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Synthesis of Glycosides Bearing Chalcone Derivatives via Ferrier
Rearrangement
Zainab Ngaini and Dayang H. Abang Kamaluddin
Department of Chemistry, Faculty of Resource Science and Technology,
Universiti Malaysia Sarawak, 94300, Kota Samarahan, Sarawak, Malaysia
Corresponding author and email address: E-mail: nzainab@frst.unimas.my
Phone : +60 82 582992, Fax: +60 82 583160
Abstract : A series of glycoside derivatives bearing chalcones moieties has been synthesized. A
convenient synthetic method was performed from the reaction of 3,4,6-tri-O-acetyl-D-glucal with (E)-
1-(4-alkyloxyphenyl)-3-(4-hydroxy-phenyl)prop-2-en-1-one (2a-2c) employing OC rearrangement
to afford C-glycoside 4a-c over prolonged reaction times, in the presence of BF3.OEt2 as a catalyst.
The compounds differ in the length of alkyl groups, CnH2n+1, where n= 7, 8 and 9.
Keywords: glycosylation, chalcones, glycosides, OC rearrangement
Received : 24.10.2012; Accepted : 15.03.2013
Introduction
Glycosides are found abundantly in nature and
serve many important roles in living organisms.1,2
Plants usually store chemicals in the form of
inactive glycosides which are activated by enzyme
hydrolysis. Naturally occurring glycosides
commonly show high potential as antibiotics. There
are a wide range of glycoside antibiotics isolated
from natural products.3. For many years, numerous
research have been devoted to the total synthesis of
C- and O-glycoside antibiotics, such as
erythromycin A, amphotericin B, olivomycin A,
urdamycinone B, vancomycin and digitoxin.4
Besides, glycosides are also increasingly utilized in
the synthesis of non-carbohydrate compounds and
carbohydrate mimetics.5 Glycosides have also been
synthesized for liquid crystalline materials. Over
the past years, tremendous attention has been
dedicated to research on the synthesis of glycoside
derivatives and studies on the application for liquid
crystal properties.6-8
Ferrier rearrangement, on the other hand, is an
attractive methodology for the synthesis of
glycoside derivatives with various alcohols. It is an
efficient reaction for the substitution at the
anomeric position with allylic rearrangement.9,10
The Ferrier rearrangement involves the addition of
nucleophile onto the intermediate allylic
oxycarbenium ion, preferentially in a quasi-axial
orientation.9 This rearrangement leads to the
formation of alkyl and aryl 2,3-unsaturated-O-
glycosides, which are versatile chiral intermediates
in the synthesis of several biologically active
natural products.9,10 2,3-unsaturated-O-glycosides
are also important building blocks in the synthesis
of some antibiotics.9
Recently, we reported on the preparation of
Lewis acid-promoted allylic rearrangement of
3,4,6-tri-O-acetyl-D-glucal with 4-
hydroxybenzaldehyde and aliphatic alcohols with
different type of catalysts in different solvents.11
This prompted us to study the reaction of glycoside
bearing chalcone derivatives via Claisen-Schmidt
condensation of aldehyde and acetophenone.
Chalcone derivatives were reported to have
outstanding non linear optic properties for optical
electronics and communications12, liquid crystal
displays13,14 and alignment film15. Chalcones were
also reported to promote excellent blue light
transmittance and good crystallability,16,17 high
photosensitivity and thermal stability for various
crystalline electro-optical devices.
We herein report the synthesis of new
glycosides bearing hydroxylated chalcone (2a-c)
which differ in the length of the alkyl groups
ranging from C7 to C9. This study could be used
as a reaction model for potential liquid crystals
compounds.
Results and Discussion
The series of chalcone derivatives (E)-1-[4-
(alkyloxy)phenyl]-3-[4-hydroxyphenyl] prop-2-en-
1-one (2a-2c) were prepared via Claisen-Schmidt
condensation of 1a-1c and 4-hydroxybenzaldehyde
by the route depicted in Scheme 1.
