Stereochemical study of the CD spectral differences between anomers of alkyl glucopyranosides

Article abstract of DOI:10.1016/S0957-4166(98)00037-8

Slightly different chair conformation geometries were demonstrated to be the origin of the C-D spectral differences observed in anomers of alkyl glucopyranosides. The study, using methyl glucopyranoside derivatives as model compounds, showed excellent agreement between CD data, ¹H NMR data, and semiempirical calculations, and the geometries found explained satisfactorily the higher amplitudes observed for the β-anomers of tetrachromophorically substituted alkyl glucopyranosides. The pairwise interactions involving the chromophore at C2, the 2/3, 2/4 and 2/6, were the most dependent on the anomeric configuration, the 2/4 interaction even showing opposite CD signs for the anomers. In addition, the 2/3 pairwise interaction was revealed to be independent of the structural nature of the aglycon.

Full text of DOI:10.1016/S0957-4166(98)00037-8

Pergamon
Tetrahedron: Asymmetry 9 (1998) 613–627
Stereochemical study of the CD spectral differences between
anomers of alkyl glucopyranosides
Juan I. Padrón and Jesús T. Vázquez ∗
Instituto Universitario de Bio-Orgánica ‘Antonio González’, Universidad de La Laguna, Carretera de La Esperanza 2, 38206
La Laguna, Tenerife, Spain
Received 9 December 1997; accepted 27 January 1998
Abstract
Slightly different chair conformation geometries were demonstrated to be the origin of the CD spectral dif-
ferences observed in anomers of alkyl glucopyranosides. The study, using methyl glucopyranoside derivatives as
model compounds, showed excellent agreement between CD data, 1H NMR data, and semiempirical calculations,
and the geometries found explained satisfactorily the higher amplitudes observed for the β-anomers of tetrachro-
mophorically substituted alkyl glucopyranosides. The pairwise interactions involving the chromophore at C2, the
2/3, 2/4 and 2/6, were the most dependent on the anomeric configuration, the 2/4 interaction even showing opposite
CD signs for the anomers. In addition, the 2/3 pairwise interaction was revealed to be independent of the structural
nature of the aglycon. © 1998 Elsevier Science Ltd. All rights reserved.
1. Introduction
The circular dichroic exciton chirality method,1 which is based on the coupled oscillator theory,2 is a
powerful tool for determining absolute configurations and conformations of organic molecules.1 The CD
spectral interpretation benefits from the existence of an additivity relation in the amplitudes (A values)3
of exciton-split CD spectra,4 and by the general validity of the pairwise additivity in exciton coupled
systems.5
The CD studies performed to prove additivities in multichromophoric systems were carried out
by using methyl glycopyranoside derivatives as model compounds. In the study of the additivity
of the amplitudes,4 the observed and calculated A values were used independently of the anomeric
configuration. However, a constant α-anomeric configuration was used in the study of the general validity
of the pairwise additivity in methyl glycopyranoside derivatives,5,6 as a consequence of the different A
values observed for some anomers in the former study.
∗
Corresponding author. E-mail: jtruvaz@ull.es
0957-4166/98/$19.00 © 1998 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(98)00037-8

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Table 1
CD data for the alkyl 2,3,4,6-tetrakis-O-(p-bromobenzoyl)-β-D- and α-D-glucopyranosides (com-
pounds type 1 and 2, respectively) (CH3CN)9
The choice of chromophoric glycopyranoside derivatives for the above-mentioned additivity stud-
ies was due to the fact that a CD microscale method was under development for identifying the
monosaccharide units and the glycosidic linkages of oligosaccharides.7 While the corresponding pro-
cedure to obtain the required monosaccharide derivatives yields methyl β-D-gluco-, β-D-galacto-, or
α-D-mannopyranosides, most components of the available CD spectral library have the α-anomeric
configuration.7 Although the differences in the CD curves of anomers are generally small, care must
be taken when CD spectra comparison of compounds of different anomeric configurations is performed.
1
We have recently reported, on the basis of CD and H NMR data, that the rotational population
of the hydroxymethyl group in alkyl β-D-glucopyranosides depends on the aglycon and its absolute
configuration,8 and that similar but not identical behavior occurs with their α-anomers.9 For both types
of anomers, this rotational dependence has its origin in the different values of the stereoelectronic exo-
anomeric effect, the endo-anomeric effect of the α-anomers not being directly involved.
In these rotational studies it was found that β-anomers of tetrachromophorically substituted alkyl
glucopyranosides (type 1 compounds) generally exhibit higher A values than the α-anomers (type
2 compounds) (see Aβ–Aα in Table 1), these differences being justified by the different rotameric
populations of the hydroxymethyl group (Pgg, Pgt and Ptg; Fig. 1).10
Unexpectedly, the almost identical A values obtained from the CD spectra of the 4,6-
bischromophorically substituted glucopyranosides (compound types 3 and 4, Table 2),9 where
only the pairwise interactions involving the chromophore at the 6 position are present, indicated that
the 2/3, 3/4 and/or 2/4 exciton interactions, which were considered to be constant by assuming no ring
distortion, are really responsible for the CD spectral differences observed in the tetrachromophorically
substituted glucopyranosides, and therefore for the fact that these interactions depend on the anomeric
configuration (Fig. 2).
In order to determine the origin of the CD spectral differences between glucopyranosyl anomers, as
well as the degree of dependence of the pairwise interactions on the anomeric configuration, the study
that follows was performed.

J. I. Padrón, J. T. Vázquez / Tetrahedron: Asymmetry 9 (1998) 613–627
615
Fig. 1. Pairwise interactions involving the chromophore at C6 for the glucopyranosyl system. Interactions responsible for the
CD sign for the 2/6, 3/6 and 4/6 pairwise interactions for both anomers are marked in boxes
Table 2
CD data for the alkyl 2,3-bis-O-acetyl-4,6-bis-O-(p-bromobenzoyl)-β-D- and α-D-glucopyranosides
(compound types 3 and 4, respectively) (CH3CN)9
Fig. 2. 2/3, 3/4 and 2/4 pairwise interactions for the glucopyranosyl system
2. Results and discussion
To study the dependence of the 2/3 pairwise interaction on the anomeric configuration and also on
the structural nature of the aglycon, anomers of methyl, isopropyl, and cyclohexyl 4,6-bis-O-acetyl-
2,3-bis-O-(p-bromobenzoyl)-D-glucopyranosides 10–15 were prepared according to Scheme 1. The
β-anomers 10–12 were obtained in good yields from the glucopyranosyl bromide 9 by using a modified
Koenigs–Knorr method.11 Anomerization of β-anomers by treatment with ferric chloride12 led to the
corresponding α-anomers 13–15.
CD analysis of compounds 10–15 revealed similar A values of the split CD curves for each set of
anomers (Table 3), showing that the 2/3 pairwise interaction is practically independent of the structural
nature of the aglycon. In addition, the A values obtained for the β-anomers are of a higher magnitude than
those of the α-anomers, as can be observed in Fig. 3, indicating that the 2/3 pairwise interaction depends
on the anomeric configuration. The proximity of the ester group at C2 to the anomeric carbon can lead
for each set of anomers to slightly different geometries in this region and, therefore, those interactions
involving the chromophore at C2, the 2/3, 2/4 and 2/6 pairwise interactions, exhibit different magnitudes.

