Microwave-assisted efficient synthesis of aryl ketone β-C-glycosides from unprotected aldoses

Article abstract of DOI:10.1016/j.carres.2010.11.027

Condensation between unprotected aldoses and dibenzoylmethane catalyzed by NaHCO₃ in the cosolvents EtOH and H₂O (4:1) under microwave irradiation gave aryl ketone β-C-glycosides 6b-i in higher yields (from 50% with C-riboside 6g up

Full text of DOI:10.1016/j.carres.2010.11.027

Carbohydrate Research 346 (2011) 352–356
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Note
Microwave-assisted efficient synthesis of aryl ketone b-C-glycosides
from unprotected aldoses
b
a
a
Weiwei Feng a, Zhijie Fang a, , Jingmei Yang , Baohui Zheng , Yuhua Jiang
⇑
a School of Chemical Engineering, Nanjing University of Science & Technology, 200 Xiaolingwei, Nanjing 210094, China
b WuXi AppTec (Shanghai) Co., Ltd, 288 Fute Zhong Road, Waigaoqiao Free Trade Zone, Shanghai 200131, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 10 October 2010
Received in revised form 23 November 2010
Accepted 25 November 2010
Available online 3 December 2010
Condensation between unprotected aldoses and dibenzoylmethane catalyzed by NaHCO3 in the cosol-
vents EtOH and H2O (4:1) under microwave irradiation gave aryl ketone b-C-glycosides 6b–i in higher
yields (from 50% with C-riboside 6g up to 99% with C-glucoside 6b) and better anomeric selectivities
(b-configuration >95%) in a shorter reaction time (90 min), compared with previous conventional meth-
odologies. This method provides an attractive alternative to the existing means for the preparation of
high value ketone b-C-glycosides.
Keywords:
Microwave
Ó 2010 Elsevier Ltd. All rights reserved.
Knoevenagel condensation
Aryl ketone b-C-glycoside
Aldose
C-Glycosides are used as building blocks for the synthesis of a
variety of biologically important natural products1,2 and synthetic
compounds.3–5 Kidamycin,6 flavone C-glycoside,7 b-C-glycoside
analogs of KRN7000,8 fagomine C-glycoside9, and C-glycoside SGLT2
inhibitors10 have been reported to exhibit antitumor, antibacterial,
antiviral, antidiabetic, and glycosidase inhibitory activities. The
interest in C-glycosides lies on the stability of the C-glycosidic link-
age, which is resistant to both enzymatic and chemical hydrolysis.
Therefore, stereoselective synthesis of C-glycosides has been a chal-
lenging task for organic chemists.
Alkyl ketone b-C-glycosides have been synthesized conve-
niently in alkaline aqueous media for many years.11–16 This meth-
odology is based on Knoevenagel condensation between the
carbanion of the b-diketone 2a and the aldehyde group of an
unprotected aldose 1 (Scheme 1). b-Elimination of water, followed
by intramolecular Michael cyclization gives the intermediate
C-glycoside 5a, which undergoes a retro-Claisen aldolization under
the basic conditions with concomitant sodium carboxylate elimi-
nation to afford alkyl ketone b-C-glycoside 6a. Pro-Xylane™, a
C-xyloside alcohol preparing from the reduction of an alkyl ketone
b-C-glycoside obtained by this method is found to stimulate
sulfated glycosaminoglycan (GAG) synthesis and has recently been
an example of ‘Green’ chemical used in cosmetics.15 However, this
method for the synthesis of aryl ketone b-C-glycosides is less
reported, and involves long reaction time (12 h) and low yields
(6% with C-xyloside,15 38% with C-galactoside and 64% with
C-glucoside16). As a result, we need faster and more efficient meth-
odologies for the synthesis of aryl ketone b-C-glycosides.
