Conformational domino effect in saccharides. 2. Anomeric configuration control

Article abstract of DOI:10.1021/jo801184q

(Chemical Equation Presented) A series of alkyl β-D-glucopyranosyl- (1→6)-α-D-glucopyranosides were synthesized and analyzed by NMR and CD techniques. As in their β-anomer series, the rotational populations of the hydroxymethyl group involved in the interglycosidic linkage (torsion angle ω) are shown to depend on the aglycon and the solvent. However, for this α-anomer series the rotational dependence arises directly from steric effects. Correlations between rotational populations and molar refractivity (MR) steric parameters, but not Taft's steric parameters (β-anomers), of the alkyl substituents were observed. The conformational domino effect previously predicted from alkyl β-(1→6)-diglucopyranosides is now supported by the conformational properties of their α-anomers, the anomeric configuration controlling the domino effect. In addition, the rotational populations around the C5′-C6′ bond (torsion angle ω′) depend weakly on the structure of the aglycon and the anomeric configuration.

Full text of DOI:10.1021/jo801184q

Conformational Domino Effect in Saccharides. 2. Anomeric
Configuration Control
Alfredo Roe¨n, Carlos Mayato, Juan I. Padro´n, and Jesu´s T. Va´zquez*
Instituto UniVersitario de Bio-Orga´nica “Antonio Gonza´lez”, Departamento de Qu´ımica Orga´nica,
UniVersidad de La Laguna, 38206 La Laguna, Tenerife, Spain
jtruVaz@ull.es
ReceiVed June 2, 2008
A series of alkyl ꢀ-D-glucopyranosyl-(1f6)-R-D-glucopyranosides were synthesized and analyzed by
NMR and CD techniques. As in their ꢀ-anomer series, the rotational populations of the hydroxymethyl
group involved in the interglycosidic linkage (torsion angle ω) are shown to depend on the aglycon and
the solvent. However, for this R-anomer series the rotational dependence arises directly from steric effects.
Correlations between rotational populations and molar refractivity (MR) steric parameters, but not Taft’s
steric parameters (ꢀ-anomers), of the alkyl substituents were observed. The conformational domino effect
previously predicted from alkyl ꢀ-(1f6)-diglucopyranosides is now supported by the conformational
properties of their R-anomers, the anomeric configuration controlling the domino effect. In addition, the
rotational populations around the C5′-C6′ bond (torsion angle ω′) depend weakly on the structure of the
aglycon and the anomeric configuration.
Introduction
NMR24 and X-ray diffraction,25,26 molecular modeling has
became another important tool for structural studies of carbo-
Carbohydrates play a central role in a variety of important
physiological events, including inflammation, metastasis, im-
mune response, and bacterial and viral infection, which has led
to an increased appreciation of these biomolecules.1 To under-
stand these events from a molecular point of view, not only
their three-dimensional structure but also their conformational
preferences in solution must be known. The conformation of
an oligosaccharide in solution may be difficult to determine,
owing to the flexibility of the glycosidic linkages and the rotation
of the hydroxymethyl2-23 and other pendant groups. Besides
(10) Senderowitz, H.; Parish, C.; Still, W. C. J. Am. Chem. Soc. 1996, 118,
2078.
(11) (a) Nishida, Y.; Ohrui, H.; Meguro, H. Tetrahedron Lett. 1984, 25, 1575.
(b) Ohrui, H.; Nishida, Y.; Watanabe, M.; Hori, H.; Meguro, H. Tetrahedron
Lett. 1985, 26, 3251. (c) Nishida, Y.; Hori, H.; Ohrui, H.; Meguro, H.
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Chem. 1995, 60, 2537. (b) Padro´n, J. I.; Va´zquez, J. T. Chirality 1997, 9, 626.
(c) Padro´n, J. I.; Va´zquez, J. T. Tetrahedron: Asymmetry 1998, 9, 613. (d) Padro´n,
J. I.; Morales, E. Q.; Va´zquez, J. T. J. Org. Chem. 1998, 63, 8247. (e) No´brega,
C.; Va´zquez, J. T. Tetrahedron: Asymmetry 2003, 14, 2793. (f) Mayato, C.;
Dorta, R.; Va´zquez, J. Tetrahedron: Asymmetry 2004, 15, 2385.
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in Sugar Chemistry in Chemical Biology; Schreiber, S. L., Kapoor, T., Wess,
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7266 J. Org. Chem. 2008, 73, 7266–7279
10.1021/jo801184q CCC: $40.75 2008 American Chemical Society
Published on Web 08/27/2008

Conformational Domino Effect in Saccharides
FIGURE 2. Schematic representation of a conformational domino
effect in linear (top) or branched (bottom) oligosaccharides. The (1f2)-,
(1f3)-, and (1f4)-bonded saccharides start a new domino effect;
however, the (1f6)-interglycosidic linkages continue the domino effect.
FIGURE 1. Torsion angle Φ around the O1-C1 bond and ω around
C5-C6 (top). Newman projections of the idealized staggered rotamers
around the O1-C1 (center) and C5-C6 bonds (bottom).
hydrates, permitting the range of attainable conformations to
be evaluated in terms of the potential energy at each point
specified by a pair of angles, φ (O5′-C1′-O6-C6) and Ψ
(C1′-O6-C6-C5), for a 1f6 linkage.26 In addition to these
torsion angles, a third torsion angle ω (O5-C5-C6-O6) needs
to be considered when the hydroxymethyl group is involved in
the linkage. Rotation around the φ angle leads to the exo-syn,
exo-anti, and non-exo rotamers, while that around the ω angle
gives the gauche-gauche (gg), gauche-trans (gt) and trans-
gauche (tg) rotamers (Figure 1).27 This last torsion angle is also
used to describe the conformation of unsubstituted hydroxym-
ethyl groups.
FIGURE 3. Model alkyl ꢀ-(1f6)-glucopyranosyl-R-D-glucopyrano-
sides and ω torsion angles around the C5-C6 and C5′-C6′ bonds under
study.
The torsion angle ω of glycosides21,23 has been proven to be
conformationally dependent on the structure of the aglycon due
to stereoelectronic and steric factors. Recent rotational studies
with C-28 and S-glycosides29 have also shown it to be dependent
on the aglycon. Besides these, stereochemical studies with
methyl diglucopyranosides containing ꢀ-glycosidic linkages
(1f2, 1f3, 1f4, and 1f6) also revealed that this angle
depends on the glycosidic linkage type,22 while studies with
alkyl diglucopyranosides demonstrated that this interglycosidic
ω angle depends on the structural nature of both the aglycon
and the solvent.20,22 These results pointed to a natural confor-
mational domino effect in oligosaccharides, where the confor-
mational properties of each (1f6) interglycosidic linkage
depend on the structure of the previous residue or its aglycon
(Figure 2).23 Furthermore, correlations were observed between
the Taft steric parameters30 of the alkyl substituents (aglycon)
versus the corresponding rotamer populations.
In this paper, we report the corresponding conformational
study of alkyl ꢀ-D-glucopyranosyl-(1f6)-R-D-glucopyranosides
in solution (Figure 3). This study revealed that the rotational
populations of the hydroxymethyl group involved in the
glycosidic linkage (residue I) depend on the structural nature
of the aglycon and on the solvent. Furthermore, correlations
were observed between the rotamer populations and molar
refractivity (MR)31 parameters of the alkyl substituents, which
are used to measure the steric effects in proportion to the molar
volume of the substituents; instead of with Taft’s steric (ES)
parameters in the ꢀ-series. This shows how the anomeric
configuration controls the rotational population behavior and
therefore the domino effect.
Results and Discussion
(23) Roe¨n, A.; Padro´n, J. I.; Mayato, C.; Va´zquez, J. T. J. Org. Chem. 2008,
73, 3351.
Synthesis. The R-anomer disaccharides were synthesized
following the general strategy used to obtain their ꢀ-anomers,23
namely by coupling different alcohols to the disaccharide 1
(Scheme 1) via the direct epoxidation of glycals and opening
(24) Duus, J. Ø.; Gotfredsen, C. H.; Bock, K. Chem. ReV. 2000, 100, 4589.
(25) Jeffrey, G. A. Acta Crystallogr. 1990, B46, 89.
(26) (a) Imberty, A.; Pe´rez, S. Chem. ReV. 2000, 100, 4567. (b) Wormald,
M. R.; Petruscu, A. J.; Pao, Y-L.; Glithero, A.; Elliott, T.; Dwek, R. A. Chem.
ReV. 2002, 102, 371.
(27) The first descriptor indicates the torsional relationship between O6 and
O5 and the second that between O6 and C4.
(28) (a) Mayato, C.; Dorta, R. L.; Va´zquez, J. T. Tetrahedron: Asymmetry
2007, 18, 931. (b) Mayato, C.; Dorta, R. L.; Va´zquez, J. T. Tetrahedron:
Asymmetry 2007, 18, 2803.
(29) Sanhueza, C. A.; Dorta, R. L.; Va´zquez, J. T. Tetrahedron: Asymmetry
2008, 19, 258.
(30) (a) Taft, R. W., Jr. J. Am. Chem. Soc. 1952, 74, 2729. (b) Taft, R. W.,
Jr. J. Am. Chem. Soc. 1952, 74, 3120. (c) Taft, R. W., Jr. J. Am. Chem. Soc.
1953, 75, 4532. (d) Taft, R. W., Jr. J. Am. Chem. Soc. 1953, 75, 4538.
(31) One of the parameters used to measure the steric effect is the molar
refractivity (MR), which is a measure of the volume occupied by an atom or
group of atoms. The greater the positive MR value of a substituent, the larger
its steric or bulk effect. (a) Hansch, C.; Leo, A.; Unger, S. H.; Kim, K. H.;
Kikaitani, D.; Lien, E. J. J. Med. Chem. 1973, 16, 1207. (b) Hansch, C.; Leo, A.
Exploring QSAR: Fundamentals and Applications in Chemistry and Biology;
American Chemical Society: Washington, DC, 1995; Vols. 1 and 2.
J. Org. Chem. Vol. 73, No. 18, 2008 7267

Roën et al.
SCHEME 1. Synthesis of the Model Disaccharides
of the resulting epoxide by a nucleophile.32,33 This procedure
led to the anomer mixture of compounds 2 and 4-6, the
R-anomers being isolated and treated similarly to the ꢀ-ano-
mers.23
butyl disaccharides 24r (Scheme 3).36,37 The tert-butyl penta-
O-acetyldisaccharide 25r was obtained by treating compound
23r with acetic anhydride and pyridine.
Characterization and Spectroscopic Analysis. All of these
compounds were characterized on the basis of their one- (1H
and 13C) and two-dimensional (COSY, HMQC, and T-ROESY)
NMR spectra. The anomeric configurations were assigned in
each case by analyzing the coupling constant between H1 and
H2 for each glucopyranosidic ring (CDCl3, doublet, ꢀ-config-
uration: 7.8-8.1 Hz; R-configuration: 3.5-3.9 Hz) (Figure 4).
The chemical shifts of C1 and H1 for compounds in the four
sets of disaccharides were shielded (90.0-101.6 ppm) or
deshielded (4.55-5.32 ppm), respectively, from methyl to tert-
butyl derivatives. Furthermore, as occurred in alkyl glycosides21
and the corresponding ꢀ series,23 NMR data comparison
between (-)- and (+)-menthyl disaccharides shows chemical
shifts for the former compounds at higher fields for C1 (4.7-5.9
ppm) and for H1 (0.10-0.13 ppm).
The 1H NMR signals of the prochiral protons at C6 and C6′
were differentiated according to the data in the literature2,11 on
their chemical shifts and coupling constants. Among the different
types of Karplus equations,38 those of Serianni39 yield the most
accurate representation of the rotameric populations in solution.
In addition, since the ω population depends to some extent on
solvation effects,20 NMR measurements were performed in polar
and nonpolar solvents.
To obtain the methyl disaccharide with the R anomeric
configuration at C1, compound 3r, an alternative procedure
(Scheme 2) had to be used, since only the ꢀ-anomer was
synthesized by the above procedure from compound 1 and
MeOH as nucleophile (Scheme 1). As shown in Scheme 2, the
methyl ꢀ-D-glucopyranosyl-(1f6)-R-D-glucopyranoside 22r
was produced similarly by coupling the glucosyl donor 21 to
the monosaccharide 20. This last monosaccharide was obtained
in four steps from the methyl R-D-glucopyranoside through the
known compounds 1734 and 18.35 Acetylation of 22r led to
the disaccharide 3r with the desired R anomeric configuration.
The tert-butyl derivative 10r under acetyl chloride/MeOH
conditions led to undesired methanolysis. However, their
protecting groups were successfully removed in two steps, first,
the silyl groups by using the HF·Py complex in dry CH3CN
and then, the acetyl groups using p-TsOH, to arrive at the tert-
(32) (a) Gervay, J.; Danishefsky, S. J. J. Org. Chem. 1991, 56, 5448. (b)
Bilodeau, Mark, T.; Danishefsky, S. J. Coupling of glycals: a new strategy for
the rapid assembly of oligosaccharides. Front. Nat. Prod. Res. 1996, 1,
171(Modern Methods in Carbohydrare Synthesis). (c) Danishefsky, S. J.;
Bilodeau, M. T. Angew. Chem., Int. Ed. Engl. 1996, 35, 1380. (d) Seeberger,
P. H.; Danishefsky, S. J. Acc. Chem. Res. 1998, 31, 685, and references cited
therein.
(33) (a) Hanessian, S.; Bacquet, C.; Lehong, N. Carbohydr. Res. 1980, 80,
C17. (b) Mukaiyama, T.; Murai, Y.; Shoda, S. Chem. Lett. 1981, 431. (c) Nicolau,
K.; Seitz, S.; Papahatjis, D. J. Am. Chem. Soc. 1983, 105, 2430. (d) Kahne, D.;
Walker, S.; Cheng, Y.; Van Engen, D. J. Am. Chem. Soc. 1989, 111, 6881. (e)
Van Boom, J. Tetrahedron Lett. 1990, 31, 1331. (f) Sinay¨, P.; Marra, A.; Esnault,
J.; Veyrieres, A. J. Am. Chem. Soc. 1992, 114, 6354. (g) Schmidt, R.; Kinzy,
W. AdV. Carbohydr. Chem. Biochem. 1994, 50, 21. (h) Danishefsky, S.; Bilodeau,
M. Angew. Chem., Int. Ed. Engl. 1996, 35, 1381. (i) Mukaiyama, T. Angew.
Chem., Int. Ed. 2004, 43, 5590. (j) Crich, D.; Lim, L. B. L. Org. React. 2004,
64, 115.
(36) Nicolau, K. C.; Webber, S. E. Synthesis 1986, 453.
(37) Gonzalez, A. G.; Brouard, I.; Leon, F.; Padron, J. I.; Bermejo, J.
Tetrahedron Lett. 2001, 42, 3187.
(38) (a) Haasnoot, C. A. G.; De Leeuw, F. A. A. M.; Altona, C. Tetrahedron
1980, 36, 2783. (b) Manor, P. C.; Saenger, W.; Davies, D. B.; Jankowski, K.;
Rabczenko, A. Biochim. Biophys. Acta 1974, 340, 472. (c) Stenutz, R.;
Carmichael, I.; Widmalm, G.; Serianni, A. S. J. Org. Chem. 2002, 67, 949.
(39) (a) Thibaudeau, C.; Stenutz, R.; Hertz, B.; Klepach, T.; Zhao, S.; Wu,
Q.; Carmichael, I.; Serianni, A. J. Am. Chem. Soc. 2004, 121, 15668. (b)
(34) Hanessian, S.; Plessas, N. R. J. Org. Chem. 1969, 34, 1035.
(35) Xin-An, L.; Chien-Hung, C.; Cheng-Chung, W.; Shang-Cheng, H. Synlett
2003, 1364.
Equations: (i) 2.8Pgg + 2.2Pgt + 11.1Ptg ) JH5,H6proS; (ii) 0.9Pgg + 10.8Pgt
4.7Ptg ) JH5,H6proR; (iii) Pgg + Pgt + Ptg ) 1.
+
7268 J. Org. Chem. Vol. 73, No. 18, 2008