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Scheme 1. (a) PhCH(OCH3)2, p-TsOH, DMF, 50°C, vacuum; (b) p-BrBzCl, Py, DMAP, 60°C; (c) p-TsOH, CH2Cl2:MeOH
(1:1); (d) Ac2O/Py; (e) HBr:AcOH (3:7), dry CH2Cl2 (f) ROH, AgOTf, TMU, dry CH2Cl2, −40°C; (g) anhydrous FeCl3, dry
CH2Cl2
Table 3
CD data of β-anomers 10–12 and α-anomers 13–15 (CH3CN). Contribution of the 2/3 pairwise
interaction
Fig. 3. CD spectra of the β- and α-anomers of cyclohexyl D-glucopyranoside derivatives 12 and 15, respectively
As can be observed in Table 3, the Aβ–Aα values of the 2/3 pairwise interaction justify only partially
the A value differences observed in the tetrachromophoric compounds (Table 1). Therefore, the spectral
differences observed for the anomers of tetrachromophoric compounds must also come from the other
pairwise interactions involved in the glucopyranosyl system. Thus, all the remaining methyl bis-O-acetyl-

J. I. Padrón, J. T. Vázquez / Tetrahedron: Asymmetry 9 (1998) 613–627
617
bis-O-(p-bromobenzoyl)-α- and β-D-glucopyranosides having one of the pairwise interactions present in
the tetrachromophoric system were prepared (Scheme 2). The combination of partial acetylation and
4-bromobenzoylation of methyl β-D-glucopyranoside yielded the β-anomers 18, 19, 24 and 25. The α-
anomers 20, 21 and 26 were obtained by anomerization of the corresponding β-anomers by means of
anhydrous ferric chloride.12 Compound 28 could not be obtained by this procedure, therefore it was
prepared directly from the methyl α-D-glucopyranoside. Table 4 shows the A values obtained from
exciton-coupled CD curves of these methyl α-D- and β-D-glucopyranoside derivatives, which represent
the remainder of the pairwise interactions present in methyl 2,3,4,6-tetrakis-O-(p-bromobenzoyl)-β-D-
and α-D-glucopyranoside (1 and 2, respectively). As can be observed, the higher differences in amplitude
(Aβ–Aα) correspond to the 2/3, 2/4, 2/6 and 3/4 pairwise interactions.
Scheme 2. (a) p-BrBzCl, Py, DMAP, 60°C; (b) Ac2O/Py; (c) anhydrous FeCl3, dry CH2Cl2
The calculated A values for compounds 1 and 2 (R00=methyl) were obtained by summation of their
corresponding pairwise interactions and compared with the observed ones. An acceptable difference of
2.9 between calculated and observed values was obtained for the β-anomer 1, while a large difference of
5.1 was obtained for the α-anomer 2.
In order to explain these spectral differences, a semiempirical calculation (MOPAC)13 was carried
out using the simpler model compounds, methyl tetrakis-O-acetyl-α- and β-D-glucopyranosides, in their
more stable gauche–gauche (gg) rotamer. Table 5 shows the values obtained for the dihedral angles
involved in each pairwise interaction of the tetrachromophoric system.14a
CD and dihedral angle data comparison (Tables 4 and 5) reveals a quite good agreement. The signs
of all split CD curves correspond with the signs of their corresponding dihedral angles, except for those
compounds representing the 2/6 pairwise interaction, compounds 18 and 20, whose signs come mainly
from the negative contribution of the second more populated rotamer (gt), since the contribution of the
most stable rotamer (gg) is practically nil as a consequence of its dihedral angle being close to 180°
(see Fig. 1). In addition, it is quite satisfactory to observe that the small positive and negative dihedral

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Table 4
A values of all pairwise interactions present in the methyl glucopyranosyl system
Table 5
Dihedral angles obtained from semiempirical calculations, MOPAC (AM1)
angles obtained for the 2/4 pairwise interaction are in excellent agreement with the positive and negative
A values observed for the β- and α-anomers, respectively.15
An excellent correlation between the magnitude of the A values and the dihedral angle values cannot
be expected since different compounds are being compared. Thus, the higher A values obtained for the
β-anomers 10 and 25 compared with the α-anomers 13 and 28, respectively, do not agree with the
dihedral angle values obtained, since theoretically the closer the dihedral angle is to 70°, the higher the
amplitude.14b
On the basis of the above comparisons, the A value obtained from compound 28 does not seem
appropriate to represent the 3/4 pairwise interaction in the α-anomers. In order to have a more accurate
A value for this pairwise interaction, other methyl α-D-glucopyranosides were prepared (Scheme 3).
The observed A values from the split CD curves of compounds 31, 32, 35 and 36 are shown in Table 6,
as well as the corresponding A value from compound 28. The contribution of the 3/4 pairwise interaction
to the observed A values in compounds 35 and 36 was calculated by subtracting from these A values
those from the 2/3 and 2/4 pairwise interactions. The resulting mean A value from these five α-anomers
representing the 3/4 pairwise interaction was −67.9. This value is of a slightly higher magnitude than
that of its β-anomer 25 (A value=−66) and is therefore now in agreement with the dihedral angle values
obtained from the semiempirical calculations. By using this more accurate mean A value, instead of
−60.3 from compound 28, in the calculation of the A value of the α-anomer 2, a value of 20.6 was
obtained (Table 4), as well as an acceptable difference of −2.5 between the calculated (20.6) and the
observed (23.1) A values for the α-anomer.
1
The vicinal H NMR coupling constants of the two sets of anomers were analyzed. Data comparison

J. I. Padrón, J. T. Vázquez / Tetrahedron: Asymmetry 9 (1998) 613–627
619
t
Scheme 3. (a) Bu(Ph)2SiCl, imidazole, DMF; (b) p-BrBzCl, Py, DMAP, 60°C; (c) CH3COCl, dry MeOH; (d) PvCl, Et3N,
DMAP, CH2Cl2; (e) Ac2O/Py
Table 6
Observed and calculated A values for the 3/4 pairwise interaction in methyl α-D-glucopyranosides
showed slightly different coupling constants between the ring trans di-axial protons, the α-anomers
having increased by 0.1–0.3 Hz their coupling constants with respect to the β-anomers. This result points
to higher dihedral angles between the trans di-axial hydrogens in the α-anomers and, therefore, to smaller
dihedral angles between their vicinal ester groups, in total agreement with the data from semiempirical
calculations, and in acceptable concordance with CD data.
1
The general agreement between CD data, H NMR coupling constants, and the dihedral angles from
the semiempirical calculations, allows us to conclude that anomers of alkyl glucopyranosides possess
4
slightly different geometries of the C1 chair conformation, especially in the anomeric region, the
more stable α-anomer being less distorted from the ideal chair conformation. These geometries explain
satisfactorily the fact that β-anomers of tetrachromophorically substituted alkyl glucopyranosides exhibit
higher amplitudes than their α-anomers, the main differences coming from the interactions involving the
chromophore at C2, the 2/3, 2/4 and 2/6 pairwise interactions.
This dependence on the anomeric configuration, although to a smaller degree, resembles that of the
anomers of methyl 2-(N-acetyl-p-bromobenzamido)-2-deoxy-D-galactopyranosides, where dramatic CD
spectral differences were observed for the anomers, as a consequence of different conformations of the
2-NAcBz group.16 In addition, it can be concluded for the glucopyranosyl system that:

