New insights into the conformational properties of α-C-glucosides

Article abstract of DOI:10.1016/j.tetasy.2007.11.002

A series of alkyl α-d-C-glucopyranosides were synthesized and their conformational properties analyzed by CD and NMR spectroscopy. The conformational analysis revealed that the hydroxymethyl group populations (torsion angle ω, O1-C1-C2-O2) and those aroun

Full text of DOI:10.1016/j.tetasy.2007.11.002

Available online at www.sciencedirect.com
Tetrahedron: Asymmetry 18 (2007) 2803–2811
New insights into the conformational properties of a-C-glucosides
*
´
Carlos Mayato, Rosa L. Dorta and Jesu´s T. Vazquez
Instituto Universitario de Bio-Orga´nica ‘Antonio Gonza´lez’, Departamento de Quı´mica Orga´nica, Universidad de La Laguna,
38206 La Laguna, Tenerife, Spain
Received 10 October 2007; accepted 5 November 2007
Abstract—A series of alkyl a-D-C-glucopyranosides were synthesized and their conformational properties analyzed by CD and NMR
spectroscopy. The conformational analysis revealed that the hydroxymethyl group populations (torsion angle x, O1–C1–C2–O2) and
those around the C-glucopyranosidic bond (torsion angle U; O2–C6–C7–C8) depend on the structural nature of the C-aglycon. The
gt and the exo–syn populations increased as the C-aglycon became more substituted. Linear correlations between these rotational pop-
ulations and proton chemical shifts versus the Taft’s steric parameters revealed the significant role of the C-aglycon in the overall con-
formation of C-glucosides. The stereoelectronic exo-deoxoanomeric effect, affecting the rotation of the hydroxymethyl group, becomes
more important as the steric hindrance of motion increases. A pseudo-anomer rotational comparison study was also performed.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
study. Correlations between rotational populations and
chemical shifts of prochiral protons H7 and H6 versus
Taft’s steric parameters support the important role of the
C-aglycon in the overall conformation of C-glucosides.
The high resistance of C-glycosides to degradation by gly-
cosidases combined with their newly identified biological
properties1 give these compounds considerable medical sig-
nificance, especially as cytotoxic compounds. A number of
contributions describe the conformational analysis of C-
2. Results and discussion
glycosides, especially those carried out by Kishi et al.2
3
´
and Jimenez-Barbero et al.
2.1. Synthesis and characterization
In a previous study, we reported the conformational prop-
erties of a series of alkyl b-C-glycosides4 and showed that
the populations around the C-glycosidic bond and also
the hydroxymethyl group are dependent on the structure
of the C-aglycon, while the exo–syn and gt rotamer popu-
lations increase with the degree of substitution on the
C-aglycon. These rotational preferences pointed to a
The addition of carbon nucleophiles to activated glycal
epoxides has been widely used6 for the preparation of C-
glycosides.7 The addition of Grignard reagents to the 1,2-
anhydrosugar,8 obtained from the addition of dimethyldi-
oxirane (DMDO)9 to the tri-O-benzyl-D-glucal, according
to Danishefsky’s protocol,10 led to a mixture of a-and b-
D-C-glucosides 1a–1f (Scheme 1).
r
CH–rÃCO stereoelectronic effect (the exo-deoxoanomeric
effect),4,5 directly involved in the rotation around the pseu-
do-glycosidic bond and indirectly around the C1–C2 bond
(hydroxymethyl group), in addition to non-bonded
interactions.
The reaction conditions of Grignard addition are critical
for the pseudo-anomeric configuration. Thus, we found
that a temperature of À40 °C and Et2O as solvent favored
a b-C-glucosidation; while a higher temperature (0 °C) and
THF as solvent favored an a-C-glucosidation. Deprotec-
tion of the benzyl groups with hydrogen and subsequent
4-bromobenzoylation led to the tetra-O-(4-bromobenzo
yl)-C-glucosides 2a–2f.
Herein, we report the rotational properties of the C-gluco-
sidic bond and the hydroxymethyl group of a series of alkyl
a-C-glucosides, as well as a pseudo-anomer comparison
*
All these compounds were characterized on the basis of
their one- (1H and 13C) and two-dimensional (COSY-G,
Corresponding author. Tel.: +34 922318581; fax: +34 922318571;
e-mail: jtruvaz@ull.es
0957-4166/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2007.11.002

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C. Mayato et al. / Tetrahedron: Asymmetry 18 (2007) 2803–2811
gg
gt
tg
O
O
HR
O
OR'
HS
HR
R'O
R
BnO
BnO
BnO
BnO
1
b
a
i
HS
OR'
O
O
HR
HS
ω
O
O
ii
BnO
BnO
OH
2
H
R
H
H
6
OBn
OBn
OBn
R
HR
R
HR
7
HS
HS
HS
1a−1f
HR
exo
−
syn
1
7
2
O
R
CH3
gg
R'O
gt
tg
HR
H
CH3
HR
H
HS
HS
6
OR'
HS
HR
HS
H
HR
OR'
O
HR
HS
R'O
R'O
OR'
4
a
b
c
O
O
H
H
H
OR'
2a−2f
R' = 4−BrBz
R =
6
CH3
CH3
CH3
CH3
CH3
HS
R
HS
R
HS
R
HR
exo
HR
HR
HS
HS
HS
HR
HR
HR
non
−
d
e
f
Figure 2. Plausible orientations of a-C-glucosyl compounds.
Scheme 1. Synthesis of model a-C-glucosides. Reagents and conditions:
(a) (i) DMDO, (CH3)2CO/CH2Cl2, 0 °C; (ii) RMgX, THF, 0 °C; (b) (i) H2,
5% Pd–C, EtOH; (ii) p-BrBzCl, DMAP, Py, 60 °C.
exo–syn rotamers were found to be the most stable, while
the exo–anti rotamer is not significant due to severe steric
interactions. Therefore, rotation around these two torsion
angles can be simplified to the six ideal staggered conform-
ers shown in Figure 2.
HMQC, and T-ROESY) NMR spectra. The stereochemis-
try at C6 (a axial) of the C-glucosides 2a–2f synthesized
was established by analyzing the 1H NMR J5,6 value
(5.8–5.9 Hz). The 1H NMR signals of the prochiral protons
of the hydroxymethyl group at C1, H1R, and H1S were
differentiated on the basis of their chemical shifts and cou-
pling constants.11,12 The assignment of H7R and H7S was
in agreement with the values of the coupling constants
JH6,H7R and JH6,H7S, as determined by Kishi et al. using
specifically deuterated C-glycosides,13 and by means of
T-ROESY experiments.14 For all these compounds, the
coupling constants JH6,H7R and JH6,H7S were obtained by
analyzing the H6 signals.
