Synthesis and evaluation of C-glycosides as hydrotropes and solubilizing agents

Article abstract of DOI:10.1007/s11426-010-4055-3

This work presents expeditious synthesis of C-glycoside amphiphiles in aqueous media from unprotected di- or mono-saccharides. A Horner-Wadsworth- Emmons/Michael addition/Barbier allylation sequence led to C-glycosides that exhibit hydrotropic properties. The hydrotropic and solubilizing properties of these homoallylic alcohols including a β-C-glycoside moiety as well as additional β-C-glycosidic ketones with a short (C₇) alkyl chain are also described and compared with those of commercial O-glucoside references.

Full text of DOI:10.1007/s11426-010-4055-3

SCIENCE CHINA
Chemistry
•
ARTICLES •
September 2010 Vol.53 No.9: 1957–1962
doi: 10.1007/s11426-010-4055-3
Synthesis and evaluation of C-glycosides as hydrotropes and
solubilizing agents
*
RANOUX Adeline, LEMIEGRE Loïc & BENVEGNU Thierry
Ecole Nationale Supérieure de Chimie de Rennes, CNRS UMR 6226, Université Européenne de Bretagne,
Avenue du Général Leclerc, CS 50837, 35708 Rennes Cedex 7, France
Received April 26, 2010; accepted June 15, 2010
This work presents expeditious synthesis of C-glycoside amphiphiles in aqueous media from unprotected di- or mono-saccharides.
A Horner-Wadsworth-Emmons/Michael addition/Barbier allylation sequence led to C-glycosides that exhibit hydrotropic
properties. The hydrotropic and solubilizing properties of these homoallylic alcohols including a -C-glycoside moiety as well
as additional -C-glycosidic ketones with a short (C
O-glucoside references.
7
) alkyl chain are also described and compared with those of commercial
C-glycoside amphiphiles, Horner-Wadsworth-Emmons reaction, Barbier allylation, green chemistry, hydrotropes
1
Introduction
The synthesis of C-glycoside derivatives has been investi-
gated for many years and it is well documented in the lit-
erature [1, 2]. However, only a few methodologies [3–6] are
applicable in aqueous media or from native sugars. Our re-
search group started a program concerning the synthesis of
C-glycoside amphiphiles to determine their potential appli-
cations as interfacial agents. Among the several strategies
that lead to C-glycoside from sugars, the Horner-Wadsworth-
Emmons (HWE) reaction is of significance. The olefination
from -EWG-phosphonates of the masked aldehyde leads to
an electrophilic double bond that may undergo a Michael
addition reaction to cyclic C-pyranosides or C-furanosides
(
Scheme 1) [7–9].
In our previous study we reinvestigated the HWE/Michael
Scheme 1 HWE/Michael addition sequence for the preparation of
C-pyranosides and/or C-furanosides.
addition combination by enlarging the scope of this power-
ful sequence to aqueous and solvent free conditions and
from native sugars [10]. We demonstrated that C-glycoside
amphiphiles are accessible from this methodology when
solvent free conditions are used. HWE reaction in aqueous
media represented an efficient strategy for the preparation of
C-glycosides from short chain length alkyl-oxo-phosphonates
(
i.e. methyl-oxo-phosphonate). Moreover, these aqueous
*
Corresponding author (email: Thierry.Benvegnu@ensc-rennes.fr)
conditions provided very good selectivity in favor of the
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1958
RANOUX Adeline, et al. Sci China Chem September (2010) Vol.53 No.9