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(i) the sign of the 2/4 pairwise interaction changes depending on the anomeric configuration: a positive
sign for the β-anomers and a negative sign for the α-anomers; and
(ii) that the 2/3 pairwise interaction shows higher amplitudes for the β-anomers (a mean of 3.7 units of
∆ε) and that this interaction is independent of the structural nature of the aglycon.
3. Experimental
3.1. General
1H NMR spectra were recorded at 400 MHz and 13C NMR were recorded 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. Optical rotations were measured on a digital polarimeter in a 1 dm cell. UV and CD
spectra were recorded in the range 400–200 nm and by using 10 mm cells. Prior to measurement of
CD spectra, all compounds were purified by HPLC by using a µ-Porasil column, 300×7.8 mm i.d.,
254 nm, and HPLC grade n-hexane/EtOAc solvent systems. The concentrations of the CD samples
were ascertained from the UV spectra, using the experimentally determined ε values at 245 nm: bis(p-
bromobenzoate) ε 38,200; and tetrakis(p-bromobenzoate) ε 76,400.4
For analytical and preparative thin-layer chromatography, silica gel ready-foils and glass-backed
plates (1 mm) were used, respectively, being developed with 254 nm UV light and/or spraying with
AcOH:H2O:H2SO4 (80:16:4) and heating at 150°C. Flash column chromatography was performed using
silica gel (0.015–0.04 mm). All reagents were obtained from commercial sources and used without
further purification. Solvents were dried and distilled before use. All reactions were performed under
a dry argon atmosphere. The prepared compounds were characterized on the basis of their one- (1H and
13C) and two-dimensional (COSY and HMQC) NMR spectra, as well as by UV and CD spectroscopy.
3.2. General procedures
The general procedure for p-bromobenzoylation, for the preparation of glucopyranosyl bromides,
and for β-glucosylation are well described by Morales et al.,8 as well as the preparation and spectro-
scopic data of compounds 5–7. The general procedure used for anomerization is well described in the
literature.12c
3.3. 4,6-Bis-O-acetyl-1,2,3-tris-O-(p-bromobenzoyl)-D-glucopyranoside 8
Acetylation of 7 (1.45 g, 1.99 mmol) led to compound 8 (1.37 g, 1.69 mmol, 85%) as a 3:7 mixture of
α- and β-anomers: 1H NMR (200 MHz, CDCl3) δ 7.98–7.27 (m, 12H), 6.75 (d, J=3.7 Hz, H-1α), 6.12
(d, J=7.7 Hz, H-1β), 6.01 (t, J=9.9 Hz), 5.72–5.69 (m), 5.55–5.39 (m), 4.45–4.30 (m), 4.25–4.06 (m),
2.13 (s), 2.12 (s), 1.97 (s), 1.96 (s).
3.4. 4,6-Bis-O-acetyl-2,3-bis-O-(p-bromobenzoyl)-α-D-glucopyranosyl bromide 9
This reaction was performed according to the general procedure for preparation of glucopyranosyl
bromides, starting from 8 (980 mg, 1.205 mmol) to obtain compound 9 (707 mg, 1.02 mmol, 85%): EQ
25
1
[α]D +204.9 (c 0.79, CHCl3); H NMR (CDCl3) δ 7.82–7.53 (aromatic-Hs, 8H), 6.75 (t, J=4.0 Hz,
H-1), 5.97 (t, J=9.9 Hz, H-3), 5.43 (t, J=9.9 Hz, H-4), 5.20 (dd, J=4.0 & 9.9 Hz, H-2), 4.41 (m, H-5 &

J. I. Padrón, J. T. Vázquez / Tetrahedron: Asymmetry 9 (1998) 613–627
621
H-6proR), 4.20 (d, J=10.6 Hz, H-6proS), 2.13 (s, 3H), 1.98 (s, 3H); 13C NMR (CDCl3) δ 170.48 (s), 169.28
(s), 164.83 (s), 164.47 (s), 131.99–127.14 (aromatic-Cs), 86.48 (d, C-1), 72.43 (d, C-5), 71.33 (d, C-2),
71.10 (d, C-3), 66.68 (d, C-4), 60.91 (t, C-6), 20.68 (q), 20.46 (q).
3.5. Methyl 4,6-bis-O-acetyl-2,3-bis-O-(p-bromobenzoyl)-β-D-glucopyranoside 10
Using 1 mL of dry MeOH, glucosylation of 9 (150 mg, 0.216 mmol) led to 10 (127.5 mg, 0.198 mmol,
25
92%): [α]D +132.43 (c 3.7, CHCl3); 1H NMR (CDCl3) δ 7.78–7.50 (aromatic Hs, 8H), 5.60 (t, J=9.7
Hz, H-3), 5.36 (dd, J=7.8 & 9.7 Hz, H-2), 5.32 (t, J=9.7 Hz, H-4), 4.63 (d, J=7.8 Hz, H-1), 4.35 (dd,
J=4.6 & 12.3 Hz, H-6proR), 4.22 (dd, J=2.3 & 12.3 Hz, H-6proS), 3.85 (ddd, J=2.3, 4.6 & 9.7 Hz, H-5),
3.52 (s, 3H), 2.12 (s, 3H), 1.94 (s, 3H); 13C NMR (CDCl3) δ 170.68 (s), 169.33 (s), 165.09 (s), 164.38
(s), 131.88–127.53 (aromatic Cs), 101.78 (d, C-1), 73.43 (d), 71.97 (d), 71.87 (d), 68.26 (d), 61.87 (t,
C-6), 57.17 (q), 20.74 (q), 20.50 (q); UV (CH3CN) λmax 245 nm; CD (CH3CN) λext (∆ε) 253 (51.7),
242 (0.0), 236 nm (−18.9).
3.6. Isopropyl 4,6-bis-O-acetyl-2,3-bis-O-(p-bromobenzoyl)-β-D-glucopyranoside 11
Using 150 mg (0.216 mmol) of 9 and 1 mL of iPrOH, compound 11 was obtained in 70% yield (101
mg, 0.151 mmol): [α]D25 +135.4 (c 1.3, CHCl3); 1H NMR (CDCl3) δ 7.78–7.51 (aromatic Hs, 8H), 5.58
(t, J=9.6 Hz, H-3), 5.30 (H-2 & H-4), 4.76 (d, J=8.0 Hz, H-1), 4.32 (dd, J=4.9 & 12.2 Hz, H-6proR), 4.19
(dd, J=2.4 & 12.2 Hz, H-6proS), 3.94 (sep, J=9.2 Hz, H-10), 3.83 (ddd, J=2.4, 4.9 & 9.6 Hz, H-5), 2.10 (s,
3H), 1.93 (s, 3H), 1.21 (d, J=6.2 Hz, 3H), 1.04 (d, J=6.2 Hz, 3H); 13C NMR (CDCl3) δ 170.68 (s), 169.34
(s), 165.11 (s), 164.24 (s), 131.89–127.63 (aromatic Cs), 99.69 (d, C-1), 73.56 (d), 73.14 (d), 72.12 (d),
71.84 (d), 68.47 (d), 62.11 (t, C-6), 23.16 (q), 21.91 (q), 20.74 (q), 20.51 (q); UV (CH3CN) λmax 244
nm; CD (CH3CN) λext (∆ε) 252 (52.2), 242 (0.0), 236 nm (−19.1).
3.7. Cyclohexyl 4,6-bis-O-acetyl-2,3-bis-O-(p-bromobenzoyl)-β-D-glucopyranoside 12
Following the general procedure for glucosylation, and using 1 mL of cyclohexanol, compound 9 (150
25
mg, 0.216 mmol) was transformed into compound 12 (123.1 mg, 0.173 mmol, 80%): [α]D +125.7 (c
0.91, CHCl3); 1H NMR (CDCl3) δ 7.78–7.51 (aromatic Hs, 8H), 5.58 (t, J=9.6 Hz, H-3), 5.34 (dd, J=7.9
& 9.6 Hz, H-2), 5.30 (t, J=9.6 Hz, H-4), 4.79 (d, J=7.9 Hz, H-1), 4.33 (dd, J=4.8 & 12.2 Hz, H-6proR),
4.19 (dd, J=2.3 & 12.2 Hz, H-6proS), 3.83 (ddd, J=2.3, 4.8 & 9.6 Hz, H-5), 3.65 (m, H-10), 2.11 (s, 3H),
1.93 (s, 3H), 1.84 (m, 1H), 1.68 (m, 2H), 1.57 (m, 1H), 1.43 (m, 2H), 1.21 (m, 4H); 13C NMR (CDCl3)
δ 170.69 (s), 169.34 (s), 165.12 (s), 164.24 (s), 131.86–127.65 (aromatic Cs), 99.42 (d, C-1), 78.12 (d),
73.58 (d, C-3), 72.12 (d, C-2), 71.79 (d, C-5), 68.49 (d, C-4), 62.09 (t, C-6), 33.12 (t), 31.48 (t), 25.33 (t),
23.61 (t), 23.43 (t), 20.75 (q), 20.52 (q); UV (CH3CN) λmax 244 nm; CD (CH3CN) λext (∆ε) 252 (51.4),
242 (0.0), 236 nm (−19.7).
3.8. Methyl 4,6-bis-O-acetyl-2,3-bis-O-(p-bromobenzoyl)-α-D-glucopyranoside 13
Using the general procedure for anomerization, compound 10 (50 mg, 0.077 mmol) was converted in
25
89% into compound 13 (30.6 mg, 0.047 mmol, 69% yield): [α]D +181.25 (c 1.12, CHCl3); 1H NMR
(CDCl3) δ 7.80–7.51 (aromatic Hs, 8H), 5.89 (t, J=9.7 Hz, H-3), 5.32 (t, J=9.7 Hz, H-4), 5.17 (dd, J=3.6
& 9.7 Hz, H-2), 5.15 (d, J=3.6 Hz, H-1), 4.33 (dd, J=4.6 & 12.3 Hz, H-6proR), 4.17 (dd, J=2.2 & 12.3
Hz, H-6proS), 4.11 (ddd, J=2.2, 4.6 & 9.7 Hz, H-5), 3.44 (s, 3H), 2.13 (s, 3H), 1.95 (s, 3H); 13C NMR