2.2.1. Conformational analysis of the C-glucosidic bond. High
values of JH6,H7S (8.9–10.1 Hz) and moderate values of
JH6,H7R (3.1–4.0 Hz) were observed in our model com-
pounds 2b–2f. These data confirm the exo–syn rotamer as
the most populated in all cases (Table 1). The rotamer pop-
ulations were calculated using the Serianni-equations,15,16
and fixing a nil exo–anti population. In addition, for com-
pounds 2b–2e, Table 1 shows a decreases in JH6,H7R values
from 4.0 to 3.1 Hz, and of JH6,H7S from 9.6 to 8.9 Hz, as
the size of the aglycon increases. This behavior involves a
decrease in the population of the non-exo rotamer and an
increase in the exo–syn. As for compound 2f, since JH6,H7R
was undetectable and JH6,H7S had the biggest value of the
series (10.1 Hz), a single glycosidic conformation can be as-
sumed, slightly distorted from the ideal exo–syn staggered
conformer (H6–C6–C7–H7R ꢀ 90°).
2.2. Conformational analysis
Rotation around the x (O1–C1–C2–O2) and U (O2–C6–
C7–C8) torsion angles in a-C-glucosides led to ideal stag-
gered conformers gg, gt, tg, and exo–syn, exo–anti, and
non-exo rotamers, respectively (Fig. 1). The gg and the
2.2.2. pseudo-Anomer C-glucosidic bond comparison.
Although both epimer series have the exo–syn rotamer
as the most stable, a straight dependence of the populations
around the C-glucosidic bond on the pseudo-anomeric con-
figuration was observed (Table 1). The rotational popu-
lations around the C6–C7 bond were more dependent on
the C-aglycon in the b-series than in the a-series. Thus,
for compounds with a linear aglycon, 2b or 2c, greater
flexibility was observed for the b-epimers (only 60–70% of
exo–syn) than for the a-epimers (80% of exo–syn). How-
ever, this behavior drastically changed with compounds
having branched aglycons (2d and 2e), where the b-epimers
exhibited high rigidity.
OR'
1
HS
O
HR
ω
2
6
Φ
R
7
HS
HR
HR
OR'
HS
C3
HR
O2
HS
C3
HS
O2
C3
O2
HR
OR'
R'O
H2
H2
H2
gg
gt
tg
HS
H
HR
H
R
H
O
O
O
2.2.3. Conformational analysis of the C-aglycosidic
bond. T-ROESY experiments were also performed with
compounds 2b–2f. The main cross-peaks observed for the
model a-C-glucosides are shown on the three most stable
rotamers around the W dihedral bond (C6–C7–C8–C9) in
Figure 3. These cross-peaks are in complete agreement with
conformer A, the most stable rotamer obtained from
R
R
HS
HR
HR
HS
exo
−syn
non−
exo
exo−anti
Figure 1. Torsion angle x around the C1–C2 bond and U around the C-
glucosidic C6–C7 bond (top). Newman projections of the idealized
staggered rotamers around the C1–C2 and C6–C7 bonds (central and
bottom).

C. Mayato et al. / Tetrahedron: Asymmetry 18 (2007) 2803–2811
2805
Table 1. JH6,H7 coupling constants (CDCl3) and calculated rotamer populations (%) around the C6–C7 bond for the model a-D-C-glucopyranosides 2b–2f
and b-2b–2f
Compd.
JH6,H7S
JH6,H7R
exo–syn
non-exo
Compd.
JH6,H7S
JH6,H7R
exo–syn
exo–anti
non-exo
2b
2c
2d
2e
2f
9.6
9.2
9.2
8.9
10.1
4.0
3.5
3.4
3.1
N.D.a
80
83
84
86
100
20
17
16
14
0
b-2b
b-2c
b-2d
b-2e
b-2f
3.0
3.8
2.2
2.3
N.D.a
8.0
7.1
9.9
9.7
8.8
69
57
91
89
100
24
27
9
11
0
7
16
0
0
0
a N.D.: Not detected.
On the other hand, the coupling constant JH1S,H2 displayed
the opposite behavior, from 2b (3.8 Hz) to 2f (3.1 Hz).
These experimental NMR data correlate with an increased
gt population and with decreased gg and tg populations, as
shown in Figure 4. Compound 2f deserves particular con-
sideration; its bulky neo-pentyl group coming near to the
hydroxymethyl group could generate non-bonded interac-
tions between these two groups, therefore decreasing the
gt population in favor of the gg. This exception also sug-
gests that there are no non-bonded interactions between
the aglycon and the hydroxymethyl groups in the rest of
the compounds (see below).
The conformation of the hydroxymethyl group was also
investigated by means of T-ROESY experiments. However,
only compound 2f showed clear cross-peaks between H1R
and H2, and between H1S and H2. The double intensity
observed for H1S and H2 compared to H1R and H2 means
much higher gt than tg populations for this compound.
2.2.5. Circular dichroism analysis. The high sensitivity
and simple spectral interpretation of the circular dichroic
exciton chirality method18 provides further conformational
data. The CD spectra (Fig. 5) were analyzed taking into
account the additivity principle,19 the interchromophoric
distances and the dihedral angles of the electric transi-
tion moments of the chromophores, namely, the p-bro-
mobenzoates. The tetra-chromophoric compounds 2a–2f
exhibited exciton Cotton effects around 251 and 234 nm
in the CD spectra in CH3CN. The intensity of the first Cot-
ton effect gradually decreased from compound 2a (17.9), 2b
(11.7), 2c (10.9), 2d (8.5), to 2e (4.8), and then increased
with compound 2f (9.2). These intensities are consistent
with decreased positive contributions from the pairwise
interactions between the chromophore at the 1-position
(gg rotamer) and those at the 3- and 4-positions, and
increased negative contributions from the interactions
between the chromophore at the 1-position (gt rotamer)
and those at the 3 and 5-positions, for compounds 2a–2e
(Fig. 6). The intensity of the first Cotton effect of com-
Figure 3. Main cross-peaks observed for the model a-C-glucosides 2b–2f
in the T-ROESY experiments (CDCl3) shown on the three most stable
rotamers A–C. Solid line: strong cross-peak; dash line: weak cross-peak.
molecular mechanics,17 and with Kishi’s extended zig-zag
conformation.2
2.2.4. Conformational analysis of the hydroxymethyl
group. The rotamer populations of the hydroxymethyl
group were calculated using the Serianni-equations.15
Analysis of the coupling constants of the prochiral protons
at C1, or their calculated rotamer populations, revealed a
relationship with the structure of the C-aglycon. On the
one hand, the JH1R,H2 coupling constants increased as the
substitution in the aglycon increased, from 2a (4.9 Hz) to
2e (6.1 Hz), except for compound 2f (5.5 Hz) (Table 2).
