390
T.-H. Yang et al. / European Journal of Medicinal Chemistry 156 (2018) 381e393
glucopyranosyl bromide tetra-acetate (1 or 2 equiv.) and tetrabutyl
ammonium bromide (TBAB, 1 or 2 equiv.) in 10 mL CHCl . After
stirring for 3 h, the reaction mixture was filtered and washed with
CHCl solution was washed by
(3 ꢁ 20 mL). Subsequently, the CHCl
(3 ꢁ 50 mL) and saturated
553.2086 (C30
H
34
O
10), cal. 553.2079.
3
0
00
00
4.4.4. Magnolol-4 -O-(3 , 4 -2acetyl)-
b
-D-glucopyranoside (7b)
ꢂ
1
3
3
White solid, m. p. 64.8e65.6 C, yield 23.1%, H NMR (600 MHz,
0
0
5
% HCl (3 ꢁ 50 mL), saturated NaHCO
3
CD
3
OD)
d
H
: 7.23 (d, 1H, J ¼ 7.8 Hz, H-5 ), 7.17 (d, 1H, J ¼ 1.8 Hz, H-6 ),
0
NaCl (3 ꢁ 50 mL) respectively and further concentrated to dryness
in vacuo [18]. Purification by column chromatography on silica gel
to get the target compounds 5 and 6. The obtained compounds 5 or
7.10 (d, 1H, J ¼ 7.8 Hz, H-2 ), 7.22 (d, 1H, J ¼ 7.2 Hz, H-6), 7.14 (d, 1H,
0
J ¼ 7.2 Hz, H-5), 7.01 (d, 1H, J ¼ 1.6 Hz, H-2), 6.04 (m, 1H, H-8 ), 5.99
0
(m, 1H, H-8), 5.13 (m, 2H, H-9 ), 5.06 (m, 2H, H-9), 4.81 (d, 1H,
0
0
0
6
was further deacetylated in sodium methoxide-methanol solu-
J ¼ 6.1, H-1 ), 4.18e3.27 (m, 6H), 3.34 (m, 4H, H-7, 7 ), 2.07 (s, 3H),
13
tion (0.8 equiv.) for different hours (4e8 h), and then purified by
column chromatography over silica gel to afford 7a-7d.
2.06 (s, 3H). C NMR (150 MHz, CD
3
OD) d: 132.5 (s, C-1),132.4 (d, C-
2), 128.9 (s, C-3), 147.8 (s, C-4), 116.5 (d, C-5), 130.1 (d, C-6), 40.2 (t,
0
0
C-7), 138.9 (d, C-8), 115.9 (t, C-9), 135.4 (s, C-1 ), 132.8 (d, C-2 ), 132.2
0
00
00
00
00
0 0 0 0 0
4
.4.1. Magnolol-4 -O-(2 , 3 , 4 , 6 -4 acetyl)-
b
-D-glucopyranoside
(s, C-3 ), 154.0 (s, C-4 ), 117.8 (d, C-5 ), 129.4 (d, C-6 ), 40.5 (t, C-7 ),
0 0 00
139.0 (d, C-8 ), 116.3 (t, C-9 ), 172.5 (s), 171.8 (s), 102.1 (d, C-1 ), 75.2
(
5)
ꢂ
1
00
00
00
00
00
White solid, m. p. 67.7e68.5 C, yield 68.7%, H NMR (400 MHz,
(d, C-2 ), 77.6 (d, C-3 ), 74.2 (d, C-4 ), 71.4 (d, C-5 ), 64.5 (t, C-6 ),
0
þ
CD
3
OD)
d
H
: 7.22 (d, 1H, J ¼ 8.4 Hz, H-5 ), 7.14 (dd, 1H, J ¼ 2.0, 8.4 Hz,
21.1 (q), 20.7 (q). HRESIMS m/z: [M þ Na] 535.1940 (C28
32 9
H O ), cal.
0
0
H-6 ), 7.06 (d, 1H, J ¼ 2.0 Hz, H-2 ), 7.00 (dd, 1H, J ¼ 8.2, 2.0 Hz, H-6),
535.1939.