Malaysian Journal of Chemistry, 2013, Vol. 15, No. 1, 013 – 019
R-Br, K2CO3,
TBAI, MEK
2a: R=C7H15
2b: R=C8H17
2c: R=C9H19
reflux
KOH,MeOH
reflux
1a: R=C7H15
1b: R=C8H17
1c: R=C9H19
Scheme 1 : Synthesis of hydroxylated chalcones 2a-c
The IR spectra of the hydroxylated chalcones
2a-2c showed the presence of bands at 2921 -2852
cm-1 which were attributed to the introduction of
aliphatic carbon chains via etherification of 4-
hydroxyacetophenone and vOH at 3100-3400 cm-1.
The presence of a new C=O stretching frequency at
1651 cm-1 substantiated to the formation of the title
compound. The chemical structures of 2a-2c were
found to be consistent with 1H NMR and 13C NMR
spectroscopic data and showed the peaks
corresponded to the structures. In 1H-NMR spectra,
the coupling constant, Jab 15.0-16.0 Hz indicated all
chalcones obtained were in trans configuration. The
relatively low yield of 2a-2c (24-64%) was
attributed to the trace amount of side products of
Cannizaro reaction or ketone auto condensation.18,19
The synthetic route for the glycosylation of the
commercially available tri-O-acetyl-D-glucal with
chalcones 2a-2c is illustrated in Scheme 2. The
reaction was performed in the presence of BF3.OEt2
as a catalyst and monitored by TLC.11
ring B as doublets at 6.89 and 7.02 ppm. Olefinic
protons which appeared as doublets at 7.40 and
7.64 ppm with coupling constant, Jab = 15.5 Hz,
indicated trans configuration of the chalcones
moiety. The signals of aromatic ring A were
resonated as doublet at 7.48 and 7.94 ppm to
indicate that the formation of O-glycoside occurred
via the hydroxyl group to form C-O-C bond.
Methyl groups of acetates were resonated as two
singlets which indicated that the acetates were
stable to the reaction condition. The 13C NMR
spectra showed the appearance of four signals
attributed to four symmetrical peaks of aromatic
carbons. The trans vinylic alkene Ca and Cb
appeared at 119.8 and 141.2 ppm. C-2 and C-3
appeared at 127.5 and 129.6 ppm respectively.20
The other compound with Rf 0.90 was also
subjected to spectroscopic analysis. The
appearance of a broad band at 3373 cm-1 indicated
the presence of hydroxyl group in the compound
structure. The stretching vibration of paraffinic
2a: R=C7H15
2b: R=C8H17
2c: R=C9H19
3a: R=C7H15
3b: R=C8H17
3c: R=C9H19
A
a
B
b
2"
2"
N2, reflux
1"
BF3.OEt2, CH3CN
4"
3"
3"
4'
2'
1'
5
3'
3'
2'
3
4
6
1
2
Scheme 2 : Proposed synthesis of glycosides 3
Two products were observed at Rf 0.22 and
0.90 after 4 h reaction. Both compounds were
characterized separately using IR, 1H and 13C NMR
spectroscopy. The IR spectra of compound with Rf
0.22 showed the presence of long paraffinic chain
at 2925 and 2855 cm-1. The conjugated C=O
stretching frequency was observed at 1680 cm-1 and
non-conjugated C=O stretching frequency at 1723
cm-1. The υCOC stretching frequency of acetates
appeared at 1357 – 1171 cm-1. The 1H NMR
spectra showed characteristic signals of aromatic
chain was observed at 2923 and 2853 cm-1 while
υCOC of acetates appeared at 1257 – 1166 cm-1. The
1H NMR spectrum showed the presence of two
signals as doublets attributed to H-5’ and H-6’ of
aromatic ring B at 6.85 and 6.95 ppm respectively
while characteristic resonance corresponded to H-2’
as singlet was observed at 7.43 ppm, which indicate
the formation of C-glycoside. Resonances
appeared as doublets assigned at 7.37 and 7.52 ppm
with Jab = 15.5 Hz, indicated the aglycone was in
trans configuration. The formation of C-glycoside
014 Zainab Ngaini & Dayang H. Abang Kamaluddin Synthesis of Glycosides Bearing Chalcone
Derivatives via Ferrier Rearrangement
is also supported by the presence of -OH which
resonated as a singlet at 9.86 ppm. The lower in
resonance of -OH might be due to the formation of
hydrogen bonding with the nearby hydrogen
moieties. 13C NMR verified the formation of the
proposed C-glycoside. 13C NMR showed the
presence of five signals attributed to five different
carbons of ring B, while two symmetrical peaks
attributed to C-3” and C-2” of ring A were
observed at 130.9 and 131.1 ppm. The peaks
present at 119.8 and 143.8 ppm were corresponded
to trans vinylic alkene. The presence of COH also
appeared in 13C NMR with the signal at 161.7
ppm.21 The formation of C-glycoside via Ferier
rearrangement is depicted in Scheme 3.