Table 2. JH1,H2 coupling constants (CDCl3) and calculated rotamer populations (%) around the C1–C2 bond for the model a-D-C-glucopyranosides 2a–2f
as well as the corresponding rotational populations for the already reported b-D-C-glucopyranosides 2a–2f4
Compd.
JH1S,H2
JH1R,H2
gg
gt
tg
Compd.
gg
gt
tg
2a
2b
2c
2d
2e
2f
3.3
3.8
3.8
3.5
3.1
3.1
4.9
5.3
5.4
5.5
6.1
5.5
54
46
45
46
43
49
37
39
40
42
50
44
9
b-2a
b-2b
b-2c
b-2d
b-2e
b-2f
57
54
51
47
44
39
37
40
41
46
50
56
6
6
8
7
6
5
15
15
12
7
7

2806
C. Mayato et al. / Tetrahedron: Asymmetry 18 (2007) 2803–2811
60
40
20
0
mers and both the gg and tg for the a-anomers. Moreover,
the rotational populations of compounds with an un-
branched aglycon 2a–c show a clear dependence on the
pseudo-anomeric configuration. That is, compounds with
an a-configuration showed lesser/higher gg/tg populations
than their corresponding b-anomers, as can be observed in
Table 2. In addition, a comparative analysis between the
neo-pentyl epimers 2f and b-2f revealed higher gg and smal-
ler gt populations for the a-anomer than for the b. In fact,
gg is the most populated rotamer in the a-epimer, as is the
gt rotamer in the b. As already explained, these results are
made clear by the existence of non-bonded interactions
between aglycon and the hydroxymethyl group in its gt
rotamer in the a-anomer, missing in the b.
2a
2b
2c
2d
2e
2f
Figure 4. Rotational populations (%) around the C1–C2 bond, calculated
from the JH1,H2 coupling constants of compounds 2a–2f (CDCl3); gg/gt/tg
rotamers (red/blue/green).
O
O
gt
gt
19
RO
RO
2a
2f
β−2f
Δε
2b
2f
2c
2d
2.2.7. Origin of the conformational preferences. The de-
creases in the non-exo rotamer populations as the C-agly-
con became more substituted can be explained by an
increase in the steric interactions between the C-aglycon
and the substituent at the 2-position (see Fig. 1 or 2). How-
ever, this conformational behavior can also be explained by
steric hindrances to motion. As seen from Figure 7, there is
an excellent linear correlation between the exo–syn and
non-exo rotational populations of compounds 2a–2f with
the corresponding Taft’s steric parameters.20 The ES values
are composite terms, derived from both potential energy
steric effects (steric strains) and kinetic energy steric effects
(steric hindrances to motions). According to Taft,20 the
introduction of a straight-chain alkyl group in place of
the standard hydrogen substituent raises the activation en-
ergy due to steric hindrance. Therefore, the bulkier alkyl
groups freeze out the rotation of the more stable exo–syn
rotamer, increasing its population. These two steric factors,
that between the C-aglycon and the substituent at the 2-
position, and due to steric hindrances to motions, are prob-
ably both simultaneously involved in the conformational
behavior around the C-glucosidic bond.
2e
0
−−7
250
350 nm
300
200
Figure 5. CD spectra comparison of compounds 2a–2f (CH3CN).
nil
nil
1
1
1
3
O
O
O
3
5
nil
5
5
4
4
gg
gt
tg
Figure 6. 1/3, 1/4, and 1/5 pairwise interactions involving the chromo-
phore at the 1-position in each of the three stable rotamers (gg, gt, and tg)
for the glucopyranosyl system.
100
75
50
25
0
pound 2f, in between 2c and 2d, is in excellent agreement
with the JH1,H2 coupling constants obtained from NMR
for these compounds and already explained on the basis
of steric interactions. Therefore, NMR and CD data of
compounds 2a–2f are in total agreement.
2.2.6. pseudo-Anomers hydroxymethyl comparison. Apply-
ing the same set of equations for comparative analysis of
the rotational populations of the hydroxymethyl group
between these compounds and their epimers at C-6 (b-pseu-
do-anomers)4,15 revealed that independent of the pseudo-
anomeric configuration, the population of the gt rotamer
increases as the substitution in the C-aglycon increases.
However, depending on that configuration, the rotamer
that decreases changed only the gg rotamer for the b-ano-
0.2
−0.3
−0.8
−1.3
−1.8
Taft’s steric parameters, ES
Figure 7. Rotational populations of exo–syn and non-exo rotamers (blue/
red) versus corresponding ES values for aliphatic substituents.
Conversely, the conformational behavior of the hydroxy-
methyl group cannot be explained in general by means of

C. Mayato et al. / Tetrahedron: Asymmetry 18 (2007) 2803–2811
2807
Table 3. Some 1H and 13C NMR chemical shifts (CDCl3) for the alkyl
a-C-glucosides 2b–2f
non-bonded interactions, since as the C-aglycon became
more substituted or branched the population of the gt rot-
amer, nearest to the exo–syn, increases. However, the plot
of the rotational populations of the hydroxymethyl group
of compounds 2a–2f versus the corresponding Taft’s steric
parameters20 reveals some relationship between them, ex-
cept for compound 2f (Fig. 8). In fact, this exception indi-
cates that for this compound at least two different effects
are acting simultaneously, one of them due to direct non-
bonded interactions between the neo-pentyl and the
hydroxymethyl group.
Compd.
H6
C6
C7
H7S
H7R
2b
2c
2d
2e
2f
4.35
4.45
4.55
4.58
4.65
74.1
72.6
71.2
70.6
71.2
18.8
27.5
33.9
34.1
36.9
2.03
2.02
2.03
1.98
1.96
1.71
1.55
1.35
1.37
1.48
1
deshielded
shielded
O
R'O
6
H
75
50
25
0
C
7
R
shielded
C
HS
HR
slightly
shielded
deshielded
Figure 10. 1H and 13C NMR chemical shift characteristics of a-C-
glucosides as the substituent R increases in size.
0.2
−0.3
−0.8
−1.3
−1.8
Taft's steric parameters, ES
5.00
4.75
4.50
4.25
4.00
Figure 8. Rotational populations of gg/gt/tg rotamers (red/blue/green)
versus corresponding ES values for aliphatic substituents.
Recently, we have proposed that a stereoelectronic
r
CH–rÃCO interaction (exo-deoxoanomeric effect) is in-
volved in the rotational preferences of the hydroxymethyl
group of b-C-glycosides.4 This effect could also apply to
the a-series, by a favorable stereoelectronic rCH–rÃCO inter-
action between the C7–H7R bonding orbital in the exo–syn
conformation and the C6–O2 antibonding orbital, since
rCH is a moderate donor and rÃCO a good acceptor
(Fig. 9).21 The rCC–rCÃ O interaction (non-exo conformer)
0.2
−0.3
−0.8
−1.3
−1.8
Taft’s steric parameters, ES
Figure 11. Chemical shifts of the pseudo-anomeric proton H6 versus
corresponding ES values for aliphatic substituents.
is not considered, since the rCC orbital is a much worse
22
donor than rCH
.
