Bergenin derivatives as α-glucosidase inhibitor
3
ethyl acetate, butanol and water. Each fraction was con-
centrated to dryness in vaccuo to give hexane, dichlo-
romethane, ethyl acetate, butanol and water fractions
respectively.
3.83–4.01 (m, 1H), 3.91 (s, 3H), 3.98 (d, J = 9.2 Hz, 1H),
4.41–4.55 (m, 4H), 4.72 (d, J = 10.4 Hz, 1H), 5.26 (dd, J1 =
1.8 Hz, J2 = 10.8 Hz, 2H), 5.40 (dd, J1 = 1.8 Hz, J2 = 17.2 Hz,
2H), 5.97–6.12 (m, 2H), 7.34 (s, 1H).
e butanol extract was fractionated to fraction 1–3 by
silica gel column chromatography with dichloromethane
and methanol as eluants. Fraction 2 was recrystallized,
thereby bergenin (1) (3.7 g) was isolated. e structure
of 1 was identified by the comparison of its physical and
11-O-benzoylbergenin (2)
Yield 25%, amorphous powder; [α]25 +66.8° (c = 0.15,
D
MeOH); IR (KBr) νmax cm−1: 3474 (OH), 1722 (ester),
1610 (arom. C=C); 1H NMR (DMSO-d6, 400 MHz) δ 3.41
(dd, J1 = 9.2 Hz, J2 = 8.8 Hz, 1H), 3.69 (m, 1H), 3.74 (s,
3H), 3.93 (ddd, J1 = 9.2 Hz, J2 = 7.2 Hz, J3 = 2.0 Hz, 1H),
4.03 (t, J = 10.0 Hz, 1H), 4.34 (dd, J1 = 12.4 Hz, J2 = 7.2
Hz, 1H), 4.78 (dd, J1 = 12.4 Hz, J2 = 2.0 Hz, 1H), 5.03 (d, J
= 10.8 Hz, 1H), 7.00 (s, 1H), 7.54 (m, 2H), 7.67 (m, 1H),
8.01 (m, 2H); 13C NMR (DMSO-d6, 100 MHz): Table 1;
EI-MS, m/z (rel. intensity) 432 [M]+ (2), 370 (4), 256 (6),
122 (53), 105 (100), 77 (56).
spectral data with those described in the literature39,44
.
Synthesis
General procedure for the synthesis of 8,10-diallyloxy-
bergenin (1a)
First, the phenolic hydroxy groups in bergenin (1)
(700 mg, 2.13 mmol) were selectively allylated. Allyl
bromide and NaI were added to a solution bergenin
and K2CO3 in anhydr. DMF (5 mL). After the mixture was
stirred 2 h at 55°C under nitrogen, it was concentrated
in vacuo. e residue was treated with water (15 mL)
and extracted with ethyl acetate (3 × 10 mL). e organic
extract was washed successively with brine (3 × 15 mL).
e extract was dried over Na2SO4 and concentrated in
vacuo. e residue was chromatographed on silica gel to
afford 1a (554 mg, 64%) as a white powder.
11-O-p-hydroxybenzoylbergenin (3)
Yield 38%, amorphous powder; [α]25 +18.3° (c = 0.15,
MeOH); IR (KBr) νmax cm−1: 3380 (OH)D, 1712 (ester), 1608
1
(arom. C=C), 1238 (C-O); H NMR (DMSO-d6, 400 MHz)
δ 3.40 (m, 1H), 3.69 (t, J = 9.2 Hz, 1H), 3.73 (s, 3H), 3.87
(ddd, J1 = 9.2 Hz, J2 = 6.4 Hz, J3 = 1.6 Hz, 1H), 4.03 (t, J =
9.8 Hz, 1H), 4.26 (dd, J1 = 12.0 Hz, J2 = 6.4 Hz, 1H), 4.71
(dd, J1 = 12.0 Hz, J2 = 1.6 Hz, 1H), 5.02 (d, J = 10.0 Hz, 1H),
6.86 (d, J = 8.8 Hz, 2H), 7.00 (s, 1H), 7.85 (d, J = 8.8 Hz,
2H); 13C NMR (DMSO-d6, 100 MHz): Table 1; EI-MS, m/z
(rel. intensity) 448 [M]+ (2), 328 (1), 208 (24), 121 (100), 81
(13), 65 (28).