Upon prolonging the reaction times (6 h), only
one product appeared with Rf 0.90 which
corresponded to C-glycoside, and the disappearance
of Rf 0.22 corresponded to O-glycosides.22 1H and
13C NMR showed good agreement to the formation
of C-glycoside. It was envisaged that compound 3
(O-glycoside) was rearranged to form compound 4
(C-glycoside) via OC glycoside rearrangement23,
in correspond to the reaction times. The overall
reaction is shown in Scheme 4.
A
B
A
2a: R = C7H15
a
B
4a: R = C7H15
b
3a: R = C7H15
(29%)
(27%)
2"
2"
N2, reflux
a
1"
BF3.OEt2, CH3CN
b
4"
2"
3"
2"
3"
1"
4'
4"
2'
3"
1'
3"
5
4'
3'
2'
3'
1'
2'
5
3
5'
4
3'
6
6'
1
3
2
4
6
2
1
Scheme 3 : Preparation of O-glycoside 3a and C-glycoside 4a
a
A
B
2a: R = C7H15
2b: R = C8H17
2c: R = C9H19
B
A
b
O C rearrangement
3a: R = C7H15
3b: R = C8H17
3c: R = C9H19
4a: R = C7H15
4b: R = C8H17
4c: R = C9H19
N2, reflux
a
b
BF3.OEt2, CH3CN
2"
2"
2"
2"
1"
1"
4"
4"
3"
3"
3"
3"
4'
4'
2'
2'
1'
1'
5
5
3'
5'
3'
3'
2'
6'
3
3
4
4
6
6
1
2
2
1
Scheme 4 : Synthesis of 4a-4c via OC rearrangement
015 Zainab Ngaini & Dayang H. Abang Kamaluddin Synthesis of Glycosides Bearing Chalcone
Derivatives via Ferrier Rearrangement
Experimental
General
4-Hydroxybenzaldehyde, 4-
hydroxyacetophenone and 1-bromoalkanes were
obtained from Merck and used without further
purification. Acetonitrile was distilled from
KMnO4 and MgSO4. All other reagents and
solvents were used as received. Melting points were
determined in open capillaries and uncorrected.
Infrared spectra were recorded on (FT-IR) 1605
Shimadzu Spectrometer using neat liquid film and
KBr pellets. 1H-NMR spectra were recorded on a
500 MHz Jeol Delta 2-NMR and 13C NMR spectra
were recorded on a 125.7 MHz using TMS as the
internal standard.
Synthesis of alkyloxyphenyl-ethanone (1a–1c)
General procedure24
Bromoalkane (72 mmol), 4-
hydroxyacetophenone (72 mmol), potassium
carbonate (K2CO3) (72 mmol),
Tetrabutylammonium iodide (TBAI) (6 mmol) in
Methyl Ethyl Ketone (200 mL) were heated at
reflux for 10 h. The mixture was filtered and cooled
at room temperature. Water (30 mL) was added to
the filtrate and the layers separated. The aqueous
layer was extracted with dichloromethane (2 x 30
mL). The combined layers were washed with water
(2 x 20 mL), dried (MgSO4), filtered, and
concentrated in vacuo. The crude was recrystallized
from ethanol to give 1a-1c. The same general
procedure gave compounds 1b–c, with the scale
(mmol, mL [1b–c]) and yields given below.