-pyranoside forms. Solvent-free HWE reaction followed by
purification. Analytical TLC was performed on Merck 60
F254 silica gel non-activated plates. A solution of 5%
SO in EtOH was used to develop the plates. Merck 60 H
a simple aqueous basic treatment yielded pure -C-glycosidic
ketones with various alkyl chain lengths. In particular,
C-glycosides derived from lactose, D-glucose and D-galac-
H
2
4
(
5–40 mm) silica gel was used for column chromatography.
1
13
H and C NMR spectra were recorded at 400 and 100
7
tose possessing a short (C ) alkyl chain 4–6 (Figure 1) were
MHz, respectively, on a Bruker Avance III. MS spectra
were recorded on a Waters Micromass Q-TOF equipped
with a Z-spray ion source, IR spectra were recorded on a
Thermo Nicolet 320 FTIR and optical rotations were re-
corded on a Perkin–Elmer 341 polarimeter. -C-glycosidic
ketones 4–6 were prepared as previously described [10].
Simulsol® SL4 and SL8 were provided by Seppic®.
obtained in moderate to good yields and high  selectivity [10].
We describe herein a two-step process carried out in
aqueous media that provides an easy access to C-glycosides
1
–3 bearing a short hydrophobic chain from unprotected
sugars (Figure 1). These original compounds would there-
fore be considered as hydrotropes that are known to in-
crease the microemulsion domains and to increase the solu-
bility of surfactants and other substances in an aqueous so-
lution [11]. Hydrotropes have found a large number of ap-
plications in health care and household products. In particu-
lar, they inhibit the formation of surfactant liquid crystalline
phases by forming mixed micellar structures with surfac-
tants. This destruction or inhibition of the liquid crystalline
phase increases the solubility of the surfactant in the aque-
ous phase and the capacity of its micellar solution to solubi-
lize materials.
2
.2 Synthesis of the 5-(-C-Glycosyl)-4-methylpent-1-
en-4-ol
General procedure
(
1) Two-step process
Lactose, D-glucose or D-galactose (1 equiv) and K
9 equiv) were dissolved in water (2 mL for 0.277 mmol of
2
CO
3
(
lactose and 0.555 mmol of D-glucose and D-galactose)
heated at 60 °C. Dimethyl-2-oxoalkylphosphonate (3 equiv)
was added and the reaction mixture was stirred at 60 °C for
Additionally, we described the surface tension properties
of both these novel C-glycosides hydrotropes 1–3 and the
C
7
alkyl -C-glycosidic ketones 4–6 (Figure 1) [10]. The
2
4 h. The reaction medium was then neutralized with a few
solubilizing properties of these original derivatives were
studied spectrophotometrically from a hydrophobic dye, i.e.,
disperse red 13 (DR-13, (2-[4-(2-chloro-4-nitrophenylazo)-
N-ethylphenylamino]ethanol) [12], in water and were com-
pared with those of O-glucoside amphiphiles Simulsol®
SL4 (butylglucoside) and SL8 (octylglucoside) as commer-
cial references. Finally, the effect of these C-glycosides on
the cloud point of the nonionic surfactant C
E (diethylene-
6 2
glycolhexylether) was evaluated as additional evidence of
their hydrotropic behavior.
drops of aq. 5% hydrochloric acid solution and freeze-dried.
Flash column chromatography on silica gel (EtOAc/MeOH/
H
2
O = 15:4:1) afforded pure C3 -C-glycoside ketone (yield:
6
7% for Lac, 75% for Glc and 85% for Gal). The ketone
was then dissolved in water (5 mL for 0.2 mmol of ketone)
and allyl bromide (1.5 equiv) and powdered indium (1.2
equiv) were added. The resulting reaction mixture was
stirred at rt for 24 h. The solution was filtered and washed
with CH
rotavapor and freeze-dried. Flash column chromatography
on silica gel (EtOAc/MeOH/H O = 15:4:1) afforded pure
-(-C-glycosyl)-4-methylpent-1-en-4-ol (yield: 92% for
Lac, 90% for Glc and 97% for Gal).
2) One-pot process
Lactose (1 mmol) and K
2 2
Cl . The aqueous phase was concentrated using a
2
5
2
Experimental
(
2
.1 General experimental
2 3
CO (9 equiv) were dissolved in
Commercially available chemicals were used without further
water (2 mL) heated at 60 °C. Dimethyl-2-oxoalkylphos-
phonate (3 equiv) was added and the reaction mixture was
stirred at 60 °C for 24 h. The reaction medium was warmed
to rt and allyl bromide (1.2 equiv) and powdered indium
(
1.2 equiv) were added. The resulting reaction mixture was
stirred at rt for an additional 24 h. The solution was filtered
and washed with CH
Cl . The aqueous phase was concen-
trated using a rotavapor and freeze-dried. Flash column
chromatography on silica gel (EtOAc/MeOH/H O = 15:4:1)
afforded pure 5-(-C-lactosyl)-4-methylpent-1-en-4-ol 1 in
2
2
2
6
5% overall yield.
5
-(-C-Lactosyl)-4-methylpent-1-en-4-ol (1)
Figure 1 Structure of C-glycoside hydrotropes 1–3, C
ketones 4–6 and commercial Simulsol® SL4 (R=C and D.P.=1) and SL8
R=C and D.P.=1.9).
7
alkyl -C-glycosidic
White hydroscopic solid. [] =+2.2 (c 1, MeOH). IR (KBr)
 (cm ): 1093, 1658, 1935, 3045. H NMR (400 MHz,
D
4
1
1
8