Conformational Domino Effect in Saccharides
SCHEME 2. Synthesis of the Disaccharide 3r
SCHEME 3. Synthesis of the tert-Butyl Disaccharides 24r and 25r
All model disaccharides contain CD exciton-coupled chro-
mophores at C4′ and C6′,40 namely p-bromobenzoates, in order
to provide their CD spectra and less crowded NMR spectra.
This approach allows the coupling constants to be determined
more accurately under a first-order NMR analysis. Therefore,
UV and CD spectroscopy were also used to characterize these
compounds; the intramolecular charge-transfer band was around
245 nm in the UV, and the exciton Cotton effects were about
251 and 234 nm in the CD spectra.
and exo-anti rotamers around the Φ torsion angle (Figure 1)
have a nonbonding electron pair located antiperiplanar to the
C1-O5 bond, so only these two rotamers have the appropiate
spatial disposition for the exo anomeric effect (nO1 f σC1-O5*).
However, the axial configuration at C1 in the R-anomers leads
Conformational Analysis. General Method. Stereoelec-
tronic effects41,42 have long been recognized to influence the
conformation of carbohydrates. Both endo and exo anomeric
effects are present in R-glucosides, while only the exo anomeric
effect is present in ꢀ-glucosides (Figure 5). In R-glucosides,
these two effects have opposing influences on the structural
parameters of the bonds involved, and as a result, these
parameters are only finely modified.41,42 The plausible exo-syn
FIGURE 4. General NMR characteristics of model disaccharides.
(40) For a monograph on exciton CD spectroscopy, see: (a) Harada, N.;
Nakanishi, K. Circular Dichroic Spectroscopy. Exciton Coupling in Organic
Stereochemistry; University Science Books: California, 1983. (b) Nakanishi, K.;
Berova, N. In The Exciton Chirality Method in Circular Dichroism, Principles
and Applications; Nakanishi, K., Berova, N., Woody, R. W., Eds.; VCH
Publishers: New York, 1994.
FIGURE 5. Orbitals involved in the exo- and endo anomeric effects
in R- and ꢀ-glucosides.
J. Org. Chem. Vol. 73, No. 18, 2008 7269

Roën et al.
TABLE 1. Coupling Constants and Calculated Rotameric Populations (%) around the C5-C6 (Residue I) for the Pentahydroxy
Disaccharides 11r-13r and 24r (DMSO-d6)
a
a
compd
R
JH5,H6R
JH5,H6S
Pgg
Pgt
Ptg
compd
JH5,H6R
JH5,H6S
Pgg
Pgt
Ptg
11r
12r
13r
24r
Me
6.8
4.6
6.4
6.0
44
63
47
50
56
37
53
50
0
0
0
0
11ꢀ
12ꢀ
13ꢀ
24ꢀ
6.8
7.4
6.6
7.2
44
38
46
40
56
62
54
60
0
0
0
0
(+)-Mn
(-)-Mn
tert-Bu
a Not detected. An estimated value of 0.9 Hz was used for calculations.
FIGURE 6. Main cross-peaks observed for the model disaccharides
11r-13r and 24r in the T-ROESY experiments (DMSO-d6). Signifi-
cant cross-peaks of the rotamers around the C5-C6 bond are shown
in blue.
to strong nonbonded interactions between the aglycon (R) and
the sugar ring under the exo-anti rotamer, which becomes very
unstable or nonexistent and the exo-syn, free of these nonbonded
interactions, the most stable. The rotameric populations around
the Φ torsion angle will depend on the bulkiness of the aglycon,
more precisely on the effective bulkiness involved in nonbonded
interactions. We will discuss below how the molar refractivity31
of the aglycons is correlated with the different rotational
populations of the interglycosidic linkage, i.e., with those of
the hydroxymethyl group around the C5-C6 bond (residue I).
Conformational Analysis of the Hydroxymethyl Group
around the C5-C6 Bond (Residue I). The conformational
study of the pentahydroxy disaccharides 11r-13r and 24r with
an R configuration in C1 was carried out in a way similar to
that of their ꢀ stereoisomers. NMR spectra were measured in
DMSO-d6, and the data are gathered in Table 1. The JH5,H6R
values were between 4.6 and 6.8 Hz, while the JH5,H6S values
could not be obtained, since the H6S signal appears as wide
doublets, the doublet with greater coupling constant correspond-
ing to the geminal coupling. These data point to very low values
of the JH5,H6S coupling constants and therefore of the tg
populations. The rotamer populations of the hydroxymethyl
groups in solution were calculated using Serianni’s equations.39
To calculate the different rotational populations, a low value
of 0.9 Hz was assigned to the JH5,H6S constant.38c The resulting
calculated populations in DMSO (Table 1) showed that the gt
rotamer was the most stable for the methyl and (-)-menthyl
disaccharides, the gg for the (+)-menthyl derivative, and gg
and gt equally populated for the tert-butyl disaccharide.
Besides confirming both anomeric configurations, the ob-
served main cross-peaks in the T-ROESY experiments (Figure
6) showed intensities in accordance with the populations shown
in Table 1. Thus, while a strong cross-peak was observed
between H6R and H5 for the (+)-menthyl derivative 12r, weak
cross-peaks were observed for the methyl, (-)-menthyl, and
tert-butyl derivatives, which possess higher gt populations than
the former.
FIGURE 7. Plot of rotamer populations around the C5-C6 bond versus
molar refractivity of the corresponding alkyl substituents of compounds
11r-13r and 24r (DMSO-d6): Pgg (red line), Pgt (blue line).43
FIGURE 8. Drawings of (-)- and (+)-menthyl derivatives in their
more stable exo-syn conformation, showing the anti or syn disposition,
respectively, of the isopropyl group with respect to residue II.
ꢀ-stereoisomers 11ꢀ-13ꢀ and 24ꢀ (Table 1), where the gt
population increased as the bulkiness of the aglycon increased.
These data indicate nonbonded interactions are responsible for
the rotational population differences for the R-series, and not
entropy (steric hindrance to motions) and stereoelectronic
effects, as in the ꢀ-series.23 Plots of the rotamer populations
against the molar refractivity of the alkyl substituents (cm3/
mol) (Figure 7) confirmed the different behavior of the two
series. The ꢀ-series follows Taft’s steric parameters30 (steric
hindrances to motions), while the R-series follows molar
refractivity.31 As can be observed in Figure 7, there is a linear
correlation of the gg and gt rotational populations around the
C5-C6 bond for compounds 11r, 12r, and 24r with the
corresponding molar refractivity parameters, but not for the (-)-
menthyl derivative 13r. For this last compound, an excellent
correlation was obtained when the cyclohexyl group was used
instead of applying its molar refractivity, signifying that the
isopropyl group on this menthyl derivative was not involved in
the nonbonded interactions (open circles in Figure 7). These
results can be explained because the “effective volume” involved
in nonbonded interactions between the aglycon and residue II
in the (-)-menthyl derivative 13r should not include the
isopropyl group. Figure 8 shows how the isopropyl group affects
the rotational populations of the hydroxymethyl group around
Analysis of the NMR data revealed higher gt and lower gg
populations for the methyl group than the secondary or tertiary
alkyl groups (menthyls and tert-butyl). The gt population
decreased as the bulkiness of the aglycon increased, especially
for the (+)-menthyl derivative, at the expense of the gg
population. This behavior is just the opposite to that of their
7270 J. Org. Chem. Vol. 73, No. 18, 2008

Conformational Domino Effect in Saccharides
TABLE 2. Coupling Constants and Calculated Rotameric Populations (%) around the C5-C6 (Residue I) for the Penta-O-acetyl
Disaccharides 14r-16r and 25r (CDCl3)
compd
R
JH5,H6R
JH5,H6S
Pgg
Pgt
Ptg
compd
JH5,H6R
JH5,H6S
Pgg
Pgt
Ptg
14r
15r
16r
25r
Me
6.5
4.2
4.5
5.7
2.0
1.1
1.9
2.1
45
66
64
52
55
34
36
48
0
0
0
0
14ꢀ
15ꢀ
16ꢀ
25ꢀ
7.4
-
6.5
7.8
1.8
-
1.9
1.7
36
64
0
a
a
(+)-Mn
(-)-Mn
tert-Bu
44
32
56
68
0
0
a H6R and H6S signals are isochronous.
FIGURE 9. Perspective view of the methyl ꢀ-D-glucopyranosyl-(1f6)-R-D-glucopyranoside derivative 14r.44
the C5-C6 bond by nonbonded interactions with residue II, so
it is appropiate to apply the molar refractivity parameter of
menthyl to the (+)-menthyl disaccharides. However, with the
(-)-menthyl disaccharides, the molar refractivity of menthyl is
too high, so that of cyclohexyl is more suitable since the
isopropyl group in these disaccharides is not involved in
nonbonded interactions with residue II.
NMR data of the penta-O-acetyl disaccharides 14r-16r and
25r (Table 2) led to rotamer populations similar to those
obtained from their pentahydroxy disaccharide precursors (Ta-
ble 1), except for the (-)-menthyl derivative. In this series, the
presence of acetyl groups permits new steric interactions with
the aglycon and possibly between the glucosidic rings. The
increased gg population of the (-)-menthyl derivative could
be due to additional steric factors. It is interesting to note the
greater gg and smaller gt populations of all R-anomers versus
the ꢀ-anomers.
Figure 9 shows four conformers of the methyl disaccharide
14r, illustrating the disposition of the methyl group, or in
general of any aglycon, with respect to residue II. While the gg
rotamer around the C5-C6 bond allows the methyl group
(aglycon) to be free from nonbonded interactions with residue
II (top two conformers), the gt conformation locates the aglycon
close to residue II (bottom two). The larger the structure of the
aglycon, the greater the steric interactions and, therefore, the
smaller the gt conformation.
Plots of the rotamer populations around the C5-C6 bond
versus molar refractivity of the corresponding alkyl substituents
of compounds 14r-16r and 25r indicate that the rotational
behavior is governed by steric effects (nonbonded interactions),
which depend on the aglycon and the solvent. Thus, Figure 10
shows excellent correlations between the rotational populations
and their corresponding molar refractivity parameters obtained
in chloroform and benzene, respectively, for the four compounds
under study. However, in polar solvents (Figure 11), only three
of the four show linearity, the (-)-menthyl derivative being
clearly excluded. As occurred with the pentahydroxy disaccha-
rides 11r-13r and 24r in DMSO-d6, when the cyclohexyl
molar refractivity parameter was used for the (-)-menthyl
derivative (open circles) in all polar solvents, excellent linearities
and high correlation coefficients were obtained in all cases.
These results can be explained as above by considering the
(41) The stereoelectronic exo-anomeric effect consists of the conformational
preference of glycosides for the gauche orientation (Lemieux, R. U.; Pavia, A. A.;
Martin, J. C.; Watanabe, K. A. Can. J. Chem. 1969, 47, 4427) as a consequence
of the stereoelectronic interaction between the p orbital of the interannular oxygen
and the σ* orbital of the pyranose C1-O5 bond. Furthermore, this effect is
responsible for the reduction and extension of C1-O1 and C1-O5 bonds,
respectively, as observed in X-ray diffraction studies. Briggs, A. J.; Glenn, R.;
Jones, P. G.; Kirby, A. J.; Ramaswamy, P. J. Am. Chem. Soc. 1984, 106, 6200).
(42) (a) Thatcher, G. R. J. In Anomeric and Associated Stereoelectronic
Effects. Scope and ControVersy in the Anomeric Effect and Associated Stereo-
electronic Effects; Thatcher, G. R. J., Ed.; ACS Symposium Series 539; American
Chemical Society: Washington, DC, 1993. (b) Juaristi, E.; Cuevas, G. In The
Anomeric Effect in New Directions in Organic and Biological Chemistry; Rees,
C. W., Ed.; CRC Press, Inc.: Boca Raton, FL, 1995.
(44) The MMX force field was used to perform the molecular mechanics
calculations (default dielectric constant ꢀ ) 1.5). PCMODEL (v. 7.0). Serena
Software.
(43) Regression line equations of Figure 8 (DMSO): Pgg ) 0.4645MR +
39.541; R2 ) 0.8401; Pgt )-0.4645MR + 60.459; R2 ) 0.8401.
J. Org. Chem. Vol. 73, No. 18, 2008 7271