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(CDCl3) δ 170.65 (s), 169.46 (s), 165.04 (s), 164.99 (s), 131.86–127.78 (aromatic Cs), 96.92 (d, C-1),
71.92 (d, C-2), 70.90 (d, C-3), 68.13 (d, C-4), 67.36 (d, C-5), 61.87 (t, C-6), 55.62 (q), 20.73 (q), 20.52
(q); UV (CH3CN) λmax 244 nm; CD (CH3CN) λext (∆ε) 253 (47.5), 243 (0.0), 236 nm (−19.4).
3.9. Isopropyl 4,6-bis-O-acetyl-2,3-bis-O-(p-bromobenzoyl)-α-D-glucopyranoside 14
Compound 11 (36 mg, 0.054 mmol) was anomerized to compound 14 (30.5 mg, 0.046 mmol, 85%):
25
1
[α]D +196.55 (c 1.45, CHCl3); H NMR (CDCl3) δ 7.81–7.51 (aromatic Hs, 8H), 5.88 (t, J=9.8 Hz,
H-3), 5.35 (d, J=3.8 Hz, H-1), 5.30 (t, J=9.8 Hz, H-4), 5.13 (dd, J=3.8 & 9.8 Hz, H-2), 4.32 (dd, J=4.6 &
12.1 Hz, H-6proR), 4.23 (ddd, J=2.2, 4.6 & 9.8 Hz, H-5), 4.15 (dd, J=2.2 & 12.1 Hz, H-6proS), 3.88 (sep,
J=6.2 Hz, H-10), 2.12 (s, 3H), 1.95 (s, 3H), 1.26 (d, J=6.2 Hz, 3H), 1.06 (d, J=6.2 Hz, 3H); 13C NMR
(CDCl3) δ 170.68 (s), 169.51 (s), 165.09 (s), 164.99 (s), 131.88–127.90 (aromatic Cs), 94.66 (d, C-1),
72.06 (d), 71.97 (d), 71.11 (d), 68.32 (d), 67.45 (d), 62.00 (t, C-6), 23.14 (q), 21.80 (q), 20.72 (q), 20.55
(q); UV (CH3CN) λmax 244 nm; CD (CH3CN) λext (∆ε) 253 (49.7), 243 (0.0), 235 nm (−19.7).
3.10. Cyclohexyl 4,6-bis-O-acetyl-2,3-bis-O-(p-bromobenzoyl)-α-D-glucopyranoside 15
Compound 12 (25 mg, 0.035 mmol) was anomerized to compound 15 (16 mg, 0.022 mmol, 64%):
25
1
[α]D +188.68 (c 0.79, CHCl3); H NMR (CDCl3) δ 7.81–7.52 (aromatic Hs, 8H), 5.90 (t, J=9.8 Hz,
H-3), 5.39 (d, J=3.8 Hz, H-1), 5.30 (t, J=9.8 Hz, H-4), 5.13 (dd, J=3.8 & 9.8 Hz, H-2), 4.31 (dd, J=4.6 &
12.0 Hz, H-6proR), 4.25 (ddd, J=1.9, 4.6 & 9.8 Hz, H-5), 4.16 (dd, J=1.9 & 12.0 Hz, H-6proS), 3.58 (m,
H-10), 2.12 (s, 3H), 1.95 (s, 3H), 1.88 (m, 1H), 1.75 (m, 1H), 1.63 (m, 2H), 1.48 (m, 2H), 1.25 (brt, J=7.1
Hz, 2H), 1.16 (brt, J=9.4 Hz, 2H); 13C NMR (CDCl3) δ 170.68 (s), 169.53 (s), 165.10 (s), 164.99 (s),
131.85–127.92 (aromatic Cs), 94.51 (d, C-1), 76.84 (d), 72.03 (d), 71.17 (d), 68.34 (d), 67.47 (d), 62.00
(t, C-6), 33.25 (t), 31.48 (t), 25.38 (t), 23.88 (t), 23.51 (t), 20.73 (q), 20.56 (q). UV (CH3CN) λmax 244
nm; CD (CH3CN) λext (∆ε) 253 (46.7), 243 (0.0), 236 nm (−19.3).
3.11. Methyl 2,6-bis-O-(p-bromobenzoyl)-β-D-glucopyranoside 16 and methyl 3,6-bis-O-(p-bromo-
benzoyl)-β-D-glucopyranoside 17
Methyl β-D-glucopyranoside (200 mg, 1.03 mmol) was partially p-bromobenzoylated by using 452
mg (2.06 mmol) of p-BrBzCl. After chromatography, compounds 16 (91 mg, 0.16 mmol) and 17 (90 mg,
0.16 mmol) were obtained in 31% yield.
25
Compound 16: [α]D −7.0 (c 0.43, CHCl3); 1H NMR (CDCl3) δ 7.94–7.59 (aromatic Hs, 8H), 5.01
(dd, J=7.8 & 9.6 Hz, H-2), 4.77 (dd, J=4.0 & 12.1 Hz, H-6proR), 4.59 (dd, J=1.6 & 12.1 Hz, H-6proS),
4.54 (d, J=7.8 Hz, H-1), 3.81 (t, J=9.6 Hz, H-3), 3.65 (m, H-5), 3.60 (t, J=9.6 Hz, H-4), 3.50 (s, 3H); 13
C
NMR (CDCl3) δ 166.53 (s), 165.70 (s), 131.85–128.39 (aromatic Cs), 101.79 (d, C-1), 75.19 (d, C-3),
74.57 (d, C-2), 73.91 (d, C-5*), 70.66 (d, C-4*), 63.66 (t, C-6), 57.00 (q).
Compound 17: [α]D25 +25.71 (c 0.59, CHCl3); 1H NMR (CDCl3) δ 7.93–7.57 (aromatic Hs, 8H), 5.20
(brt, J=9.0 Hz, H-3), 4.70 (brd, J=11.9 Hz, H-6), 4.62 (d, J=12.0 Hz, H-60), 4.36 (d, J=7.7 Hz, H-1), 3.71
(brs, H-4 & H-5), 3.64 (brt, J=9.0 Hz, H-2), 3.58 (s, 3H); 13C NMR (CDCl3) δ 166.97 (s), 166.26 (s),
131.81–128.20 (aromatic Cs), 103.86 (d, C-1), 78.42 (d), 74.39 (d), 72.20 (d), 69.34 (d), 63.80 (t, C-6),
57.42 (q).