Plots of the chemical shifts of the pseudo-anomeric proton
H6 and of prochiral protons H7, for compounds 2b–2f,
versus the corresponding Taft’s steric parameters20 are
shown in Figures 11 and 12, respectively. The correlations
between these parameters and the chemical shifts are good
in all cases but H7R of compound 2f, due to direct non-
ω
1
ω
O
O
2
6
H
R
σCH
H
HS
HS
HR
7
σ*CO
HR
R
exo-syn
non-exo
Figure 9. Molecular orbitals involved in the exo-deoxoanomeric effect.
2.50
2.00
1.50
1.00
The rCH–rÃCO interaction increases as the exo–syn popula-
tion increases, due to the above steric factors. Analysis of
the 1H and 13C NMR chemical shifts of the pseudo-
anomeric and prostereogenic protons, H6, H7R and H7S,
and carbons C6 and C7 (Table 3) revealed some notewor-
thy behavior as the C-aglycon became branched. The pro-
chiral hydrogens H7R and H6 showed a displacement
toward higher and lower fields, respectively. As for the car-
bons, the chemical shifts of C6 and C7 were, respectively,
shielded and deshielded. The observed shielding for H7R
and C6 can be attributed to greater electron densities
around such nuclei. These behavior patterns are summa-
rized in Figure 10.
0.2
−0.3
−0.8
−1.3
−1.8
Taft’s steric parameters, ES
Figure 12. Chemical shifts of prochiral protons H7S (dashed line) and
H7R (solid line) versus corresponding ES values for aliphatic substituents.

2808
C. Mayato et al. / Tetrahedron: Asymmetry 18 (2007) 2803–2811
bonded interactions between the neo-pentyl and hydroxy-
methyl groups. This exception correlates with the irregu-
lar intensity of the first CD cotton effect and the
rotational populations derived from NMR for this com-
pound. It thus supports a relationship between the
hydroxymethyl group and the electron densities around
the pseudo-anomeric carbon and therefore with the exo-
deoxoanomeric effect.
4.2. General procedure for the preparation of a-C-glucosides
A solution of dimethyldioxirane in acetone (2 equiv, ca
0.075 M) was added to a stirred solution of the corre-
sponding tri-O-benzyl-D-glucal in dry CH2Cl2 (5 mL/
mmol) at 0 °C under a nitrogen atmosphere, and the reac-
tion stirred at 0 °C for 30 min. The 1,2-anhydrosugar thus
obtained was concentrated under reduced pressure and
left under vacuum for 2 h. It was then dissolved in dry
THF (10 mL/mmol) under dry nitrogen, cooled at 0 °C
and the corresponding Grignard reagent added. When
the reaction was completed, it was diluted with Et2O,
quenched with NH4Cl saturated solution and extracted
three times with Et2O. The combined organic layers were
washed with a saturated NaHCO3 solution and brine,
dried over anhydrous MgSO4, filtered, and evaporated in
vacuum. The product was purified by silica gel column
chromatography.
3. Conclusions
On the basis of the 1H NMR coupling constant values and
CD spectral data, we conclude that the conformational
preferences of the hydroxymethyl group and of the C-glu-
cosidic bond in a-C-glucosides depend on the structure of
the C-aglycon. The population of the exo–syn rotamer in-
creased and that of the non-exo decreased as the substitu-
tion of the C-aglycon increased, due to interactions
between the C-aglycon and the substituent at the 2-position
and/or to steric hindrances to motions. The correlation
between these rotational populations and Taft’s steric
parameters is highly satisfactory.
4.3. General procedure for the debenzylation and
p-bromobenzoylation
To a solution of the substrate in dry ethanol (10 mL/
mmol) were added 100 mg/mmol of palladium at 5% on
activated carbon with sufficient hydrogen. After the reac-
tion was complete, the mixture was diluted in ethanol,
filtered through a bed of Celite and evaporated under
reduced pressure. The crude reaction mixture was then
dissolved in dry pyridine (10 mL/mmol), and treated with
6 equiv of p-bromobenzoyl chloride and DMAP as cata-
lyst. The solution was heated at 60 °C and stirred
overnight. The solvent was removed under reduced pres-
sure in the presence of toluene and the residue
chromatographed.
The hydroxymethyl group populations of the gt rotamer
increased and those of the tg and gg decreased, as the de-
gree of substitution of the C-aglycon increased. The corre-
lation between the hydroxymethyl group populations
(Table 2), the CD data (Fig. 5), and the chemical shifts
(Table 3) of compounds 2b–2f, supports the proposal of
the influence of the C-aglycon on the rotational behavior
of the hydroxymethyl group through the stereoelectronic
exo-deoxoanomeric effect.
4. Experimental
4.1. General
4.4. 2,6-Anhydro-1,3,4-tri-O-benzyl-7-deoxy-D-glycero-
L-gulo-heptitol 1a
1H NMR spectra were recorded at 400 or 500 MHz, and
13C NMR at 100 MHz, VTU 300.0 K. Chemical shifts
are reported in parts per million. The residual solvent peak
(CDCl3) was used as an internal reference, 7.26 for proton
and 77.0 ppm for the central peak of carbon NMR. Optical
rotations were measured on a digital polarimeter in a 1 dm
cell. UV and CD spectra were recorded in the range 350–
200 nm using 10 mm cells. The concentrations of the CD
samples were ascertained from the UV spectra, using the
experimentally determined e values at 245 nm: tetrakis-(4-
bromobenzoate) = 76,400. For analytical thin-layer chro-
matography, silica gel ready-foils were used, developed
with 254 nm UV light and/or spraying with AcOH/H2O/
H2SO4 (80:16:4) and heating at 150 °C. Flash column chro-
Following the general procedure for the preparation of
a-C-glucosides, 351 mg of tri-O-benzyl-D-glucal yielded
281 mg of 1a (0.63 mmol, 74%) as an epimer mixture
a/b = 1, after flash column chromatography (n-hexane/
EtOAc, 7:3). Spectroscopy data were in agreement with
previously reported information.6c
4.5. 2,6-Anhydro-1,3,4-tri-O-benzyl-7,8-dideoxy-D-
glycero-L-gulo-octitol 1b
Following the general procedure for the preparation of a-
C-glucosides, 238 mg of tri-O-benzyl-D-glucal yielded
177 mg of 1b (0.38 mmol, 67%) as an epimer mixture a/
b = 2, after flash column chromatography (n-hexane/
EtOAc, 8.5:1.5). Spectroscopy data were in agreement with
those previously reported.23
˚
matography was performed using silica gel (60 A). All re-
agents were obtained from commercial sources and used
without further purification. Solvents were dried and dis-
tilled before use. All reactions were performed under a
dry nitrogen atmosphere. The compounds prepared were
characterized on the basis of their one- (1H and 13C) and
two-dimensional (COSY-G, HMQC, and T-ROESY)
NMR spectra, as well as by elemental analysis, HRMS,
UV, and CD spectroscopy.