1-(4-heptyloxyphenyl)-ethanone (1a)
Bromoheptane (5.66 mL, 36.0 mmol), 4-
hydroxyacetophenone (4.08 g, 30.0 mmol), gave
colourles crystals 1a (4.57 g, 65%), m.p. 40.0 oC; Rf
0.93 (hexane:ethyl acetate, 3:1); The FTIR and
NMR data were consistent with the reported
literature.25 The same general procedure gave
compounds 1b–c, with the scale (mL, mmol,
[bromoalkane]) and yields given below.
1-(4-octyloxyphenyl)-ethanone (1b)
Bromooctane (6.26 mL, 36.0 mmol), 4-
hydroxyacetophenone (4.08 g, 30.0 mmol), gave
colourless crystals 1b (3.88 g, 52%), m.p. 44.4 oC;
Rf 0.93 (hexane:ethyl acetate, 3:1); FTIR and NMR
data were consistent with the reported literature.25
1-(4-nonyloxyphenyl)-ethanone (1c)
Bromononane (6.78 mL, 36.0 mmol), 4-
hydroxyacetophenone (4.08 g, 30.0 mmol), gave
colourless crystals 1c (6.45 g, 87%), m.p. 46.0 oC;
Rf 0.95 (hexane:ethyl acetate, 3:1); FTIR and NMR
data were consistent with the reported literature.25
Synthesis of (alkyloxy)phenyl-
hydroxyphenyl]prop-2-en-1-one (2a–2)
General procedure26
A mixture of p-hydroxybenzaldehydes (12.5
mmol), 1a-c (12.5 mmol) in 35 mL of methanol
was added under stirring to a solution of KOH
(2.52 g) in methanol (10 mL). The mixture was
heated at reflux for 10 h. The reaction was cooled
to room temperature and acidified with cold diluted
HCl (2N). The resulting precipitate was filtered,
washed and dried. The crude product was
recrystallized from hexane:ethanol (7:1) to give
(2a–2c). The same general procedure gave
compounds 2b–c, with the scale (mL, mmol,
[bromoalkane]) and yields given below.
(E)-1-(4-heptyloxyphenyl)-3-(4-
hydroxyphenyl)prop-2-en-1-one (2a)
4-hydroxybenzaldehyde (1.22 g, 10.0 mmol),
1a (3.38 g, 10.0 mmol) gave yellow crystals 2a
(0.81 g, 24%), m.p. 100.0 oC; Rf 0.67
(hexane:THF, 3:2); FTIR and NMR data were
consistent with the reported literature.25
(E)-1-(4-octyloxyphenyl)-3-(4-
hydroxyphenyl)prop-2-en-1-one (2b)
4-hydroxybenzaldehyde (1.22 g, 10.0 mmol),
1b (3.52 g, 10.0 mmol), gave yellow crystals 2b
(1.80 g, 51%), m.p. 105.0 oC; Rf 0.65
(hexane:THF, 3:2); FTIR and NMR data were
consistent with the reported literature.25
(E)-1-(4-nonyloxyphenyl)-3-(4-
hydroxyphenyl)prop-2-en-1-one (2c)
4-hydroxybenzaldehyde (1.22 g, 10.0 mmol),
1c (3.66 g, 10.0 mmol) gave yellow crystals 2c
(2.34 g, 64%), m.p. 115.0 oC; Rf 0.64
(hexane:THF, 3:2); FTIR and NMR data were
consistent with the reported literature.25
Synthesis of chalcone glycosides (3a, 4a-4c)
General procedure
Chalcone 2a-2c was added into tri-O-acetyl-D-
glucal in dry acetonitrile under nitrogen
atmosphere. BF3.OEt2 was added and the mixture
was heated at reflux. The mixture was cooled to
room temperature, quenched with saturated sodium
hydrogen carbonate and extracted with diethyl
ether. The combined organic layers were washed
with brine, dried over anhydrous magnesium
sulfate, filtered and concentrated. The product was
purified by column chromatography on silica gel 60
(70-230 mesh ASTM).