J. I. Padrón, J. T. Vázquez / Tetrahedron: Asymmetry 9 (1998) 613–627
623
25
3.12. Methyl 3,4-bis-O-acetyl-2,6-bis-O-(p-bromobenzoyl)-β-D-glucopyranoside 18
Acetylation of 16 (55.8 mg, 0.099 mmol) led to compound 18 (49 mg, 0.076 mmol, 77%): [α]D
+46.1 (c 1.23, CHCl3); 1H NMR (CDCl3) δ 7.92–7.59 (aromatic Hs, 8H), 5.42 (t, J=9.5 Hz, H-3), 5.27
(t, J=9.5 Hz, H-4), 5.24 (dd, J=7.8 & 9.5 Hz, H-2), 4.58 (d, J=7.8 Hz, H-1), 4.55 (dd, J=2.5 & 12.3 Hz,
H-6proS), 4.42 (dd, J=4.7 & 12.3 Hz, H-6proR), 3.90 (ddd, J=2.5, 4.7 & 9.5 Hz, H-5), 3.48 (s, 3H), 2.03
(s, 3H), 1.91 (s, 3H); 13C NMR (CDCl3) δ 170.15 (s), 169.36 (s), 165.44 (s), 164.36 (s), 131.85–128.07
(aromatic Cs), 101.77 (d, C-1), 72.53 (d), 71.92 (2×d), 68.63 (d), 62.70 (t, C-6), 57.07 (q), 20.58 (q),
20.49 (q); UV (CH3CN) λmax 245 nm; CD (CH3CN) λext (∆ε) 253 (−3.5), 246 (0.0), 237 nm (6.3).
3.13. Methyl 2,4-bis-O-acetyl-3,6-bis-O-(p-bromobenzoyl)-β-D-glucopyranoside 19
Compound 17 (89.6 mg, 0.16 mmol) was acetylated to give compound 19 (95.5 mg, 0.148 mmol,
25
1
92%): [α]D +33.7 (c 2.90, CHCl3); H NMR (CDCl3) δ 7.91–7.55 (aromatic Hs, 2H), 5.46 (t, J=9.6
Hz, H-3), 5.32 (t, J=9.6 Hz, H-4), 5.15 (dd, J=7.9 & 9.6 Hz, H-2), 4.54 (d, J=7.9 Hz, H-1), 4.53 (dd,
J=2.4 & 12.3 Hz, H-6proS), 4.42 (dd, J=4.7 & 12.3 Hz, H-6proR), 3.91 (ddd, J=2.4, 4.7 & 9.6 Hz, H-5),
3.51 (s, 3H), 1.95 (s, 3H), 1.91 (s, 3H); 13C NMR (CDCl3) δ 169.34 (s), 169.24 (s), 165.37 (s), 165.08
(s), 131.92–127.59 (aromatic Cs), 101.60 (d, C-1), 73.62 (d), 71.74 (d), 71.11 (d), 68.45 (d), 62.62 (t,
C-6), 57.00 (q), 20.56 (q), 20.45 (q); UV (CH3CN) λmax 245 nm; CD (CH3CN) λext (∆ε) 250 (11.0),
239 (0.0), 232 nm (−2.5).
3.14. Methyl 3,4-bis-O-acetyl-2,6-bis-O-(p-bromobenzoyl)-α-D-glucopyranoside 20
25
Anomerization of 18 (26 mg, 0.040 mmol) led to compound 20 (19 mg, 0.029 mmol, 73%): [α]D
+89.8 (c 0.80, CHCl3); 1H NMR (CDCl3) δ 7.93–7.60 (aromatic Hs, 8H), 5.70 (t, J=9.8 Hz, H-3), 5.22 (t,
J=9.8 Hz, H-4), 5.11 (d, J=3.4 Hz, H-1), 5.05 (dd, J=3.4 & 9.8 Hz, H-2), 4.50 (brd, J=11.9 Hz, H-6proS),
4.40 (dd, J=4.7 & 12.2 Hz, H-6proR), 4.16 (brd, J=9.8 Hz, H-5), 3.41 (s, 3H), 2.05 (s, 3H), 1.95 (s, 3H);
13C NMR (CDCl3) δ 170.12 (s), 169.53 (s), 165.46 (s), 164.98 (s), 131.95–127.88 (aromatic Cs), 96.74
(d, C-1), 71.86 (d), 69.95 (d), 68.58 (d), 67.29 (d), 62.72 (t, C-6), 55.56 (q), 20.64 (2×q); UV (CH3CN)
λmax 245 nm; CD (CH3CN) λext (∆ε) 254 (−3.4), 246 (0.0), 237 nm (4.1).
3.15. Methyl 2,4-bis-O-acetyl-3,6-bis-O-(p-bromobenzoyl)-α-D-glucopyranoside 21
Compound 19 (35 mg, 0.054 mmol) was anomerized to compound 21 (18 mg, 0.028 mmol, 52%):
25
1
[α]D +109.1 (c 1.05, CHCl3); H NMR (CDCl3) δ 7.93–7.57 (aromatic Hs, 8H), 5.74 (t, J=9.8 Hz,
H-3), 5.30 (t, J=9.8 Hz, H-4), 5.08 (dd, J=3.6 & 9.8 Hz, H-2), 4.99 (d, J=3.6 Hz, H-1), 4.51 (dd, J=2.3
& 12.3 Hz, H-6proS), 4.41 (dd, J=4.7 & 12.3 Hz, H-6proR), 4.19 (ddd, J=2.3, 4.7 & 9.8 Hz, H-5), 3.46
(s, 3H), 1.98 (s, 3H), 1.93 (s, 3H); 13C NMR (CDCl3) δ 170.16 (s), 169.45 (s), 165.46 (s), 164.96 (s),
131.93–127.94 (aromatic Cs), 96.99 (d, C-1), 71.02 (d), 70.72 (d), 68.57 (d), 67.37 (d), 62.67 (t, C-6),
55.56 (q), 20.65 (q), 20.53 (q); UV (CH3CN) λmax 245 nm; CD (CH3CN) λext (∆ε) 250 (11.8), 240 (0.0),
232 nm (−2.8).