Roën et al.
FIGURE 10. Plot of rotamer populations around the C5-C6 bond
versus molar refractivity of the corresponding alkyl substituents of
compounds 14r-16r and 25r: top, CDCl3; bottom, C6D6; Pgg, red
line; Pgt, blue line.45
“effective volume” involved in nonbonded interactions (Fig-
ure 8), thus confirming the origin of these rotational differences.
As shown in Figures 10 and 11, the rotational populations
around the interglycosidic linkage depend on the structural
nature of the solvent. A plot between the JH5,H6R of compounds
14r-16r and 25r and the dielectric constant of the solvents
under study (Figure 12) reveals that (i) each aglycon exhibited
different JH5,H6R and, therefore, gt rotational populations, (ii) in
nonpolar solvents, (+)- and (-)-menthyl derivatives have similar
JH5,H6R values (and gt populations), and (iii) in polar solvents
the JH5,H6R values are further apart, especially for the menthyl
derivatives 15r and 16r, which exhibit different values, and
(iv) as the dielectric constant increases the JH5,H6R values (or gt
populations) generally decrease.
FIGURE 11. Plot of rotamer populations around the C5-C6 bond
versus molar refractivity of the corresponding alkyl substituents of
compounds 14r-16r and 25r: top, (CD3)2CO; middle, CD3CN;
bottom, DMSO-d6; Pgg, red line; Pgt, blue line.46
Comparison of the pentahydroxy (Table 1) and penta-O-acetyl
disaccharide anomers (Table 2) revealed higher JH5,H6R and
lower JH5,H6S coupling constants and, therefore, larger gt and
smaller gg populations for the disaccharides with the ꢀ anomeric
configuration. This result is independent of the solvent. Figure
13 shows the plot of JH5,H6R coupling constants for the anomers
at C1 of the methyl disaccharides 14r and 14ꢀ and tert-butyl
disaccharides 25r and 25ꢀ against the dielectric constants of
the solvents used in this study. It can be observed how the
dashed lines (ꢀ-anomers) are above the solid lines (R-anomers),
the differences being wider for the bulkier tert-butyl disaccharides.
Conformational Analysis of the Hydroxymethyl Group
around the C5′-C6′ Bond (Residue II). Calculating the
FIGURE 12. Plot of JH5,H6R coupling constants versus dielectric
constants for disaccharides 14r-16r and 25r: methyl 14r (red), tert-
butyl 25r (green), (-)-menthyl 16r (light blue), and (+)-menthyl 15r
(dark blue).
(45) Regression line equations of Figure 10: (a) (top, CDCl3): Pgg
)
0.5028MR + 42.119; R2 ) 0.9933; Pgt )-0.5028MR + 57.881; R2 ) 0.9933;
(b) (bottom, C6D6): Pgg ) 0.3172MR + 37.018; R2 ) 0.9949; Pgt )-0.3592MR
+ 63.452; R2 ) 0.9464.
populations around C5′-C6′ (torsion angle ω′) for compounds
11r-16r, 24r, and 25r from JH5′,H6′R and JH5′,H6′S coupling
constants, the gg rotamer has the highest population (50-60%),
then the gt (35-45%), and finally tg (3-10%). These propor-
tions depend slightly on the solvent, the aglycon, and type of
(46) Regression line equations of Figure 11: (a) (top, acetone-d6): Pgg
)
0.575MR + 40.97; R2 ) 0.9779; Pgt )-0.575MR + 59.03; R2 ) 0.9779; (b)
(middle, CD3CN): Pgg ) 0.4727MR + 51.216; R2 ) 0.9945; Pgt )-0.4727MR
+ 48.784; R2 ) 0.9945; (c) (bottom, DMSO-d6): Pgg ) 0.5437MR + 42.983;
R2 ) 0.9852; Pgt )-0.5437MR + 57.017; R2 ) 0.9852.
7272 J. Org. Chem. Vol. 73, No. 18, 2008

Conformational Domino Effect in Saccharides
TABLE 3. Coupling Constants and Calculated Rotameric Populations (%) around the C5′-C6′ Bond (Residue ΙΙ) for the Pentahydroxy
Disaccharides 11r-13r and 24r (DMSO-d6)
compd
R
JH5′,H6′R
JH5′,H6′S
Pgg
Pgt
Ptg
compd
JH5′,H6′R
JH5′,H6′S
Pgg
Pgt
Ptg
11r
12r
13r
24r
Me
4.8
3.0
58
37
5
11ꢀ
12ꢀ
13ꢀ
24ꢀ
4.7
4.9
4.9
5.1
3.1
3.1
2.9
3.0
58
56
57
54
36
38
39
40
6
6
4
6
(+)-Mn
(-)-Mn
tert-Bu
5.6
5.1
2.8
2.8
51
56
46
41
3
3
TABLE 4. Coupling Constants and Calculated Rotameric Populations (%) around the C5′-C6′ Bond (Residue ΙΙ) for the Penta-O-acetyl
Disaccharides 14r-16r and 25r (CDCl3)
compd
R
JH5′,H6′R
JH5′,H6′S
Pgg
Pgt
Ptg
compd
JH5′,H6′R
JH5′,H6′S
Pgg
Pgt
Ptg
14r
15r
16r
25r
Me
4.8
5.0
4.8
5.0
3.3
3.5
3.5
3.4
55
52
54
52
36
37
35
38
9
11
11
10
14ꢀ
15ꢀ
16ꢀ
25ꢀ
4.9
4.9
4.9
5.1
3.2
3.3
3.3
3.2
55
54
54
53
37
37
37
39
8
9
9
8
(+)-Mn
(-)-Mn
tert-Bu
TABLE 5. CD Data for the Pentahydroxy Disaccharides 11r-13r
and 24r (EtOH)
compd
R
1EC 2EC
A
compd 1EC 2EC
A
∆Aꢀ-R
11r Me
11.8 -3.7 15.5 11ꢀ 13.3 -4.2 17.5
2.0
2.6
1.8
0.6
12r (+)-Mn 11.1 -3.1 14.2 12ꢀ 12.9 -3.9 16.8
13r (-)-Mn 12.0 -3.1 15.1 13ꢀ 13.0 -3.9 16.9
24r tert-Bu 12.2 -3.9 16.1 24ꢀ 12.8 -3.9 16.7
TABLE 6. CD Data for the Penta-O-acetyl Disaccharides
14r-16r and 25r (CH3CN)
compd
R
1EC 2EC
A
compd 1EC 2EC
A
∆Aꢀ-R
14r Me
15.0 -7.0 22.0 14ꢀ 15.3 -7.0 22.3
0.3
1.8
0.0
0.2
15r (+)-Mn 13.8 -6.7 20.5 15ꢀ 14.6 -7.7 22.3
16r (-)-Mn 15.1 -6.9 22.0 16ꢀ 15.1 -6.9 22.0
25r tert-Bu 14.4 -7.3 21.7 25ꢀ 14.9 -7.0 21.9
FIGURE 13. Plot of JH5,H6R coupling constants versus dielectric
constants for disaccharides 14r and 25r and their respective ꢀ-anomers
at C1 14ꢀ and 25ꢀ: methyl 14r and 14ꢀ (red), tert-butyl 25r and 25ꢀ
(green); ꢀ-anomers (dashed lines), and R-anomers (solid lines).
residue I). However, comparing the population differences
(∆PR-ꢀ), R-anomers possess smaller gg, similar gt, and greater
tg populations than their corresponding ꢀ-anomers. Figure 14
shows this result for the four disaccharides in five solvents.
Since the CD exciton chirality method40 has proven to be an
extremely sensitive technique commonly used for conforma-
tional analysis, the rotational populations around the C5′-C6′
bond were also analyzed by this technique. CD data for the
model pentahydroxy disaccharides are shown in Table 5 (EtOH),
while those for penta-O-acetyl disaccharides are shown in Table
6 (CH3CN). Positive A values47 were obtained for all these
compounds, small differences being observed on changing the
structure of the aglycon. Analysis of the pairwise interactions
between the chromophores at C4′ and C6′ in the three rotamers
around the C5′-C6′ bond (Figure 15)48 did not reveal a clear
pattern, in agreement with NMR results.
FIGURE 14. 3D plot of ∆P(R - ꢀ) for the gg, gt, and tg rotamers of
disaccharides 14r-16r and 25r in several solvents. Negative ∆P(R
- ꢀ) are represented by red cones, while positive values are blue.
Colorless cones signify differences below two percent, while black spots
mean zero differences.
As mentioned above, NMR data comparison between anomers
at C1 (Figure 14) revealed very similar rotational populations,
although the R-anomers have very slightly lower gg and higher
tg populations, especially in polar solvents. Analogous CD
analysis of both anomeric configurations of the model pentahy-
substituents (Tables 3 and 4). As occurs with stereoisomers
having a ꢀ configuration at C1, those with the R configuration
at C1 exhibited stronger cross-peaks between H6′S and H5 than
between H6′R and H5 in T-ROESY spectra, indicating greater
gt populations around the C5′-C6′ bond than tg.
Anomer comparison analysis revealed that disaccharides
having the R anomeric configuration at C1 did not exhibit any
clear correlation unlike the ꢀ-series, which exhibited a linear
correlation between the gg and gt populations at residue II and
Taft’s steric parameters for aliphatic substituents (aglycon,
(47) The amplitude (A value) of split CD Cotton effects is defined as A )
∆1-∆2 where ∆ꢀ1 and ∆ꢀ2 are intensities of the first and second Cotton effects,
respectively. Occasionally the presence of a background ellipticity alters the
intensity of the Cotton effects at short wavelengths. For this reason, the intensities
of the second Cotton effects and the amplitudes (A values) of the CD spectra of
our model compounds may not be precise; the intensities of the first Cotton
effects are thus more accurate for comparative analysis.
(48) According to the CD exciton chirality method, the pairwise interaction
between the chromophores at C4 and C6 in the three dispositions have a positive
exciton contribution for the gg rotamer, negative for the gt, and null for the tg.
Furthermore, the pairwise interaction for the gg rotamer is stronger due to the
smaller distance between the chromophores in these positions and to a favorable
dihedral angle.
J. Org. Chem. Vol. 73, No. 18, 2008 7273

Roën et al.
FIGURE 15. Sign and relative intensities for the pairwise interaction
between the chromophores at C4′ and C6′ in the three rotamers.
FIGURE 18. Schematic representation of the remote conformational
effect in alkyl ꢀ-D-glucopyranosyl-(1f6)-ꢀ- and R-D-glucopyranosides.
mational dependences, largely stereoelectronic and steric for the
ꢀ-anomers, and only steric for the R-anomers.
Conclusions
A series of alkyl ꢀ-D-glucopyranosyl-(1f6)-R-D-glucopyra-
nosides containing different aglycons were synthesized and
analyzed by CD and NMR techniques. The results revealed that
the rotational populations of the hydroxymethyl group involved
in the interglycosidic linkage (torsion angle ω, O5-C5-C6-O6)
depend on the structure of the aglycon and on the solvent; gg
or gt being the most stable rotamers. Contrary to what happens
with alkyl ꢀ-D-glucopyranosyl-(1f6)-ꢀ-D-glucopyranosides,
where steric and stereoelectronic effects are responsible for the
rotational populations of the hydroxymethyl group involved in
the interglycosidic linkage, the populations of those with the R
configuration at C1 depend only on steric effects. Besides this,
while the populations of the alkyl ꢀ-D-glc-(1f6)-ꢀ-D-glc
correlate with the Taft steric (ES) parameter of the alkyl
substituents, the rotational populations of their corresponding
R-anomers (alkyl ꢀ-D-glc-(1f6)-R-D-glc) correlate with the
molar refractivity (MR) parameters of the alkyl substituents.
All these results support the predicted conformational domino
effect in saccharides and show how important the anomeric
configuration at each sugar residue is in determining the
conformational populations of its glycosidic linkage with the
next sugar residue (Figure 17).
FIGURE 16. CD spectra of methyl disaccharides: 11r (red line) and
11ꢀ (black line) in EtOH.
In addition, the rotational populations around the C5′-C6′
bond (torsion angle ω′) in alkyl ꢀ-D-glc-(1f6)-R-D-glc are
shown to depend weakly on the structural nature of the aglycon
(residue I) and the solvent, the gg rotamer being the most stable
in all cases (Figure 18). Anomer comparison analysis between
the rotational populations around the C5′-C6′ bond indicated
that, in general, independently of the solvent, the gg population
is slightly smaller, the gt is similar, and tg slightly higher in
the R series that in the ꢀ. This observation agrees with CD data,
where smaller amplitudes were obtained for the R-anomers. This
tiny remote conformational dependence in the second sugar
residue, through simply changing the anomeric configuration
in the first residue, supports the above-mentioned domino effect
in (1f6)-linked oligosaccharides.
FIGURE 17. Schematic representation of a conformational domino
effect in (1f6)-linked oligosaccharides.
droxy- or penta-O-acetyldisaccharides confirmed this. The
results obtained showed very similar amplitudes (A values)
between the two series, although the ∆Aꢀ-R values were between
0.0 and 2.6, confirming slight conformational differences in the
hydroxymethyl group at residue II on varying the configuration
in the first residue. According to the sign and relative intensity
of the pairwise interaction between the chromophores at C4′
and C6′ in the three rotamers (Figure 15), smaller gg and/or
larger gt populations should be expected for R-anomer disac-
charides. The more intense Cotton effects for ꢀ-than R-anomers
can be observed in the CD spectrum shown in Figure 16.
The results provide evidence for a remote conformational
relay from the aglycon to the hydroxymethyl group at residue
II. It is very small, due to the great distance between the groups,
and follows a different pattern than the ꢀ-anomers, since no
relationship was observed between the gg and gt populations
and the Taft steric parameters of the aglycons. This differing
anomer behavior confirms the separate origin of these confor-
Experimental Section
General Procedure for Preparation of Disaccharides 2r,
4r-6r, and 22r. A solution of dimethyldioxirane in acetone (2
equiv) was added to a stirred solution of disaccharide 1 in dry
CH2Cl2 (5 mL/mmol) at 0 °C under an argon atmosphere, and the
reaction was stirred 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
7274 J. Org. Chem. Vol. 73, No. 18, 2008

