Practical approach for the stereoselective introduction of β-arabinofuranosides

Article abstract of DOI:10.1021/ja0629817

A practical approach for the stereoselective introduction of β-arabinofuranosides has been developed on the basis of locking an arabinosyl donor in a conformation in which nucleophilic attack from the β face is favored. The new glycosyl donor was designed by analyzing optimized geometries of low-energy conformers of the arabinofuranosyl oxacarbenium ion. The Newman projection of the E₃ conformer indicated that nucleophilic attack from the α face is disfavored because an eclipsed H-2 will be encountered. On the other hand, an approach from the β face was expected to be more favorable, because it will experience only staggered substituents. The arabinofuranosyl oxacarbenium ion could be locked in the E₃ conformation by employing a 3,5-O-di-tert-butylsilane protecting group, which places C-5 and O-3 in a pseudoequatorial orientation, resulting in a perfect chair conformation of the protecting group. The new glycosyl donor gave excellent β selectivities in a range of glycosylations with glycosyl acceptors having primary and secondary alcohols. The attractiveness of the new methodology was demonstrated by the chemical synthesis of a fragment of arabinogalactan, which is an important constituent of the primary plant cell wall.

Full text of DOI:10.1021/ja0629817

Published on Web 08/22/2006
Practical Approach for the Stereoselective Introduction of
â-Arabinofuranosides
Xiangming Zhu, Sameer Kawatkar, Yu Rao, and Geert-Jan Boons*
Contribution from the Complex Carbohydrate Research Center, UniVersity of Georgia, 315
RiVerbend Road, Athens, Georgia 30602
Received April 28, 2006; E-mail: gjboons@ccrc.uga.edu
Abstract: A practical approach for the stereoselective introduction of â-arabinofuranosides has been
developed on the basis of locking an arabinosyl donor in a conformation in which nucleophilic attack from
the â face is favored. The new glycosyl donor was designed by analyzing optimized geometries of low-
energy conformers of the arabinofuranosyl oxacarbenium ion. The Newman projection of the E3 conformer
indicated that nucleophilic attack from the R face is disfavored because an eclipsed H-2 will be encountered.
On the other hand, an approach from the â face was expected to be more favorable, because it will
experience only staggered substituents. The arabinofuranosyl oxacarbenium ion could be locked in the E3
conformation by employing a 3,5-O-di-tert-butylsilane protecting group, which places C-5 and O-3 in a
pseudoequatorial orientation, resulting in a perfect chair conformation of the protecting group. The new
glycosyl donor gave excellent â selectivities in a range of glycosylations with glycosyl acceptors having
primary and secondary alcohols. The attractiveness of the new methodology was demonstrated by the
chemical synthesis of a fragment of arabinogalactan, which is an important constituent of the primary plant
cell wall.
Introduction
4,6-O-benzylidine-protected mannoside, which can be formed
in situ from various glycosyl donors, has found general use.8
The stereoselective introduction of glycosidic linkages pre-
sents the principal challenge to the chemical synthesis of
complex oligosaccharides of biological importance.1-4 In gen-
eral, 1,2-trans-glycosides can be obtained by neighboring group
participation of a 2-O-acyl protecting group of a glycosyl donor.
In these reactions, a promoter activates an anomeric leaving
group, resulting in its departure and the formation of an
oxacarbenium ion. Subsequent neighboring group participation
of the 2-O-acyl protecting group will give a more stable 1,2-
cis-acyloxonium ion. Nucleophilic attack at the anomeric center
of the acyloxonium ion by an alcohol will give a 1,2-trans-
glycoside. Recently, the stereoselective introduction of 1,2-cis-
pyranosyl glycosidic linkages, such as R-glucopyranosides and
R-galactopyranosides, has been accomplished by employing a
participating (S)-phenylthiomethylbenzyl group at C-2 of a
glycosyl donor.5 In this glycosylation, an intermediate anomeric
â-sulfonium ion is formed, which upon displacement by a sugar
hydroxyl gives only R-glycopyranosides. Several elegant meth-
ods have been reported for the introduction of â-mannopyra-
nosides.6,7 In particular, the displacement of an R-triflate of a
Unfortunately, methods for the stereoselective introduction
of furanosides are not as well developed as for pyranosides.9
These glycosides are, however, important constituents of
microbial and plant polysaccharides.10-12 For example, the
mycobacterium cell wall contains galactans and lipomannnans,
which are substituted by R- and â-D-arabinofuranosides. Inter-
estingly, while the primary cell walls of plants also contain
galactans, they are modified by â-L-arabinofuranosides. There
is evidence that these highly complex polysaccharides are
involved in plant cell differentiation.13
In general, 1,2-trans-furanosides can be obtained in a
straightforward manner by neighboring group participation of
an acyl ester at C-2 of a furanosyl donor. On the other hand,
furanosyl donors having a nonparticipating protecting group at
C-2 give in general glycosides with poor anomeric selectivity.
The stereoselective introduction of 1,2-cis-furanosides, such as
â-arabinofuranosyl glycosides, has only been accomplished by
indirect protocols. For example, Lowary’s method employs a
2,3-anhydrofuranosyl donor, which can be stereoselectively
glycosylated to give â-glycosides.14,15 The oxirane of the
(8) Crich, D.; Sun, S. X. J. Am. Chem. Soc. 1998, 120, 435-436.
(9) Lowary, T. L. Curr. Opin. Chem. Biol. 2003, 7, 749-756.
(10) Brennan, P. J.; Nikaido, H. Annu. ReV. Biochem. 1995, 64, 29-63.
(11) Lindberg, B. AdV. Carbohydr. Chem. Biochem. 1990, 48, 279-318.
(12) Delederkremer, R. M.; Colli, W. Glycobiology 1995, 5, 547-552.
(13) Fincher, G. B.; Stone, B. A.; Clarke, A. E. Annu. ReV. Plant Physiol. 1983,
34, 47-70.
(1) Boons, G.-J. Contemp. Org. Synth. 1996, 3, 173-200.
(2) Demchenko, A. V. Synlett 2003, 1225-1240.
(3) Davis, B. G. J. Chem. Soc., Perkin Trans. 1 2000, 2137-2160.
(4) Boons, G. J. Tetrahedron 1996, 52, 1095-1121.
(5) Kim, J. H.; Yang, H.; Park, J.; Boons, G. J. J. Am. Chem. Soc. 2005, 127,
12090-12097.
(6) El Ashry, E. S. H.; Rashed, N.; Ibrahim, E. S. I. Curr. Org. Synth. 2005,
2, 175-213.
(14) Gadikota, R. R.; Callam, C. S.; Wagner, T.; Del Fraino, B.; Lowary, T. L.
J. Am. Chem. Soc. 2003, 125, 4155-4165.
(7) Gridley, J. J.; Osborn, H. M. I. J. Chem. Soc., Perkin Trans. 1 2000, 10,
1471-1491.
(15) Gadikota, R. R.; Callam, C. S.; Lowary, T. L. Org. Lett. 2001, 3, 607-
610.
9
11948
J. AM. CHEM. SOC. 2006, 128, 11948-11957
10.1021/ja0629817 CCC: $33.50 © 2006 American Chemical Society

Stereoselective Introduction of
â
-Arabinofuranosides
A R T I C L E S
resulting product can then be opened in a regioselective manner
using lithium benzyl alkoxide in the presence of (-)-sparteine
to give a â-arabinofuranoside. In another approach, â-Araf
residues have been installed using an intramolecular aglycon
delivery approach whereby a glycosyl acceptor is first tethered
to the C-2 hydroxyl of an arabinofuranosyl donor followed by
glycosylation.16,17 â-Arabinofuranoside selectivity has also been
improved by deactivation of the glycosyl donor and acceptor.18
We report here a practical approach for the stereoselective
introduction of â-arabinofuranosides by locking a donor in a
conformation in which attack from the â face is favored. As a
result, a range of glycosylations of the novel arabinofuranosyl
donor with primary and secondary glycosyl acceptors gave the
corresponding glycosides with excellent â selectivities. The new
glycosyl donor was designed by analyzing optimized geometries
of low-energy conformers of the arabinofuranosyl oxacarbenium
ion. The attractiveness of the new methodology has been
demonstrated by the chemical synthesis of a fragment of
arabinogalactan, which is an important constituent of the primary
plant cell wall.