Compared to conventional heating techniques, such as use of an
oil bath, microwave irradiation is a clean, cheap, and convenient
method. This method of heating usually shows noticeable
improvements such as shorter reaction times, higher yields, and
better selectivities, so the use of microwave irradiation has become
popular in recent years among chemists both to improve classical
organic reactions and to promote new reactions. Nevertheless, the
application of microwave heating in carbohydrate chemistry is less
well investigated.17–19 A microwave-assisted conversion of carbo-
hydrates has been recently explored in our laboratory.20
In this paper, we describe a rapid and stereospecific synthesis of
several aryl ketone b-C-glycoside derivatives catalyzed by inor-
ganic base in EtOH–H2O (4:1, v/v) via the microwave-assisted
Knoevenagel condensation between unprotected aldoses and dib-
enzoylmethane, which gives moderate to excellent yields and al-
most exclusively (>95%) the thermodynamic b-configuration as
shown by 1H and 13C NMR spectroscopy. To the best of our knowl-
edge, this methodology has not been previously reported.
In order to optimize the reaction conditions, we chose D-glucose
as a model substrate for this condensation. First, the effect of var-
ious solvents and inorganic bases was investigated (Table 1). Sur-
prisingly, the solvent had a tremendous effect on the reaction
yield. When the reaction was performed in pure water (entry 1),
only trace amounts of aryl ketone b-C-glucoside 6b were obtained.
This low yield (7%) can be explained by the poor solubility of
dibenzoylmethane in pure water. However, we were pleased to
observe that the combined use of ethanol with water made
⇑
Corresponding author. Tel./fax: +86 25 84314906.
E-mail address: zjfang@mail.njust.edu.cn (Z.J. Fang).
0008-6215/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2010.11.027

W. Feng et al. / Carbohydrate Research 346 (2011) 352–356
353
R
R
Na +
O
OH
OH
O
OH
O
O
O
OH
O-
NaHCO3
R
R
-H2O
HO
HO
HO
HO
HO
HO
+
OH
R
R
-
OH
+
OH
OH
OH
Na
O
1
2a R = Me
2b R = Ph
3a
3b
4a R = Me
4b R = Ph
R = Me
R = Ph
O
OH
O
-
OH
O
O
R
R
OH-
HO
HO
HO
HO
R
-ROONa
OH
OH
Na+
O
O
5a R = Me
5b R = Ph
6a R = Me
6b R = Ph
Scheme 1. Condensation of
D
-glucose with a b-diketone.
dibenzoylmethane more soluble and led to great improvements in
the yields (entries 2–4), the increase in the volume ratio of ethanol
to water raised the yield of C-glucoside 6b, and the best yield (97%)
was achieved at the ratio of 4:1 (entry 4). Then, after the maxi-
mum, the yield dropped rapidly and was only 12% when pure eth-
anol was used as solvent (entry 5), because of the poor solubility of
110
100
90
80
D
-glucose in pure ethanol. Other co-solvents were also tested (en-
70
tries 6–9), such as THF–H2O (4:1), CH3CN–H2O (4:1), DMF–H2O
(4:1), DMSO–H2O (4:1), which all gave low yields. The lowest yield
(4%) in THF–H2O (4:1) may probably be correlated to the low boil-
ing point (66 °C) and low microwave-absorbing (loss tangent, tan
d = 0.047) of the solvent THF.21
60
50
100 200 300 400
500 600 700 800 900
Irradiation power (W)
Besides the difference of solvents, dissimilarities were observed
when changing the species of inorganic bases. D-Glucose was con-
Figure 1. Effect of microwave irradiation power on the yield of C-glucoside 6b.
Condition (j): -glucose (1 mmol), dibenzoylmethane (2 mmol), NaHCO3
(2 mmol), and 5 mL EtOH–H2O (4:1) under microwave irradiation with the given
power, reflux, 60 min; condition B (N): -glucose (1 mmol), dibenzoylmethane
(1.5 mmol), NaHCO3 (1.5 mmol), and 5 mL EtOH–H2O (4:1) under microwave
irradiation with the given power, reflux, 90 min. The yield was determined by HPLC.