RANOUX Adeline, et al. Sci China Chem September (2010) Vol.53 No.9
1959
CD
3
OD, ppm):  1.27 (s, 3H, CH
.3 Hz, CH ), 1.98 (dd, 1H, J = 13.5, 10.0 Hz, CH
H, J = 9.3 Hz, CH -O), 2.25 (m, 2H, CH
H, O-CH), 3.43–3.60 (m, 5H, O-CH), 3.66–3.88 (m, 5H,
3
), 1.59 (dd, 1H, J = 14.8,
), 3.08 (t,
), 3.26–3.38 (m,
2.4 Solubilization experiments
9
1
2
2
2
2
All solutions containing water and the studied compounds at
an appropriate concentration were saturated with a suffi-
cient amount of DR-13 and left under stirring for 24 h for
equilibration. The solutions were then filtered in order to
separate the nonsolubilized excess of the dye from the solu-
tions. The absorbance of the filtered solutions was measured
with a UV-visible spectrophotometer Varian Cary 50 Probe
at a wavelength of 525 nm corresponding to the wavelength
2
1
’
O-CH), 4.32 (d, 1H , J = 7.7 Hz, CH-O), 5.04 (d, 2H, J =
13
1
4.8 Hz, CH=CH
2 2
), 5.86 (m, 1H, J = 7.8 Hz, CH=CH ). C
NMR (100 MHz, CD OD, ppm):  26.3 (CH ), 42.6 (CH
3
3
2
dia 1), 43.1 (CH
9.3 (C4′), 70.2 (Cq), 71.5 (C2′), 73.7 (C4), 74.4 (C2), 76.9
C3′), 77.0 (C1), 79.0 (C3), 80.07 (C5′), 80.10 (C5), 104.1
2
dia 2), 47.4 (CH2), 61.0 (C6), 61.7 (C6′),
6
(
(
+
max of DR-13. Before each measure, zero absorbance was
2
C1′), 117.1 (CH =), 134.8 (CH=). HRMS (ESI ): calcd for
+
done with the corresponding solution without dyes. When
the measured absorbance was above a critical value, suit-
able dilutions were done by using the same solution but
without dyes. The resulting absorbance reflects, through the
Beer-Lambert law, the concentration of the hydrophobic
dye solubilized in the corresponding aqueous hydrotropic
solutions.
18 32
C H O11 [M+Na] : 447.1842; found : 447.1839.
5
-(-C-Glucosyl)-4-methylpent-1-en-4-ol (2)