4.6. 2,6-Anhydro-1,3,4-tri-O-benzyl-7,8,9-trideoxy-D-
glycero-L-gulo-nonitol 1c
Following the general procedure for the preparation of a-
C-glucosides, 700 mg of tri-O-benzyl-D-glucal yielded
603 mg of 1c (1.27 mmol, 75%) as an epimer mixture a/

C. Mayato et al. / Tetrahedron: Asymmetry 18 (2007) 2803–2811
2809
b = 4, after flash column chromatography (n-hexane/
4.9. 2,6-Anhydro-1,3,4-tri-O-benzyl-7,8,9-trideoxy-8,8-
dimethyl-D-glycero-L-gulo-nonitol 1f
EtOAc, 8.5:1.5): TLC Rf = 0.3 (n-hexane/EtOAc, 8:2);
[a]D = +29.5 (c 1.0, CHCl3); HRMS (EI): (MÀC7H7)+
1
calcd for C23H29O5, 385.2015; found, 385.2017; H NMR
Following the general procedure for the preparation of a-
C-glucosides, 500 mg of tri-O-benzyl-D-glucal yielded
361 mg of compound a-1f (0.72 mmol, 60%), after flash
column chromatography (n-hexane/EtOAc, 9:1): TLC
Rf = 0.3 (n-hexane/EtOAc, 8:2); [a]D = +24.2 (c 2.2,
CHCl3); HRMS (EI): (MÀC7H7)+ calcd for C25H33O5,
(CDCl3) d 7.41–7.30 (m, 15H), 4.78 (d, J = 11.7 Hz, 1H),
4.74 (d, J = 10.7 Hz, 1H), 4.71 (d, J = 11.7 Hz, 1H),
4.68–4.62 (m, 2H), 4.60 (d, J = 12.1 Hz, 1H), 4.05 (m, H-
2), 3.99 (m, H-6), 3.90 (dd, J = 5.5 and 10.2 Hz, H-1),
3.85–3.78 (m, 3H), 3.73 (t, J = 5.5 Hz, H-3), 3.07 (br s,
OH), 1.78 (m, 1H), 1.68–1.57 (m, 2H), 1.46 (m, 1H), 1.04
(t, J = 7.2 Hz, 3H); 13C NMR (CDCl3) d 138.0 (s), 138.0
(s), 137.4 (s), 128.3–127.4, 78.5 (d, C-4), 75.4 (d, C-3),
73.4 (t), 73.1 (t), 72.9 (t), 72.8 (d, C-2), 71.7 (d, C-6), 69.9
(d, C-5), 68.2 (t, C-1), 29.6 (t, C-7), 18.5 (t, C-8), 13.9 (q,
C-9); Anal. Calcd for C30H36O5: C, 75.60; H, 7.61. Found:
C, 75.59; H, 7.86.
1
413.2328; found, 413.2311; H NMR (CDCl3) d 7.37–7.24
(m, 15H), 4.75 (d, J = 11.7 Hz, 1H), 4.68 (d, J = 11.4 Hz,
1H), 4.64 (d, J = 11.4 Hz, 1H), 4.61 (d, J = 12.0 Hz, 1H),
4.58 (d, J = 11.7 Hz, 1H), 4.53 (d, J = 12.0 Hz, 1H), 4.14
(m, H-6), 4.03 (m, H-2), 3.83 (dd, J = 5.1 and 10.0 Hz,
H-1), 3.75–3.72 (m, 2H), 3.69–3.63 (m, 2H), 2.86 (d,
J = 7.0 Hz, OH), 1.68 (dd, J = 9.6 and 14.9 Hz, H-7),
1.46 (d, J = 14.9 Hz, H-7), 1.00 (s, 9H); 13C NMR (CDCl3)
d 138.1 (s), 138.0 (s), 137.6 (s), 128.5–127.6, 78.2 (d, C-4),
75.4 (d, C-3), 73.6 (t), 73.3 (t), 73.1 (d, C-2), 72.8 (t), 70.9
(d, C-5), 69.8 (d, C-6), 68.3 (t, C-1), 40.2 (t, C-7), 30.1 (s,
C-8), 29.9 (q), 29.9 (q), 29.9 (q); Anal. Calcd for
C32H40O5: C, 76.16; H, 7.99. Found: C, 76.16; H, 8.11.
4.7. 2,6-Anhydro-1,3,4-tri-O-benzyl-7,8,9-trideoxy-8-
methyl-D-glycero-L-gulo-nonitol 1d
Following the general procedure for the preparation of a-
C-glucosides, 500 mg of tri-O-benzyl-D-glucal yielded
413 mg of 1d (0.84 mmol, 70%) as an epimer mixture a/
b = 5, after flash column chromatography (n-hexane/
EtOAc, 8.5:1.5): TLC Rf = 0.3 (n-hexane/EtOAc, 8:2);
[a]D = +22.2 (c 1.4, CHCl3); HRMS (EI): (MÀC7H7)+
4.10. 2,6-Anhydro-1,3,4,5-tetra-O-(p-bromobenzoyl)-7-
deoxy-D-glycero-L-gulo-heptitol 2a
Debenzylation of compound 1a (101 mg, 0.23 mmol) and
then p-bromobenzoylation was performed as in the general
procedure, giving compound 2a (192 mg, 0.21 mmol, 94%)
after column chromatography (n-hexane/EtOAc, 8:2):
TLC Rf = 0.6 (n-hexane/EtOAc, 7.5:2.5); [a]D = +49.6 (c
1.0, CHCl3); 1H NMR (CDCl3) d 7.87 (d, J = 8.5 Hz,
2H), 7.80 (d, J = 8.5 Hz, 2H), 7.74 (d, J = 8.5 Hz, 2H),
7.72 (d, J = 8.5 Hz, 2H), 7.56 (d, J = 8.5 Hz, 2H), 7.54
(d, J = 8.6 Hz, 2H), 7.48 (d, J = 8.6 Hz, 2H), 7.47 (d,
J = 8.6 Hz, 2H), 5.93 (t, J = 9.3 Hz, H-4), 5.53 (t,
J = 9.2 Hz, H-3), 5.45 (dd, J = 5.8 and 9.5 Hz, H-5), 4.66
(dddd, J = 5.8, 6.9, 6.9, and 6.9 Hz, H-6), 4.55 (dd,
J = 3.3 and 12.0 Hz, H-1proS), 4.51 (dd, J = 4.9 and
12.0 Hz, H-1proR), 4.31 (ddd, J = 3.3, 4.9, and 9.2 Hz, H-
2), 1.47 (d, J = 6.9 Hz, 3H); 13C NMR (CDCl3)d 165.4
(s), 165.1 (s), 164.6 (s), 164.5 (s), 131.9–131.2, 128.9 (s),
128.9 (s), 128.8 (s), 128.4 (s), 128.4 (s), 127.7 (s), 127.6
(s), 127.6 (s), 71.5 (d, C-5), 70.7 (d, C-4), 70.0 (d, C-3),
69.1 (d, C-6), 69.0 (d, C-2), 63.3 (t, C-1), 12.8 (q, C-7);
UV (CH3CN) kmax 245 nm; CD (CH3CN) kext (De)
251 nm (17.9), 234 nm (À6.6); Anal. Calcd for
C35H26Br4O9: C, 46.19; H, 2.88. Found: C, 46.19; H, 3.07.