[2-(acetoxymethyl)-6-[4-[3-(4-heptoxyphenyl)-3-
oxo-prop-1-enyl]phenoxy]-3,6-dihydro-2H-pyran-
3-yl] acetate (3a)
016 Zainab Ngaini & Dayang H. Abang Kamaluddin Synthesis of Glycosides Bearing Chalcone
Derivatives via Ferrier Rearrangement
Tri-O-acetyl-D-glucal (0.272 g, 1.0 mmol) was
dissolved in a solution of 2a (0.338 g, 1.0 mmol) in
dry acetonitrile (10 mL) under nitrogen atmosphere.
BF3.OEt2 (0.258 mL, 2.0 mmol) was added and the
mixture was heated at reflux for 4 h. The reaction
was cooled to room temperature and worked up
according to general procedure. The crude was
purified by column chromatography on silica gel
(hexane:ethyl acetate, 5:1 and 10:1) to give 3a
(0.16 g, 29%) as yellow waxy liquid with Rf 0.22
(hexane:ethyl acetate, 3:1); Anal. calcd. (%)
C32H38O8 C, 69.84; H, 6.91; Found (%):C, 69.78;
H, 6.88. υmax (thin films/cm-1); 2925, 2855
(CH2CH3), 1723 (C=O, CH3CO), 1680 (C=O,
conjugated), 1601, 1575, 1510, 1467 (C=C), 1420,
1377 (bending CH3), 1357, 1305, 1255, 1217, 1171
(COC, CH3CO), 1114, 1021 (COC, ether), 954
(trans vinylic C=C), 828 (para disubstituted
benzene), 723 (cis C=C); 1H NMR (CDCl3): 7.94
(d, J = 9.2 Hz, 2H, 2 x ArH), 7.64 (d, J = 15.5 Hz,
1H, olefinic H), 7.48 (d, J = 8.6 Hz, 2H, 2 x ArH),
7.40 (d, J = 15.5 Hz, 1H, olefinic H), 7.02 (d, J =
8.0 Hz, 2H, 2 x ArH), 6.89 (d, J = 8.6 Hz, 2H, 2 x
ArH), 5.63 (m, 1H, H-3), 5.49 (m, 1H, H-2), 4.74
(d, J = 9.6 Hz, 1H, H-1), 4.51 (m, 1H, H-4), 4.37 (t,
J = 4.6 Hz, 2H, H2-1”), 3.97-3.40 (m, 3H, H-5, H-
6a, H-6b), 2.10 (s, 3H, CH3CO-C6), 2.09 (s, 3H,
CH3CO-C4), 1.76 (q, 2H, H2-2”), 1.49-1.19 (m, 8H,
4 x CH2), 0.81 (t, J = 6.9 Hz, 3H, H3-7”); 13C NMR
(CDCl3): 189.4 (C=O), 173.2 (C=O, CH3CO-C4),
170.0 (C=O, CH3CO-C6), 161.3 (COC), 141.2
(trans vinylic C=C), 131.9 (C-1”), 130.9 (C-2”),
129.6 (C-3), 128.2 (C-3”), 127.5 (C-2), 123.8 (C-
1’), 119.8 (trans vinylic C=C), 115.4 (C-2’), 114.4
(C-3’), 90.7 (C-1), 70.7 (C-4), 68.0 (C-1”), 64.0 (C-
6), 60.2 (C-5), 37.8 (C-2”), 29.6, 29.3, 26.0, 22.6 (4
x CH2), 21.3 (CH3, CH3CO-C6), 20.7 (CH3,
CH3CO-C4), 14.0 (C-7”).