1
Colorless oil. [] = +5.4 (c 1, MeOH). IR (film)  (cm ):
D
1
1160, 1655, 2940, 3430. H NMR (400 MHz, CD
 1.29 (3H, s, CH ), 1.69 (1H, m, CH ), 2.10 (1H, td, J=14.8,
2.4 Hz, CH ), 2.37 (2H, m, CH ), 3.12 (1H, t, J = 8.8 Hz,
3
OD, ppm):
3
2
2
2
2
1
O-CH ), 3.30–3.40 (3H, m, O-CH), 3.54 (1H , tt, J = 8.8,
6
2.5 Cloud point measurements
2
2
.4 Hz, O-CH), 3.64 (1H, m, O-CH ), 3.91 (1H, dt, J=12.0,
.4 Hz, O-CH ), 5.20 (2H, m, CH=CH ), 6.04 (1H, m,
2
6
2
2
The cloud points (CP) of aqueous solutions of nonionic
surfactant C E (Fluka, > 98%) (1% concentrated) with or
13
CH=CH2). C NMR (100 MHz, CD OD, ppm):  27.9
3
6
2
(
(
(
[
CH
3 2 2
), 44.3 (CH ), 48.4 (CH ), 63.5 (C6), 71.2 (Cq), 72.4
without the addition of 10% hydrotropes 1–3 (or SL4) or
% C C-glycosides 4–5 (or SL8) were measured in glass
C4), 76.1 (C2), 78.7 (C1), 80.1 (C3), 81.9 (C5), 118.6
CH
M+Na] : 285.1314; found 285.1313.
1
7
+
2 22 6
=), 136.2 (CH=). HRMS (ESI ): calcd for C12H O
tubes. The temperature was changed in steps of about 1–2 °C,
and the solutions were allowed to equilibrate for a few min-
utes before visually observing whether they had become
cloudy. When the temperature was 5 °C higher than the
temperature of cloud formation, the solution was left to
warm up. The temperature at which the cloud disappeared
corresponded to the cloud point.
+
5
-(-C-Galactosyl)-4-methylpent-1-en-4-ol (3)
White hydroscopic solid. [] =4.0 (c 1, MeOH). IR (KBr)
D
1
1
(cm ): 1063, 1134, 1654, 1936, 3395. H NMR (400 MHz,
CD OD, ppm):  1.35 (3H, s, CH ), 1.82 (1H, m, CH ), 2.16
3
3
2
(
1H, td, J = 15.6, 2.4 Hz, CH
2 2
), 2.42 (2H, m, CH ),
3
.50–3.66 (4H, m, O-CH), 3.77–3.80 (2H, m, O-CH
2
), 3.96
), 6.04 (1H, m,
CH=CH2). C NMR (100 MHz, CD OD, ppm):  27.8
4
3 Results and discussion
(
1H, m, O-CH ), 5.20 (2H, m, CH=CH
2
13
3
3.1 Synthesis of C-glycosidic hydrotropes 1–3
(
(
(
[
CH
3 2 2
), 44.2 (CH ), 49.9 (CH ), 63.3 (C6), 71.19 (C4), 71.22
The HWE reaction was carried out from methyl-oxo-phos-
phonate 7 (3 equiv) and lactose, D-glucose and D-galactose
Cq), 73.1 (C2), 76.6 (C3), 79.3 (C5), 80.5 (C1), 118.5
CH
M+Na] : 285.1314; found 285.1314.
+
2 22 6
=), 136.3 (CH=). HMRS (ESI ): calcd for C12H O
+
(
6
(
1 equiv) [10]. Potassium carbonate (9 equiv) in water at
0 °C was sufficient to provide the corresponding C-glycosides
8–10) in good yields and selectivity in favor of the -
2
.3 Surface tension measurements
pyranoside derivatives, which were isolated after flash
The surface tension of aqueous solutions of C-glycosides in
water was measured with a drop tensiometer. A syringe
with a U-shaped needle was lowered into the sample cell
containing the aqueous solution of C-glycoside amphiphiles
and an air bubble was produced from the syringe. The dy-
namic surface tension was measured by filming the rising
bubble and analyzing the contour of the bubble according to
axiasymmetric drop shape analysis, ADSA, with the Tracker
instrument, IT Concept. The surface tension was thus de-
termined at room temperature for several concentrations of
compounds after calibration and with time (around 3 h until
the equilibrium state).
chromatography (Scheme 2).
In order to elongate the alkyl chain and therefore increase
the hydrophobicity of the C-glycosides, we took advantage
of the ketone function to envisage a Barbier-type allylation
from allyl bromide and indium metal which provide smooth
reactions in aqueous media [13–15]. The oxo-C-glycosides
8
–10 were involved in this allylation step in the presence of
1
.2 equiv of both allyl bromide and indium in aqueous me-
dia at room temperature (Scheme 3). These reaction condi-
tions provided the expected homoallylic alcohols 1–3 in
excellent yields (87%–92%). It is noteworthy that careful
1
analysis of the H NMR spectra showed that the reaction