General procedure for the synthesis of bergenin derivatives
(2–4, 6–9)
Firstly, to a solution of 1a in anhydr. THF (2 mL/mmol),
various benzoic acids and Ph3P (2 equiv) were dissolved.
DIAD (1.7 equiv) was added dropwise under 0°C. e
mixture was stirred for 2 h under nitrogen. It was concen-
trated in vacuo. e residue was chromatographed on
silica gel to afford benzoic acid ester of 1a (yield 79–92%)
as a white powder.
Secondly, the allyl protected esters and Pd(PPh3)4
(1 mol%, freshly prepared) were dissolved in degassed
anhydrous. THF (2mL/mmol) and morpholine (10 equiv
per allylgroup to be cleaved) was added dropwise. e
mixture was stirred at r.t and concentrated in vacuo. e
residue was taken up in EtOAc. e organic layer was
washed several times with small amounts of 1 N HCl,
dried and concentrated. e crude material was purified
by silica gel column chromatography. e purified mate-
rial was bergenin derivatives (2–4, 6–9) in yield 28–59%
(Scheme 1).
11-O-p-methoxybenzoylbergenin (4)
Yield 24%, amorphous powder; [α]25 +44.4° (c = 0.15,
MeOH); IR (KBr) νmax cm−1: 3373 (DOH), 2959 (C-H),
1720 (ester), 1609 (arom. C=C), 1237 (C-O); 1H NMR
(DMSO-d6, 400 MHz) δ 3.40 (t, J = 8.8 Hz, 1H), 3.69 (t, J
= 8.8 Hz, 1H), 3.74 (s, 3H), 3.89 (m, 1H), 3.83 (s, 3H), 4.04
(t, J = 10.0 Hz, 1H), 4.29 (dd, J1 = 12.0 Hz, J2 = 6.8 Hz, 1H),
4.74 (dd, J1 = 12.0 Hz, J2 =2.1Hz, 1H), 5.03 (d, J = 10.0 Hz,
1H), 7.00 (s, 1H), 7.05 (d, J = 8.8 Hz, 2H), 7.95 (d, J = 8.8 Hz,
2H); 13C NMR (DMSO-d6, 100 MHz): Table 1; EI-MS, m/z
(rel. intensity) 462 [M]+ (17), 250 (11), 208 (50), 152 (93),
135 (100), 92 (34), 77 (17).
11-O-protocatechuoylbergenin (5)
Yield 16%, amorphous powder; [α]25 +25.2° (c = 0.25,
D
MeOH); IR (KBr) νmax cm−1: 3364 (OH), 1709 (ester),
Synthesis of 11-O-protocatechuoylbergenin (5)
1
Firstly, the phenolic hydroxy groups in protocatechual-
dehyde were selectively allylated. Secondly, 3,4-dially-
loxy-protocatechuic acid was accomplished according
to previous study45. en, the same procedure as for 2–4,
6–9 was used by starting from 1a (Scheme 2).
1610 (arom. C=C), 1227 (C-O); H NMR (DMSO-d6, 400
MHz) δ 3.39 (t, J = 9.2 Hz, 1H), 3.69 (t, J = 9.2 Hz, 1H),
3.74 (s, 3H), 3.86 (m, 1H), 4.01 (t, J = 10.0 Hz, 1H), 4.26
(dd, J1 = 11.6 Hz, J2 = 6.0 Hz, 1H), 4.67 (brd, J = 11.6 Hz,
1H), 5.05 (d, J = 10.4 Hz, 1H), 6.81 (d, J = 8.4 Hz, 1H), 7.00
(s, 1H), 7.35 (d, J = 8.4 Hz, 1H), 7.38 (d, J = 1.6 Hz, 1H);
13C NMR (DMSO-d6, 100 MHz): Table 1; EI-MS, m/z (rel.
intensity) 464 [M]+ (11), 328 (23), 262 (15), 137 (100), 77
(54), 55 (32).
8,10-diallyloxy-bergenin (1a)
1
Yield 64%, white powder. H NMR (CDCl3, 400 MHz) δ
3.54–3.59 (m, 1H), 3.54–3.59 (m, 1H), 3.68–3.73 (m, 1H),
© 2012 Informa UK, Ltd.