Conformational Domino Effect in Saccharides
argon, and molecular sieves 3 Å and the corresponding nucleophile
were added. The reaction mixture was cooled to -78 °C, and then
0.5 equiv of a 1.0 M solution of ZnCl2 in diethyl ether was added.
The reaction was allowed to warm to room temperature and stirred
overnight. The mixture was diluted with EtOAc, filtered, and
washed with water, the combined organic layers were dried over
MgSO4 and filtered, and the solvent was removed under reduced
pressure. After this, 2 mL of a 1:1 solution of dry pyridine/acetic
anhydride was added at room temperature and stirred overnight.
Excess solvent was removed under reduced pressure and the residue
purified with column chromatography.
General Procedure for Debenzylation. DDQ (2.5 equiv) at
room temperature was added to a stirred solution of the starting
material in CH2Cl2/H2O (9:1, 50 mL/mmol). This was then diluted
with CH2Cl2 and washed with saturated NaHCO3 solution. The
aqueous layer was extracted with CH2Cl2 twice, the combined
organic layers were dried over MgSO4 and filtered, and the solvent
was removed under reduced pressure. The residue was purified with
column chromatography.
H-4′), 5.06 (t, J ) 8.5 Hz, H-2′), 4.83 (d, J ) 3.6 Hz, H-1), 4.73
(d, J ) 10.9 Hz, 1H), 4.63 (dd, J ) 3.6, 9.7 Hz, H-2), 4.48 (d, J
) 8.0 Hz, H-1′), 4.44 (dd, J ) 2.7, 12.1 Hz, H-6′proS), 4.43 (d, J )
11.3 Hz, 1H), 4.35 (dd, J ) 4.9, 12.1 Hz, H-6′proR), 4.06 (t, J )
9.2 Hz, H-3), 4.04 (dd, J ) 1.7, 10.5 Hz, H-6proS), 3.99 (t, J ) 8.9
Hz, H-3′), 3.83 (m, H-5′), 3.78 (s, 3H), 3.76 (m, H-5), 3.53 (dd, J
) 6.1, 10.5 Hz, H-6proR), 3.30 (s, 3H), 3.26 (t, J ) 9.4 Hz, H-4),
2.11 (s, 3H), 2.06 (s, 3H), 0.89 (s, 9H), 0.72 (s, 9H), 0.10 (s, 3H),
0.06 (s, 3H), -0.01 (s, 3H), -0.20 (s, 3H); 13C NMR (δ, CDCl3)
170.4 (s), 169.0 (s), 165.4 (s), 164.3 (s), 159.2 (s), 131.8-128.4,
113.8 (2d), 101.0 (d, C-1′), 96.6 (d, C-1), 79.1 (d, C-4), 74.5 (t),
74.3 (d, C-2), 73.4 (d, C-2′), 72.9 (d, C-3′), 72.4 (d, C-4′), 71.9 (d,
C-3), 71.7 (d, C-5′), 69.6 (d, C-5), 68.1 (t, C-6), 63.7 (t, C-6′),
55.3 (q), 54.9 (q), 25.8 (3q), 25.4 (3q), 21.3 (2q), 18.0 (s), 17.7
(s), -4.0 (q), -4.2 (q), -4.5 (2q); UV (CH3CN) λmax 245 nm; CD
(CH3CN) λ (∆ε) 251 (13.7), 234 nm (-3.3). Anal. Calcd for
C51H70Br2O16Si2: C, 53.0; H, 6.1. Found: C, 53.01; H, 6.30.
(+)-Menthyl 2-O-Acetyl-6-O-[2-O-acetyl-4,6-bis-O-(4-bro-
mobenzoyl)-3-O-(tert-butyldimethylsilyl)-ꢀ-D-glucopyranosyl]-
3-O-(tert-butyldimethylsilyl)-4-O-(4-methoxybenzyl)-r-D-glu-
copyranoside (4r). Following the general procedure, 136 mg (0.13
mmol) of compound 1 was epoxidized and treated with 100 mg of
(+)-menthol (0.64 mmol, 5 equiv) to provide, after column
chromatography (n-hexane/EtOAc, 9.5:0.5), 65 mg of compound
4 (0.05 mmol) with a 40% yield as anomer mixture (ꢀ/R ) 1.2:1).
Compound 4r: TLC Rf ) 0.61 (n-hexane/EtOAc, 7:3); mp )
142.1-144.4 °C; [R]25D ) +48.7 (c 1.4, CHCl3); MS (FAB) 1280,
1278, 1276 (0.1, 0.1, 0.1 [M + Na]+), 687, 685, 683 (3, 5, 2,
[C28H33SiBr2O8]), 185, 183 (9, 10, [BrBz]), 121 (100, [C8H9O];
1H NMR (δ, CDCl3) 7.82 (d, J ) 8.6 Hz, 2H), 7.74 (d, J ) 8.5
Hz, 2H), 7.54 (d, J ) 8.6 Hz, 2H), 7.46 (d, J ) 8.5 Hz, 2H), 7.25
(d, J ) 8.6 Hz, 2H), 6.87 (d, J ) 8.6 Hz, 2H), 5.33 (t, J ) 9.1 Hz,
H-4′), 5.14 (d, J ) 3.8 Hz, H-1), 5.10 (d, J ) 8.3 Hz, H-2′), 4.76
(d, J ) 10.5 Hz, 1H), 4.56 (dd, J ) 3.8, 9.8 Hz, H-2), 4.50 (d, J
) 10.7 Hz, 1H), 4.45 (d, J ) 7.8 Hz, H-1′), 4.42 (dd, J ) 3.8, 12.0
Hz, H-6′proS), 4.33 (dd, J ) 5.3, 12.0 Hz, H-6′proR), 4.04 (t, J ) 9.1
Hz, H-3), 3.99 (m, H-6proS, H-3′), 3.84 (m, H-5′), 3.80 (s, 3H),
3.77 (m, H-5), 3.75 (dd, J ) 3.0, 10.3 Hz, H-6proR), 3.44 (t, J )
9.3 Hz, H-4), 3.31 (m, 1H), 2.13 (m, 1H), 2.06 (s, 3H), 2.05 (s,
3H), 1.83 (m, 1H), 1.62 (m, 2H), 1.25 (m, 3H), 0.90 (s, 9H), 0.88
(d, J ) 6.5 Hz, 3H), 0.86 (d, J ) 6.5 Hz, 3H), 0.72 (s, 9H), 0.68
(d, J ) 6.9 Hz, 3H), 0.10 (s, 3H), 0.09 (s, 3H), -0.01 (s, 3H),
-0.18 (s, 3H); 13C NMR (δ, CDCl3) 170.3 (s), 168.8 (s), 165.4
(s), 164.3 (s), 159.3 (s), 131.8-128.2, 113.9 (2d), 100.7 (d, C-1′),
92.8 (d, C-1), 78.6 (d, C-4), 77.0 (d), 74.5 (t), 74.4 (d, C-2), 73.3
(d, C-2′), 73.0 (d, C-3′), 72.4 (d, C-4′), 72.0* (d, C-3), 71.9 (d,
C-5′), 69.9 (d, C-5), 67.2 (t, C-6), 63.9 (t, C-6′), 55.3 (q), 47.7 (d),
40.2 (t), 34.4 (t), 31.2 (d), 25.8 (3q), 25.4 (3q), 25.4 (d), 22.6 (t),
22.3 (q), 21.3 (q), 21.2 (q), 21.1 (q), 18.0 (s), 17.7 (s), 15.2 (q),
-4.0 (q), -4.2 (q), -4.4 (2q); UV (CH3CN) λmax 245 nm; CD
(CH3CN) λ (∆ε) 251 (12.0), 234 nm (-4.0). Anal. Calcd for
C60H86Br2O16Si2: C, 56.30; H, 6.80. Found: C, 56.28; H, 7.23.
(-)-Menthyl 2-O-Acetyl-6-O-[2-O-acetyl-4,6-bis-O-(4-bro-
mobenzoyl)-3-O-(tert-butyldimethylsilyl)-ꢀ-D-glucopyranosyl]-
3-O-(tert-butyldimethylsilyl)-4-O-(4-methoxybenzyl)-r-D-glu-
copyranoside (5r). Following the general procedure for preparation
of disaccharides, 140 mg (0.13 mmol) of compound 1 was
epoxidized and treated with 100 mg of (-)-menthol (0.64 mmol, 5
equiv) to give, after column chromatography (n-hexane/EtOAc, 9.5:
0.5), 87 mg (0.07 mmol) of compound 5 in 52% yield as an anomer
mixture (ꢀ/R ) 1.5:1). Compound 5r: TLC Rf ) 0.50 (n-hexane/
General Procedure for Deprotection of Silyl and Acetyl
Groups. A solution of starting material in dry diethylether (40 mL/
mmol) was added to a stirred solution of acetyl chloride (40 equiv)
in dry methanol (40 mL/mmol). When the reaction was completed,
it was concentrated under vacuum, and the residue was purified by
Sephadex column chromatography (n-hexane/CHCl3/MeOH,
2:1:1).
1,2-Di-O-acetyl-6-O-[2-O-acetyl-4,6-bis-O-(4-bromobenzoyl)-
3-O-(tert-butyldimethylsilyl)-ꢀ-D-glucopyranosyl]-3-O-(tert-bu-
tyldimethylsilyl)-4-O-(4-methoxybenzyl)-r-D-glucopyranose (2r).
Following the general procedure for preparation of disaccharides,
130 mg (0.12 mmol) of compound 1 was epoxidized and treated
with 500 µL of water giving, after acetylation, compound 2 (127
mg, 0.11 mmol) as a mixture R/ꢀ ) 2:1 with a 87% yield, isolated
after column chromatography (n-hexane/EtOAc, 8:2). Thus, 85.6
mg of R- and 41.7 mg of ꢀ-anomer were obtained. Compound 2r:
1
colorless syrup; H NMR (δ, CDCl3) 7.82 (d, J ) 8.5 Hz, 2H),
7.75 (d, J ) 8.4 Hz, 2H), 7.54 (d, J ) 8.5 Hz, 2H), 7.46 (d, J )
8.5 Hz, 2H), 7.21 (d, J ) 8.5 Hz, 2H), 6.84 (d, J ) 8.6 Hz, 2H),
6.24 (d, J ) 3.5 Hz, H-1), 5.34 (t, J ) 9.2 Hz, H-4′), 5.02 (t, J )
8.4 Hz, H-2′), 4.81 (dd, J ) 3.6, 9.8 Hz, H-2), 4.72 (d, J ) 10.7
Hz, 1H), 4.52 (d, J ) 7.9 Hz, H-1′), 4.48 (d, J ) 10.7 Hz, 1H),
4.47 (dd, J ) 3.7, 12.1 Hz, H-6′proS), 4.34 (dd, J ) 5.0, 12.1 Hz,
H-6′proR), 4.05 (t, J ) 9.0, H-3), 4.04 (dd, J ) 1.6, 10.9 Hz, H-6proS),
3.99 (t, J ) 8.9 Hz, H-3′), 3.87 (m, H-5′, H-5), 3.78 (s, 3H), 3.60
(dd, J ) 5.5, 10.9 Hz, H-6proR), 3.37 (t, J ) 8.8 Hz, H-4), 2.10 (s,
3H), 2.04 (s, 3H), 2.03 (s, 3H), 0.89 (s, 9H), 0.71 (s, 9H), 0.08 (s,
6H), -0.01 (s, 3H), -0.20 (s, 3H); 13C NMR (δ, CDCl3): 169.9
(s), 169.1 (s), 165.4 (s), 164.3 (s), 159.3 (s), 131.8-128.2, 113.8
(2d), 100.8 (d, C-1′), 89.6 (d, C-1), 78.2 (d, C-4), 74.8 (t), 73.3 (d,
C-2′), 72.9 (d, C-5), 72.9 (d, C-3′), 72.5 (d, C-2), 72.3 (d, C-4′),
71.8 (d, C-3), 71.7 (d, C-5′), 67.3 (t, C-6), 63.6 (t, C-6′), 55.3 (q),
25.7 (3q), 25.4 (3q), 21.1 (q), 20.8 (q), 18.0 (s), 17.7 (s), -4.0 (q),
-4.4 (2q), -4.5 (q); UV (CH3CN) λmax 245 nm; CD (CH3CN) λ
(∆ε) 251 (13.8), 234 nm (-5.8). Anal. Calcd for C52H70Br2O17Si2:
C, 52.79; H, 5.96. Found: C, 52.90; H, 6.05.
Methyl 2-O-Acetyl-6-O-[2-O-acetyl-4,6-bis-O-(4-bromoben-
zoyl)-3-O-(tert-butyldimethylsilyl)-ꢀ-D-glucopyranosyl]-3-O-(tert-
butyldimethylsilyl)-4-O-(4-methoxybenzyl)-r-D-glucopyrano-
side (3r). Compound 22r (179 mg, 0.17 mmol) was dissolved in
6 mL of a 1:1 solution of dry pyridine/acetic anhydride. Excess
solvent was removed under reduced pressure to give, after column
chromatography (n-hexane/EtOAc, 8:2), compound 3r (188.8 mg,
98% yield): TLC Rf ) 0.38 (n-hexane/EtOAc, 7:3); mp )
144.4-145.0 °C; [R]25D ) +26.4 (c 0.39, CHCl3); MS (FAB) 1179,
1177, 1175 (0.1, 0.1, 0.1, [M + Na]+), 687, 685, 683 (2, 4, 2,
[C28H33SiBr2O8]), 185, 183 (10, 10, [BrBz]), 121 (100, [C8H9O]);
1H NMR (δ, CDCl3) 7.82 (d, J ) 8.6 Hz, 2H), 7.75 (d, J ) 8.6
Hz, 2H), 7.54 (d, J ) 8.6 Hz, 2H), 7.45 (d, J ) 8.5 Hz, 2H), 7.21
(d, J ) 8.6 Hz, 2H), 6.85 (d, J ) 8.6 Hz, 2H), 5.34 (t, J ) 9.3 Hz,
EtOAc, 8:2); mp ) 142.1-144.4 °C; [R]25 ) +27.1 (c 0.92,
D
CHCl3); MS (FAB) 1280, 1278, 1276 (0.1, 0.1, 0.1 [M + Na]+),
687, 685, 683 (3, 5, 2, [C28H33SiBr2O8]), 185, 183 (10, 11, [BrBz]),
1
121 (100, [C8H9O]); H NMR (δ, CDCl3) 7.82 (d, J ) 8.6 Hz,
2H), 7.74 (d, J ) 8.5 Hz, 2H), 7.53 (d, J ) 8.5 Hz, 2H), 7.46 (d,
J ) 8.6 Hz, 2H), 7.24 (d, J ) 8.6 Hz, 2H), 6.86 (d, J ) 8.6 Hz,
2H), 5.33 (t, J ) 9.2 Hz, H-4′), 5.08 (t, J ) 8.4 Hz, H-2′), 5.04
(d, J ) 3.6 Hz, H-1), 4.77 (d, J ) 10.8 Hz, 1H), 4.57 (dd, J ) 3.6,
J. Org. Chem. Vol. 73, No. 18, 2008 7275