1960
RANOUX Adeline, et al. Sci China Chem September (2010) Vol.53 No.9
®
Figure 2 Surface tension curves for C-glycosides 1–3 and Simulsol SL4.
Scheme 2 Synthesis of C-glycosides by HWE reaction in aqueous media.
Scheme 3 Allylation of C-glycosides 8-10 in aqueous media.
®
Figure 3 Surface tension curves for C-glycosides 4–6 and Simulsol SL8.
proceeded without any stereocontrol leading to 1:1 mixtures
of the two epimers.
activity in water at high concentrations. The surface tension
Additionally, we demonstrated that the two-step se-
quence could be performed in a one-pot process. After the
completion of HWE reaction, the reaction medium was al-
lowed to cool down to room temperature and allylation re-
agents were added (allyl bromide, indium) to perform the
second step and led to the corresponding homoallylic alco-
hol. Applied to lactose, this simplified procedure provided
the expected -pyranoside product (1) in a good overall
yield (65%) (Scheme 4).
1
decreased from 72 mN m for water to values around
1
1
3
5–40 mN m (33 mN m forl SL4). The minimal concen-
tration required for hydrotrope aggregation termed Mini-
mum Aggregation Concentration (MAC) was measured for
1
hydrotrope 2 (350 mM; 0.092 g mL ) and SL4 (500 mM;
1
0
.118 g mL ) from the inflection point in the vs. logC
curve as for the determination of the critical micelle con-
centration (CMC). In the case of lactosyl and galactosyl
derivatives 1 and 3, MAC values were not determined be-
cause solutions were saturated before MAC was reached
3
.2 Surface tensiometry
(
around 200 mM for 1 and 350 mM for 3).
C-Glycoside ketones 4–6 reduced the surface tension to
the values (29–30 mN m ) favorably comparable with those
Figures 2 and 3 show the individual surface tension curves
for the three hydrotropes 1–3 and SL4 and for the three sur-
factants 4–6 and SL8. Despite their weak hydrophobic
characteristic, hydrotropes 1–3 exhibited significant surface
1
obtained with commercial nonionic (octyl-O-glucoside, OG;
–1
 = 30 mN m ) and anionic (Sodium dodecyl sulfate, SDS;
–1

= 34 mN m ) surfactants. Interestingly, even if the sugar
moieties have significant structural differences (Lac, Glc,
Gal), the surface tensions and the CMC values (17–18 mM)
were found to be independent of the sugar residue. SL8 ref-
erence exhibited better surface active properties (CMC=2.5
1
mM;  = 27 mN m ).
3
.3 Solubilization curves
The measured absorbance obtained for the DR-13 as a function
1
of concentration (g L ) of hydrotropes 2, 4, 5 and SL4, SL8
in water is plotted in Figure 4. The hydrotrope concentration
at which the increase in the hydrophobic compound solubil-
ity becomes significant, also called minimum hydro tropic
Scheme 4 One-pot synthesis of homoallylic alcohol 1 from lactose.