A
D
densed with dibenzoylmethane in co-solvents EtOH–H2O (4:1)
using either sodium bicarbonate, sodium carbonate, potassium
carbonate, potassium hydroxide, or sodium hydroxide as catalyst.
The yield of C-glucoside 6b decreased accordingly with increasing
the catalyst basicity (entries 3 and 10–13). Thus, sodium bicarbon-
ate proved to be the best choice of catalyst.
D
Following the initially promising result, we then turned our
attention to the optimization of the reaction conditions with re-
spect to microwave irradiation power, irradiation time, and dib-
enzoylmethane (or sodium bicarbonate)–glucose molar ratio.
Two different reaction conditions were studied by varying the
microwave irradiation power from 200 to 800 W (Fig. 1). It ap-
peared that irradiation power had no significant impact on the
reaction outcome. The yield of C-glucoside 6b reached 97% at
400 W in condition A.
Figure 2 shows the influence of irradiation time on the yield of
C-glucoside 6b at an irradiation power of 400 W. For the condensa-
tion of glucose with dibenzoylmethane, the yield reached the
maximum (almost 100%) after 90 min, and decreased remarkably
at longer irradiation times as side reactions increased. The by-
product 2,5-disubstituted furan was formed from a reversible ring
closure between the carbonyl group of ketone b-C-glycoside and
the C-20 hydroxyl group to give
dehydration.12
a hemiacetal, followed by
Table 1
Effects of various solvents and inorganic bases on the yield of C-glucoside 6ba
105
100
95
Entry
Solvent
Base
Time (min)
Yieldb (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
H2O
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
K2CO3
90
90
60
60
90
60
60
60
60
60
60
60
60
7
59
78
97
12
4
58
69
59
68
64
49
39
EtOH–H2O (1:1)
EtOH–H2O (2:1)
EtOH–H2O (4:1)
EtOH
THF–H2O (4:1)
CH3CN–H2O (4:1)
DMF–H2O (4:1)
DMSO–H2O (4:1)
EtOH–H2O (2:1)
EtOH–H2O (2:1)
EtOH–H2O (2:1)
EtOH–H2O (2:1)
90
85
80
Na2CO3
KOH
NaOH
0
15
30
45
60
75
90
105 120
Irradiation time (min)
a
Reactions were performed with
D-glucose (1 mmol), dibenzoylmethane
Figure 2. Influence of microwave irradiation time on the yield of C-glucoside 6b.
Reactions were performed with -glucose (1 mmol), dibenzoylmethane (2 mmol),
NaHCO3 (2 mmol), and 5 mL EtOH–H2O (4:1) under microwave irradiation with a
power of 400 W, refluxing for the given time. The yield was determined by HPLC.
(2 mmol), base (2 mmol, except 1 mmol for K2CO3 or Na2CO3), and 5 mL solvent
under microwave irradiation with a power of 400 W, refluxing for the given time.
D
b
Determined by HPLC.