1
calcd for C24H31O5, 399.2172; found, 399.2199; H NMR
(CDCl3) d 7.41–7.29 (m, 15H), 4.78 (d, J = 11.6 Hz, 1H),
4.74–4.62 (m, 4H), 4.59 (d, J = 12.1 Hz, 1H), 4.10 (m, H-
6), 4.05 (dd, J = 5.5 and 10.0 Hz, H-2), 3.91 (dd, J = 5.1
and 10.0 Hz, H-1), 3.76–3.71 (m, 4H), 3.05 (br s, OH),
1.92–1.77 (m, 2H), 1.42 (m, 1H), 1.04 (d J = 6.7 Hz, 3H);
1.02 (d J = 6.5 Hz, 3H); 13C NMR (CDCl3) d 138.0 (s),
138.0 (s), 137.4 (s), 128.3–127.4, 78.6 (d, C-4), 75.3 (d, C-
3), 73.4 (t), 73.1 (t), 72.9 (t), 72.8 (d, C-2), 70.1 (d, C-6),
70.1 (d, C-5), 68.2 (t, C-1), 36.2 (t, C-7), 24.0 (d, C-8),
23.4 (q), 21.7 (q); Anal. Calcd for C31H38O5: C, 75.89; H,
7.81. Found: C, 75.84; H, 7.99.
4.8. 2,6-Anhydro-1,3,4-tri-O-benzyl-7-cyclohexyl-7-deoxy-
D-glycero-L-gulo-heptitol 1e
Following the general procedure for the preparation of a-
C-glucosides, 230 mg of tri-O-benzyl-D-glucal yielded
131 mg of compound a-1e (0.24 mmol, 45%), after flash
column chromatography (n-hexane/EtOAc, 9:1): TLC
Rf = 0.3 (n-hexane/EtOAc, 8.5:1.5); [a]D = +26.9 (c 1.0,
CHCl3); HRMS (EI): (MÀC7H7)+ calcd for C27H35O5,
1
439.2484; found, 439.2469; H NMR (CDCl3) d 7.37–7.26
4.11. 2,6-Anhydro-1,3,4,5-tetra-O-(p-bromobenzoyl)-7,8-
dideoxy-D-glycero-L-gulo-octitol 2b
(m, 15H), 4.74 (d, J = 11.7 Hz, 1H), 4.69–4.61 (m, 4H),
4.56 (d, J = 12.2 Hz, 1H), 4.10 (m, H-6), 4.05 (m, H-2),
3.87 (m, H-1), 3.79–3.74 (m, 2H), 3.68–3.66 (m, 2H), 2.91
(br s, OH), 1.86 (br d, J = 12.1 Hz, 1H), 1.74–1.67 (m,
5H), 1.52 (m, 1H), 1.40 (m, 1H), 1.31–1.20 (m, 3H), 1.03
(t, J = 11.4 Hz, 1H); 0.93 (t, J = 11.6 Hz, 1H); 13C NMR
(CDCl3) d 138.1 (s), 138.0 (s), 137.5 (s), 128.4–127.5, 78.4
(d, C-4), 75.4 (d, C-3), 73.5 (t), 73.2 (t), 73.0 (d, C-2),
72.9 (t), 70.1 (d, C-5), 69.3 (d, C-6), 68.3 (t, C-1), 35.2 (t,
C-7), 34.1 (t), 33.5 (d), 32.6 (t), 26.5 (t), 26.2 (t), 26.1 (t);
Anal. Calcd for C34H42O5: C, 76.95; H, 7.98. Found: C,
76.86; H, 7.81.
Debenzylation of compound 1b (121 mg, 0.26 mmol) and
then p-bromobenzoylation was performed as in the general
procedure, giving compound 2b (216 mg, 0.23 mmol, 89%)
after column chromatography (n-hexane/EtOAc, 8:2):
TLC Rf = 0.5 (n-hexane/EtOAc, 8:2); [a]D = +29.3 (c 0.9,
CHCl3); 1H NMR (CDCl3) d 7.87 (d, J = 8.6 Hz, 2H),
7.80 (d, J = 8.6 Hz, 2H), 7.75–7.71 (m, 4H), 7.56 (d,
J = 8.5 Hz, 2H), 7.53 (d, J = 8.6 Hz, 2H), 7.48 (d, J =
8.5 Hz, 2H), 7.47 (d, J = 8.5 Hz, 2H), 5.92 (t, J = 9.2 Hz,
H-4), 5.50 (t, J = 9.2 Hz, H-3), 5.48 (dd, J = 5.8 and

2810
C. Mayato et al. / Tetrahedron: Asymmetry 18 (2007) 2803–2811
9.5 Hz, H-5), 4.53 (dd, J = 3.8 and 12.1 Hz, H-1proS), 4.50
(dd, J = 5.3 and 12.1 Hz, H-1proR), 4.35 (ddd, J = 4.0, 5.8,
and 9.6 Hz, H-6), 4.22 (ddd, J = 3.8, 5.3, and 9.2 Hz, H-2),
2.03 (ddddd, J = 7.3, 7.3, 7.3, 9.6, and 14.5 Hz, H-7proS),
1.71 (ddddd, J = 4.0, 7.3, 7.3, 7.3, and 14.5 Hz, H-7proR),
1.02 (t, J = 7.3 Hz, 3H); 13C NMR (CDCl3) d 165.4 (s),
165.1 (s), 164.5 (s), 164.5 (s), 131.9–131.1, 128.9 (s), 128.9
(s), 128.8 (s), 128.4 (s), 128.4 (s), 127.7 (s), 127.6 (s),
127.6 (s), 74.1 (d, C-6), 71.5 (d, C-5), 70.9 (d, C-4), 70.0
(d, C-3), 68.8 (d, C-2), 63.5 (t, C-1), 18.8 (t, C-7), 9.4 (q,
C-8); UV (CH3CN) kmax 245 nm; CD (CH3CN) kext (De)
251 nm (11.7), 234 nm (À4.3); Anal. Calcd for
C36H28Br4O9: C, 46.78; H, 3.05. Found: C, 46.81; H, 3.00.