RANOUX Adeline, et al. Sci China Chem September (2010) Vol.53 No.9
1961
pounds 1–3 can be considered as hydrotropes which may
raise the cloud point of nonionic surfactants, thereby pre-
venting the surfactant phase separation in liquid formula-
tions at high temperatures. Cloud points were determined
6 2
from a 1% solution of C E (diethyleneglycol hexylether) in
the presence of 10% of hydrotropes 1–3 or of 1% of
C-glycosidic surfactants 4 and 5. For comparison we evaluated
the commercially available O-glucoside derivatives SL4 and
SL8 using the same methodology. The results, presented in
Table 2, showed that all compounds considered in this study
permitted a clear increase of the cloud point. Moreover, the
most hydrophilic C-glucoside 2 afforded the best increase
Figure 4 DR-13-solubilizing curves for C-glycosides 2, 4, 5 and Simul-
sol SL4, SL8.
®
(+10 °C) in comparison with lactosyl 1 or galactosyl 3 hy-
drotropes. Thus C-glycosides 1–3 may act as good hydro-
tropes that increase cloud points of nonionic surfactants.
C-glycosides are known to exhibit enhanced stabilities
against acidic conditions. Therefore, they would be useful
for applications that require low pH conditions. Indeed,
comparative chemical stability studies revealed that about
concentration (MHC), allowed us to characterize the hydro-
tropic and solubilizing efficiencies of the studied com-
pounds in comparison with the commercial references (Ta-
ble 1). The C-glucoside hydrotrope 2 appeared to be the
most efficient solubilizing agent even towards commercial
SL4 (MHC (2) ≈ 1.5 M against 2 M (SL4)). C-Glycoside
ketones 4–5 with a short alkyl chain revealed slightly lower
efficiencies than for SL8 but they exhibited higher solubi-
lizing activities than the corresponding homoallylic alcohols.
Consequently, the higher volume of the hydrophobic parts
of ketones 4–5 and SL8 significantly increases their abilities
to solubilize the hydrophobic compounds in water. In sum-
mary, the solubilizing properties of the compounds de-
scribed herein seem to be mainly related with their hydro-
phobic characteristic [12].
8
0% of the C-glycoside hydrotropes remained unchanged
after 70 days at pH 2.6 against 40% with O-butylglucoside
SL4.
C-glycosides 4 and 5 with a longer C
7
alkyl chain also
led to interesting results (+19 and +21 °C), but the values
obtained were slightly lower than those for SL8.
4
Conclusions
In summary, we have developed expeditious aqueous syn-
thesis of C-glycoside amphiphiles from unprotected di- or
mono-saccharides. The two steps (HWE and Barbier allyla-
tion) involved in this procedure were combined in one pot.
These original C-glycosides provided interesting physico-
chemical properties that are in total accordance with hydro-
tropic properties. Additionally, -C-glycosidic ketones with
3
.4 Effect of the cloud point of C
6 2
E surfactants
As mentioned in the introduction, the three original com-
®
Table 1 MHC values for C-glycosides 1, 2, 4, 5 and Simulsol SL4, SL8
determined by solubilizing experiments of DR-13
MHC
1.5 M
MHC
7
a short (C ) alkyl chain were found to exhibit attractive


1
1
2
SL4
4
0.39 g mL
solubilizing properties comparatively to O-glycoside refer-
ences. We are now evaluating the influence of these hydro-
tropes on the formation and properties of oil-in-water mi-
croemulsion systems. This new family of hydrotropes
would therefore be of interest for the preparation of applied
products requiring acidic conditions.
2.0 M
0.47 g mL