354
W. Feng et al. / Carbohydrate Research 346 (2011) 352–356
By changing the dibenzoylmethane (or sodium bicarbonate)–
ture reports.15,16,22,23 C-Mannoside 6c was also prepared with an
excellent yield (entry 2). C-Galactoside 6d afforded a good yield
(entry 3), and was found to further dehydrate to give 2,5-disubsti-
tuted furan by TLC analysis.12 It is worth pointing out that in the 1H
NMR (300 MHz, DMSO-d6) spectra of C-pentoside (entries 4–6), the
hydrogen atoms of the hydroxyl groups were all doublet peaks,
indicating the carbon which –OH connected to only had one hydro-
gen atom, namely there was no HOCH2– group. Therefore, all the
three C-pentosides (6e–g) were pyranose rather than furanose iso-
mers. In the case of C-arabinoside 6f, the anomeric configuration
was determined through NOESY spectra (500 MHz, D2O). The sig-
nificant Nuclear Overhauser Effect between H-10 with H-50a indi-
glucose molar ratio, a comparison between microwave irradiation
and classical oil bath heating has been performed to analyze the
different effects between the two heating systems (Fig. 3). Experi-
ments under classical oil bath heating have been conducted using
conditions similar to those under microwave irradiation: same
quantity of reactants, heating in a thermostatic oil bath at the
refluxing temperature. The yield of C-glucoside 6b under micro-
wave irradiation appeared to be strongly dependent on the dib-
enzoylmethane (or sodium bicarbonate)–glucose molar ratio. The
highest yield (almost 100%) was provided at a dibenzoylmethane
(or sodium bicarbonate)–glucose molar ratio of 2:1 and an irradia-
tion power of 400 W. Higher molar ratio (>2:1) did not lead to bet-
ter results. Oil bath heating had no significant impact on the
reaction outcome, and gave lower yields (80–91%) with longer
reaction time (15 h). A possible reason for the higher yields under
microwave irradiation is that ‘specific’ or ‘nonthermal’ microwave
effects cause a decrease in activation energy or an increase in the
pre-exponential factor. Furthermore, the condensation performed
in the co-solvents EtOH–H2O (4:1) by oil bath heating gave higher
yields than previous reports.12,15,16,22
cated that compound 6f was b-configuration, not
a-configuration
(Fig. 4). Indeed, we noticed that the disaccharyl C-glycosides were
obtained along with the monosaccharyl C-glycosides as monitored
by TLC analysis, which could be attributed to the degradation of
either disaccharide or disaccharyl C-glycosides or both in the con-
ditions of the reaction. Consequently, disaccharide only afforded
moderate yields (55% with C-maltoside 6h, 60% with C-lactoside
6i, entries 7 and 8). In conclusion, this approach gave higher yields
and better anomeric selectivities (b-configuration >95%) in a short-
er reaction time (90 min), compared with previously reported
methods.12,15,16,22
Based on these results, we next explored the synthetic general-
ity of this microwave-assisted condensation protocol. Thus, a series
of unprotected aldose substrates, including
-galactose, -xylose, -arabinose, -ribose,
drate, and -lactose monohydrate, all of which exist as common
D
-glucose,
D
-mannose,
In summary, we have described a detailed optimization proce-
dure for the microwave-assisted synthesis of aryl ketone b-C-gly-
coside in D-glucose case and investigated the scope of this
D
D
D
D
D-maltose monohy-
D
glycosidic components in many C-glycosides, were used for the
condensation with dibenzoylmethane into aryl ketone b-C-glyco-
sides 6b–i (Table 2). The nature of the aldoses had an impact on
the reaction yields (from 50% with C-riboside 6g up to 99% with
C-glucoside 6b).
C-Glucoside 6b (entry 1) was separated by silica gel column
chromatography and the structure was established by 1H NMR,
13C NMR, and ESI-LCMS spectra. In the 1H NMR (300 MHz) spec-
trum, the H-10 signal was a characteristic doublet of doublet dou-
methodology for the preparation of several C-glycoside derivatives.
This one-step protocol involves direct condensation between
unprotected aldoses and dibenzoylmethane catalyzed by inorganic
base in EtOH–H2O (4:1). Faced with environmental concerns, this
methodology offers attractive features, including high yields,
excellent anomeric selectivities, and short reaction times. In our
opinion, the present method of the microwave-assisted Knoevena-
gel condensation provides an efficient alternative to the existing
means to synthesize ketone b-C-glycosides, and could open new
vistas for the preparation of high value ketone b-C-glycosides that
could be expanded to large scale production.
0
0
blets with a large coupling constant (J1 ,2 9.3 Hz), indicating a
trans-diaxial orientation of the C-10 and C-20 hydrogen atoms as ex-
pected for b-
mation. Analogously, the 1H and 13C NMR spectral data were
consistent with a b anomeric configuration and a 4C1 (
) conforma-
D
configured pyranose moiety adopting a 4C1 confor-
1. Experimental
D
tion for other products as well as compared with previous litera-
Microwave irradiation was performed in a MAS-1 microwave
reactor apparatus (Shanghai Sineo Microwave Chemistry Technol-
ogy Co., Ltd). Melting points (mp) were determined on a WRS-1B
digital melting-point apparatus (Shanghai Shenguang Instrument
Co., Ltd). Optical rotations were measured on a WZZ-2B automatic
polarimeter (Shanghai Precision & Scientific Instrument Co., Ltd).