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J. I. Padrón, J. T. Vázquez / Tetrahedron: Asymmetry 9 (1998) 613–627
3.16. Methyl 2,6-bis-O-acetyl-β-D-glucopyranoside 22 and methyl 3,6-bis-O-acetyl-β-D-glucopyra-
noside 23
Methyl β-D-glucopyranoside (300 mg, 1.54 mmol) was partially acetylated using 2 equiv. of acetic
anhydride (290 µL, 3.08 mmol) to give compounds 22 (30 mg) and 23 (60 mg), the former being directly
25
p-bromobenzoylated. Compound 23: [α]D −17.9 (c 0.89, CHCl3); 1H NMR (CDCl3) δ 4.92 (brt, J=9.4
Hz, H-3), 4.42 (dd, J=3.6 & 11.9 Hz, H-6proR), 4.33 (brd, J=11.9 Hz, H-6proS), 4.26 (d, J=7.8 Hz, H-1),
3.55 (s, 3H), 3.51 (brd, J=5.5 Hz, H-4 & H-5), 3.46 (dd, J=7.8 & 9.4 Hz, H-2), 2.15 (s, 3H), 2.12 (s, 3H);
13C NMR (CDCl3) δ 172.35 (s), 171.62 (s), 103.74 (d, C-1), 77.46 (d, C-3), 74.10 (d, C-4*), 72.04 (d,
C-2), 68.95 (d, C-5*), 63.07 (t, C-6), 57.32 (q), 21.01 (q), 20.83 (q).
3.17. Methyl 3,6-bis-O-acetyl-2,4-bis-O-(p-bromobenzoyl)-β-D-glucopyranoside 24
Compound 23 (42 mg, 0.151 mmol) was p-bromobenzoylated to compound 24 (75.3 mg, 0.12 mmol,
25
1
78%): [α]D +1.25 (c 0.56, CHCl3); H NMR (CDCl3) δ 7.86–7.58 (aromatic Hs, 8H), 5.57 (t, J=9.6
Hz, H-3), 5.39 (t, J=9.6 Hz, H-4), 5.29 (brt, J=9.2, H-2), 4.62 (d, J=7.9 Hz, H-1), 4.29 (dd, J=4.8 & 12.2
Hz, H-6proR), 4.23 (brd, J=9.7 Hz, H-6proS), 3.91 (m, H-5), 3.52 (s, 3H), 2.04 (s, 3H) 1.81 (s, 3H); 13C
NMR (CDCl3) δ 170.57 (s), 170.10 (s), 164.44 (s), 164.35 (s), 132.01–127.63 (aromatic Cs), 101.83 (d,
C-1), 72.27 (d, C-5*), 71.96 (d, C-3*), 71.91 (d, C-2*), 69.57 (d, C-4), 62.31 (t, C-6), 57.13 (q), 20.66
(q), 20.42 (q); UV (CH3CN) λmax 245 nm; CD (CH3CN) λext (∆ε) 252 nm (+0.7).
3.18. Methyl 2,6-bis-O-acetyl-3,4-bis-O-(p-bromobenzoyl)-β-D-glucopyranoside 25
p-Bromobenzoylation of 22 (28 mg, 0.100 mmol) led to compound 25 (37.2 mg, 0.058 mmol, 58%):
25
[α]D −108.7 (c 0.08, CHCl3); 1H NMR (CDCl3) δ 7.75–7.51 (aromatic Hs, 8H), 5.60 (t, J=9.6 Hz, H-
3), 5.46 (t, J=9.6 Hz, H-4), 5.20 (dd, J=7.9 & 9.6, H-2), 4.58 (d, J=7.9 Hz, H-1), 4.29 (dd, J=4.8 & 12.3
Hz, H-6proR), 4.23 (dd, J=3.0 & 12.3 Hz, H-6proS), 3.92 (ddd, J=3.0, 4.8 & 9.6 Hz, H-5), 3.56 (s, 3H), 2.04
(s, 3H) 1.97 (s, 3H); 13C NMR (CDCl3) δ 170.59 (s), 169.40 (s), 165.09 (s), 164.44 (s), 131.88–127.55
(aromatic Cs), 101.68 (d, C-1), 73.39 (d, C-3), 71.84 (d, C-5), 71.12 (d, C-2), 69.49 (d, C-4), 62.27 (t,
C-6), 57.11 (q), 20.67 (q), 20.63 (q); UV (CH3CN) λmax 245 nm; CD (CH3CN) λext (∆ε) 253 (−49.3),
243 (0.0), 235 nm (16.7).
3.19. Methyl 3,6-bis-O-acetyl-2,4-bis-O-(p-bromobenzoyl)-α-D-glucopyranoside 26
Anomerization of compound 24 (38.5 mg, 0.059 mmol) led to compound 26 (25 mg, 0.039 mmol,
77%) with a conversion of 84%: [α]D25 +49.1 (c 0.54, CHCl3); 1H NMR (CDCl3) δ 7.87–7.59 (aromatic
Hs, 8H), 5.85 (t, J=9.8 Hz, H-3), 5.36 (t, J=9.8 Hz, H-4), 5.15 (d, J=3.6 Hz, H-1), 5.10 (dd, J=3.6 & 9.8,
H-2), 4.27 (dd, J=5.1 & 12.3 Hz, H-6proR), 4.17 (m, H-5 & H-6proS), 3.43 (s, 3H), 2.06 (s, 3H) 1.84 (s,
3H); 13C NMR (CDCl3) δ 170.56 (s), 170.03 (s), 164.97 (s), 164.56 (s), 131.98–127.70 (aromatic Cs),
96.79 (d, C-1), 71.84 (d, C-2), 69.67 (d, C-3), 69.48 (d, C-4), 67.28 (d, C-5), 62.26 (t, C-6), 55.61 (q),
20.67 (q), 20.55 (q); UV (CH3CN) λmax 246 nm; CD (CH3CN) λext (∆ε) 253 (−6.5), 243 (0.0), 235 nm
(3.1).