Results and Discussion
Figure 1. Optimized geometries (B3LYP/6-31G**) of the 3E and E3
conformers of the oxacarbenium ions of 2,3,5-tri-O-methyl-L-arabinofurase.
The Newman projection along t eC-1-C-2 bond indicates that, in the case
of the 3E conformer, the H-2 hydrogen is in a pseudoequatorial orientation,
whereas the O-2 oxygen is in a pseudoaxial orientation, resulting in the
preferred 1,2-trans attack of the incoming nucleophile. In the case of the
E3 conformer, however, the H-2 hydrogen is in a pseudoaxial orientation
and would result in an eclipsing interaction with the incoming nucleophile,
making 1,2-trans (R) attack disfavored. In contrast, the 1,2-cis (â) attack
would be favored in this case, as the incoming nucleophile would approach
the anomeric carbon in a staggered fashion.
Several factors have complicated the development of a general
method for the stereoselective introduction of 1,2-cis(â)-
arabinofuranosides. For example, the weak anomeric effects of
furanosides, which differ little between R and â anomers, makes
it difficult to exploit in situ anomerization protocols for
controlling anomeric selectivities.19,20 Furthermore, furanosides
are inherently flexible due to their ability to assume several twist
and envelope conformations, which can interconvert via pseu-
dorotational itineraries.9 As a result, furanosides can glycosylate
through several different transition states, which may compro-
mise anomeric selectivities. In this respect, it is well accepted
that high asymmetric inductions are only achieved when
reactions proceed through rigid and well-organized transition
states, in which a reactant experiences differential interactions
from preexisting stereochemical elements of the substrate along
alternative trajectories.21 These differential interactions may arise
from avoidance of steric interactions, minimization of torsional
strain, and optimization of orbital interactions.
There is evidence to support that transition states of glyco-
sylations possess substantial oxacarbenium ion character.22,23
We reasoned that, by examining possible conformers of the
arabinofuranosyl oxacarbenium ion, we might be able to identify
one that favors attack from the â face. Locking an arabinofura-
nosyl donor in this conformation should provide a compound
that will give mainly â-glycosides in glycosylations.
Oxacarbenium ions have significant double-bond character
between the endocyclic oxygen and C-1, which places these
two atoms and C-2 and C-4 in one plane. As a result,
oxacarbenium ions of L-furanosides can adopt two possible low-
energy conformations in which C-3 is either above (3E) or below
the plane (E3) of C-4, O(endo), C-1, and C-2 (the descriptors
for 3E and E3 are opposite for the D series). The geometries of
these conformations for the methyl-protected arabinofuranosyl
oxacarbenium ion have been optimized by density functional
theory (DFT) quantum mechanical calculations at the BL3LYP/
6-31G** level (Figure 1). As expected, the C-4-O(endo)-C-
1-C-2 dihedral angle of the optimized 3E conformer was very
small (4.7°), placing these atoms in one plane. The computed
bond length between O(endo) and C-1 is 1.25 Å, indicating
partial double-bond character. Analysis of the Newman projec-
tion indicates that nucleophilic attack from the â face would
suffer significant steric interactions from an eclipsed C-2
substituent. On the other hand, an approach from the R face is
expected to be preferred, because it will encounter only
staggered substituents. In contrast, nucleophilic attack from the
R face of the E3 conformer is predicted to be disfavored because
it will experience an eclipsed H-2.24-26 In this case, an approach
from the â face is more favorable because it will encounter only
staggered constituents.
Thus, the computational studies indicate that high â selectivity
will be achieved when an arabinofuranosyl oxacarbenium ion
is locked in the E3 conformer. It was anticipated that this can
be achieved by employing arabinoside 3, which has a 3,5-O-
di-tert-butylsilane protecting group.27 Thus, the E3 conformer
(16) Ito, Y.; Ogawa, T. Angew. Chem., Int. Ed. 1994, 33, 1765-1767.
(17) Marotte, K.; Sanchez, S.; Bamhaoud, T.; Prandi, J. Eur. J. Org. Chem.
2003, 3587-3598.
(18) Lee, Y. J.; Lee, K.; Jung, E. H.; Jeon, H. B.; Kim, K. S. Org. Lett. 2005,
7, 3263-3266.
(19) Ellervik, U.; Magnusson, G. J. Am. Chem. Soc. 1994, 116, 2340-2347.
(20) Houseknecht, J. B.; Lowary, T. L.; Hadad, C. M. J. Phys. Chem. A 2003,
107, 5763-5777.
(24) Larsen, C. H.; Ridgway, B. H.; Shaw, J. T.; Smith, D. M.; Woerpel, K. A.
J. Am. Chem. Soc. 2005, 127, 10879-10884.
(21) Eliel, E. L.; Wilen, S. H. Stereochemistry of Organic Compounds; Wiley:
New York, 1994.
(25) Larsen, C. H.; Ridgway, B. H.; Shaw, J. T.; Woerpel, K. A. J. Am. Chem.
Soc. 1999, 121, 12208-12209.
(22) Crich, D.; Chandrasekera, N. S. Angew. Chem., Int. Ed. 2004, 43, 5386-
5389.
(26) Smith, D. M.; Tran, M. B.; Woerpel, K. A. J. Am. Chem. Soc. 2003, 125,
14149-14152.
(23) Sinnott, M. L. AdV. Phys. Org. Chem. 1988, 24, 113-204.
9
J. AM. CHEM. SOC. VOL. 128, NO. 36, 2006 11949

A R T I C L E S
Zhu et al.
Table 1. Experimental Homonuclear Coupling Constants of
Compounds 3 and 4a
3
4
JH1-H2
JH2-H3
JH3-H4
JH4-H5a
JH4-H5b
5.1 (5.7)
6.5 (7.5)
10.0 (10.2)
5.0 (4.1)
3.0
3.0
6.3
3.9
4.7
10.0 (10.2)
a The experimental coupling constants indicate that the two compounds
have different conformational properties. In the case of compound 3, an
excellent agreement was obtained between the experimental and computed
proton-proton coupling constants, indicating that the five-membered ring
of 3 is in the E3 conformation.
2 using benzyl bromide and sodium hydride in DMF. Interest-
ingly, the vicinal proton coupling constants of 3 and 4 differed
significantly, thus demonstrating that the two compounds
possess different conformational properties (Table 1). It was
expected that compound 3 resides mainly in the E3 conforma-
tion. This was confirmed by optimizing the E3 conformation
using DFT quantum mechanical calculations. The validity of
the resulting structure was confirmed by computing vicinal
proton coupling constants of the geometry-optimized conformer
using an empirical Karplus type equation,28 which were then
compared with experimentally determined values. As can be
seen in Table 1, the computed and experimentally determined
coupling constants were in excellent agreement, confirming that
3 adopts mainly the E3 conformation.
Figure 2. (A) Optimized geometry (B3LYP/6-31G**) of compound 3. The
five-membered ring of 3 is in an E3 conformation, and the six-membered
ring of the cyclic protecting group is in a chair conformation. (B) Optimized
structure of the oxacarbenium ion of compound 3. The five- and six-
membered rings are in E3 and chair conformations, respectively. (C)
Newman projection along the C-1-C-2 bond of the oxacarbenium ion,
indicating that the 1,2-trans (R) attack is disfavored, as it would encounter
an eclipsing H-2 hydrogen. The 1,2-cis (â) attack will be staggered and is
the favored mode of reaction, resulting in the observed stereoselectivity.
Scheme 1 a
Having glycosyl donors 3 and 4 at hand, attention was focused
on the glycosylation of a range of different glycosyl acceptors.