6
.91 (d, 1H, J ¼ 2.0 Hz, H-2), 6.78 (d, 1H, J ¼ 8.2 Hz, H-5), 6.00 (m, 1H,
0
0
0
H-8 ), 5.98 (m, 1H, H-8), 5.11 (m, 2H, H-9 ), 5.08 (m, 2H, H-9), 5.01
(
1
4.4.5. Magnolol-4 -O-
b
-D
-glucopyranoside (7c)
0
0
00
ꢂ
1
d, 1H, J ¼ 8.1, H-1 ), 4.32 (dd, 1H, J ¼ 5.2, 12.4 Hz, H-6 a), 4.18 (dd,
White solid, m. p. 68.9e70.1 C, yield 79.8%, H NMR (400 MHz,
00
00
0
H, J ¼ 2.4, 12.4 Hz, H-6 b), 4.00 (m, 1H, H-5 ), 3.38 (d, 2H,
CD
3
OD)
d
H
: 7.19 (dd, 1H, J ¼ 8.4, 1.8 Hz, H-6 ), 7.16 (d, 1H, J ¼ 1.8 Hz,
0
0
0
J ¼ 6.8 Hz, H-7 ), 3.36 (d, 2H, J ¼ 6.2 Hz, H-7), 2.09 (s, 3H), 2.03 (s,
H-2 ), 7.14 (d, 1H, J ¼ 8.4 Hz, H-5 ), 7.03 (dd, 1H, J ¼ 8.0, 2.0 Hz, H-6),
6.98 (d, 1H, J ¼ 2.0 Hz, H-2), 6.85 (d, 1H, J ¼ 8.0 Hz, H-5), 5.96 (m, 1H,
13
3
3
H), 1.94 (s, 3H), 1.71 (s, 3H). C NMR (100 MHz, CD OD) d: 134.7 (s,
0 0
H-8 ), 5.95 (m, 1H, H-8), 5.11 (m, 2H, H-9 ), 5.09 (m, 2H, H-9), 4.99
C-1), 131.2 (d, C-2), 129.2 (s, C-3), 151.6 (s, C-4), 116.6 (d, C-5), 128.3
0
00
00
(
(
3
(
d, C-6), 38.9 (t, C-7),137.6 (d, C-8),114.1 (t, C-9),136.8 (s, C-1 ),131.7
(d, 1H, J ¼ 7.7, H-1 ), 3.96 (dd, 1H, J ¼ 1.8, 12.4 Hz, H-6 a), 3.69 (dd,
0
0
0
0
0
00
0
d, C-2 ), 130.6 (s, C-3 ), 152.7 (s, C-4 ), 116.6 (d, C-5 ), 128.1 (d, C-6 ),
9.0 (t, C-7 ), 138.1 (d, C-8 ), 114.5 (t, C-9 ), 170.9 (s), 170.1 (s), 169.8
s), 169.4 (s), 99.2 (d, C-1 ), 70.9 (d, C-2 ), 72.9 (d, C-3 ), 68.4 (d, C-
), 71.5 (d, C-5 ), 61.8 (t, C-6 ), 19.3 (q), 19.3 (q), 19.1 (q), 19.1 (q).
1H, J ¼ 5.6, 12.4 Hz, H-6 b), 3.38 (d, 2H, J ¼ 6.1 Hz, H-7 ), 3.33 (d, 2H,
0
0
0
13
J ¼ 7.8 Hz, H-7), 1.92 (s, 3H), 1.91 (s, 3H), 1.90 (s, 3H). C NMR
0
0
00
00
3
(100 MHz, CD OD) d: 131.8 (s, C-1), 131.3 (d, C-2), 126.8 (s, C-3),
0
0
00
00
4
151.7 (s, C-4), 116.2 (d, C-5), 128.3 (d, C-6), 39.0 (t, C-7), 137.7 (d, C-
-
0 0 0
8), 114.2 (t, C-9), 133.8 (s, C-1 ), 131.4 (d, C-2 ), 128.5(s, C-3 ), 153.0(s,
HRESIMS m/z: [M ꢀ H] 595.2185 (C32
36
H O
11), cal. 595.2185.
0
0
0
0
0
C-4 ), 116.3(d, C-5 ), 128.4(d, C-6 ), 39.0(t, C-7 ), 138.0(d, C-8 ),
0
00
00
00
00
0 00 00 00
4
.4.2. Magnolol-4, 4 -di-O-(2 , 3 , 4 , 6 -4 acetyl)-
b
-D-
114.5(t, C-9 ), 101.0(d, C-1 ), 73.4(d, C-2 ), 76.8 (d, C-3 ), 69.9 (d, C-
0
0
00
00
þ
glucopyranoside (6)
4 ), 76.4 (d, C-5 ), 61.2 (t, C-6 ). HRESIMS m/z: [M þ Na] 451.1724
ꢂ
1
White solid, m. p. 66.3e67.2 C, yield 78.6%, H NMR (400 MHz,
(C24H
28
O
7
), cal. 451.1727.