1
19 mM
10 mM
3.5 mM
8.3 g L
2.8 g L
1.5 g L
1
1
5
SL8
Table 2 Cloud points (CP) of C
E
6 2
(1% solution) without and with hydrotropes (10%) and surfactants (1%)
+ 1 + 2 + 3
+ SL4
39 44 41 43
a)
C
6
E
2
C
6
E
2
C
6
E
2
C
6
E
2
C
6
E
2
C
6
E
2
+ 4
C
6
E
2
+ 5
C
6
E
2
+ SL8
CP (°C)
34
53
55
68
a) Value measured in our laboratory

1962
RANOUX Adeline, et al. Sci China Chem September (2010) Vol.53 No.9
We thank the ANRT (Association Nationale de la Recherche et de la Tech-
nologie) and the Armor Protéines Company for a grant to AR and for
funding. SEPPIC is acknowledged for Simulsol samples.
8
9
Davidson AH, Hughes LR, Qureshi SS, Wright B. Witiig reactions
on unprotected aldohexoses: Formation of optically active tetrahy-
drofurans and tetrahydropyrans. Tetrahedron Lett, 1988, 29: 693–696
Nicotra F, Ronchetti F, Russo G, Toma L. C-Glycosides through the
Wittig-cyclization procedure: Observations on the influence of the
nature of the substrate. Tetrahedron Lett, 1984, 25: 5697–5700
®
®
1
2
Postema MHD. C-Glycoside Synthesis. Boca Raton: CRC Press Inc, 1995
Levy DE, Tang C. The Chemistry of C-Glycosides. Tarrytown, New
York: Pergamon Press, 1995
10 Ranoux A, Lemiègre L, Benoit M, Guégan JP, Benvegnu T.
Horner-Wadsworth-Emmons reaction of unprotected sugars in water
or in the absence of any solvent: One-step access to C-glycoside am-
phiphiles. Eur J Org Chem, 2010: 1314–1323
11 Hodgdon TK, Kaler EW. Hydrotropic solutions. Cur Opin Colloid
Interf Sci, 2007, 12: 121–128
12 Bauduin P, Renoncourt A, Kopf A, Touraud D, Kunz W. Unified
concept of solubilization in water by hydrotropes and cosolvents.
Langmuir, 2005, 21: 6769–6775
13 Li CJ, Chan TH. Organometallic reactions in aqueous media with in-
dium. Tetrahedron Lett, 1991, 32: 7017–7020
3
4
5
Riemann I, Papadopoulos MA, Knorst, M, Fessner WD. C-glycosides
by aqueous condensation of -dicarbonyl compounds with unpro-
tected sugars. Aust J Chem, 2002, 55: 147–154
Rodrigues F, Canac Y, Lubineau A. A convenient, one-pot, synthesis
of -C-glycosidic ketones in aqueous media. Chem Commun, 2000:
2
049–2050
Hersant Y, Abou-Jneid R, Canac Y, Lubineau A, Philippe M, Se-
meria D, Radisson X, Scherrmann MC. One-step synthesis of

-C-glycolipid derivatives from unprotected sugars. Carbohydr Res,
2
004, 339: 741–745
14 Wang JX, Jia X, Meng T, Xin L. Rapid and solvent-free synthesis of
homoallyl or homopropargyl alcohols mediated by zinc powder.
Synthesis 2005: 2838–2844
6
7
Jeanmart S, Taylor RJK. A protecting group-free approach to
C-glycosides using Ramberg-Bäcklund reaction. Tetrahedron Lett,
2
005, 46: 9043–9048
15 Tan KT, Chng, SS, Cheng HS, Loh TP. Development of a highly
-regioselective metal-mediated allylation reaction in aqueous media:
New mechanistic proposal for the origin of -homoallylic alcohols. J
Am Chem Soc, 2003, 125: 2958–2963
Allevi P, Ciuffreda P, Colombo D, Monti D, Speranza G, Manitto P.
Epimerization of - to -C-glucopyranosides under mild basic condi-
tions. J Chem Soc, Perkin trans 1, 1989:1281–1283