Thus, coupling of the conformationally constrained glycosyl
donor 3 with the glycosyl acceptor 5 in the presence of the
powerful thiophilic promoter system N-iodosuccinimide/silver
triflate (NIS/AgOTf)29 in DCM at -30 °C gave disaccharide 6
with excellent â selectivity (â/R ) 15/1) in a yield of 91%
(Scheme 2). On the other hand, a similar glycosylation of the
flexible glycosyl donor 4 with 5 provided disaccharide 7 in good
yield but as a mixture of anomers (â/R ) 3/1).
In general, the anomeric configuration of arabinofuranosides
is established by a combination of chemical shift and coupling
constant data.30 In this respect, R-arabinofuranosides are char-
a Reagents and conditions: (a) t-BuSi(OTf)2, 2,6-lutidine, DMF/DCM,
0 °C (81%); (b) BnBr, NaH, THF (79%); (c) BnBr, NaH, DMF (86%).
3
acterized by JH-1,H-2 ) 1-3 Hz and δ(C-1) 104-110 ppm,
of the oxacarbenium ion of 3 places C-5 and O-3 in a
pseudoequatorial orientation, resulting in a perfect chair con-
formation of the protecting group. In the alternative 3E
conformation, the 3,5-O-di-tert-butylsilane chair is distorted,
inducing considerable ring strain. Indeed, quantum mechanical
calculations indicate that the oxacarbenium ion of 3 will adopt
an E3 conformation, in which nucleophilic attack from the R
face is disfavored due to unfavorable steric interactions with
H-2 (Figure 2).
whereas analogous â-glycosides have 3JH-1,H-2 ) 4-5 Hz and
δ(C-1) 97-104 ppm values. The 13C chemical shift of the
anomeric carbon of the major product of 6 was in the expected
region for a â anomer (δ(C-1) 100.3). The geometry-optimized
models of the R and â anomers of 3,5-O-di-tert-butylsilane-
protected arabinofuranosides predicted, however, dihedral angles
of H-1 and H-2 of 131.6 and 34.0°, respectively, corresponding
to similar 3JH-1,H-2 coupling constants of ∼5.5 Hz. Indeed, the
3
major and minor anomers of 6 gave JH-1,H-2 ) 5.1 and 5.2
Compound 3 was conveniently prepared according to a two-
step procedure starting from the readily available thioglycoside
1 (Scheme 1). Thus, treatment of 1 with di-tert-butylsilane bis-
(trifluoromethanesulfonate) in the presence of 2,6-lutidine in a
mixture of DMF and DCM27 gave compound 2 in 81% yield.
The C-2 hydroxyl of 2 could be benzylated in high yield to
give 3 by reaction with benzyl bromide in the presence of NaH
in THF. The reference compound 4, having benzyl ethers at
C-3, C-4, and C-5, could easily be prepared by benzylation of
Hz, respectively. Furthermore, the models indicate that R-fura-
nosides will display an NOE between H-1 and H-3, whereas
this interaction is absent in the â anomer. As expected, no NOE
was observed between H-1 and H-3 of the major product of 6,
whereas this interaction was present in the minor component.
To obtain additional proof of the â-anomeric configuration of
(28) Haasnoot, C. A. G.; Deleeuw, F.; Altona, C. Tetrahedron 1980, 36, 2783-
2792.
(29) Veeneman, G. H.; van Leeuwen, S. H.; van Boom, J. H. Tetrahedron Lett.
1990, 31, 1331-1334.
(27) Imamura, A.; Ando, H.; Korogi, S.; Tanabe, G.; Muraoka, O.; Ishida, H.;
(30) Mizutani, K.; Kasai, R.; Nakamura, M.; Tanaka, O.; Matsuura, H.
Carbohydr. Res. 1989, 185, 27-38.
Kiso, M. Tetrahedron Lett. 2003, 44, 6725-6728.
9
11950 J. AM. CHEM. SOC. VOL. 128, NO. 36, 2006

Stereoselective Introduction of
â
-Arabinofuranosides
A R T I C L E S
Scheme 2 a
a Reagents and conditions: NIS/AgOTf, DCM, -30 °C.
the major component of 6, the di-tert-butylsilane protecting
group was removed by treatment with TBAF and the resulting
hydroxyls acetylated with acetic anhydride in pyridine. Gratify-
ingly, the chemical shift and coupling constant data of the
resulting compound were in agreement with literature values
for â anomers (3JH-1,H-2 ) 4.0 Hz and δ(C-1) 101.2).30
To determine the generality of the methodology, the di-tert-
butylsilane-protected 3 was coupled with glycosyl acceptors 8,
9
J. AM. CHEM. SOC. VOL. 128, NO. 36, 2006 11951

A R T I C L E S
Scheme 3 a
Zhu et al.
a Reagents and conditions: (a) NIS, AgOTf, DCM, MS 4A, -20 °C; (b) Bu2BOTf, BH3, THF, DCM, 0 °C; (c) Et3N, DCM; (d) H2NNH2, DCM/MeOH;
(e) TBAF, THF; (f) NaOMa, MeOH, 50 °C; (g) Pd/C, H2, pyridine; (h) Pd(OH)2, H2, AcOH, H2O.
11, 14, 16, 18, and 20 having primary and secondary hydroxyls.
In each case, the corresponding disaccharides 9, 12, 15, 17, 19,
and 21 were isolated in excellent yields as mainly or exclusively
the â anomer. For each compound, the chemical shift of C-1
was in the expected region for â anomers (97-102 ppm) and
no NOE was observed between H-1 and H-3. Coupling of the
conformationally flexible 4 with glycosyl acceptors 8 and 11
gave the corresponding disaccharides 10 and 13 with poor
anomeric selectivities. These results support our model, which
predicts that nucleophilic attack at the R face of the oxacarbe-
nium ion of 3 is disfavored due to unfavorable steric interactions.
Having established a robust methodology for the stereose-
lective introduction of â-arabinofuranosides, attention was
focused on the preparation of compound 32, which is a fragment
of arabinogalactans.13 These polysaccharides are important
constituents of the primary plant cell wall, having a 1,3-â-D-
galactosyl backbone branched by 1,6-â-linked D-galactosides,
which in turn are extended by 1,3- and 1,6-â-linked L-
arabinofuranosides. There is evidence that components of the
primary cell wall play key roles in the development and
differentiation of plant cells. The lack of sensitive methods to
detect particular saccharides of the primary cell wall has,
however, complicated the determination of structural elements
that may regulate development. We are addressing this defi-
ciency by eliciting antibodies against well-defined synthetic
oligosaccharides derived from the primary cell wall. Antibodies
modified by a fluorescence label will be used to visualize
particular saccharide structures in the developing plant.
It was envisaged that the terminal 1,3- and 1,6-linked arabino-
â-L-furanosides of 32 could be installed using the conforma-
tionally constrained arabinosyl donor 3 (Scheme 3). Further-
more, trisaccharide 27, carrying the orthogonal 9-fluorenylmeth-
oxycarbonyl (Fmoc) and levulinoyl (Lev) protecting groups,31
was expected to be an appropriate precursor for the introduction
of the arabino-â-L-furanosides. This trisaccharide, in turn, could
be assembled from galactosyl building blocks 22-24. Thus,
NIS/AgOTf-mediated glycosylation29 of the thioglycosyl donor
22 with the spacer-containing acceptor 23 gave the disaccharide
(31) Zhu, T.; Boons, G. J. Tetrahedron: Asymmetry 2000, 11, 199-205.
9
11952 J. AM. CHEM. SOC. VOL. 128, NO. 36, 2006

Stereoselective Introduction of
â
-Arabinofuranosides
A R T I C L E S
70-230 mesh silica gel. Solvents were evaporated under reduced
pressure while the water bath temperature was maintained below 40
°C. NMR spectra were recorded on Varian spectrometers (Models
Inova300, Inova500, and Inova600) equipped with Sun workstations.