0
CD
3
OD)
d
H
: 7.18 (dd, 2H, J ¼ 8.4, 1.8 Hz, H-6, 6 ), 7.14 (d, 2H,
0
0
0
J ¼ 1.8 Hz, H-2, 2 ), 7.03 (d, 2H, J ¼ 8.4 Hz, H-5, 5 ), 6.00 (m, 2H, H-8,
4.4.6. Magnolol-4, 4 -di-
b
-D-glucopyranoside (7d)
0
0
ꢂ
1
8
1
), 5.11 (dd, 2H, J ¼ 1.5, 16.8 Hz, H-9, 9 a), 5.06 (dd, 2H, J ¼ 1.5,
White solid, m. p. 89.9e91.4 C, yield 80.6%, H NMR (400 MHz,
0
00 000
0
0.0 Hz, H-9, 9 b), 4.96 (d, 2H, J ¼ 8.0 Hz, H-1 , 1 ), 4.30 (dd, 2H,
CD
3
OD)
d
H
: 7.18 (dd, 2H, J ¼ 8.4, 1.8 Hz, H-6, 6 ), 7.14 (d, 2H,
0
0
000
00 000
00
0
0
J ¼ 5.2, 12.3 Hz, H-6 a, 6 a), 4.16 (dd, 2H, J ¼ 2.1, 12.3 Hz, H-6 b,
J ¼ 1.8 Hz, H-2, 2 ), 7.06 (d, 2H, J ¼ 8.4 Hz, H-5, 5 ), 6.00 (m, 2H, H-8,
0
00
0
0
0
6
3
b), 3.95 (m, 2H, H-5 , 5 ), 3.37 (d, 4H, J ¼ 6.8 Hz, H-7, 7 ), 2.09 (s,
8 ), 5.11 (dd, 2H, J ¼ 1.5, 16.8 Hz, H-9a, 9 a), 5.07 (dd, 2H, J ¼ 1.5,
1
3
0
00 000
H), 2.03 (s, 3H), 1.96 (s, 3H), 1.75 (s, 3H). C NMR (100 MHz,
10.0 Hz, H-9b, 9 b), 4.92 (d, 2H, J ¼ 8.0 Hz, H-1 , 1 ), 3.85 (d, 2H,
0
0
0
0
00
000
00
000
CD
3
OD)
d
: 134.8 (s, C-1, 1 ), 131.7 (d, C-2, 2 ), 128.9 (s, C-3, 3 ), 152.4
J ¼ 11.3 Hz, H-6 a, 6 a), 3.69 (dd, 2H, J ¼ 4.5, 11.3 Hz, H-6 b, 6 b),
0
0
0
00 000 00 000 00 000 00 000
(
s, C-4, 4 ), 117.3 (d, C-5, 5 ), 128.4 (d, C-6, 6 ), 38.9 (t, C-7, 7 ), 137.5
3.42e3.34 (m, 8H, H-2 , 2 , 3 , 3 , 4 , 4 , 5 , 5 ), 3.37 (m, 4H, H-7,
0
0
0
13
0
0
0
0
(
d, C-8, 8 ), 114.8 (t, C-9, 9 ), 171.2 (s), 170.4 (s), 170.1 (s), 169.5 (s),
7 ). C NMR (100 MHz, CD
3
OD)
d
: 133.9 (s, C-1, 1 ), 131.4 (d, C-2, 2 ),
0
0
00
00
00
0
0
9
5
9.5 (d, C-1 ), 71.2 (d, C-2 ), 72.9 (d, C-3 ), 68.4 (d, C-4 ), 71.5 (d, C-
), 61.8 (t, C-6 ), 19.4 (q), 19.3 (q), 19.2 (q), 19.1 (q). HRESIMS m/z:
129.0 (s, C-3, 3 ), 152.6 (s, C-4, 4 ), 115.8 (d, C-5, 5 ), 128.3 (d, C-6, 6 ),
0
0
00
0 0 0 00 000
39.0 (t, C-7, 7 ), 137.7 (d, C-8, 8 ), 114.6 (t, C-9, 9 ), 100.6 (d, C-1 , 1 ),
þ
00 000 00 000 00 000 00
73.4 (d, C-2 , 2 ), 76.6 (d, C-3 , 3 ), 70.0 (d, C-4 , 4 ), 76.6 (d, C-5 ,
[M þ Na] 949.3099 (C46
H
54
O
20), cal. 949.3101.