1H, 13C, and NOESY NMR spectra were recorded on a Bruker DRX-
300 (DRX-400 or AVANCE III 500) spectrometer. ESI-LCMS spectra
were obtained on a Shimadzu LCMS-2010EV mass spectrometer.
HRESIMS were recorded on a Thermo Finnigan TSQ Quantum-LC/
MS/MS spectrometer. Samples were analyzed on a Shimadzu LC-
20A High Performance Liquid Chromatography with internal stan-
dard peracetylated C-glucoside 6b derivative (purity >99%), using
a SPD-20A prominence UV/vis detector which was set at 254 nm
110
100
90
80
70
and a Shimadzu Shim-pack VP-ODS (5
l
m, 4.6 ꢀ 250 mm) LC
60
Column with the eluent MeOH–H2O (7:3, v/v) at a flow rate of
1 mL minꢁ1. All chemicals were analytical pure and used without
further purification, except internal standard peracetylated C-glu-
coside 6b derivative was prepared in our own laboratory.
50
0.9
1.1
1.3
1.5
1.7
1.9
2.1
2.3
2.5
Dibenzoylmethane (or sodium bicarbonate) / glucose molar ratio
1.1. General procedure for condensation under microwave
irradiation
Figure 3. Comparison between microwave irradiation and oil bath heating at
different dibenzoylmethane (or sodium bicarbonate)/glucose molar ratio. Reaction
conditions: D-glucose (1 mmol), dibenzoylmethane, NaHCO3 (the amount given in
Unprotected aldose (1 mmol), dibenzoylmethane (449 mg,
2 mmol), sodium bicarbonate (168 mg, 2 mmol), and 5 mL (or
10 mL for disaccharide) EtOH–H2O (4:1) were introduced and
this figure), and 5 mL EtOH–H2O (4:1) under microwave irradiation with a power of
300 W (j) or 400 W (ꢀ), refluxing for 90 min, or under oil bath heating (N),
refluxing for 15 h. The yield of C-glucoside 6b was determined by HPLC.

W. Feng et al. / Carbohydrate Research 346 (2011) 352–356
355
Table 2
Microwave-assisted Knoevenagel condensation of unprotected aldoses with dibenzoylmethane catalyzed by NaHCO3 in the co-solvents EtOH–H2O (4:1)a
Product 6b–ib
d (H-10), (J1 ,2 /Hz)
d (C-10)
Yieldd (%)
Ref.e
0
0
Entry
Substrate
OH
O
HO
HO
3.77 (9.3)
79.6
Ph
Ph
1
99
12,15,22,23
D
D
D
-Glucose
OH
O
O
6b
OH
HO
O
HO
HO
4.02 (—c)
80.0
2
3
98
71
22,23
-Mannose
-Galactose
6c
OH
OH
O
3.73 (9.0)
76.2
Ph
16
HO
OH
O
6d
O
HO
Ph
HO
3.57 (—c)
77.2
4
5
6
89
53
50
15,22,23
D
D
D
-Xylose
OH
6e
HO
O
O
HO
HO
3.60 (—c)
77.3
Ph
Ph
—
-Arabinose
-Ribose
O
O
OH
6f
O
3.91 (9.6)
71.8
22,23
OH
OH
6g
OH
O
HO
HO
OH
3.78 (9.2)
78.1
OH
7
8
55
—
D
-Maltose monohydrate
O
O
Ph
HO
OH
O
6h
HO
OH
OH
O
O
3.82 (9.2)
78.5
O
60
—
D-Lactose monohydrate
HO
Ph
HO
OH
OH
O
6i
a
Reaction conditions: unprotected aldose (1 mmol), dibenzoylmethane (2 mmol), NaHCO3 (2 mmol), and 5 mL (or 10 mL for disaccharide) EtOH–H2O (4:1) under
microwave irradiation with a power of 400 W, reflux, 90 min.
b
All the products were characterized by 1H NMR, 13C NMR, and MS spectra.