J. I. Padrón, J. T. Vázquez / Tetrahedron: Asymmetry 9 (1998) 613–627
625
3.20. Methyl 2,6-bis-O-acetyl-α-D-glucopyranoside 27
Methyl α-D-glucopyranoside (400 mg, 2.06 mmol) was partially acetylated by using 389 µL (4.12
mmol) of Ac2O, to obtain after chromatography 47 mg (0.17 mmol) of 27, which was directly p-
bromobenzoylated.
3.21. Methyl 2,6-bis-O-acetyl-3,4-bis-O-(p-bromobenzoyl)-α-D-glucopyranoside 28
25
p-Bromobenzoylation of compound 27 (20 mg, 0.072 mmol) led to compound 28 in high yield: [α]D
−56.25 (c 0.48, CHCl3); 1H NMR (CDCl3) δ 7.76–7.50 (aromatic Hs, 8H), 5.89 (t, J=9.7 Hz, H-3), 5.45
(t, J=9.7 Hz, H-4), 5.14 (dd, J=3.6 & 9.7, H-2), 5.03 (d, J=3.6 Hz, H-1), 4.27 (dd, J=5.4 & 12.8 Hz, H-
6
proR), 4.20 (m, H-5 & H-6proS), 3.49 (s, 3H), 2.07 (s, 3H) 1.99 (s, 3H); 13C NMR (CDCl3) δ 170.55 (s),
170.15 (s), 164.87 (s), 164.55 (s), 131.85–127.62 (aromatic Cs), 97.04 (d, C-1), 70.72 (d, C-2*), 70.69
(d, C-3*), 69.51 (d, C-4), 67.36 (d, C-5), 62.20 (t, C-6), 55.61 (q), 20.68 (q), 20.66 (q); UV (CH3CN)
λmax 246 nm; CD (CH3CN) λext (∆ε) 252 (−43.2), 243 (0.0), 235 nm (17.1).
3.22. Methyl 2,6-bis-O-(tert-butyldiphenylsilyl)-α-D-glucopyranoside 29
To a stirred solution of methyl α-D-glucopyranoside (2.0 g, 10.29 mmol) in dry DMF (20 mL) and
under Ar, imidazole (1.5 g, 22.65 mmol) and tert-butyldiphenylsilyl chloride (4.3 mL, 16.46 mmol) were
added, and the reaction was monitored by TLC. Then, the solvent was removed under reduced pressure
25
and the resulting oil chromatographed to afford compound 29 (2.33 g, 3.48 mmol): mp 46–48°C; [α]D
1
+35.5 (c 1.69, CHCl3); H NMR (CDCl3) δ 7.74–7.39 (aromatic Hs), 4.22 (d, J=3.6 Hz, H-1), 3.96 (t,
J=9.2 Hz, H-3), 3.83 (dd, J=4.4 & 10.8 Hz, H-6), 3.78 (dd, J=5.0 & 10.8 Hz, H-60), 3.62 (m, H-2 & H-5),
3.44 (t, J=9.2 Hz, H-4), 3.21 (s, 3H), 1.10 (s, 9H), 1.02 (s, 9H); 13C NMR (CDCl3) δ 135.93–127.53
(aromatic Cs), 99.17 (d, C-1), 74.26 (d, C-3*), 73.96 (d, C-5*), 71.71 (d, C-4), 70.53 (d, C-2), 64.53 (t,
C-6), 54.73 (q), 27.12 (3×q), 26.89 (3×q), 19.38 (s), 19.38 (s).
3.23. Methyl 2,6-bis-O-(tert-butyldiphenylsilyl)-3,4-bis-O-(p-bromobenzoyl)-α-D-glucopyranoside 30
p-Bromobenzoylation of 29 (454 mg, 0.67 mmol) led to compound 30 (622 mg, 0.589 mmol, 88%):
25
1
[α]D −73.3 (c 1.97, CHCl3); H NMR (CDCl3) δ 7.71–7.29 (aromatic Hs), 5.92 (t, J=9.7 Hz, H-3),
5.18 (t, J=9.7 Hz, H-4), 4.34 (d, J=3.6 Hz, H-1), 3.98 (m, H-2 & H-5), 3.68 (dd, J=6.0 & 11.4 Hz, H-60),
3.65 (dd, J=2.7 & 11.4 Hz, H-6), 3.33 (s, 3H), 0.96 (s, 9H), 0.92 (s, 9H); 13C NMR (CDCl3) δ 165.11
(s), 164.61 (s), 135.86–127.52 (aromatic Cs), 98.84 (d, C-1), 73.74 (d, C-3), 71.97 (d, C-5*), 70.12 (d,
C-4*), 70.08 (d, C-2*), 63.22 (t, C-6), 54.80 (q), 26.64 (3×q), 26.59 (3×q), 19.07 (s), 19.05 (s).
3.24. Methyl 3,4-bis-O-(p-bromobenzoyl)-α-D-glucopyranoside 31
To 8 mL of dry MeOH under Ar, 768 µL (10.80 mmol) of acetyl chloride was added. After 5 min.,
this solution was treated with 280 mg (0.27 mmol) of 30 in dry ethyl ether (7 mL) and was monitored
25
by TLC (5 days). Compound 31 (128 mg, 0.23 mmol) was obtained in 85% yield: [α]D −63.4 (c 0.73,
1
CHCl3); H NMR (CDCl3) δ 7.80–7.50 (aromatic Hs, 8H), 5.70 (t, J=9.8 Hz, H-3), 5.34 (t, J=9.8 Hz,
H-4), 4.93 (d, J=3.8 Hz, H-1), 3.93 (m, H-5 & H-2), 3.78 (dd, J=1.8 & 12.8 Hz, H-6), 3.66 (dd, J=3.7 &
12.8 Hz, H-6), 3.52 (s, 3H); 13C NMR (CDCl3) δ 165.93 (s), 165.59 (s), 131.93–127.41 (aromatic Cs),