[2-(acetoxymethyl)-6-[2-hydroxy-5-[3-(4-
heptoxyphenyl)-3-oxo-prop-1-enyl]phenyl]-3,6-
dihydro-2H-pyran-3-yl] acetate (4a)
Tri-O-acetyl-D-glucal (0.272 g, 1.0 mmol) was
added to a solution of 2a (0.338 g, 1.0 mmol) in dry
acetonitrile (10 mL) under nitrogen atmosphere.
BF3.OEt2 (0.258 mL, 2.0 mmol) was added and the
mixture was heated at reflux for 6 h. The reaction
was cooled to room temperature and worked up
according to general procedure. The mixture was
purified by column chromatography on silica gel
(hexane:ethyl acetate, 10:1) to afford 4a (0.13 g,
24%) as yellow waxy liquid. Rf 0.90 (hexane: ethyl
acetate, 3:1). Anal. calcd. (%) C32H38O8: C, 69.84;
H, 6.91; Found (%): C, 69.73; H, 6.78. υmax (thin
films/cm-1); 3373 (OH), 2923, 2853 (CH2CH3),
1738 (C=O, CH3CO), 1660 (C=O, conjugated),
1601, 1581, 1513, 1463, 1456 (C=C), 1422, 1377
(bending CH3), 1257, 1225, 1166 (COC, CH3CO),
1116, 1080, 1027 (COC, ether), 972 (trans vinylic
C=C), 826 (para disubstituted benzene), 722 (cis
C=C); 1H NMR (CDCl3): 9.86 (s, 1H, OH), 8.02 (d,
J = 7.5 Hz, 1H, ArH), 7.78 (d, J = 8.6 Hz, 1H,
ArH), 7.52 (d, J = 14.9 Hz, 1H, olefinic H), 7.43 (s,
1H, H-2’), 7.37 (d, J = 15.5 Hz, 1H, olefinic H),
6.95 (d, J = 8.0 Hz, 2H, 2 x ArH), 6.85 (d, J = 9.2
Hz, 2H, 2 x ArH), 6.00 (m, 1H, H-3), 5.78 (m, 1H,
H-2), 5.07 (s, 1H, H-1), 4.92 (d, J = 9.7 Hz, 1H, H-
4), 4.49 (d, J = 4.6 Hz, 2H, H2-1”), 4.29-3.98 (m,
3H, H-5, H-6a, H-6b), 2.04 (s, 3H, CH3CO-C6),
2.03 (s, 3H, CH3CO-C4), 1.77 (q, 2H, H2-2”), 1.42-
1.22 (m, 8H, 4 x CH2), 0.87 (t, J = 6.9 Hz, 3H, H3-
9”); 13C NMR (CDCl3): 191.6 (C=O), 173.9 (C=O,
CH3CO-C4), 171.5 (C=O, CH3CO-C6), 161.7 (C-
4), 160.4 (C-4”), 143.8 (trans vinylic C=C, CH),
132.3 (C-1”), 131.1 (C-2”, CH), 130.8 (C-3”, CH),
129.6 (C-3, CH), 129.0 (C-1’), 128.3 (C-2’, CH),
126.6 (C-2, CH), 124.7 (C-6’, CH), 119.8 (trans
vinylic C=C, CH), 115.9 (C-5’, CH), 114.5 (C-3’,
CH), 89.5 (C-1, CH), 69.2 (C-4, CH), 68.1 (C-1’”,
CH2), 64.0 (C-6, CH2), 59.4 (C-5, CH), 38.7
(aliphatic, CH2), 29.6, 29.5, 26.4, 23.2 (4 x CH2),
22.6 (CH3CO-C6, CH3), 22.3 (CH3CO-C4, CH3,),
14.0 (aliphatic , CH3).
[2-(acetoxymethyl)-6-[2-hydroxy-5-[3-(4-
octoxyphenyl)-3-oxo-prop-1-enyl]phenyl]-3,6-
dihydro-2H-pyran-3-yl] acetate (4b)
Tri-O-acetyl-D-glucal (0.272 g, 1.0 mmol) was
added to a solution of 2b (0.353 g, 1.0 mmol) in dry
acetonitrile (10 mL) under nitrogen atmosphere.