Anomeric proton peaks overlapped with sugar skeletal proton peaks.
c
d
Isolated yields after purification by column chromatography on silica gel.
e
1H NMR, 13C NMR, MS spectra data, and yields were compared with these references.
H5'b
HO
wave irradiation started, the EtOH–H2O (4:1) began to reflux with-
in 1 minute. After the microwave reactor was turned off, the
solutions were allowed to cool to rt and treated with cation ex-
change resin (sodium form) to reach pH 5. The resin was filtered
and EtOH was evaporated. The aq soln was washed with CH2Cl2
and concentrated. The products were analyzed by HPLC or purified
by column chromatography on silica gel (step gradient from 20:1
to 4:1 EtOAc–EtOH) with the yields given in Table 2.
O
HO
Ph
H5'a
OH
O
H1'
6f
Figure 4. Nuclear Overhauser effect observed between H-10 with H-50a in C-
arabinoside 6f.
mixed in a 50 mL single-necked flask equipped with a reflux con-
denser. The microwave irradiation power and irradiation time
were set at the experimental conditions given above. When micro-
1.1.1. 1-Phenyl-2-C-(b-D-arabinopyranosyl)ethanone (6f)
Yield: 53% as a white solid; mp 145–147 °C; ½a D20
ꢁ10.0 (c 1.0,
ꢂ
MeOH); 1H NMR (500 MHz, D2O): d 3.13–3.18 (dd, 1H, J = 9.4,

356
W. Feng et al. / Carbohydrate Research 346 (2011) 352–356
16.7 Hz, H-2a), 3.41–3.45 (dd, 1H, J = 2.3, 16.7 Hz, H-2b), 3.47–3.49
(m, 1H, H-40), 3.50 (s, 1H, H-20), 3.53–3.55 (dd, 1H, J = 3.3, 9.5 Hz,
H-30), 3.66–3.72 (m, 2H, H-50), 3.87 (s, 1H, H-10), 7.41–7.44 (t, 2H,
J = 7.8 Hz, Ph),7.55–7.58 (t, 1H, J = 7.4 Hz, Ph), 7.84–7.86 (d, 2H,
J = 7.7 Hz, Ph); 1H NMR (300 MHz, DMSO-d6): d 3.06–3.15 (dd,
1H, J = 9.0, 15.9 Hz, H-2a), 3.22–3.33 (m, 4H, H-2b, H-40, H-20, H-
30), 3.50–3.62 (m, 3H, H-50, H-10), 4.46–4.47 (d, 1H, J = 3.6 Hz,
OH), 4.67–4.69 (d, 1H, J = 5.4 Hz, OH), 4.94–4.96 (d, 1H, J = 5.1 Hz,
OH), 7.48–7.53 (t, 2H, J = 7.5 Hz, Ph), 7.59–7.64 (m, 1H, Ph), 7.91–
7.94 (dd, 2H, J = 1.5, 8.0 Hz, Ph); 13C NMR (75 MHz, DMSO-d6): d
41.1, 68.9, 69.9, 70.5, 73.9, 77.3, 128.0, 128.6, 133.0, 137.1, 198.7;
ESI-MS: m/z = 275.1 [M+Na]+; HRESIMS: m/z = 253.1059 [M+H]+
(calcd for C13H17O5 253.1071).
equipped with a reflux condenser. The reaction mixture was stirred
at the boiling point of the co-solvents for 15 h. After the reactions
were complete, the mixture was treated as described above.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.carres.2010.11.027.