1H NMR spectra were recorded in CDCl3 and referenced to residual
CHCl3 at 7.26 ppm, and 13C NMR spectra were referenced to the central
peak of CDCl3 at 77.0 ppm. One-dimensional NOE data were collected
with an mixing time of 200 ms on a Varian Inova 500 MHz
spectrometer using the standard pulse sequence provided. MS spectra
were recorded on a VOYAGER-DE Applied Biosystems instrument
in the positive mode by using 2,5-dihydroxylbenzoic acid in THF as
matrix.
25 in a yield of 79%. Due to neighboring group participation
of the C-2 benzoyl ester of 22, disaccharide 25 was only formed
as a â anomer. Next, the benzylidine acetal of 25 was
regioselectively opened by treatment with Bu2BOTf in the
presence of BH3‚THF complex in DCM32 to give compound
26. The resulting C-6 hydroxyl of 26 was glycosylated with
galactosyl donor 24, using NIS/AgOTf as the promoter, to give
trisaccharide 27 in good yield as only the â anomer. The Fmoc
protecting group of 27 was selectively removed by treatment
with the hindered base triethylamine in DCM to afford 28. As
expected, these reaction conditions did not affect the Lev esters.
Gratifyingly, a glycosylation of arabinosyl donor 3 with 28 using
standard reaction conditions gave tetrasaccharide 29 as only the
â anomer. Next, the Lev ester of 29 was removed using
hydrazine acetate in a mixture of DCM and methanol to give
the glycosyl acceptor 30, which was coupled with 3 using
standard conditions to give the expected pentasaccharide 31.
In the latter glycosylation, only the â-linked 1,6-arabinofura-
noside could be detected. Finally, deprotection of 31 to afford
the target compound 32 was accomplished according to a four-
step procedure involving removal of the di-tert-butylsilane
protecting group by treatment with TBAF in THF, saponification
of the acetyl and benzoyl esters using sodium methoxide in
methanol, catalytic hydrogenolysis over Pd in pyridine to convert
the azido moiety into an amine, and finally catalytic hydro-
genolysis in a mixture of methanol and acetic acid to remove
the benzyl esters. NMR and MS confirmed the structural
Phenyl 3,5-O-(Di-tert-butylsilanediyl)-1-thio-R-L-arabinofurano-
side (2). To a solution of phenyl 1-thio-R-L-arabinofuranoside (1.08 g,
4.47 mmol) in a mixture of CH2Cl2 (35 mL) and DMF (7 mL) at 0 °C
were added 2,6-lutidine (2.1 mL, 18 mmol) and di-tert-butylsilyl bis-
(trifluoromethanesulfonate) (1.5 mL, 4.12 mmol). The resulting reaction
mixture was stirred for 2 h, after which it was concentrated in vacuo,
diluted with EtOAc (80 mL), and washed successively with water (20
mL) and brine (20 mL). The organic layer was dried (MgSO4) and
concentrated in vacuo to give a residue that was purified by flash
column chromatography (hexane/EtOAc, 15/1 f 10/1) to afford 2 (1.39
g, 81%) as a white amorphous solid: Rf ) 0.43 (hexane/EtOAc, 5.5/
1). [R]25D ) -247.6° (c 3.7, CH2Cl2). 1H NMR (500 MHz, CDCl3): δ
7.51 (m, 2H, Ar), 7.30 (m, 3H, Ar), 5.32 (d, J ) 6.0 Hz, 1H, H-1),
4.34 (m, 1H, H-5a), 4.15 (m, 1H, H-3), 4.02 (dd, J ) 9.5, 7.5 Hz, 1H,
H-2), 3.94 (m, 2H, H-4, H-5b), 2.53 (d, J ) 3.0 Hz, 1H, OH), 1.06 (s,
t
t
9H, Bu), 0.99 (s, 9H, Bu). 13C NMR (75 MHz, CDCl3): δ 134.53,
131.65 (×2), 129.25 (×2), 127.77, 91.33, 81.48, 80.97, 73.92, 67.56,
27.72, 27.39, 22.89, 20.37. MALDI HR-MS: m/z 405.1621 [M + Na]+,
calcd for C19H30O4SSi 405.1634.
3
integrity of compound 32 (Araf, JH-1,H-2 ) 4.5 Hz, δ(C-1)
3
101.2 ppm; Araf′, JH-1,H-2 ) 4.5 Hz, δ(C-1) 98.9 ppm; Gal,
Phenyl 2-O-Benzyl-3,5-O-(di-tert-butylsilanediyl)-1-thio-R-L-ara-
binofuranoside (3). BnBr (1.5 mL, 12.6 mmol) and NaH (0.17 g, 6.84
mmol) were added to a solution of 2 (1.31 g, 3.42 mmol) in dry THF
(25 mL), and the mixture was kept stirring at 0 °C for 2 h. The reaction
was quenched by the addition of CH3OH, and solvent was removed in
vacuo. The reaction mixture was diluted with CH2Cl2 and sequentially
washed with a solution of 1 N HCl, a saturated solution of NaHCO3,
water, and brine. The organic phase was dried (MgSO4) and concen-
trated under reduced pressure. The residue was then purified by flash
column chromatography (hexane/EtOAc, 60/1 f 30/1) to afford 3 (1.28
3
3JH-1,H-2 ) 8.0 Hz, δ(C-1) 103.4 ppm; Gal′, JH-1,H-2 ) 7.5
3
Hz, δ(C-1) 103.5 ppm; Gal, JH-1,H-2 ) 8.0 Hz, δ(C-1) 103.1
ppm).
In conclusion, arabinofuranosides can be introduced with high
â selectivity using the conformationally constrained arabino-
furanosyl donor 3. This glycosyl donor has a 3,5-O-di-tert-
butylsilane protecting group, which locks the corresponding
oxacarbenium ion in an E3 conformer. The Newman projection
of this conformer indicated that nucleophilic attack from the â
face is favored. Indeed, glycosylation with the new glycosyl
donor gave excellent â selectivities with glycosyl acceptors
having primary and secondary alcohols. The new methodology
was sufficiently robust for an efficient synthesis of an ara-
binogalactan fragment derived from the plant cell wall. This
paper demonstrates that analysis of conformations of putative
intermediates of glycosylations may lead to the design of highly
steroeselective glycosylation. Furthermore, the introduction of
protecting groups that modify the conformational properties of
a glycosyl donor may be an attractive strategy to improve the
stereoselectivity of a glycosylation.18,33,34
g, 79%) as a pale yellow oil: Rf ) 0.65 (hexane/EtOAc, 8/1). [R]25
D
) -69.2° (c 4.5, CH2Cl2). 1H NMR (500 MHz, CDCl3): δ 7.41-7.27
(m, 10H, Ar), 5.43 (d, J1,2 ) 5.1 Hz, 1H, H-1), 4.79 (AB, J ) 12.0 Hz,
2H, PhCH2), 4.34 (q-like, J4,5a ) 5.0 Hz, 1H, H-5a), 4.15 (m, J2,3
)
6.5 Hz, J3,4 ) 10.0 Hz, 1H, H-3), 4.03-3.97 (m, J4,5b ) 10.0 Hz, 3H,
t
t
H-2, H-4, H-5b), 1.08 (s, 9H, Bu), 0.99 (s, 9H, Bu). 13C NMR (75
MHz, CDCl3): δ 137.9, 134.9, 131.5, 129.2, 128.7, 128.3, 128.2, 127.6,
90.2, 87.1, 81.6, 74.0, 72.5, 67.6, 27.8, 27.4, 22.9, 20.4. MALDI HR-
MS: m/z 495.2132 [M + Na]+, calcd for C26H36O4SSi 495.2104.