Roën et al.
9.9 Hz, H-2), 4.50 (d, J ) 10.8 Hz, 1H), 4.46 (d, J ) 7.8 Hz,
H-1′), 4.45 (dd, J ) 3.8, 12.0 Hz, H-6′proS), 4.34 (dd, J ) 5.1, 12.0
Hz, H-6′proR), 4.13 (t, J ) 9.2 Hz, H-3), 4.02 (br d, J ) 10.5 Hz,
H-6proS), 3.99 (t, J ) 8.9 Hz, H-3′), 3.89 (m, H-5), 3.82 (m, H-5′),
3.80 (s, 3H), 3.72 (dd, J ) 3.8, 10.6 Hz, H-6proR), 3.39 (t, J ) 9.3
Hz, H-4), 3.18 (m, 1H), 2.15 (m, 2H), 2.08 (s, 3H), 2.05 (s, 3H),
1.63 (m, 2H), 1.26 (m, 2H), 0.90 (s, 9H), 0.87 (d, J ) 6.5 Hz, 3H),
0.86 (d, J ) 6.5 Hz, 3H), 0.72 (s, 9H), 0.69 (d, J ) 7.0 Hz, 3H),
0.09 (s, 3H), 0.07 (s, 3H), -0.01 (s, 3H), -0.19 (s, 3H); 13C NMR
(δ, CDCl3) 170.3 (s), 168.80 (s), 165.4 (s), 164.3 (s), 159.20 (s),
131.8-128.2, 113.8 (2d), 100.9 (d, C-1′), 97.5 (d, C-1), 81.8 (d),
78.9 (d, C-4), 74.6 (d, C-2), 74.4 (t), 73.4 (d, C-2′), 73.0 (d, C-3′),
72.4 (d, C-4′), 71.8 (C-5′, C-3), 69.8 (d, C-5), 67.4 (t, C-6), 63.8
(t, C-6′), 55.3 (q), 48.6 (d), 42.7 (t), 34.3 (t), 31.5 (d), 25.8 (3q),
25.4 (3q), 25.2 (d), 23.1 (t), 22.3 (q), 21.3 (q), 21.0 (2q), 18.0 (s),
17. (s), 16.10 (q), -4.0 (q), -4.2 (q), -4.4 (2q); UV (CH3CN)
(s, 3H); 13C NMR (δ, CDCl3) 170.4 (s), 169.3 (s), 165.5 (s), 164.3
(s), 131.8-128.4, 101.2 (d, C-1′), 96.9 (d, C-1), 73.8 (d, C2), 73.5
(d, C2′), 73.0 (d, C3′), 72.5 (d, C3), 72.0 (2d, C4, C4′), 71.9 (d,
C5′), 69.7 (d, C5), 68.6 (t, C6), 63.2 (t, C6′), 55.0 (q), 25.7 (3q),
25.4 (3q), 21.2 (q), 21.1 (q), 18.1 (s), 17.7 (s), -4.4 (q), -4.5 (3q).
Anal. Calcd for C43H62Br2O15Si2: C, 49.90; H, 6.04. Found: C,
49.89; H, 6.15.
(+)-Menthyl 2-O-Acetyl-6-O-[2-O-acetyl-4,6-bis-O-(4-bro-
mobenzoyl)-3-O-(tert-butyldimethylsilyl]-ꢀ-D-glucopyranosyl]-
3-O-(tert-butyldimethylsilyl)-r-D-glucopyranoside (8r). Follow-
ing the general procedure for debenzylation, 125 mg (0.10 mmol)
of compound 4r yielded 112 mg of compound 8r (98%): TLC Rf
) 0.42 (n-hexane/EtOAc, 8:2); mp ) 86.4-87.5 °C;[R]25D ) +54.3
(c 1.15, CHCl3); MS (FAB) 1183, 1181 (0.3, 0.2, [M + Na]+),
687, 685, 683 (24, 47, 18, [C28H33SiBr2O8]), 185, 183 (100, 99,
[BrBz]); 1H NMR (δ, CDCl3) 7.82 (d, J ) 8.5 Hz, 2H), 7.80 (d, J
) 8.5 Hz, 2H), 7.54 (d, J ) 8.5 Hz, 2H), 7.51 (d, J ) 8.5 Hz, 2H),
5.35 (t, J ) 9.3 Hz, H-4′), 5.15 (d, J ) 3.9 Hz, H-1), 5.04 (d, J )
8.7 Hz, H-2′), 4.57-4.55 (H-2, H-1′), 4.48 (dd, J ) 3.3, 12.1 Hz,
H-6′proS), 4.38 (dd, J ) 4.6, 12.1 Hz, H-6′proR), 4.01 (t, J ) 9.3 Hz,
H-3′), 3.97 (dd, J ) 2.6, 10.7 Hz, H-6proS), 3.92 (m, H-3, H-5′),
3.81 (dd, J ) 3.1, 10.7 Hz, H-6proR), 3.74 (m, H-5), 3.54 (br t, J )
9.5, H-4), 3.32 (dt, J ) 3.8, 10.5, 1H), 2.46 (s, 1H), 2.16 (m, 1H),
2.10 (s, 3H), 2.07 (s, 3H), 1.82 (m, 1H), 1.65 (m, 2H), 0.86 (m,
15H), 0.71 (m, 12H), 0.12 (s, 3H), 0.09 (s, 3H), -0.00 (s, 3H),
-0.19 (s, 3H); 13C NMR (δ, CDCl3) 170.4 (s), 169.2 (s), 165.5
(s), 164.3 (s), 131.9-128.3, 101.3 (d, C-1′), 93.0 (d, C-1), 76.9
(d), 74.0 (d, C-2), 73.6 (d, C-2′), 73.0 (d, C-3′), 72.3* (d, C-4′),
72.1* (d, C-5′), 72.0* (d, C-3), 71.7* (d, C-4), 69.9 (d, C-5), 68.4
(t, C-6), 63.4 (t, C-6′), 47.7 (d), 40.1 (t), 34.4 (t), 31.3 (d), 25.7
(3q), 25.5 (d), 25.4 (3q), 22.7 (t), 22.3 (q), 21.2 (q), 21.1 (q), 21.0
(q), 18.1 (s), 17.7 (s), 15.3 (q), -4.4 (q), -4.5 (2q), -4.5 (q). Anal.
Calcd for C52H78Br2O15Si2: C, 53.88; H, 6.78. Found: C, 53.87; H,
6.44.
λmax 245 nm; CD (CH3CN) λ (∆ε) 251 (13.5), 234 nm (-4.4). Anal.
Calcd for C60H86Br2O16Si2: C, 56.30; H, 6.80. Found: C, 56.26; H,
7.10.
tert-Butyl 2-O-Acetyl-6-O-[2-O-acetyl-4,6-bis-O-(4-bromoben-
zoyl)-3-O-(tert-butyldimethylsilyl)-ꢀ-D-glucopyranosyl]-3-O-(tert-
butyldimethylsilyl)-4-O-(4-methoxybenzyl)-r-D-glucopyrano-
side (6r). Following the general procedure, 151 mg (0.14 mmol)
of compound 1 was epoxidized and treated with 1 mL of tert-butyl
alcohol to give, after column chromatography (n-hexane/EtOAc,
9:1), 84 mg (0.07 mmol) of compound 6 with a 56% yield as
anomer mixture (ꢀ/R ) 1.4:1). Compound 6r: TLC Rf ) 0.49 (n-
hexane/EtOAc, 7.5:2.5); mp ) 140.7-142.2 °C; [R]25 ) +43.7
D
(c 1.3, CHCl3); MS (FAB) 1221, 1219, 1217 (0.1, 0.2, 0.1 [M +
Na]+), 687, 685, 683 (3, 5, 3, [C28H33SiBr2O8]), 185, 183 (11, 11,
1
[BrBz]), 121 (100, [C8H9O]); H NMR (δ, CDCl3) 7.82 (d, J )
8.5 Hz, 2H), 7.74 (d, J ) 8.5 Hz, 2H), 7.54 (d, J ) 8.6 Hz, 2H),
7.46 (d, J ) 8.5 Hz, 2H), 7.23 (d, J ) 8.6 Hz, 2H), 6.84 (d, J )
8.6 Hz, 2H), 5.34 (t, J ) 9.2 Hz, H-4′), 5.24 (d, J ) 3.7 Hz, H-1),
5.10 (t, J ) 8.5 Hz, H-2′), 4.74 (d, J ) 10.6 Hz, 1H), 4.51 (d, J )
7.8 Hz, H-1′), 4.51 (dd, J ) 3.7, 9.8 Hz, H-2), 4.46 (d, J ) 10.9
Hz, 1H), 4.45 (dd, J ) 3.7, 12.0 Hz, H-6′proS), 4.34 (dd, J ) 5.0,
12.0 Hz, H-6′proR), 4.10 (t, J ) 9.2 Hz, H-3), 4.03 (dd, J ) 1.8,
10.5 Hz, H-6proS), 3.97 (m, H-3′, H-5), 3.83 (m, H-5′), 3.78 (s, 3H),
3.68 (dd, J ) 4.8, 10.5 Hz, H-6proR), 3.30 (dd, J ) 8.9, 9.8 Hz,
H-4), 2.08 (s, 3H), 2.07 (s, 3H), 1.15 (s, 9H), 0.90 (s, 9H), 0.71 (s,
(-)-Menthyl 2-O-Acetyl-6-O-[2-O-acetyl-4,6-bis-O-(4-bro-
mobenzoyl)-3-O-(tert-butyldimethylsilyl)-ꢀ-D-glucopyranosyl]-
3-O-(tert-butyldimethylsilyl)-r-D-glucopyranoside (9r). Follow-
ing the general procedure for debenzylation, 83 mg (0.07 mmol)
of compound 5r yielded 64.8 mg of compound 9r (86% yield):
TLC Rf ) 0.39 (n-hexane/EtOAc, 8:2); mp ) 85.8-87.8 °C; [R]25
D
) +36.8 (c 0.55, CHCl3); MS (FAB) 1183, 1181, 1179 (0.2, 0.4,
9H), 0.09 (s, 3H), 0.08 (s, 3H), -0.02 (s, 3H), -0.20 (s, 3H); 13
C
0.1, [M + Na]+), 687, 685, 683 (17, 41, 18, [C28H33SiBr2O8]), 185,
1
NMR (δ, CDCl3) 170.3 (s), 168.8 (s), 165.4 (s), 164.3 (s), 159.2
(s), 131.8-128.2, 113.8 (2d), 100.6 (d, C-1′), 90.1 (d, C-1), 79.2
(d, C-4), 75.0 (d, C-2), 74.6 (t), 73.2 (d, C-2′), 73.1* (d, C-3′),
72.4 (d, C-4′), 71.8 (C-5′, C-3), 69.6* (d, C-5), 67.8 (t, C-6), 63.7
(t, C-6′), 55.2 (q), 29.3 (3q), 25.8 (3q), 25.5 (3q), 21.3 (q), 21.1
(q), 18.0 (s), 17.7 (s), -4.0 (q), -4.3 (q), -4.5 (2q); UV (CH3CN)
λmax 245 nm; CD (CH3CN) 112 (∆ε) 251 (13.8), 234 nm (-3.4).
Anal. Calcd for C54H76Br2O16Si2: C, 54.20; H, 6.40. Found: C,
54.23; H, 6.81.
183 (82, 100, [BrBz]); H NMR (δ, CDCl3) 7.85 (d, J ) 8.5 Hz,
2H), 7.84 (d, J ) 8.5 Hz, 2H), 7.55 (d, J ) 8.5 Hz, 2H), 7.54 (d,
J ) 8.5 Hz, 2H), 5.36 (t, J ) 9.4 Hz, H-4′), 5.04 (m, H-2′, H-1),
4.60 (m, H-2), 4.59 (d, J ) 8.0 Hz, H-1′), 4.56 (dd, J ) 3.7, 12.2
Hz, H-6′proS), 4.30 (dd, J ) 4.1, 12.2 Hz, H-6′proR), 4.04-3.94 (H-
3′, H-6proS, H-3), 3.87-3.80 (H-5′, H-6proR, H-4), 3.46 (m, H-5),
3.18 (dt, J ) 4.2, 10.5 Hz, 1H), 2.50 (d, J ) 4.6 Hz, 1H), 2.13 (m,
2H), 2.10 (s, 3H), 2.05 (s, 3H), 1.54 (m, 2H), 1.25 (m, 3H), 0.86
(15H), 0.71 (12H), 0.12 (s, 3H), 0.09 (s, 3H), -0.01 (s, 3H), -0.20
(s, 3H); 13C NMR (δ, CDCl3) 170.2 (s), 169.2 (s), 165.5 (s), 164.3
(s), 131.9-128.4, 101.3 (d, C-1′), 97.8 (d, C-1), 81.9 (d), 74.3 (d,
C-2), 73.7 (d, C-2′), 73.1 (d, C-3′), 72.3 (d, C-3), 72.0* (d, C-4),
72.0* (d, C-4′), 72.0* (d, C-5), 70.2 (d, C-5′), 68.5 (t, C-6), 63.0
(t, C-6′), 48.6 (d), 42.8 (t), 34.2 (t), 31.5 (d), 25.7 (3q), 25.4 (3q),
25.1 (d), 23.1 (t), 22.3 (q), 21.3 (q), 21.0 (q), 20.9 (q), 18.1 (s),
17.7 (s), 16.1 (q), -4.3 (q), -4.4 (q), -4.5 (q), -4.5 (q). Anal.
Calcd for C52H78Br2O15Si2: C, 53.88; H, 6.78. Found: C, 53.91; H,
6.94.
Methyl 2-O-Acetyl-6-O-[2-O-acetyl-4,6-bis-O-(4-bromoben-
zoyl)-3-O-(tert-butyldimethylsilyl)-ꢀ-D-glucopyranosyl]-3-O-(tert-
butyldimethylsilyl)-r-D-glucopyranoside (7r). Following the
general procedure for debenzylation, 123 mg (0.11 mmol) of
compound 3r yielded 106.2 mg of compound 7r (93%): TLC Rf
) 0.31 (n-hexane/EtOAc, 7:3); mp ) 88.5-90.1 °C; [R]25
)
D
+45.2 (c 1.09, CHCl3); MS (FAB) 1059, 1057, 1055 (0.2, 1, 0.3,
[M + Na]+), 687, 685, 683 (21, 41, 18, [C28H33SiBr2O8]), 185,
1
183 (98, 100, [BrBz]); H NMR (δ, CDCl3) 7.83 (d, J ) 8.5 Hz,
2H), 7.82 (d, J ) 8.5 Hz, 2H), 7.55 (d, J ) 8.9 Hz, 2H), 7.53
(d, J ) 8.9 Hz, 2H), 5.36 (t, J ) 9.4 Hz, H-4′), 5.05 (dd, J ) 8.2,
8.9 Hz, H-2′), 4.86 (d, J ) 3.6 Hz, H-1), 4.62 (dd, J ) 3.6, 9.8 Hz,
H-2), 4.58 (d, J ) 8.0 Hz, H-1′), 4.50 (dd, J ) 3.4, 12.2 Hz,
H-6′proS), 4.35 (dd, J ) 4.5, 12.2 Hz, H-6′proR), 4.09 (br d, J ) 8.4
Hz, H-6proS), 4.01 (t, J ) 9.0 Hz, H-3′), 3.94 (t, J ) 8.7 Hz, H-3),
3.88 (m, H5′), 3.75-3.68 (H-6proR, H5), 3.43 (m, H-4), 3.32 (s,
3H), 2.34 (d, J ) 4.0 Hz, 1H), 2.11 (s, 3H), 2.10 (s, 3H), 0.86 (s,
9H), 0.71 (s, 9H), 0.11 (s, 3H), 0.09 (s, 3H), 0.00 (s, 3H), - 0.19
tert-Butyl 2-O-Acetyl-6-O-[2-O-acetyl-4,6-bis-O-(4-bromoben-
zoyl)-3-O-(tert-butyldimethylsilyl)-ꢀ-D-glucopyranosyl]-3-O-(tert-
butyldimethylsilyl)-r-D-glucopyranoside (10r). Following the
general procedure for debenzylation, 90 mg (0.08 mmol) of
compound 6r yielded 74.4 mg of compound 10r (92%): TLC Rf
) 0.45 (n-hexane/EtOAc, 7:3); mp ) 83.3-84.7 °C; [R]25
)
D
+52.3 (c 0.79, CHCl3); FAB-MS: 1101, 1099, 1197 (1, 2, 1, [M +
Na]+), 687, 685, 683 (52, 95, 41, [C28H33SiBr2O8]), 185, 183 (100,
1
99, [BrBz]); H NMR (δ, CDCl3) 7.82 (d, J ) 8.5 Hz, 2H), 7.81
7276 J. Org. Chem. Vol. 73, No. 18, 2008

