR (400 MHz, CDCl3)
a
]
25 ꢀ 9.8 (c 0.008, CDCl3); 1H
bis(allyloxy)phenylacetyl)-6-O-alloc-
b-D-glucopyranosid
(com-
D
d
7.59 (d, J ¼ 15.9 Hz,1H), 7.08e7.05 (m, 2H),
pound 18e) was obtained from the condensation of compounds 16
6.87 (d, J ¼ 8.1 Hz, 1H), 6.80 (d, J ¼ 8.1 Hz, 1H), 6.75 (d, J ¼ 1.8 Hz,
1H), 6.71 (dd, J ¼ 1.8 Hz, 8.1 Hz, 1H), 6.18 (d, J ¼ 15.9 Hz, 1H),
6.13e6.01 (m, 4H), 5.94e5.84 (m, 1H), 5.46e5.21 (m, 11H), 5.15 (t,
J ¼ 9.6 Hz, 1H), 5.01 (dd, J ¼ 8.0 Hz, 9.6 Hz, 1H), 4.65e4.56 (m, 10H),
4.52 (d, J ¼ 7.9 Hz, 1H), 4.22e4.26 (m, 2H), 4.08 (dt, J ¼ 6.4 Hz,
9.4 Hz, 1H), 3.81e3.77 (m, 1H), 3.65 (dt, J ¼ 6.4 Hz, 9.4 Hz, 1H), 2.80
(t, J ¼ 6.8 Hz, 2H), 1.96 (s, 3H), 1.91 (s, 3H); 13C NMR (100 MHz,
and 10a as a colorless oil (95% yield): [
a
]
25 ꢀ 10.3 (c 0.016, CDCl3);
D
1H NMR (400 MHz, CDCl3)
d
6.85e6.68 (m, 6H), 6.12e6.00 (m, 4H),
5.95e5.86 (m, 1H), 5.46e5.32 (m, 5H), 5.29e5.22 (m, 5H), 5.18 (t,
J ¼ 9.5 Hz, 1H), 5.00 (dd, J ¼ 9.6 Hz, 9.8 Hz, 1H), 4.93 (dd, J ¼ 9.0 Hz,
9.7 Hz, 1H), 4.62e4.55 (m, 10H), 4.47 (d, J ¼ 8.0 Hz, 1H), 4.21e4.10
(m, 2H), 4.05 (dt, J ¼ 6.5 Hz, 9.5 Hz, 1H), 3.71e3.66 (m, 1H), 3.62 (dt,
J ¼ 9.5 Hz, 6.5 Hz, 1H), 3.48 (dd, J ¼ 14.6 Hz, 2.6 Hz, 2H), 2.78 (t,
J ¼ 6.8 Hz, 2H), 1.88 (s, 3H), 1.75 (s, 3H); 13C NMR (100 MHz, CDCl3)
CDCl3)
d 170.2, 169.3, 165.6, 154.6, 151.1, 148.7, 148.5, 147.2, 146.6,
133.7, 133.6, 133.0, 132.8, 131.6, 131.4, 127.1, 123.2, 121.4, 119.0, 118.0,
117.9, 117.4, 117.3, 115.5, 114.6, 113.9, 113.5, 112.9, 100.7, 72.6, 72.1,
71.3, 70.7, 70.2, 70.03, 70.00, 69.7, 68.7, 66.2, 35.6, 20.6, 20.5; ESI-
HRMS [MþNa]þ calcd for C43H50NaO15 829.3042, found 829.3052.
3,4-Bis(allyloxy)phenylethyl 2,3-di-O-acetyl-4-O-((trans)-3,4-
d 170.3, 170.0, 169.1, 154.5, 148.6, 148.4, 147.9, 147.1, 133.7, 133.6,
133.4, 133.3, 131.5, 131.3, 126.0, 121.8, 119.0, 117.5, 117.46, 117.37,
117.3, 115.4, 115.2, 114.6, 114.4, 100.6, 72.3, 71.7, 71.2, 70.7, 70.1, 70.0,
69.93, 69.87, 68.9, 68.7, 65.8, 40.5, 35.5, 20.4, 20.3; ESI-HRMS
[MþNH4]þ calcd for C42H54NO15 812.3488, found 812.3465.
difluorocinnamoyl)-6-O-alloc-
b
-D
-glucopyranoside
(compound
18b) was obtained from the condensation of compounds 16 and 17a
4.1.9. General procedure for the preparation of 19aee
(commercially available) as a colorless oil (86% yield): [
a]
25 ꢀ16.5 (c
To a solution of the O-acetyl-protected compound in MeOH/
D