Phenyl 2,3,5-Tri-O-benzyl-1-thio-R-L-arabinofuranoside (4). Phen-
yl 1-thio-R-L-arabinofuranoside (1.45 g, 5.97 mmol) was dissolved in
DMF (50 mL), and the solution was then cooled to 0 °C. NaH (60%
dispersion in oil, 1.4 g, 35 mmol) was added to the above solution,
followed by the dropwise addition of BnBr (7.2 mL, 60.6 mmol). After
it was stirred at 0 °C for 30 min, the suspension was warmed to room
temperature while stirring was continued for 6 h, after which the reaction
was quenched by the addition of MeOH. The resulting mixture was
concentrated in vacuo, and the resulting residue was diluted with EtOAc
(100 mL), washed successively with 1 N HCl (30 mL) and brine (30
mL), and then dried (MgSO4) and concentrated in vacuo. The residue
was purified by flash column chromatography (hexane/EtOAc, 20/1
f 9/1) to give 4 (2.63 g, 86%) as a colorless syrup: Rf ) 0.33 (hexane/
EtOAc, 10/1). [R]25D ) -128.2° (c 2.5, CH2Cl2). 1H NMR (300 MHz,
CDCl3): δ 7.60 and 7.33 (m, 20H, Ar), 5.69 (d, J1,2 ) 3.0 Hz, 1H,
H-1), 4.72-4.54 (m, 6H, PhCH2), 4.48 (m, J3,4 ) 6.3 Hz, 1H, H-4),
Experimental Section
General Methods and Materials. Solvents were purified according
to the standard procedures. Reactions were performed under argon
unless stated otherwise. Reactions were monitored by thin-layer
chromatography (TLC) using silica gel 60 F254, and the compounds
were visualized with UV light (254 nm) or by treatment with a solution
of 10% H2SO4 in ethanol. Flash chromatography was performed on
(32) Grathwohl, M.; Schmidt, R. R. Synthesis 2001, 15, 2263-2272.
(33) Imoto, M.; Kusunose, N.; Matsuura, Y.; Kusumoto, S.; Shiba, T. Tetra-
hedron Lett. 1987, 28, 6277-6280.
(34) Orgueira, H. A.; Bartolozzi, A.; Schell, P.; Seeberger, P. H. Angew. Chem.,
Int. Ed. 2002, 41, 2128-2131.
9
J. AM. CHEM. SOC. VOL. 128, NO. 36, 2006 11953

A R T I C L E S
Zhu et al.
4.21 (t, J2,3 ) 3.0 Hz, 1H, H-2), 4.14 (m, 1H, H-3), 3.76-3.72 (m,
J4,5a ) 3.9 Hz, J4,5b ) 4.7 Hz, 2H, H-5a, H-5b). 13C NMR (75 MHz,
CDCl3): δ 138.4, 138.1, 137.7, 135.2, 131.5, 129.2, 128.8, 128.7, 128.6,
128.28, 128.25, 128.13, 128.11, 128.0, 127.9, 127.4, 90.6, 88.8, 83.7,
80.9, 73.6, 72.6, 72.5, 72.4, 69.4. MALDI HR-MS: m/z 535.2385 [M
+ Na]+, calcd for C32H32O4S 535.2321.
General Procedure for the Synthesis of Disaccharides 6, 7, 9,
10, 12, 13, 15, 17, 19, and 21. A mixture of a thioglycoside (0.16
mmol) and an alcohol (0.10 mmol) in CH2Cl2 (10 mL) was stirred at
room temperature in the presence of 4 Å molecular sieves (500 mg)
for 30 min. After the mixture was cooled to -30 °C, NIS (54 mg, 0.24
mmol) followed by a solution of AgOTf (21 mg, 80 µmol) in toluene
(0.2 mL) were added. The reaction mixture was warmed slowly to room
temperature, and stirring was continued for 15 min. The reaction was
quenched by the addition of Et3N or pyridine. The suspension was
diluted with EtOAc (50 mL) and filtered through a pad of Celite, and
the filtrate was washed successively with 10% Na2S2O3 (10 mL) and
brine (20 mL). The organic layer was dried (MgSO4) and concentrated
in vacuo to give a residue, which was purified by flash column
chromatography to afford the corresponding disaccharide.
78.1, 73.9, 71.7, 70.4, 70.3, 69.8, 68.1, 67.1, 66.9, 55.3, 27.5, 27.2,
22.5, 20.1. MALDI HR-MS: m/z 891.3483 [M + Na]+, calcd for
C48H56O13Si 891.3490.
Methyl 2,3,5-Tri-O-benzyl-R/â-L-arabinofuranosyl-â-(1f6)-2,3,4-
1
tri-O-benzoyl-R-D-mannopyranoside (10). R/â H NMR (300 MHz,
CDCl3): δ 8.11 (d, J ) 7.2 Hz, 2H, Ar), 7.97 (d, J ) 7.2 Hz, 2H, Ar),
7.85 (d, J ) 7.2 Hz, 2H, Ar), 7.58-7.47 (m, 2H, Ar), 7.45-7.19 (m,
22H, Ar), 5.92-5.88 (m, 2H, H-3, H-4), 5.69 (s, 1H, H-2), 5.16 (s,
0.34H, H-1′R), 4.98 (d, J ) 1.2 Hz, 0.33H, H-1R), 4.94-4.90 (m,
1.34H, H-1â, H-1′â), 4.69-4.27 (m, 8H), 4.14-3.97 (m, 4H), 3.61-
3.54 (m, 3H), 3.50 (s, 1H, OMeR), 3.47 (s, 2H, OMeâ). 13C NMR (75
MHz, CDCl3): δ 165.8, 165.7, 138.5, 138.4, 138.3, 138.2, 138.1, 137.9,
133.7, 133.3, 130.2, 130.1, 130.0, 129.9, 129.6, 129.5, 129.48, 129.42,
129.3, 128.8, 128.7, 128.6, 128.57, 128.50, 128.28, 128.20, 128.04,
128.01, 127.97, 127.93, 127.85, 127.82, 127.7, 107.4 (C-1′R), 101.2
(C-1′â), 98.7 (C-1R,â), 88.7, 84.3, 83.6, 83.5, 80.7, 77.7, 77.5, 77.3,
76.8, 73.6, 73.4, 73.1, 72.5, 72.3, 72.2, 70.8, 70.6, 70.4, 70.3, 70.0,
69.7, 67.6, 67.0, 55.6. MALDI HR-MS: m/z 931.3401 [M + Na]+,
calcd for C54H52O13 931.3408.
Methyl 2-O-Benzyl-3,5-O-(di-tert-butylsilanediyl)-â-L-arabino-
furanosyl-(1f6)-2,3-di-O-acetyl-4-O-benzyl-â-D-glucopyranoside (12).