BF3.OEt2 (0.258 mL, 2.0 mmol) was added and the
mixture was heated at reflux for 6 h. The reaction
was cooled to room temperature and worked up
according to general procedure. The mixture was
purified by column chromatography on silica gel
(hexane:ethyl acetate, 10:1) to afford 4b (0.16 g,
29%) as yellow waxy liquid. Rf 0.91 (hexane: ethyl
acetate, 3:1). Anal. calcd. (%) C33H40O8: C, 70.24;
H, 7.09; Found (%): C, 70.10; H, 7.01. υmax (thin
films/cm-1); 3290 (OH), 2924, 2854 (CH2CH3),
1739 (C=O, CH3CO), 1654 (C=O, conjugated),
1601, 1583, 1512, 1466, 1455 (C=C), 1442, 1364
(bending CH3), 1298, 1246, 1167 (COC, CH3CO),
1111, 1072, 1025 (COC, ether), 990 (trans vinylic
C=C), 831 (para disubstituted benzene), 737 (cis
C=C); 1H NMR (CDCl3): 9.86 (s, 1H, OH), 8.01 (d,
J = 7.5 Hz, 1H, ArH), 7.80 (d, J = 8.6 Hz, 1H,
ArH), 7.52 (d, J = 14.9 Hz, 1H, olefinic H), 7.46 (s,
1H, ArH), 7.37 (d, J = 15.5 Hz, 1H, olefinic H),
6.97 (d, J = 8.6 Hz, 2H, 2 x ArH), 6.89 (d, J = 9.2
Hz, 2H, 2 x ArH), 5.79 (m, 1H, H-3), 5.61 (m, 1H,
H-2), 5.00 (s, 1H, H-1), 4.90 (d, J = 10.3 Hz, 1H,
H-4), 4.49 (t, J = 4.6 Hz, 2H, H2-aliphatic), 4.32-
3.99 (m, 3H, H-5, H-6a, H-6b), 2.03 (s, 3H, CH3CO-
C6), 2.02 (s, 3H, CH3CO-C4), 1.80 (q, 2H, H2-
aliphatic), 1.45-1.24 (m, 10H, 5 x CH2), 0.87 (t, J =
017 Zainab Ngaini & Dayang H. Abang Kamaluddin Synthesis of Glycosides Bearing Chalcone
Derivatives via Ferrier Rearrangement
6.7 Hz, 3H, H3- aliphatic); 13C NMR (CDCl3):
190.1 (C=O), 173.9 (C=O, CH3CO-C4), 171.4
(C=O, CH3CO-C6), 163.0 (C-4), 159.1 (C-4”),
144.1 (trans vinylic C=C, CH), 132.9 (C-1”), 131.8
(C-2”, CH), 130.4 (C-3”, CH), 130.0 (C-3, CH),
128.8 (C-1’), 128.5 (C-2’, CH), 127.0 (C-2), 123.9
(C-6’, CH), 118.9 (trans vinylic C=C, CH), 115.7
(C-5’, CH), 115.2 (C-3’, CH), 89.9 (C-1, CH), 69.9
(C-4, CH), 68.0 (aliphatic, CH2), 64.1 (C-6, CH2),
59.2 (C-5, CH), 37.0 (aliphatic, CH2), 30.1, 30.0,
29.2, 25.8, 23.3 (5 x CH2), 22.6 (CH3CO-C6, CH3),
22.1 (CH3CO-C4, CH3), 14.1 (aliphatic, CH3).
[2-(acetoxymethyl)-6-[2-hydroxy-5-[3-(4-
nonoxyphenyl)-3-oxo-prop-1-enyl]phenyl]-3,6-
dihydro-2H-pyran-3-yl] acetate (4c)
Tri-O-acetyl-D-glucal (0.272 g, 1.0 mmol) was
added to a solution of 2c (0.367 g, 1.0 mmol) in dry
acetonitrile (10 mL) under nitrogen atmosphere.