Conformational Domino Effect in Saccharides
(d, J ) 8.5 Hz, 2H), 7.54 (t, J ) 8.5 Hz, 2H), 7.52 (t, J ) 8.5 Hz,
2H), 5.36 (t, J ) 9.3 Hz, H-4′), 5.25 (d, J ) 3.5 Hz, H-1), 5.05 (t,
J ) 8.5 Hz, H-2′), 4.59 (d, J ) 8.0 Hz, H-1′), 4.49 (m, H-2,
H-6′proS), 4.36 (dd, J ) 4.5, 12.1 H-6′proR), 4.00 (m, H-3′, H-6proS),
3.93 (t, J ) 8.9 Hz, H-3), 3.87 (m, H-5, H-5′), 3.75 (dd, J ) 4.8,
10.4 Hz, H-6proR), 3.44 (dt, J ) 3.2, 9.0, H-4), 2.34 (d, J ) 3.2 Hz,
1H), 2.10 (s, 3H), 2.05 (s, 3H), 1.17 (s, 9H), 0.87 (s, 9H), 0.71 (s,
+43.4 (c 0.32, CHCl3); MS (FAB) 531, 529, 527 (0.8, 3, 1,
[C20H17Br2O7]), 307 (9, [C12H19O9]), 185, 183 (9.60, 11, [BrBz]),
154 (100); 1H NMR (δ, DMSO) 7.89 (d, J ) 8.6 Hz, 2H), 7.86 (d,
J ) 8.6 Hz, 2H), 7.76 (d, J ) 8.6 Hz, 2H), 7.72 (d, J ) 8.6 Hz,
2H), 5.53 (d, J ) 5.3 Hz, 1H), 5.30 (d, J ) 4.7 Hz, 1H), 4.99 (d,
J ) 7.0 Hz, 1H), 4.98 (t, J ) 9.6 Hz, H-4′), 4.86 (br s, 1H), 4.73
(d, J ) 3.7 Hz, H-1), 4.64 (d, J ) 5.6 Hz, 1H), 4.46 (d, J ) 7.8
Hz, H-1′), 4.40 (dd, J ) 2.8, 12.0 Hz, H-6′proS), 4.28 (dd, J ) 5.6,
10.8 Hz, H-6′proR), 3.98 (m, H-5′), 3.98 (d, J ) 10.1 Hz, H-6proS),
3.80 (m, H-5), 3.69 (dd, J ) 6.4, 11.0 Hz, H-6proR), 3.64 (m, H-3′),
3.42 (br t, J ) 7.5 Hz, H-3), 3.26-3.19 (m, H-2, H-2′, 1H), 3.12
(m, H-4), 2.43 (m, 1H), 2.25 (br d, J ) 12.2 Hz, 1H), 1.57 (m,
2H), 1.35 (m, 2H), 1.14 (m, 1H), 0.95 (m, 2H), 0.89 (d, J ) 6.5
Hz, 3H), 0.83 (d, J ) 7.0 Hz, 3H), 0.78 (m, 1H), 0.73 (d, J ) 6.9
Hz, 3H); 13C NMR (δ, DMSO) 165.8 (s), 165.5 (s), 132.7-128.4,
104.8 (d, C-1′), 101.6 (d, C-1), 81.3* (d), 74.6* (d, C-2), 74.6* (d,
C-3′), 73.9 (d, C-3), 73.4 (d, C-4′), 73.2* (d, C-2′), 72.5 (d, C-5),
71.6 (d, C-5′), 70.3 (d, C-4), 70.8 (t, C-6), 64.7 (t, C-6′), 49.4 (d),
43.4 (t), 34.9 (t), 32.1 (d), 24.9 (d), 23.5 (t), 23.3 (q), 21.9 (q),
17.0 (q); UV (EtOH) λmax 245 nm; CD (EtOH) λ (∆ε) 251 (12.0),
234 nm (-3.1). Anal. Calcd for C36H46Br2O13: C, 51.08; H, 5.48.
Found: C, 51.07; H, 5.64.
9H), 0.11 (s, 3H), 0.09 (s, 3H), -0.01 (s, 3H), -0.20 (s, 3H); 13
C
NMR (δ, CDCl3) 170.4 (s), 169.2 (s), 165.5 (s), 164.3 (s),
131.9-128.4, 101.1 (d, C-1′), 90.4 (d, C-1), 75.2 (s), 74.1 (d, C-2),
73.5 (d, C-2′), 73.1 (d, C-3′), 72.4 (d, C-3), 72.2 (d, C-4′), 72.1 (d,
C-4), 71.9 (d, C-5), 69.5 (d, C-5′), 68.5 (t, C-6), 63.4 (t, C-6′),
29.7 (q), 29.3 (q), 28.4 (3q), 25.7 (3q), 25.4 (3q), 21.3 (q), 21.0
(q), 18.1 (s), 17.7 (s), -4.5 (4q). Anal. Calcd for C46H68Br2O15Si2:
C, 51.30; H, 6.36. Found: C, 51.42; H, 6.53.
Methyl 6-O-[4,6-Bis-O-(4-bromobenzoyl)-ꢀ-D-glucopyrano-
syl]-r-D-glucopyranoside (11r). Following the general procedure
for desilylation and deacetylation, 35 mg (0.08 mmol) of compound
7r yielded 17.3 mg of compound 11r (63%): TLC Rf ) 0.17
(CH2Cl2/MeOH, 9:1); mp ) 160.2-161.5 °C; [R]25 ) +74.6 (c
D
0.39, CHCl3); MS (FAB) 745 (0.4, [M + Na]+), 531, 529, 527 (3,
7, 4, [C20H17Br2O7]), 307 (17, [C12H19O9]), 185, 183 (30, 29,
1
[BrBz]), 154 (100); H NMR (δ, DMSO) 7.89 (d, J ) 8.5 Hz,
Methyl 2,3,4-Tri-O-acetyl-6-O-[2,3-di-O-acetyl-4,6-bis-O-(4-
bromobenzoyl)-ꢀ-D-glucopyranosyl]-r-D-glucopyranoside (14r).
Compound 11r (65 mg, 0.09 mmol) was dissolved in 1 mL of a
1:1 solution of dry pyridine/acetic anhydride. Excess solvent was
removed under reduced pressure to give, after column chromatog-
raphy (n-hexane/EtOAc, 8:2), compound 14r (66.0 mg) in 79%
yield: TLC Rf ) 0.36 (n-hexane/EtOAc, 1:1); mp ) 230.5-232.9
2H), 7.85 (d, J ) 8.5 Hz, 2H), 7.75 (d, J ) 8.6 Hz, 2H), 7.73 (d,
J ) 8.5 Hz, 2H), 5.49 (d, J ) 5.6 Hz, 1H), 5.38 (d, J ) 4.9 Hz,
1H), 5.05 (d, J ) 6.4 Hz, 1H), 5.02 (t, J ) 9.6 Hz, H-4′), 4.88 (br
s, 1H), 4.76 (d, J ) 6.3 Hz, 1H), 4.55 (d, J ) 3.6 Hz, H-1), 4.51
(d, J ) 7.8 Hz, H-1′), 4.39 (dd, J ) 3.0, 12.0 Hz, H-6′proS), 4.32
(dd, J ) 4.8, 12.0 Hz, H-6′proR), 4.00 (br d, J ) 11.0, H-6proS), 3.96
(m, H5′), 3.68 (dd, J ) 6.8, 11.3 Hz, H-6proR), 3.62 (m, H5, H3′),
3.42 (m, H-3), 3.30 (s, 3H), 3.22 (m, H-2, H-2′), 3.11 (m, H-4);
13C NMR (δ, DMSO) 165.7 (s), 165.4 (s), 132.8-128.4, 104.6 (d,
C-1′), 100.6 (d, C-1), 74.6* (d, C-3′), 74.5* (d, C-2′), 74.2 (d, C-3),
73.2 (d, C-4′), 72.8* (d, C-2), 72.2* (d, C-5), 71.6 (d, C-5′), 71.3
(d, C-4), 70.3 (t, C-6), 64.5 (t, C-6′), 55.4 (q); UV (EtOH) λmax
245 nm; CD (EtOH) λ (∆ε) 251 (11.8), 234 nm (-3.7). Anal. Calcd
for C27H30Br2O13: C, 44.90; H, 4.19. Found: C, 44.91; H, 4.54.
(+)-Menthyl 6-O-[4,6-Bis-O-(4-bromobenzoyl)-ꢀ-D-glucopy-
ranosyl]-r-D-glucopyranoside (12r). Following the general pro-
cedure for desilylation and deacetylation, 45.5 mg (0.04 mmol) of
compound 8r yielded 27.3 mg of compound 12r (81%): TLC Rf
°C dec; [R]25 ) +46.7 (c 1.63, CHCl3); MS (FAB) 933 (0.6,
D
[M]+), 615, 613, 611 (9, 17, 8, [C24H21Br2O9]), 307 (25,
1
[C12H19O9]), 185, 183 (21, 22, [BrBz]), 154 (100); H NMR (δ,
CDCl3) 7.81 (d, J ) 8.5 Hz, 2H), 7.77 (d, J ) 8.5 Hz, 2H), 7.54
(d, J ) 8.5 Hz, 4H), 5.45 (t, J ) 9.6 Hz, H-4′), 5.42 (t, J ) 9.4 Hz,
H-3′), 5.39 (t, J ) 9.4 Hz, H-3), 5.10 (t, J ) 8.0 Hz, H-2′), 4.92
(d, J ) 3.5 Hz, H-1), 4.91 (t, J ) 9.4 Hz, H-4), 4.84 (dd, J ) 3.5,
10.2 Hz, H-2), 4.66 (d, J ) 7.9 Hz, H-1′), 4.53 (dd, J ) 3.3, 12.1
Hz, H-6′proS), 4.39 (dd, J ) 4.8, 12.1 Hz, H-6′proR), 3.97-3.92 (H-
5′, H-5, H-6proS), 3.57 (dd, J ) 6.5, 11.1 Hz, H-6proR), 3.38 (s, 3H),
2.07 (s, 6H), 1.99 (s, 6H), 1.90 (s, 3H); 13C NMR (δ, CDCl3) 170.1
(2s), 170.0 (s), 169.6 (s), 169.3 (s), 165.3 (s), 164.4 (s), 132.0-127.6,
101.1 (d, C-1′), 96.5 (d, C-1), 72.3 (d, C-3), 71.8 (d, C-5′), 71.1
(d, C-2′), 70.9 (d, C-2), 70.1 (d, C-4′), 69.9 (d, C-3′), 69.0 (d, C-4),
68.2 (d, C-5), 68.2 (t, C-6), 63.1 (t, C-6′), 55.3 (q), 20.6 (4q), 20.5
(q); UV (CH3CN) λmax 245 nm; CD (CH3CN) λ (∆ε) 251 (15.0),
234 nm (-7.0). Anal. Calcd for C37H40Br2O18: C, 47.66; H, 4.32.
Found: C, 47.67; H, 4.49.
) 0.37 (CH2Cl2/MeOH, 9:1); mp ) 158.3-159.7 °C; [R]25
)
D
+7.5 (c 0.43, CHCl3); MS (FAB) 871, 869, 867 (1, 1, 1, [M +
Na]+), 531, 529, 527 (5, 10, 5, [C20H17Br2O7]), 307 (26,
1
[C12H19O9]), 185, 183 (16, 17, [BrBz]), 154 (100); H NMR (δ,
DMSO) 7.89 (d, J ) 8.5 Hz, 2H), 7.84 (d, J ) 8.6 Hz, 2H), 7.75
(d, J ) 8.6 Hz, 2H), 7.71 (d, J ) 8.4 Hz, 2H), 5.50 (d, J ) 5.7 Hz,
1H), 5.28 (d, J ) 4.9 Hz, 1H), 5.01 (d, J ) 5.6 Hz, 1H), 5.00 (t,
J ) 9.6 Hz, H-4′), 4.86 (d, J ) 3.8 Hz, H-1), 4.82 (d, J ) 4.4 Hz,
1H), 4.47 (d, J ) 6.8 Hz, 1H), 4.45 (d, J ) 8.1 Hz, H-1′), 4.35 (d,
J ) 4.0 Hz, H-6′proS, H-6′proR), 3.96 (m, H-5′), 3.92 (d, J ) 10.0
Hz, H-6proS), 3.71 (dd, J ) 4.6, 10.8 Hz, H-6proR), 3.64-3.59 (m,
H-5, H-3′), 3.42-3.32 (m, H-3), 3.30 (m, H-4), 3.25-3.20 (m, H-2,
H-2′), 2.22 (m, 1H), 2.10 (br d, J ) 12.2 Hz, 1H), 1.61 (m, 2H),
1.33 (m, 1H), 1.21 (m, 1H), 1.05 (m, 1H), 0.91 (d, J ) 6.4 Hz,
3H), 0.87 (d, J ) 6.9 Hz, 3H), 0.69 (d, J ) 6.8 Hz, 3H); 13C NMR
(δ, DMSO) 165.6 (s), 165.4 (s), 132.7-128.4, 104.2 (d, C-1′), 95.7
(d, C-1), 75.3* (d, C-3), 74.7* (d, C-5), 74.5* (d, C-2′), 74.0* (d),
73.3 (d, C-4′), 72.5* (d, C-2), 72.5* (d, C-3′), 71.5 (d, C-5′), 70.5*
(d, C-4), 69.3 (t, C-6), 64.6 (t, C-6′), 48.6 (d), 40.4 (t), 35.0 (t),
31.7 (d), 25.6 (d), 23.3 (t), 23.2 (q), 22.1 (q), 16.3 (q); UV (EtOH)
(+)-Menthyl 2,3,4-Tri-O-acetyl-6-O-[2,3-di-O-acetyl-4,6-bis-
O-(4-bromobenzoyl)-ꢀ-D-glucopyranosyl]-r-D-glucopyrano-
side (15r). Compound 12r (15 mg, 0.02 mmol) was dissolved in
1 mL of a 1:1 solution of dry pyridine/acetic anhydride. Excess
solvent was removed under reduced pressure to give, after column
chromatography (n-hexane/EtOAc, 8:2), compound 15r (14.5 mg,
0.05 mmol) in 76% yield: TLC Rf ) 0.35 (n-hexane/EtOAc, 6:4);
mp ) 236.3-238.7 °C (dec); [R]25 ) +77.6 (c 1.02, CHCl3);
D
MS (FAB) 1077 (0.4, [M + Na]+), 903, 901, 899 (5, 10, 4,
[C37H44Br2O17]), 615, 613, 611 (43, 83, 42, [C24H21Br2O9]), 185,
1
183 (97, 100, [BrBz]); H NMR (δ, CDCl3) 7.80 (d, J ) 8.6 Hz,
2H), 7.76 (d, J ) 8.6 Hz, 2H), 7.53 (d, J ) 8.6 Hz, 2H), 7.50 (d,
J ) 8.6 Hz, 2H), 5.45-5.35 (m, H-4′, H-3, H-3′), 5.24 (d, J ) 3.9
Hz, H-1), 5.08 (dd, J ) 7.9, 9.4 Hz, H-2′), 5.01 (t, J ) 9.8 Hz,
H-4), 4.78 (dd, J ) 3.9, 10.4 Hz, H-2), 4.59 (d, J ) 7.9 Hz, H-1′),
4.50 (dd, J ) 3.5, 12.1 Hz, H-6′proS), 4.40 (dd, J ) 4.9, 12.1 Hz,
H-6′proR), 4.01-3.90 (m, H-5′, H-6proS, H-5), 3.50 (dd, J ) 4.2,
10.5 Hz, H-6proR), 3.38 (dt, J ) 3.9, 10.5 Hz, 1H), 2.18 (m, 1H),
2.09 (s, 3H), 2.03 (s, 3H), 2.02 (s, 3H), 1.99 (s, 3H), 1.90 (s, 3H),
1.83 (m, 1H), 1.70 (m, 2H), 1.31 (m, 2H), 0.92 (d, J ) 6.9 Hz,
3H), 0.87 (d, J ) 6.5 Hz, 3H), 0.70 (d, J ) 6.9 Hz, 3H); 13C NMR
(δ, CDCl3) 170.1 (3s), 169.5 (s), 169.4 (s), 165.3 (s), 164.4 (s),
λ
max 245 nm; CD (EtOH) λ (∆ε) 251 (11.1), 234 nm (-3.1). Anal.
Calcd for C36H46Br2O13: C, 51.08; H, 5.48. Found: C, 51.08; H,
5.64.
(-)-Menthyl 6-O-[4,6-Bis-O-(4-bromobenzoyl)-ꢀ-D-glucopy-
ranosyl]-r-D-glucopyranoside (13r). Following the general pro-
cedure for desilylation and deacetylation, 33.0 mg (0.03 mmol) of
compound 9r yielded 21.0 mg of compound 13r (88% yield): TLC
Rf ) 0.35 (CH2Cl2/MeOH, 9:1); mp ) 157.7-158.9 °C; [R]25
)
D
J. Org. Chem. Vol. 73, No. 18, 2008 7277