Methyl 2-O-Benzyl-3,5-O-(di-tert-butylsilanediyl)-â-L-arabino-
furanosyl-(1f6)-2,3,4-tri-O-benzoyl-R-D-glucopyranoside (6). Rf )
0.53 (hexane/EtOAc, 2.5/1). [R]25D ) -16.7° (c 1.8, CH2Cl2). 1H NMR
(500 MHz, CDCl3): δ 7.98 (d, J ) 7.5 Hz, 2H, Ar), 7.94 (d, J ) 7.0
Hz, 2H, Ar), 7.86 (d, J ) 7.5 Hz, 2H, Ar), 7.51 (t, J ) 7.5 Hz, 2H,
Ar), 7.44-7.27 (m, 12H, Ar), 6.12 (t, J ) 10.0, 9.5 Hz, 1H, H-3),
5.56 (t, J ) 10.0 Hz, 1H, H-4), 5.22 (m, 2H, H-1, H-2), 4.94 (d, J )
5.0 Hz, 1H, H-1′), 4.78 (AB, J ) 12.0 Hz, 2H, PhCH2), 4.42 (t, J )
9.0 Hz, 1H, H-3′), 4.25 (m, 1H, H-5), 4.17 (dd, J ) 9.0, 5.0 Hz, 1H,
H-2′), 3.92 (dd, J ) 9.0, 5.0 Hz, 1H, H-4′), 3.89 (dd, J ) 11.0, 6.0 Hz,
1H, H-6a), 3.85 (t, J ) 9.5 Hz, 1H, H-5′a), 3.62 (m, 2H, H-6b, H-5′b),
Rf ) 0.75 (hexane/EtOAc, 1.5/1). [R]25 ) -210.4° (c 0.5, CH2Cl2);
D
1H NMR (500 MHz, CDCl3): δ 7.48 (d, J ) 7.5 Hz, 2H, Ar), 7.37 (t,
J ) 7.5 Hz, 2H, Ar), 7.29 (m, 4H, Ar), 7.22 (d, J ) 7.0 Hz, 2H, Ar),
5.17 (t, J ) 10.0, 9.5 Hz, 1H, H-3), 5.14 (d, J ) 5.0 Hz, 1H, H-1′),
4.86 (dd, J ) 9.5, 8.5 Hz, 1H, H-2), 4.81 (AB, J ) 12.0 Hz, 2H,
PhCH2), 4.65 and 4.50 (AB, J ) 11.5 Hz, 2H, PhCH2), 4.37 (d, J )
8.0 Hz, 1H, H-1), 4.36 (t, J ) 8.5 Hz, 1H), 4.29 (dd, J ) 9.5, 5.0 Hz,
1H), 4.03 (dd, J ) 12.0, 4.0 Hz, 1H, H-2′), 3.97 (dd, J ) 9.0, 5.5 Hz,
1H, H-5), 3.87 (t, J ) 10.0 Hz, 1H), 3.82 (m, 2H), 3.66 (dt, J ) 10.0,
5.0 Hz, 1H, H-4), 3.49 (dd, J ) 9.5, 2.0 Hz, 1H), 3.46 (s, 3H, OMe),
t
t
t
t
3.45 (s, 3H, OMe), 1.08 (s, 9H, Bu), 0.98 (s, 9H, Bu). 13C NMR (75
MHz, CDCl3): δ 165.81, 165.79, 165.0, 138.0, 133.3, 133.0, 129.9,
129.8, 129.7, 129.3, 129.13, 129.10, 128.4, 128.3, 128.2, 128.1, 127.7,
100.3 (C-1′), 96.8 (C-1), 80.7, 78.2, 73.9, 72.2, 71.7, 70.7, 69.3, 68.7,
68.1, 66.5, 55.4, 27.5, 27.2, 22.5, 20.1. MALDI HR-MS: m/z 891.3488
[M + Na]+, calcd for C48H56O13Si 891.3490.
2.04, 1.86 (2 × s, 6H, Ac), 1.05 (s, 9H, Bu), 1.00 (s, 9H, Bu). 13C
NMR (75 MHz, CDCl3): δ 170.1, 169.7, 138.0, 137.8, 128.41, 128.36,
128.0, 127.9, 127.8, 127.6, 101.5 (C-1), 101.0 (C-1′), 81.0, 78.6, 75.7,
74.9, 74.8, 74.7, 73.5, 71.9, 71.8, 68.4, 66.7, 356.7, 27.5, 27.1, 22.6,
20.8, 20.7, 20.1. MALDI HR-MS: m/z 753.3330 [M + Na]+, calcd
for C38H54O12Si 753.3385.
Methyl 2,3,5-Tri-O-benzyl-R/â-L-arabinofuranosyl-(1f6)-2,3,4-
tri-O-benzoyl-R-D-glucopyranoside (7). R/â 1H NMR (500 MHz,
CDCl3): δ 8.04 (d, J ) 7.5 Hz, 2H, Ar), 7.97 (d, J ) 7.0 Hz, 2H, Ar),
7.91 (d, J ) 7.5 Hz, 2H, Ar), 7.54 (m, 2H, Ar), 7.44-7.27 (m, 22H,
Ar), 6.24-6.20 (m, 1H, H-3R, Η-3â), 5.64-5.59 (m, 1H, H-4R, Η-4â),
5.37-5.15 (m, 3.4H, H-1R, H-1â, H-2â, H-1′â), 4.78-4.40 (m, 6H,
PhCH2), 4.32-3.97 (m, 6H), 3.89-3.63 (m, 4H), 3.49 (s, 2.3H, OMeâ),
3.44 (s, 0.7H, OMeR). 13C NMR (75 MHz, CDCl3): δ 165.9, 165.8,
165.7, 138.5, 138.4, 138.3, 138.2, 138.1, 138.0, 133.6, 133.5, 133.1,
133.0, 130.2, 130.1, 130.0, 129.9, 129.7, 129.5, 129.43, 129.41, 129.2,
128.9, 128.7, 128.6, 128.5, 128.4, 128.2, 128.1, 128.06, 128.03, 127.95,
127.93, 127.84, 127.80, 127.7, 107.7 (C-1′R), 101.5 (C-1′â), 97.4 (C-
1), 88.6, 84.3, 83.5, 83.4, 80.7, 77.6, 77.3, 76.8, 73.6, 73.4, 73.1, 72.5,
72.3, 72.2, 70.8, 70.6, 70.4, 70.3, 70.0, 69.7, 67.6, 67.0, 55.6. MALDI
HR-MS: m/z 931.3410 [M + Na]+, calcd for C54H52O13 931.3408.
Methyl 2-O-Benzyl-3,5-O-(di-tert-butylsilanediyl)-â-L-arabino-
furanosyl-(1f6)-2,3,4-tri-O-benzoyl-R-D-mannopyranoside (9). Rf )
0.40 (hexane/EtOAc, 3.5/1). [R]25D ) -162.6° (c 1.6, CH2Cl2). 1H NMR
(500 MHz, CDCl3): δ 8.12 (d, J ) 7.0 Hz, 2H, Ar), 7.97 (d, J ) 7.5
Hz, 2H, Ar), 7.83 (d, J ) 7.5 Hz, 2H, Ar), 7.58 (t, J ) 7.5 Hz, 1H,
Ar), 7.53 (t, J ) 7.5 Hz, 1H, Ar), 7.48-7.38 (m, 7H, Ar), 7.25 (m,
5H, Ar), 5.90 (t, J ) 10.0 Hz, 1H, H-4), 5.86 (dd, J ) 10.0, 3.0 Hz,
H-3), 5.69 (s, 1H, H-2), 5.00 (s, 1H, H-1), 4.96 (d, J ) 5.0 Hz, 1H,
H-1′), 4.76 (AB, J ) 12.5 Hz, 2H, PhCH2), 4.48 (t, J ) 9.0 Hz, 1H),
4.30 (t, J ) 7.0 Hz, 1H, H-5), 4.19 (dd, J ) 9.0, 5.5 Hz, 1H, H-3′),
4.00-3.90 (m, 3H, H-2′, H-6a), 3.66 (m, 2H), 3.53 (s, 3H, OMe), 1.09
Methyl 2,3,5-Tri-O-benzyl-R/â-L-arabinofuranosyl-â-(1f6)-2,3-
di-O-acetyl-4-O-benzyl-â-D-glucopyranoside (13). R/â 1H NMR (300
MHz, CDCl3): δ 7.44-7.19 (m, 20H, Ar), 5.24-5.14 (m, 1.35H, H-3â,
H-1′â), 4.92-4.46 (m, 10.2H), 4.37 (m, 1H, H-1R, H-1â), 4.18-3.96
(m, 4H), 3.89-3.51 (m, 6H), 3.46 (s, 3H, OMeR, OMeâ), 2.04 (s, 3H,
AcR, Acâ), 1.94 (s, 1H, AcR), 1.86 (s, 2H, Acâ). 13C NMR (75 MHz,
CDCl3): δ 170.4, 170.1, 170.0, 138.4, 138.3, 138.1, 138.04, 138.03,
137.8, 137.7, 128.8, 128.72, 128.68, 128.58, 128.3, 128.2, 128.1, 128.0,
127.9, 127.8, 106.8 (C-1′R), 101.8 (C-1R), 101.7 (C-1â), 101.5 (C-
1′â), 88.5, 84.4, 83.7, 83.2, 80.9, 80.5, 77.7, 77.2, 76.9, 76.0, 75.3,
74.8, 74.7, 73.6, 73.4, 72.8, 72.4, 72.2, 72.1, 69.9, 66.6, 65.8, 57.1,
56.9, 21.0, 20.9. MALDI HR-MS: m/z 793.3311 [M + Na]+, calcd
for C44H50O12 793.3302.