0
00
00
000
e
5
), 61.2 (t, C-6 , 6 ). HRESIMS m/z: [M ꢀ H] 589.2286
0
00
00
00
4
.4.3. Magnolol-4 -O-(3 , 4 , 6 -3 acetyl)-
b-D-glucopyranoside
(C30H O12), cal. 589.2291.
38
(
7a)
ꢂ
1
White solid, m. p. 60.1e61.4 C, yield 30.8%, H NMR (400 MHz,
4.5. General synthetic procedures for 8a-8c
0
CD
3
OD)
d
H
: 7.20 (dd, 1H, J ¼ 8.2, 1.8 Hz, H-6 ), 7.13 (d, 1H, J ¼ 1.8 Hz,
0
0
H-6 ), 7.06 (d, 1H, J ¼ 8.2 Hz, H-2 ), 6.91 (dd, 1H, J ¼ 8.4, 1.8 Hz, H-6),
These derivatives were synthesized by the Steglich esterification
reaction of 7c (0.5 mmol) with the corresponding acid (1.2 equiv.)
and DCC (1.2 equiv.) in the presence of DMAP (0.6 equiv.), which had
the similar treatment process to preparation of compounds 1a-1g.
6
.88 (d, 1H, J ¼ 2.0 Hz, H-2), 6.78 (d, 1H, J ¼ 8.2 Hz, H-5), 5.89 (m, 1H,
0
0
H-8 ), 5.87 (m, 1H, H-8), 5.04 (m, 2H, H-9 ), 5.01 (m, 2H, H-9), 4.99
(
1
0
0
00
d, 1H, J ¼ 6.8, H-1 ), 4.16 (dd, 1H, J ¼ 5.2, 12.4 Hz, H-6 a), 4.01 (dd,
00
00
H, J ¼ 2.4, 12.4 Hz, H-6 b), 3.87 (m, 1H, H-5 ), 3.27 (d, 2H,
0
0
J ¼ 6.4 Hz, H-7 ), 3.22 (d, 2H, J ¼ 6.8 Hz, H-7), 1.92 (s, 3H), 1.91 (s,
4.5.1. Magnolol-4-O-benzoyl-4 -O-
b
-D-glucopyranoside (8a)
H), 1.90 (s, 3H). 13C NMR (150 MHz, CD
OD)
d
: 133.0 (s, C-1), 132.9
White solid, m. p. 76.8e77.5 C, yield 87.2%, H NMR (600 MHz,
ꢂ
1
3
3
0
00
000
(
4
2
d, C-2), 127.7 (s, C-3), 153.1 (s, C-4), 116.4 (d, C-5), 129.7 (d, C-6),
CD
3
OD)
d
H
: 7.92 (d, 2H, J ¼ 7.2 Hz, H-3 , 7 ), 7.42 (t, 1H, J ¼ 7.8 Hz,
0
000
000
000
0.4 (t, C-7), 139.0 (d, C-8), 115.6 (t, C-9), 135.6 (s, C-1 ), 133.0 (d, C-
H-5 ), 7.31 (dd, 2H, J ¼ 7.2, 7.8 Hz, H-4 , 6 ), 7.25 (dd, 1H, J ¼ 7.8,
0
0
0
0
0
0
0
), 130.2 (s, C-3 ), 154.1 (s, C-4 ), 117.5 (d, C-5 ), 129.6 (d, C-6 ), 40.4
1.8 Hz, H-6 ), 7.19 (d, 1H, J ¼ 1.8 Hz, H-2 ), 7.12 (d, 1H, J ¼ 7.8 Hz, H-
0
0
0
0
(
t, C-7 ), 139.5 (d, C-8 ), 115.9 (t, C-9 ), 172.3 (s), 172.0 (s), 171.4 (s),
5 ), 7.11 (dd, 1H, J ¼ 8.0, 2.2 Hz, H-6), 7.09 (d, 1H, J ¼ 2.2 Hz, H-2),
0
0
00
00
00
0
1
5
02.1 (d, C-1 ), 72.9 (d, C-2 ), 76.1 (d, C-3 ), 69.9 (d, C-4 ), 72.9 (d, C-
7.05 (d, 1H, J ¼ 8.0 Hz, H-5), 6.04 (m, 1H, H-8 ), 5.78 (m, 1H, H-8),
0
0
00
-
0
00
), 63.2 (t, C-6 ), 20.8 (q), 20.7 (q), 20.6 (q). HRESIMS m/z: [M ꢀ H]
5.14 (m, 2H, H-9 ), 5.06 (m, 2H, H-9), 5.01 (d, 1H, J ¼ 7.2, H-1 ), 3.76