BF3.OEt2 (0.258 mL, 2.0 mmol) was added and the
mixture was refluxed for 6 h. The reaction was
cooled to room temperature and worked up
according to general procedure. The mixture was
purified by column chromatography on silica gel
(hexane:ethyl acetate, 10:1) to afford 4c (0.26 g,
45%) as yellow waxy liquid. Rf 0.94 (hexane: ethyl
acetate, 3:1). Anal. calcd. (%) C34H42O8 : C, 70.61;
H, 7.26; Found (%): C, 70.46; H, 7.14. υmax (thin
films/cm-1); 3408 (OH), 2923, 2853 (CH2CH3),
1739 (C=O, CH3CO), 1689 (C=O, conjugated),
1606, 1579, 1513, 1494, 1469, 1463, 1434 (C=C),
1397, 1377 (bending CH3), 1258, 1208, 1169
(COC, CH3CO), 1127, 1080, 1065, 1015 (COC,
ether), 963 (cis C=C), 846 (para disubstituted
benzene), 742 (cis C=C); 1H NMR (CDCl3): 9.83
(s, 1H, OH), 8.00 (d, J = 7.5 Hz, 1H, ArH), 7.75 (d,
J = 8.6 Hz, 1H, ArH), 7.51 (d, J = 14.9 Hz, 1H,
olefinic H), 7.45 (s, 1H, ArH), 7.36 (d, J = 15.5 Hz,
1H, olefinic H), 6.94 (d, J = 8.6 Hz, 2H, 2 x ArH),
6.87 (d, J = 7.5 Hz, 2H, 2 x ArH), 6.00 (m, 1H, H-
3), 5.78 (m, 1H, H-2), 5.06 (s, 1H, H-1), 4.89 (d, J
= 9.2 Hz, 1H, H-4), 4.48 (t, J = 4.6 Hz, 2H, H2-
aliphatic), 4.38-4.04 (m, 3H, H-5, H-6a, H-6b), 2.06
(s, 3H, CH3CO-C6), 2.03 (s, 3H, CH3CO-C4), 1.76
(q, 2H, H2- aliphatic), 1.45-1.23 (m, 12H, 6 x CH2),
0.84 (t, J = 7.5 Hz, 3H, H3- aliphatic); 13C NMR
(CDCl3, DEPT): 190.2 (C=O), 174.0 (C=O,
CH3CO-C4), 170.6 (C=O, CH3CO-C6), 162.8 (C-
4), 158.8 (C-4”), 144.0 (trans vinylic C=C, CH),
133.6 (C-1”), 132.4 (C-2”, CH), 130.9 (C-3”, CH),
129.4 (C-3), 128.7 (C-1’), 128.2 (C-2’, CH), 126.8
(C-2), 123.9 (C-6’, CH), 119.7 (trans vinylic C=C,
CH), 115.4 (C-5’, CH), 114.6 (C-3’, CH), 90.2 (C-
1, CH), 70.9 (C-4, CH), 68.0 (aliphatic, CH2), 63.5
(C-6, CH2), 58.9 (C-5, CH), 37.3 (aliphatic, CH2),
31.7, 29.6, 29.3, 29.2, 26.0, 23.5 (6 x CH2), 22.6
(CH3CO-C6, CH3), 22.0 (CH3CO-C4, CH3), 14.0
(aliphatic, CH3).
Conclusion
We have successfully synthesized chalcone
glycosides 3a and 4a-4c by incorporation of
chalcone derivatives onto 3,4,6-tri-O-acetyl-D-
glucal. Over prolonged reaction times resulted in
the formation of C-glycosides 4a-4c via OC
rearrangements. Overall, synthetic approaches
towards chalcone glycosides were developed during
this study. This study has provided a better
understanding towards the glycosylation reactions
involving aromatic compounds.
Acknowledgements
We are grateful to Universiti Malaysia
Sarawak and Ministry of Science, Technology and
Innovation for the financial support through
FRGS/01(14)/743/2010 (29).
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