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J. I. Padrón, J. T. Vázquez / Tetrahedron: Asymmetry 9 (1998) 613–627
99.44 (d, C-1), 73.88 (d, C-3), 71.18 (d, C-2), 69.68 (d, C-5), 69.18 (d, C-4), 60.98 (t, C-6), 55.77 (q);
UV (CH3CN) λmax 245 nm; CD (CH3CN) λext (∆ε) 251 (−49.6), 241 (0.0), 235 nm (18.8).
3.25. Methyl 3,4-bis-O-(p-bromobenzoyl)-2,6-bis-O-pivaloyl-α-D-glucopyranoside 32
To a stirred solution of 31 (32 mg, 0.056 mmol) in CH2Cl2 (2 mL), pivaloyl chloride (17 µL, 0.140
mmol), Et3N (8 µL), and DMAP in catalytic amounts were added. The reaction mixture was monitored
by TLC and quenched by adding a few drops of H2O. The solvent was eliminated and the resulting oil
25
chromatographed to afford compound 32 (40 mg, 0.055 mmol, 98%): [α]D −65.1 (c 0.91, CHCl3);
1H NMR (CDCl3) δ 7.76–7.50 (aromatic Hs, 8H), 5.92 (t, J=9.6 Hz, H-3), 5.42 (t, J=9.6 Hz, H-4), 5.01
(m, H-1 & H-2), 4.21 (m, H-5 & 2H-6), 3.46 (s, 3H), 1.22 (s, 9H), 1.05 (s, 9H); 13C NMR (CDCl3)
δ 178.02 (s), 177.70 (s), 164.85 (s), 164.45 (s), 131.83–127.68 (aromatic Cs), 96.94 (d, C-1), 70.74 (d,
C-2*), 70.71 (d, C-3*), 69.43 (d, C-4), 67.62 (d, C-5), 62.26 (t, C-6), 55.64 (q), 38.83 (s), 38.66 (s), 27.11
(3×q), 26.73 (3×q); UV (CH3CN) λmax 246 nm; CD (CH3CN) λext (∆ε) 253 (−52.7), 243 (0.0), 235
nm (18.0).
3.26. Methyl 6-O-(tert-butyldiphenylsilyl)-α-D-glucopyranoside 33
To a stirred solution of methyl α-D-glucopyranoside (2.0 g, 10.29 mmol) in dry DMF (7 mL) and
under Ar, imidazole (1.5 g, 22.65 mmol) and tert-butyldiphenylsilyl chloride (2.9 mL, 11.32 mmol) were
added, and the reaction was monitored by TLC (5 h). Then, the reaction was diluted with ethyl ether
and washed with NH4Cl and NaHCO3. The combined organic layers were dried over sodium sulfate,
filtered, and concentrated. Flash column chromatography led to compound 33 (4.29 g, 9.91 mmol) in
96% yield: mp 116–118°C; [α]D25 +55.0 (c 0.54, CHCl3); 1H NMR (CDCl3) δ 7.69–7.38 (aromatic Hs,
10H), 4.70 (d, J=3.6 Hz, H-1), 3.92 (dd, J=3.4 & 10.9 Hz, H-6), 3.84 (brdd, J=5.4 & 10.9, H-6), 3.75 (t,
J=9.2 Hz, H-3), 3.63 (m, H-5), 3.48 (m, H-2 & H-4), 3. 35 (s, 3H), 1.06 (s, 9H); 13C NMR (CDCl3) δ
135.62–127.67 (aromatic Cs), 99.19 (d, C-1), 74.49 (d, C-3), 72.12 (d, C-2), 71.33 (2×d, C-5 & C-4),
64.21 (t, C-6), 54.99 (q), 26.80 (3×q), 19.23 (s).
3.27. Methyl 2,3,4-tris-O-(p-bromobenzoyl)-6-O-(tert-butyldiphenylsilyl)-α-D-glucopyranoside 34
p-Bromobenzoylation of 33 (200 mg, 0.46 mmol) led to compound 34 (325 mg, 0.33 mmol, 72%):
25
1
[α]D +26.3 (c 2.10, CHCl3); H NMR (CDCl3) δ 7.83–7.26 (aromatic Hs), 6.04 (t, J=9.8 Hz, H-3),
5.58 (t, J=9.8 Hz, H-4), 5.24 (dd, J=3.6 & 9.8 Hz, H-2), 5.21 (d, J=3.6 Hz, H-1), 4.11 (m, H-5), 3.81 (m,
2H-6), 3.46 (s, 3H), 1.03 (s, 9H); 13C NMR (CDCl3) δ 165.15 (s), 165.07 (s), 164.36 (s), 135.58–127.59
(aromatic Cs), 96.74 (d, C-1), 72.21 (d, C-2), 71.17 (d, C-3), 70.23 (d, C-5), 69.43 (d, C-4), 62.73 (t,
C-6), 55.38 (q), 26.66 (3×q), 19.14 (s).
3.28. Methyl 2,3,4-tris-O-(p-bromobenzoyl)-α-D-glucopyranoside 35
To 5 mL of dry MeOH under Ar, 241 µL (3.39 mmol) of acetyl chloride was added. After 5 min., this
solution was treated with 115 mg (0.117 mmol) of 34 in dry ethyl ether (5 mL) and was monitored by
TLC (1 day). Then, the solvent was evaporated, and the residue chromatographed to afford compound 35
25
1
(85.6 mg, 0.115 mmol, 98%): [α]D +20.2 (c 1.20, CHCl3); H NMR (CDCl3) δ 7.81–7.44 (aromatic
Hs), 6.13 (t, J=9.8 Hz, H-3), 5.48 (t, J=9.8 Hz, H-4), 5.25 (dd, J=3.6 & 9.8 Hz, H-2), 5.22 (d, J=3.6 Hz,
H-1), 4.03 (brd, J=10.0 Hz, H-5), 3.82 (m, H-6), 3.71 (brd, J=12.8 Hz, H-60), 3.47 (s, 3H); 13C NMR

J. I. Padrón, J. T. Vázquez / Tetrahedron: Asymmetry 9 (1998) 613–627
627
(CDCl3) δ 165.45 (s), 165.08 (s), 165.00 (s), 131.95–127.36 (aromatic Cs), 97.01 (d, C-1), 71.96 (d,
C-2), 70.49 (d, C-3), 69.62 (d, C-4*), 69.53 (d, C-5*), 61.00 (t, C-6), 55.67 (q); UV (CH3CN) λmax 246
nm; CD (CH3CN) λext (∆ε) 252 (−10.3), 241 (0.0), 236 nm (2.6).
3.29. Methyl 6-O-acetyl-2,3,4-tris-O-(p-bromobenzoyl)-α-D-glucopyranoside 36
Compound 35 (46 mg, 0.062 mmol) was acetylated to give compound 36 (43 mg, 0.055 mmol) in
25
88% yield: [α]D +22.7 (c 2.09, CHCl3); 1H NMR (CDCl3) δ 7.81–7.44 (aromatic Hs), 6.06 (t, J=9.8
Hz, H-3), 5.54 (t, J=9.8 Hz, H-4), 5.26 (dd, J=3.6 & 9.8 Hz, H-2), 5.20 (d, J=3.6 Hz, H-1), 4.31 (dd,
J=4.8 & 12.3 Hz, H-6proR), 4.26 (m, H-5 & H-6proS), 3.48 (s, 3H), 2.08 (s, 3H); 13C NMR (CDCl3) δ
170.53 (s), 165.00 (2×s), 164.52 (s), 131.87–127.57 (aromatic Cs), 96.94 (d, C-1), 71.86 (d, C-2), 70.68
(d, C-3), 69.28 (d, C-4), 67.37 (d, C-5), 62.19 (t, C-6), 55.68 (q), 20.68 (q); UV (CH3CN) λmax 246 nm;
CD (CH3CN) λext (∆ε) 253 ((10.3), 241 (0.0), 236 nm (2.3).
Acknowledgements
Support of this work by the Dirección General de Enseñanza Superior, Ministerio de Educación y
Cultura (Spain), through grant PB96-1040, is gratefully acknowledged.
References
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3. The amplitude (A value) of split CD Cotton effects is defined as A=∆ε1−∆ε2 where ∆ε1 and ∆ε2 are intensities of the first
and second Cotton effects, respectively.
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9. Padrón, J. I.; Vázquez, J. T. Chirality 1997, 9, 626.
10. The rotamer population of the hydroxymethyl group about the C5–C6 bond in alkyl glucopyranosides possess for both
anomers the following order Pgg>Pgt>Ptg, although with different magnitudes. For further information see Ref. 9.
11. (a) Hanessian, S.; Banoub, J. Carbohydr. Res. 1977, 53, C13. (b) Banoub, J.; Bundle, D. R. Can. J. Chem. 1979, 57, 2091.
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12. (a) Park, M. H.; Takeda, R.; Nakanishi, K. Tetrahedron Lett. 1987, 28, 3823. (b) Ikemoto, N.; Kim, O. K.; Lo, L.-C.;
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13. MOPAC (v 6.0, AM1) was used to perform the semiempirical calculations, under precise, gnorm=0.001, and EF conditions.
14. Some aspects of practical significance for the interpretation of the split CD curves: (a) the electric transition moments of the
1La bands of the p-bromobenzoate chromophores (245 nm, ε 19,500) are always approximately parallel to the C–O ester
bond; (b) the sign of split CD curves is unchanged from 0° to 180°, the largest A value being encountered around a dihedral
angle of 70°. For further information see Ref. 1.
15. Negative A values have also been found in methyl α-D-glucopyranosides having a 2/4 homo p-methoxycinnamate
interaction, as well as possessing 2/4 hetero p-bromobenzoate/p-methoxycinnamate interactions. See Ref. 5: entry 7
(CACA) in Table I, and entries 3 (BACA) and 4 (CABA) in Table II.
16. Lo, L.-C.; Berova, N.; Nakanishi, K.; Morales, E. Q.; Vázquez, J. T. Tetrahedron: Asymmetry 1993, 4, 321.