Roën et al.
131.9-127.6, 100.9 (d, C-1′), 92.4 (d, C-1), 77.2 (d), 72.4* (d,
C-4′), 71.7* (d, C-5), 71.1 (d, C-2′), 70.9 (d, C-2), 70.2* (d, C-3′),
69.9* (d, C-3), 68.9 (d, C-4), 68.1* (d, C-5′), 67.8 (t, C-6), 63.2 (t,
C-6′), 47.6 (d), 40.0 (t), 34.2 (t), 31.2 (d), 25.4 (d), 22.6 (t), 22.2
(q), 21.2 (q), 20.7 (q), 20.6 (3q), 20.5 (q), 15.2 (q); UV (CH3CN)
with EtOAc, and washed with saturated NH4Cl solution. The
aqueous layer was extracted with EtOAc (3 times), and the
combined organic layers were dried over MgSO4, filtered, and
concentrated. Flash column chromatography (n-hexane/EtOAc, 7:3)
of the residue gave 20 (364 mg) in 56% yield: TLC Rf ) 0.23
(n-hexane/EtOAc, 6:4); colorless syrup; [R]25D ) +108.1 (c 0.58,
CHCl3); MS (FAB) 428 (6, [M]+), 411 (7, [C4H9]), 154 (15,
λmax 245 nm; CD (CH3CN) λ (∆ε) 251 (13.8), 234 nm (-6.7). Anal.
Calcd for C46H56Br2O18: C, 52.28; H, 5.34. Found: C, 52.28; H,
5.41.
1
[C8H10O3]), 137 (9, [C8H9O2]), 121 (100, [C8H9O]); H NMR (δ,
CDCl3) 7.26 (d, J ) 8.6 Hz, 2H), 6.87 (d, J ) 8.6 Hz, 2H), 4.81
(d, J ) 11.1 Hz, 1H), 4.73 (d, J ) 3.8 Hz, H-1), 4.54 (d, J ) 11.1
Hz, 1H), 3.83 (t, J ) 9.4 Hz, H-3), 3.80 (s, OCH3), 3.75 (m,
H-6proS), 3.65 (m, H-6proR), 3.59 (m, H-5), 3.46 (dt, J ) 3.8, 9.4
Hz, H-2), 3.39 (s, OCH3), 3.36 (t, J ) 9.4 Hz, H-4), 1.88 (d, J )
9.4 Hz, OH), 1.68 (br s, OH), 0.95 (s, 9H), 0.15 (s, 3H), 0.12 (s,
3H); 13C NMR (δ, CDCl3) 159.3-113.8, 99.5 (d, C-1), 77.9 (d,
C-4), 76.1 (d, C-3), 74.6 (t), 73.4 (d, C-2), 71.0 (d, C-5), 61.9 (t,
C-6), 55.3 (q), 55.2 (q), 26.0 (3q), 18.6 (s), -4.0 (q), -4.2 (q).
Anal. Calcd for C21H36O7Si: C, 58.85; H, 8.47. Found: C, 58.91;
H, 8.63.
(-)-Menthyl 2,3,4-Tri-O-acetyl-6-O-[2,3-di-O-acetyl-4,6-bis-
O-(4-bromobenzoyl)-ꢀ-D-glucopyranosyl]-r-D-glucopyrano-
side (16r). Compound 13r (14.0 mg, 0.02 mmol) was dissolved
in 1 mL of a 1:1 solution of dry pyridine/acetic anhydride. Excess
solvent was removed under reduced pressure to give, after column
chromatography (n-hexane/EtOAc, 8:2), compound 16r (14.7 mg)
in 84% yield: TLC Rf ) 0.37 (n-hexane/EtOAc, 6:4); mp )
230.2-231.8 °C dec; [R]25D ) +38.4 (c 1.14, CHCl3); MS (FAB)
1077 (2, [M + Na]+), 903, 901, 899 (3, 4, 2, [C37H44Br2O17]), 615,
613, 611 (39, 70, 36, [C24H21Br2O9]), 185, 183 (99, 100, [BrBz]);
1H NMR (δ, CDCl3) 7.80 (d, J ) 8.5 Hz, 2H), 7.76 (d, J ) 8.5
Hz, 2H), 7.53 (d, J ) 8.6 Hz, 2H), 7.52 (d, J ) 8.6 Hz, 2H), 5.48
(t, J ) 9.8 Hz, H-3), 5.41 (m, H-4′, H-3′), 5.13 (d, J ) 3.7 Hz,
H-1), 5.09 (t, J ) 8.5 Hz, H-2′), 4.99 (t, J ) 9.5 Hz, H-4), 4.79
(dd, J ) 3.7, 10.0 Hz, H-2), 4.62 (d, J ) 7.9 Hz, H-1′), 4.52 (dd,
J ) 3.5, 12.1 Hz, H-6′proS), 4.41 (dd, J ) 4.8, 12.1 Hz, H-6′proR),
4.11 (m, H-5), 3.99 (dd, J ) 2.4, 10.8 Hz, H-6proS), 3.96 (m, H-5′),
3.54 (dd, J ) 4.5, 10.8 Hz, H-6proR), 3.25 (dt, J ) 4.10, 10.3 Hz,
1H), 2.17 (m, 1H), 2.10 (s, 3H), 2.01 (s, 3H), 2.00 (s, 3H), 1.99 (s,
3H), 1.90 (s, 3H), 1.62 (m, 2H), 1.39 (m, 1H), 1.27 (m, 2H), 0.99
(m, 1H), 0.88 (d, J ) 6.5 Hz, 3H), 0.87 (d, J ) 7.1 Hz, 3H), 0.82
(m, 1H), 0.67 (d, J ) 7.0 Hz, 3H); 13C NMR (δ, CDCl3) 170.3 (s),
170.1 (s), 170.0 (s), 169.5 (s), 169.4 (s), 165.3 (s), 164.4 (s),
131.9-127.6, 101.1 (d, C-1′), 97.4 (d, C-1), 82.5 (d), 72.4 (d, C-4′),
71.8 (d, C-5′), 71.2 (d, C-2′), 71.1 (d, C-2), 70.3 (d, C-3), 69.9 (d,
C-3′), 69.1 (d, C-4), 68.0 (t, C-6), 67.9 (d, C-5), 63.2 (t, C-6′),
48.5 (d), 42.8 (t), 34.1 (t), 31.5 (d), 24.9 (d), 22.8 (t), 22.3 (q),
21.0 (q), 20.7 (q), 20.6 (2q), 20.5 (2q), 15.8 (q); UV (CH3CN) λmax
245 nm; CD (CH3CN) λ (∆ε) 251 (15.1), 234 nm (-6.9). Anal.
Calcd for C46H56Br2O18: C, 52.28; H, 5.34. Found: C, 52.29; H,
5.35.
Methyl 6-O-[4,6-Bis-O-(4-bromobenzoyl)-3-O-(tert-butyldim-
ethylsilyl)-ꢀ-D-glucopyranosyl]-3-O-(tert-butyldimethylsilyl)-4-
O-(4-methoxybenzyl)-r-D-glucopyranoside (22r). The methyl
glucopyranosyl glucopyranoside 22r (213.0 mg) was obtained in
43% yield by coupling the glucosyl donor 21 (290 mg, 0.46 mmol)
with 2 equiv of the glucosyl aceptor 20 (400 mg, 0.93 mmol)
according to the general procedure: TLC Rf ) 0.30 (n-hexane/
EtOAc, 7:3); colorless syrup; [R]25D ) +0.6 (c 0.59, CHCl3); MS
(FAB) 1095, 1093, 1091 (0.1, 0.1, 0.1 [M + Na]+), 185, 183 (11,
1
11, [BrBz]), 121 (100, [C8H9O]); H NMR (δ, CDCl3) 7.82 (d, J
) 8.5 Hz, 2H), 7.76 (d, J ) 8.5 Hz, 2H), 7.54 (d, J ) 8.5 Hz, 2H),
7.46 (d, J ) 8.5 Hz, 2H), 7.24 (d, J ) 8.6 Hz, 2H), 6.86 (d, J )
8.6 Hz, 2H), 5.26 (t, J ) 9.5 Hz, H-4′), 4.83 (d, J ) 11.0 Hz, 1H),
4.75 (d, J ) 3.8 Hz, H-1), 4.51 (d, J ) 10.9 Hz, 1H), 4.45 (dd, J
) 3.6, 12.0 Hz, H-6′proS), 4.34 (dd, J ) 5.1, 12.0 Hz, H-6′proR),
4.32 (d, J ) 7.7 Hz, H-1′), 4.09 (dd, J ) 2.0, 11.0 Hz, H-6proS),
3.84-3.75 (H-3′, H-5′, H-3, H-5), 3.79 (s, 3H), 3.68 (dd, J ) 5.2,
11.1 Hz, H-6proR), 3.54 (br t, J ) 8.3 Hz, H-2′), 3.47 (dt, J ) 3.9,
9.3 Hz, H-2), 3.39 (s, 3H), 3.32 (t, J ) 9.3 Hz, H-4), 1.88 (d, J )
9.3 Hz, 1H), 1.67 (br s, 1H), 0.94 (s, 9H), 0.72 (s, 9H), 0.15 (s,
3H), 0.10 (s, 3H), 0.08 (s, 3H), -0.12 (s, 3H); 13C NMR (δ, CDCl3)
165.4 (s), 164.5 (s), 159.1 (s), 131.8-128.2, 113.8 (2d), 103.4 (d,
C-1′), 99.4 (d, C-1), 78.5 (d, C-4), 76.1* (d, C-3′), 75.1* (d, C-5′),
74.5 (t), 74.2 (d, C-2′), 73.2 (d, C-2), 72.4 (d, C-4′), 71.7* (d, C-3),
70.1* (d, C-5), 68.7 (t, C-6), 63.9 (t, C-6′), 55.3 (2q), 26.0 (3q),
25.6 (3q), 18.2 (s), 18.0 (s), -3.9 (q), -4.2 (2q), -4.8 (q). Anal.
Calcd for C47H66Br2O14Si2: C, 52.71; H, 6.21. Found: C, 52.73; H,
6.39.
Methyl 2-O-Acetyl-3-O-(tert-butyldimethylsilyl)-4,6-O-(p-
methoxybenzyliden)-r-D-glucopyranoside (19). Compound 18
(492 mg, 1.39 mmol) was dissolved in dry CH2Cl2 (10 mL) under
an argon atmosphere and treated with imidazole (379 mg, 5.56
mmol), tert-butyldimethylsilyl chloride (419 mg, 2.77 mmol), and
DMAP as catalyst. When the reaction was completed, it was diluted
with CH2Cl2 and washed with saturated NaHCO3 solution. The
aqueous layer was extracted with CH2Cl2 twice, the combined
organic layers were dried over MgSO4 and filtered, and the solvent
was removed under reduced pressure. The residue was then purified
by column chromatography (n-hexane/EtOAc, 8:2) to lead to
compound 19 (601 mg, 1.28 mmol, 92%): TLC Rf ) 0.42
tert-Butyl 2-O-Acetyl-6-O-[2-O-acetyl-4,6-bis-O-(4-bromoben-
zoyl)-ꢀ-D-glucopyranosyl]-r-D-glucopyranoside (23r). Com-
pound 10r (50.0 mg, 0.05 mmol) was dissolved in 3 mL of dry
acetonitrile under an argon atmosphere at 0 °C, treated with 10 µL
of HF-Py (0.12 mmol), and left at room temperature. When the
reaction was completed, it was diluted with CH2Cl2 and washed
with a saturated solution of NaHCO3. The aqueous layer was
extracted with CH2Cl2 (2 times). The combined extracts were dried
over MgSO4, filtered, and concentrated. Sephadex chromatography
of the residue (n-hexane/CHCl3/MeOH, 2:1:1) furnished 23r (30.5
mg) in 77% yield: TLC Rf ) 0.52 (CH2Cl2/MeOH, 9:1); colorless
(n-hexane/EtOAc, 8:2); colorless syrup; [R]25 ) -16.7 (c 2.7,
D
CHCl3); MS (FAB) 469 (53, [M]++1), 411 (54, [C4H9]), 154 (13,
[C8H10O3]), 137 (19, [C8H9O2]), 121 (17, [C8H9O]), 73 (100,
1
[C5H13]); H NMR (δ, CDCl3) 7.40 (d, J ) 8.7 Hz, 2H), 6.87 (d,
J ) 8.7 Hz, 2H), 5.47 (s, 1H), 4.90 (d, J ) 3.7 Hz, H-1), 4.78 (dd,
J ) 3.8, 9.4 Hz, H-2), 4.25 (dd, J ) 4.4, 9.8 Hz, H-6proR), 4.12 (t,
J ) 9.2 Hz, H-3), 3.81 (m, H-5), 3.80 (s, OCH3), 3.72 (t, J ) 10.1
Hz, H-6proS), 3.48 (t, J ) 9.2 Hz, H-4), 3.38 (s, OCH3), 2.12 (s,
3H), 0.82 (s, 9H), 0.05 (s, 3H), 0.01 (s, 3H); 13C NMR (δ, CDCl3)
170.4 (s), 160.0-113.4, 101.8 (d), 97.8 (d, C-1), 82.1 (d, C-4),
74.3 (d, C-2), 69.5 (d, C-3), 68.9 (t, C-6), 62.2 (d, C-5), 55.2 (2q),
25.6 (3q), 21.0 (q), 18.1 (s), -4.3 (q), -4.7 (q). Anal. Calcd for
C23H36O7Si: C, 58.95; H, 7.74. Found: C, 58.70; H, 7.86.
syrup; [R]25 ) +58.7 (c 0.78, CHCl3); MS (FAB) 873, 871, 869
D
(5, 13, 4, [M + Na]+), 777, 775, 773 (7, 11, 5, [M - C4H9O]),
573, 571, 569 (19, 29, 19, [C22H19Br2O8]), 307 (42, [C12H19O9]),
1
185, 183 (97, 100, [BrBz]); H NMR (δ, CDCl3) 7.85 (d, J ) 8.5
Hz, 2H), 7.83 (d, J ) 8.5 Hz, 2H), 7.54 (d, J ) 8.5 Hz, 2H), 7.52
(d, J ) 8.5 Hz, 2H), 5.30 (t, J ) 9.7 Hz, H-4′), 5.27 (d, J ) 3.8
Hz, H-1), 4.97 (dd, J ) 7.9, 9.3 Hz, H-2′), 4.66 (d, J ) 7.8 Hz,
H-1′), 4.61 (dd, J ) 3.0, 12.1 H-6′proS), 4.56 (dd, J ) 3.8, 10.1,
H-2), 4.40 (dd, J ) 5.1, 12.1 H-6′proR), 4.02 (dd, J ) 2.8, 10.7 Hz,
H-6proS), 3.98-3.92 (H-3, H-5, H-5′), 3.91 (t, J ) 9.3 Hz, H-3′),
3.82 (dd, J ) 4.8, 10.7 Hz, H-6proR), 3.53 (t, J ) 9.3 Hz, H-4),
Methyl 3-O-(tert-Butyldimethylsilyl)-4-O-(p-methoxybenzyl)-
r-D-glucopyranoside (20). To a solution of compound 19 (714
mg, 1.52 mmol) in dry CH2Cl2 (15 mL) at 0 °C under argon a 1.0
M solution of DIBAL-H (6.01 mL) was added dropwise. The
reaction was quenched with the addition of methanol (3 mL), diluted
7278 J. Org. Chem. Vol. 73, No. 18, 2008