131.2, 128.9 (s), 128.9 (s), 128.8 (s), 128.4 (s), 128.4 (s),
127.8 (s), 127.6 (s), 127.5 (s), 71.5 (d, C-5), 71.2 (d, C-6),
71.0 (d, C-4), 70.1 (d, C-3), 69.0 (d, C-2), 63.6 (t, C-1),
33.9 (t, C-7), 24.2 (d, C-8), 23.5 (q), 21.3 (q); UV (CH3CN)
kmax 245 nm; CD (CH3CN) kext (De) 251 nm (8.5), 234 nm
(À3.5); Anal. Calcd for C38H32Br4O9: C, 47.93; H, 3.39.
Found: C, 48.03; H, 3.43.
4.14. 2,6-Anhydro-1,3,4,5-tetra-O-(p-bromobenzoyl)-7-
cyclohexyl-7-deoxy-D-glycero-L-gulo-heptitol 2e
Debenzylation of compound 1e (75 mg, 0.14 mmol) and
then p-bromobenzoylation, performed as in the general
procedure, led to compound 2e (134 mg, 0.14 mmol, 96%)
after column chromatography (n-hexane/EtOAc, 9:1):
TLC Rf = 0.3 (n-hexane/EtOAc, 9:1); [a]D = +26.7 (c 0.8,
CHCl3); 1H NMR (CDCl3) d 7.90 (d, J = 8.5 Hz, 2H),
7.79 (d, J = 8.5 Hz, 2H), 7.76 (d, J = 8.6 Hz, 2H), 7.72
(d, J = 8.6 Hz, 2H), 7.56 (d, J = 8.5 Hz, 2H), 7.54 (d,
J = 8.6 Hz, 2H), 7.49 (d, J = 8.6 Hz, 2H), 7.47 (d,
J = 8.6 Hz, 2H), 5.92 (t, J = 9.4 Hz, H-4), 5.48 (t,
J = 9.2 Hz, H-3), 5.45 (dd, J = 5.8 and 9.7 Hz, H-5), 4.58
(ddd, J = 3.1, 5.8, and 8.9 Hz, H-6), 4.51 (dd, J = 3.1 and
12.0 Hz, H-1proS), 4.46 (dd, J = 6.1 and 12.0 Hz, H-1proR),
4.25 (ddd, J = 3.1, 6.1, and 9.3 Hz, H-2), 1.98 (ddd,
J = 3.6, 8.9, and 14.9 Hz, H-7proS), 1.77 (m, 2H), 1.68–
1.53 (m, 3H), 1.48 (m, 1H), 1.37 (ddd, J = 3.1, 9.5, and
14.9 Hz, H-7proR), 1.15–0.97 (m, 4H), 0.83 (m, 1H); 13C
NMR (CDCl3) 165.3 (s), 165.1 (s), 164.5 (s), 164.5 (s),
131.9–131.1, 128.9 (s), 128.8 (s), 128.7 (s), 128.4 (s), 128.4
(s), 127.7 (s), 127.6 (s), 127.5 (s), 71.5 (d, C-5), 70.9 (d,
C-4), 70.6 (d, C-6), 70.1 (d, C-3), 68.9 (d, C-2), 63.7 (t,
C-1), 34.1 (t, C-7), 33.4 (d), 32.5 (t), 32.0 (t), 26.3 (t),
26.3 (t), 25.9 (t); UV (CH3CN) kmax 245 nm; CD (CH3CN)
kext (De) 251 nm (4.8), 234 nm (À2.7); Anal. Calcd
for C41H36Br4O9: C, 49.62; H, 3.66. Found: C, 49.59; H,
3.74.
4.12. 2,6-Anhydro-1,3,4,5-tetra-O-(p-bromobenzoyl)-7,8,9-
trideoxy-D-glycero-L-gulo-nontitol 2c
Debenzylation of compound 1c (156 mg, 0.33 mmol) and
then p-bromobenzoylation, performed as in the general
procedure, led to compound 2c (303 mg, 0.32 mmol, 99%)
after column chromatography (n-hexane/EtOAc, 9:1):
TLC Rf = 0.5 (n-hexane/EtOAc, 8:2); [a]D = +37.5 (c 1.0,
CHCl3); 1H NMR (CDCl3) d 7.87 (d, J = 8.6 Hz, 2H),
7.80 (d, J = 8.6 Hz, 2H), 7.74 (d, J = 8.5 Hz, 2H), 7.72
(d, J = 8.5 Hz, 2H), 7.56 (d, J = 8.6 Hz, 2H), 7.54 (d,
J = 8.6 Hz, 2H), 7.49 (d, J = 8.6 Hz, 2H), 7.47 (d,
J = 8.6 Hz, 2H), 5.92 (t, J = 9.3 Hz, H-4), 5.51 (t,
J = 9.2 Hz, H-3), 5.47 (dd, J = 5.8 and 9.6 Hz, H-5), 4.52
(dd, J = 3.8 and 12.1 Hz, H-1proS), 4.49 (dd, J = 5.4 and
12.1 Hz, H-1proR), 4.45 (ddd, J = 3.5, 5.8, and 9.2 Hz,
H-6), 4.23 (ddd, J = 3.8, 5.4, and 9.2 Hz, H-2), 2.02 (m,
H-7proS), 1.60–1.50 (m, 2H), 1.38 (m, H-8), 0.96 (t,
J = 7.2 Hz, 3H); 13C NMR (CDCl3) d 165.4 (s), 165.1 (s),
164.6 (s), 164.6 (s), 132.0–131.2, 128.9 (s), 128.9 (s), 128.8
(s), 128.4 (s), 128.4 (s), 127.8 (s), 127.6 (s), 127.6 (s), 72.6
(d, C-6), 71.5 (d, C-5), 70.9 (d, C-4), 70.0 (d, C-3), 68.9
(d, C-2), 63.5 (t, C-1), 27.5 (t, C-7), 18.2 (t, C-8), 13.7 (q,
C-9); UV (CH3CN) kmax 245 nm; CD (CH3CN) kext (De)
251 nm (10.9), 234 nm (À3.4); Anal. Calcd for
C37H30Br4O9: C, 47.36; H, 3.22. Found: C, 47.40; H, 3.47.