Methyl 2-O-Benzyl-3,5-O-(di-tert-butylsilanediyl)-â-L-arabino-
furanosyl-(1f6)-2,3,4-tri-O-acetyl-â-D-galactopyranoside (15). Rf )
0.57 (hexane/EtOAc, 1.5/1). [R]25D ) -152.2° (c 0.5, CH2Cl2). 1H NMR
(500 MHz, CDCl3): δ 7.41 (d, J ) 7.5 Hz, 2H, Ar), 7.35 (t, J ) 7.5
Hz, 2H, Ar), 7.29 (t, J ) 7.0 Hz, 1H, Ar), 5.45 (d, J ) 2.5 Hz, 1H,
H-4), 5.18 (dd, J ) 10.0, 8.0 Hz, 1H, H-2), 4.99 (dd, J ) 10.5, 3.0 Hz,
H-3), 4.85 (d, J ) 5.0 Hz, 1H, H-1′), 4.78 (AB, J ) 12.5 Hz, 2H,
PhCH2), 4.36 (d, J ) 7.5 Hz, 1H, H-1), 4.32 (t, J ) 9.0 Hz, 1H, H-3′),
4.28 (dd, J ) 9.0, 5.0 Hz, 1H), 3.96 (t, J ) 10.0 Hz, 1H), 3.89 (m, 2H,
H-2′, H-5′a), 3.73 (dd, J ) 10.5, 6.0 Hz, 1H, H-5′b), 3.61 (m, 2H, H-4′),
3.49 (s, 3H, OMe), 2.12, 2.05, 1.97 (3 × s, 9H, Ac), 1.07 (s, 9H, tBu),
0.98 (s, 9H, tBu). 13C NMR (75 MHz, CDCl3): δ 170.11, 169.95, 169.5,
137.8, 128.3, 128.1, 127.7, 102.0 (C-1), 101.1 (C-1′), 80.5, 78.2, 73.8,
71.83, 71.79, 71.1, 69.1, 68.2, 67.5, 66.7, 56.9, 27.5, 27.1, 22.5, 20.8,
20.7, 20.6, 20.0. MALDI HR-MS: m/z 705.2890 [M + Na]+, calcd
for C33H50O13Si 705.3021.
t
t
(s, 9H, Bu), 1.01 (s, 9H, Bu). 13C NMR (75 MHz, CDCl3): δ 165.6,
165.4, 165.3, 137.9, 133.34, 133.27, 133.0, 130.0, 129.74, 129.71, 129.3,
129.2, 128.5, 128.4, 128.2, 128.1, 127.6, 100.3 (C-1′), 98.4 (C-1), 80.8,
9
11954 J. AM. CHEM. SOC. VOL. 128, NO. 36, 2006

Stereoselective Introduction of
â
-Arabinofuranosides
A R T I C L E S
3-Azidopropyl 2-O-Benzyl-3,5-O-(di-tert-butylsilanediyl)-â-L-ara-
binofuranosyl-(1f3)-2-O-benzoyl-4,6-O-benzylidene-â-D-galactopy-
ranoside (17). Rf ) 0.16 (hexane/EtOAc, 2/1). H NMR (500 MHz,
which was purified by flash column chromatography (hexane/EtOAc,
5/1 f 1/1) to give 25 (691 mg, 79%) as a white foam: Rf ) 0.61
(hexane/EtOAc, 1/1). [R]25D ) -119.3° (c 0.7, CH2Cl2). 1H NMR (300
MHz, CDCl3): δ 8.03 (t, J ) 7.5 Hz, 4H, Ar), 7.93 (d, J ) 7.8 Hz,
2H, Ar), 7.75 (d, J ) 8.1 Hz, 2H, Ar), 7.69-7.19 (m, 23H, Ar), 7.11
(t, J ) 7.5 Hz, 1H, Ar), 7.01 (t, J ) 7.5 Hz, 1H, Ar), 5.87 (d, J ) 3.3
Hz, 1H, H-4), 5.78 (dd, J ) 9.9, 8.4 Hz, 1H, H-2), 5.65 (t, J ) 9.1 Hz,
1H, H-2′), 5.57 (s, 1H, PhCH), 5.48 (dd, J ) 10.2, 3.3 Hz, H-3′), 5.02
(dd, J ) 10.5, 3.3 Hz, 1H, H-3), 4.74 (d, J ) 7.8 Hz, 1H, H-1), 4.57
(d, J ) 7.8 Hz, 1H, H-1′), 4.49 (d, J ) 3.0 Hz, 1H, H-4′), 4.43 (d, J
) 12.6 Hz, 1H, H-6a), 4.28 (d, J ) 7.5 Hz, 2H), 4.18 (m, 1H), 4.08
(m, 3H), 3.84 (dd, J ) 10.5, 7.5 Hz, 1H), 3.61 (m, 2H, H-5), 3.26 (m,
1H, H-6b), 3.07 (t, J ) 6.9 Hz, 2H, CH2CH2N3), 1.53 (m, 2H, CH2-
CH2N3). 13C NMR (75 MHz, CDCl3): δ 165.81, 165.64, 165.52, 165.10,
154.71, 143.31, 143.19, 141.37, 137.59, 133.72, 133.48, 133.38, 130.27,
130.05, 129.96, 129.86, 129.78, 129.52, 129.34, 129.09, 128.78, 128.66,
128.44, 127.98, 127.29, 126.59, 125.35, 125.29, 120.15, 101.46, 101.16,
75.72, 73.68, 73.40, 71.97, 70.56, 70.09, 69.22, 69.02, 68.56, 66.54,
66.49, 48.04, 46.62, 28.97. MALDI HR-MS: m/z 1174.3673 [M +
Na]+, calcd for C65H57N3O17 1174.3688.
1
CDCl3): δ 8.07 (d, J ) 7.5 Hz, 2H, Ar), 7.57 (t, J ) 7.5 Hz, 1H, Ar),
7.50 (d, J ) 7.0 Hz, 2H), 7.45 (t, J ) 7.5 Hz, 2H), 7.29-7.19 (m, 8H,
Ar), 5.60 (dd, J ) 10.0, 8.5 Hz, 1H, H-2), 5.54 (s, 1H, PhCH), 5.18
(d, J ) 5.0 Hz, 1H, H-1′), 4.65 (d, J ) 8.0 Hz, 1H, H-1), 4.60 (AB
peak, J ) 12.0 Hz, 2H, PhCH2), 4.37 (m, 2H), 4.15 (t, J ) 9.0 Hz,
1H), 4.10 (m, 2H), 4.00 (m, 2H), 3.89 (dd, J ) 9.0, 5.0 Hz, 1H), 3.56
(m, 2H), 3.49 (t, J ) 9.0 Hz, 2H, CH2CH2N3), 3.23 (m, 2H, CH2-
t
t
CH2N3), 1.78 (m, 2H), 0.91 (s, 9H, Bu), 0.79 (s, 9H, Bu). 13C NMR
(75 MHz, CDCl3): δ 164.9, 138.1, 137.4, 133.0, 130.0, 129.7, 128.9,
128.4, 128.12, 128.11, 127.7, 127.3, 126.3, 101.4, 101.1, 97.2 (C-1′),
80.5, 77.3, 74.5, 74.2, 72.3, 70.9, 70.2, 69.2, 68.2, 66.7, 65.7, 48.0,
29.0, 27.2, 27.1, 22.3, 20.0. MALDI MS: m/z 841.3605 [M + Na]+,
calcd for C43H55N3O11Si 840.3606.