Conformational Domino Effect in Saccharides
2.14 (s, 3H), 2.10 (s, 3H), 1.18 (s, 9H); 13C NMR (δ, CDCl3) 171.0
(2s), 165.5 (s), 165.3 (s), 131.8-127.9, 100.9 (d, C-1′), 90.3 (d,
C-1), 75.4 (s), 74.0 (d, C-2′), 73.6 (d, C-2), 73.6* (d, C-3′), 72.2
(d, C-4′), 71.8* (d, C-5), 71.4* (d, C-5′), 71.2 (d, C-4), 69.5* (d,
C-3), 68.9 (t, C-6), 63.3 (t, C-6′), 25.3 (3q), 20.9 (2q). Anal. Calcd
for C34H40Br2O15: C, 48.13; H, 4.75. Found: C, 48.17; H, 4.92.
tert-Butyl 6-O-[4,6-Bis-O-(4-bromobenzoyl)-ꢀ-D-glucopyra-
nosyl]-r-D-glucopyranoside (24r). Compound 23r (15.0 mg, 0.02
mmol) was dissolved in 2 mL of CH2Cl2/MeOH (9:1) and p-TsOH-
H2O (6.9 mg, 0.04 mmol) added. When the reaction was completed,
it was diluted with CH2Cl2 and washed with a saturated NaHCO3
solution. The aqueous layer was extracted with CH2Cl2 (two times).
The combined extracts were dried over MgSO4, filtered, and
concentrated. Sephadex chromatography of the residue (n-hexane/
CHCl3/MeOH, 2:1:1) led to 24r (11.2 mg) in 81% yield: TLC Rf
removed under reduced pressure to give, after column chromatog-
raphy (n-hexane/EtOAc, 8:2), compound 25r (10.7 mg) in 83%
yield: TLC Rf ) 0.43 (n-hexane/EtOAc, 1:1); mp ) 227.5-230.2
°C dec; [R]25D ) +55.7 (c 0.79, CHCl3); MS (FAB) 903, 901, 899
(4, 8, 5, [C37H44Br2O17]), 615, 613, 611 (21, 49, 21, [C24H21Br2O9]),
1
185, 183 (97, 100, [BrBz]); H NMR (δ, CDCl3) 7.81 (d, J ) 8.5
Hz, 2H), 7.77 (d, J ) 8.5 Hz, 2H), 7.54 (d, J ) 8.5 Hz, 2H), 7.53
(d, J ) 8.5 Hz, 2H), 5.46 (t, J ) 9.4 Hz, H-3), 5.40 (m, H-4′,
H-3′), 5.32 (d, J ) 3.6 Hz, H-1), 5.09 (t, J ) 7.9 Hz, H-2′), 4.91
(t, J ) 9.5 Hz, H-4), 4.72 (dd, J ) 3.6, 10.3 Hz, H-2), 4.63 (d, J
) 7.9 Hz, H-1′), 4.53 (dd, J ) 3.4, 12.2 Hz, H-6′proS), 4.39 (dd, J
) 4.9, 12.2 Hz, H-6′proR), 4.15 (m, H-5), 3.94 (m, H-5′), 3.91 (dd,
J ) 2.1, 10.8 Hz, H-6proS), 3.52 (dd, J ) 5.7, 10.8 Hz, H-6proR),
2.07 (s, 3H), 2.03 (s, 3H), 2.00 (s, 3H), 1.99 (s, 3H), 1.90 (s, 3H),
1.20 (s, 9H); 13C NMR (δ, CDCl3) 170.2 (2s), 170.1 (s), 169.7 (s),
169.3 (s), 165.3 (s), 164.4 (s), 132.0-127.6, 100.8 (d, C-1′), 90.0
(d, C-1), 76.0 (s), 72.5* (d, C-4′), 71.8 (d, C-5′), 71.1 (d, C-2′,
C-2), 70.3 (d, C-3), 69.9* (d, C-3′), 69.3 (d, C-4), 68.1 (t, C-6),
67.8 (d, C-5), 63.2 (t, C-6′), 28.3 (3q), 20.7 (2q), 20.6 (2q), 20.5
(q); UV (CH3CN) λmax 245 nm; CD (CH3CN) λ (∆ε) 251 (14.4),
234 nm (-7.3). Anal. Calcd for C40H46Br2O18: C, 49.30; H, 4.76.
Found: C, 49.30; H, 4.79.
) 0.29 (CH2Cl2/MeOH, 9:1); mp ) 152.3-154.0 °C; [R]25
)
D
+69.0 (c 0.40, CHCl3); MS (FAB) 789, 787, 785 (0.4, 1, 0.2, [M
+ Na]+), 531, 529, 527 (3, 5, 3, [C20H17Br2O7]), 307 (16,
1
[C12H19O9]), 185, 183 (14, 15, [BrBz]), 154 (100); H NMR (δ,
DMSO) 7.81 (d, J ) 8.6 Hz, 2H), 7.79 (d, J ) 8.4 Hz, 2H), 7.70
(d, J ) 8.4 Hz, 2H), 7.67 (d, J ) 8.4 Hz, 2H), 5.42 (d, J ) 5.7 Hz,
1H), 5.23 (d, J ) 5.0 Hz, 1H), 4.94 (t, J ) 9.7 Hz, H-4′), 4.90 (d,
J ) 5.3 Hz, 1H), 4.86 (d, J ) 3.7 Hz, H-1), 4.68 (d, J ) 4.5 Hz,
1H), 4.41 (d, J ) 7.8 Hz, H-1′), 4.32 (dd, J ) 3.0, 12.0 Hz, H-6′proS),
4.26 (dd, J ) 5.1, 12.0 Hz, H-6′proR), 4.24 (d, J ) 7.1 Hz, 1H),
3.90 (m, H5′), 3.87 (d, J ) 11.5, H-6proS), 3.75 (m, H5), 3.63 (dd,
J ) 6.0, 11.1 Hz, H-6proR), 3.56 (m, H3′), 3.34 (m, H-3), 3.29-3.07
(H-2, H-2′, H-4), 1.14 (s, 9H); 13C NMR (δ, DMSO) 165.2 (s),
164.9 (s), 132.3-127.9, 104.1 (d, C-1′), 93.4 (d, C-1), 74.4 (d),
74.1 (d, C-3′), 74.1* (d, C-4), 73.7 (d, C-3), 72.8 (d, C-4′), 72.2*
(d, C-2′), 71.4 (d, C-5), 71.0 (d, C-5′), 70.8* (d, C-2), 69.9 (t, C-6),
64.1 (t, C-6′), 28.8 (3q); UV (EtOH) λmax 245 nm; CD (EtOH) λ
(∆ε) 251 (12.2), 234 nm (-3.9). Anal. Calcd for C30H36Br2O13: C,
47.14; H, 4.75. Found: C, 47.15; H, 5.05.
Acknowledgment. This research was supported by the
Ministerio de Educacio´n y Ciencia (Spain) through Grant No.
CTQ2007-67532-C02-02/BQU. A.R. and C.M. thank Banco
Santander and the Consejer´ıa de Educacio´n y Deportes (Gobi-
erno de Canarias), respectively, for fellowships. J.I.P. thanks
the Spanish MCYT-FSE for a Ramo´n y Cajal contract.
Supporting Information Available: Tables containing NMR
and CD data for disaccharides 2r-16r and 23r-25r, atom
coordinates of the rotamers of the disaccharide 14r, as well as
1H and 13C NMR spectra of all new compounds. This material
is available free of charge via the Internet at http://pubs.acs.org.
tert-Butyl 2,3,4-Tri-O-acetyl-6-O-[2,3-di-O-acetyl-4,6-bis-O-
(4-bromobenzoyl)-ꢀ-D-glucopyranosyl]-r-D-glucopyranoside (25r).
Compound 23r (11.3 mg, 0.01 mmol) was dissolved in 1 mL of a
1:1 solution of dry pyridine/acetic anhydride. Excess solvent was
JO801184Q
J. Org. Chem. Vol. 73, No. 18, 2008 7279