4.15. 2,6-Anhydro-1,3,4,5-tetra-O-(p-bromobenzoyl)-7,8,9-
trideoxy-8,8-dimethyl-D-glycero-L-gulo-nonitol 2f
4.13. 2,6-Anhydro-1,3,4,5-tetra-O-(p-bromobenzoyl)-7,8,9-
trideoxy-8-methyl-D-glycero-L-gulo-nontitol 2d
Debenzylation of compound 1f (384 mg, 0.76 mmol) and
then p-bromobenzoylation, performed as in the general
procedure, gave compound 2f (601 mg, 0.62 mmol, 82%)
after column chromatography (n-hexane/EtOAc, 9:1):
TLC Rf = 0.3 (n-hexane/EtOAc, 9:1); [a]D = +23.6 (c 0.8,
CHCl3); 1H NMR (CDCl3) d 7.85 (d, J = 8.5 Hz, 2H),
7.79 (d, J = 8.5 Hz, 2H), 7.75 (d, J = 8.5 Hz, 2H), 7.71
(d, J = 8.5 Hz, 2H), 7.54 (d, J = 8.5 Hz, 2H), 7.53 (d,
J = 8.5 Hz, 2H), 7.48 (d, J = 8.6 Hz, 2H), 7.46 (d, J =
8.6 Hz, 2H), 5.84 (t, J = 9.4 Hz, H-4), 5.52 (t, J = 9.3 Hz,
H-3), 5.41 (dd, J = 5.9 and 10.1 Hz, H-5), 4.65 (dd,
J = 5.9 and 10.1 Hz, H-6), 4.53 (dd, J = 3.1 and 12.0 Hz,
H-1proS), 4.45 (dd, J = 5.5 and 12.0 Hz, H-1proR), 4.35
(ddd, J = 3.1, 5.5, and 9.3 Hz, H-2), 1.96 (dd, J = 10.1
and 15.0 Hz, H-7proS), 1.48 (d, J = 15.0 Hz, H-7proR),
0.95 (s, 9H); 13C NMR (CDCl3) d 165.4 (s), 165.1 (s),
164.5 (s), 164.5 (s), 132.0–131.1, 128.8 (s), 128.8 (s), 128.7
(s), 128.4 (s), 128.3 (s), 127.7 (s), 127.5 (s), 127.5 (s), 71.5
(d, C-5), 71.2 (d, C-6), 70.8 (d, C-4), 70.1 (d, C-3), 68.7
(d, C-2), 63.7 (t, C-1), 36.9 (t, C-7), 30.4 (s, C-8), 29.6
(q), 29.6 (q), 29.6 (q); UV (CH3CN) kmax 245 nm; CD
Debenzylation of compound 1d (510 mg, 1.04 mmol) and
then p-bromobenzoylation, performed as in the general
procedure, led to compound 2d (955 mg, 1.00 mmol,
96%) after column chromatography (n-hexane/EtOAc,
9:1): TLC Rf = 0.3 (n-hexane/EtOAc, 9:1); [a]D = +32.3
1
(c 1.4, CHCl3); H NMR (CDCl3)d 7.86 (d, J = 8.6 Hz,
2H), 7.80 (d, J = 8.6 Hz, 2H), 7.75 (d, J = 8.6 Hz, 2H),
7.72 (d, J = 8.6 Hz, 2H), 7.56 (d, J = 8.5 Hz, 2H), 7.54
(d, J = 8.5 Hz, 2H), 7.49 (d, J = 8.6 Hz, 2H), 7.47 (d,
J = 8.6 Hz, 2H), 5.92 (t, J = 9.3 Hz, H-4), 5.51 (t,
J = 9.2 Hz, H-3), 5.47 (dd, J = 5.9 and 9.7 Hz, H-5), 4.55
(ddd, J = 3.4, 5.8, and 9.2 Hz, H-6), 4.52 (dd, J = 3.5 and
12.0 Hz, H-1proS), 4.48 (dd, J = 5.5 and 12.0 Hz, H-1proR),
4.23 (ddd, J = 3.5, 5.5, and 9.2 Hz, H-2), 2.03 (ddd,
J = 4.5, 9.2, and 14.7 Hz, H-7proS), 1.80 (m, H-8), 1.35
(ddd, J = 3.4, 9.5, and 14.7 Hz, H-7proR), 0.99 (d,
J = 6.7 Hz, 3H), 0.90 (d, J = 6.5 Hz, 3H); 13C NMR
(CDCl3) d 165.4 (s), 165.2 (s), 164.6 (s), 164.6 (s), 132.0–

C. Mayato et al. / Tetrahedron: Asymmetry 18 (2007) 2803–2811
2811
7. For reviews see: (a) Levy, D. E.; Tang, C. The Chemistry of
C-Glycosides; Elsevier: Tarrytown, NY, 1995; (b) Postema,
M. H. D. C-Glycoside Synthesis; CRC Press: Boca Raton,
Florida, 1995; (c) Dwek, R. A. Chem. Rev. 1996, 96, 683–720;
(d) Du, Y.; Linhardt, R. J.; Vlahov, I. R. Tetrahedron 1998,
54, 9913–9959.
(CH3CN) kext (De) 251 nm (9.2), 234 nm (À4.3); Anal.
Calcd for C39H34Br4O9: C, 48.48; H, 3.55. Found: C,
48.49; H, 3.61.
8. Allwein, S. P.; Cox, J. M.; Howard, B. E.; Johnson, H. W. B.;
Rainier, J. D. Tetrahedron 2002, 58, 1997–2009.
9. Murray, R. W.; Jeyaraman, R. J. Org. Chem. 1985, 50, 2847–
2853.
10. Danishefsky, S. J.; Halcomb, R. L. J. Am. Chem. Soc. 1989,
111, 6661–6666.
11. (a) Nishida, Y.; Ohrui, H.; Meguro, H. Tetrahedron Lett.
1984, 25, 1575–1578; (b) Ohrui, H.; Nishida, Y.; Watanabe,
M.; Hori, H.; Meguro, H. Tetrahedron Lett. 1985, 26, 3251–
3254; (c) Ohrui, H.; Nishida, Y.; Higuchi, H.; Hori, H.;
Meguro, H. Can. J. Chem. 1987, 65, 1145–1153; (d) Nishida,
Y.; Hori, H.; Ohrui, H.; Meguro, H. J. Carbohydr. Chem.
1988, 7, 239–250.
12. In general, for the 4-bromobenzoyl series of glucosides, H1R
proton signals appear at a higher field than H1S signals
(dH1S > dH1R). On the other hand, as a general rule, JH1R,H2
Acknowledgments
Support of this work by the Universidad de La Laguna
(Spain) is gratefully acknowledged. C.M. thanks the Con-
sejerıa de Educacion, Cultura y Deportes (Gobierno de
´
´
Canarias) for a fellowship.
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