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1.1.2. 1-Phenyl-2-C-(b-D-maltosyl) ethanone (6h)
Yield: 55% as a white solid; mp 230–232 °C (dec.); ½a D20
ꢂ
+74.9 (c
1.0, H2O); 1H NMR (400 MHz, D2O): d 3.10–3.16 (m, 1H), 3.21–3.28
(m, 2H), 3.30–3.72 (m, 11H), 3.75–3.81 (ddd, 1H, J = 3.2, 9.2 Hz, H-
10), 5.26–5.27 (d, 1H, J = 3.6 Hz, H-100), 7.40–7.44 (t, 2H, J = 8.0 Hz,
Ph), 7.54–7.58 (t, 1H, J = 7.6 Hz, Ph), 7.84–7.86 (d, 2H, J = 7.2 Hz,
Ph); 13C NMR (100 MHz, D2O): d 41.2, 60.5, 60.7, 69.4, 71.8, 72.7,
72.9, 73.2, 75.7, 77.1, 77.8, 78.1, 99.7, 128.4, 128.9, 134.2, 136.4,
202.6; ESI-MS: m/z = 467.1 [M+Na]+; HRESIMS: m/z = 467.1517
[M+Na]+ (calcd for C20H28O11Na 467.1524).
11. Rodrigues, F.; Canac, Y.; Lubineau, A. Chem. Commun. 2000, 2049–2050.
12. Riemann, I.; Papadopoulos, M. A.; Knorst, M.; Fessner, W.-D. Aust. J. Chem. 2002,
55, 147–154.
13. Hersant, Y.; Abou-Jneid, R.; Canac, Y.; Lubineau, A.; Philippe, M.; Semeria, D.;
Radisson, X.; Scherrmann, M.-C. Carbohydr. Res. 2004, 339, 741–745.
14. Bragnier, N.; Scherrmann, M.-C. Synthesis 2005, 814–818.
15. Cavezza, A.; Boulle, C.; Guéguiniat, A.; Pichaud, P.; Trouille, S.; Ricard, L.; Dalko-
Csiba, M. Bioorg. Med. Chem. Lett. 2009, 19, 845–849.
16. Caraballo, R.; Sakulsombat, M.; Ramström, O. ChemBioChem 2010, 11, 1600–
1606.
17. Richel, A.; Laurent, P.; Wathelet, B.; Wathelet, J.-P.; Paquot, M. C. R. Chimie,
2010, in press.
1.1.3. 1-Phenyl-2-C-(b-D-lactosyl) ethanone (6i)
Yield: 60% as a white solid; mp 170–172 °C; ½a D20
ꢂ
+26.9 (c 1.0,
H2O); 1H NMR (400 MHz, D2O): d 3.12–3.19 (m, 1H), 3.23–3.30
(m, 1H), 3.36–3.47 (m, 3H), 3.50–3.57 (m, 3H), 3.58–3.69 (m,
4H), 3.71–3.79 (m, 2H), 3.79–3.85 (ddd, 1H, J = 3.2, 9.2 Hz, H-10),
4.32–4.33 (d, 1H, J = 7.6 Hz, H-100), 7.42–7.46 (t, 2H, J = 8.0 Hz,
Ph), 7.56–7.60 (t, 1H, J = 7.6 Hz, Ph), 7.87–7.89 (d, 2H, J = 7.8 Hz,
Ph); 13C NMR (100 MHz, D2O): d 41.2, 60.1, 61.1, 68.6, 71.0, 72.6,
73.0, 75.4, 75.7, 75.9, 78.4, 78.5, 102.9, 128.4, 128.9, 134.2, 136.4,
202.7; ESI-MS: m/z = 466.8 [M+Na]+; HRESIMS: m/z = 467.1538
[M+Na]+ (calcd for C20H28O11Na 467.1524).
18. Corsaro, A.; Chiacchio, U.; Pistarà, V.; Romeo, G. Curr. Org. Chem. 2004, 8, 511–
538.
19. Das, S. K. Synlett 2004, 915–932.
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172.
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1.2. General procedure for condensation under oil bath heating
D
-Glucose (180 mg, 1 mmol), dibenzoylmethane, sodium bicar-
bonate (the amount given in Fig. 3), and 5 mL EtOH–H2O (4:1)
were introduced and mixed in 25 mL single-necked flask
a