Allyl 2-O-Benzyl-3,5-O-(di-tert-butylsilanediyl)-â-L-arabinofura-
nosyl-(1f3)-2-O-benzyl-4,6-O-benzylidene-â-D-glucopyranoside (19).
Rf ) 0.32 (hexane/EtOAc, 6/1). 1H NMR (500 MHz, CDCl3): δ 7.43-
7.17 (m, 15H, Ar), 5.91 (m, 1H, OCH2CHCH2), 5.42 (s, 2H, PhCH2),
5.31 (d, J ) 17.5 Hz, 1H, OCH2CHCHaCHb), 5.19 (d, J ) 10.5 Hz,
1H, OCH2CHCHaCHb), 4.87 (AB peak, J ) 11.5 Hz, 2H, PhCH2),
4.76 and 4.59 (AB, J ) 12.5 Hz, 2H), 4.56 (d, J ) 7.5 Hz, 1H, H-1),
4.37 (dd, J ) 13.0, 5.5 Hz, 1H, OCHaHbCHCH2), 4.34 (t, J ) 9.5 Hz,
1H), 4.32 (dd, J ) 10.5, 4.5 Hz, 1H), 4.15 (m, 1H), 4.13 (d, J ) 5.0
Hz, 1H, H-1′), 3.99 (t, J ) 9.0 Hz, 1H), 3.85 (dd, J ) 9.5, 5.5 Hz,
1H), 3.74 (t, J ) 10.0 Hz, 1H), 3.72 (t, J ) 10.0, 1H), 3.67 (t, J ) 9.5
Hz, 1H), 3.58 (m, 1H), 3.53 (t, J ) 8.0 Hz, 1H), 3.41 (dt, J ) 9.5, 5.0
3-Azidopropyl 2-O-Benzoyl-4-O-benzyl-3-O-(9-fluorenylmethoxy-
carbonyl)-â-D-galactopyranosyl-(1f6)-2,3,4-tri-O-benzoyl-â-D-ga-
lactopyranoside (26). To a stirred and cooled (0 °C) solution of 25
(507 mg, 0.44 mmol) in CH2Cl2 (15 mL) were added successively BH3‚
THF (1.0 M in THF, 5 mL, 5 mmol) and Bu2BOTf (1.0 M in CH2Cl2,
0.5 mL, 0.5 mmol). After it was stirred for 2 h, the reaction mixture
was concentrated to a small volume and then diluted with EtOAc (30
mL), washed successively with saturated aqueous NaHCO3 (15 mL)
and brine (20 mL), dried (MgSO4), and concentrated in vacuo. The
residue was purified by flash column chromatography (hexane/EtOAc,
2/1 f 1/1) to give the alcohol 26 (305 mg, 60%) as a white foam: Rf
) 0.52 (hexane/EtOAc, 1/1). [R]25D ) -78.4° (c 1.0, CH2Cl2). 1H NMR
(300 MHz, CDCl3): δ 8.05 (d, J ) 6.9 Hz, 4H, Ar), 7.95 (d, J ) 7.2
Hz, 2H, Ar), 7.76 (d, J ) 7.8 Hz, 2H, Ar), 7.69-7.09 (m, 25H, Ar),
5.89 (br s, 1H, H-4), 5.75 (t, J ) 8.7 Hz, 1H, H-2′), 5.68 (t, J ) 8.4
Hz, 1H, H-2), 5.51 (d-like, J ) 10.5 Hz, 1H, H-3), 5.03 (d, J ) 10.8
Hz, 1H, H-3′), 4.85 and 4.54 (AB, J ) 11.5 Hz, 2H, PhCH2), 4.66 (d,
J ) 8.1 Hz, 1H), 4.63 (d, J ) 8.4 Hz, 1H), 4.30 (m, 2H), 4.08 (m,
4H), 3.83 (m, 2H), 3.61 (m, 3H), 3.33 (m, 1H), 3.10 (m, 2H,
CH2CH2N3), 1.58 (m, 2H, CH2CH2N3). 13C NMR (75 MHz, CDCl3):
δ 165.6, 165.4, 165.2, 164.9, 154.5, 143.1, 142.7, 141.1, 141.0, 137.3,
133.5, 133.2, 133.1, 129.9, 129.8, 129.6, 129.5, 129.2, 128.9, 128.7,
128.53, 128.46, 128.4, 128.2, 128.1, 127.8, 127.0, 125.0, 124.8, 101.4,
101.3, 77.8, 77.2, 74.95, 74.85, 73.3, 73.2, 71.6, 70.1, 70.0, 69.8, 68.9,
68.5, 66.2, 61.5, 47.7, 46.4, 28.7. MALDI HR-MS: m/z 1176.3878
[M + Na]+, calcd for C65H59N3O17 1176.3845.
3-Azidopropyl 2,3-Di-O-acetyl-4-O-benzyl-6-O-levulinoyl-â-D-ga-
lactopyranosyl-(1f6)-2-O-benzoyl-4-O-benzyl-3-O-(9-fluorenyl-
methoxycarbonyl)-â-D-galactopyranosyl-(1f6)-2,3,4-tri-O-benzoyl-
â-D-galactopyranoside (27). The coupling of the glycosyl donor 24
(110 mg, 0.22 mmol) and the acceptor 26 (145 mg, 0.13 mmol) was
performed as described for 25 to give the trisaccharide 27 (160 mg,
81%) as a white amorphous solid: Rf ) 0.21 (hexane/EtOAc, 1/1). 1H
NMR (500 MHz, CDCl3): δ 8.04 (d, J ) 7.5 Hz, 2H, Ar), 8.01 (d, J
) 8.0 Hz, 2H, Ar), 7.93 (d, J ) 7.5 Hz, 2H, Ar), 7.74 (d, J ) 7.5 Hz,
2H, Ar), 7.66 (d, J ) 8.0 Hz, 1H, Ar), 7.64 (d, J ) 7.5 Hz, 1H, Ar),
7.60 (t, J ) 7.5 Hz, 1H, Ar), 7.52-7.25 (m, 23H, Ar), 7.22 (t, J ) 8.0
Hz, 2H, Ar), 7.12 (t, J ) 8.0 Hz, 1H, Ar), 7.08 (t, J ) 7.5 Hz, 1H,
Ar), 5.79 (d, J ) 3.0 Hz, 1H), 5.67 (dd, J ) 10.5, 8.0 Hz, 1H), 5.64
(dd, J ) 10.0, 8.0 Hz, 1H), 5.47 (dd, J ) 10.5, 3.5 Hz, 1H), 5.34 (dd,
J ) 10.0, 8.0 Hz, 1H), 4.98 (dd, J ) 7.0, 3.0 Hz, 1H), 4.96 (dd, J )
7.0, 3.0 Hz, 1H), 4.74 and 4.55 (AB, J ) 11.5 Hz, 2H), 4.70 and 4.60
(AB, J ) 11.0 Hz, 2H), 4.62 (d, J ) 10.5 Hz, 2H), 4.46 (d, J ) 8.5
Hz, 1H), 4.26 (dd, J ) 10.5, 7.0 Hz, 1H), 4.21 (m, 2H), 4.17-3.99
(m, 6H), 3.94 (d, J ) 3.0 Hz, 1H), 3.72 (m, 4H), 3.58 (dt, J ) 10.0,
5.0 Hz, 1H), 3.28 (m, 1H), 3.06 (t, J ) 6.5 Hz, 2H, CH2CH2N3), 2.69
t
t
Hz, 1H), 1.04 (s, 9H, Bu), 0.94 (s, 9H, Bu). 13C NMR (75 MHz,
CDCl3): δ 138.5, 137.9, 137.2, 133.7, 129.2, 128.4, 128.2, 127.6, 127.5,
127.45, 127.42, 126.2, 117.7, 103.0, 101.6, 100.8, 81.5, 80.3, 80.2,
79.2, 78.2, 75.1, 73.6, 71.2, 70.8, 68.8, 68.3, 65.7, 27.5, 27.1, 22.5,
20.0. MALDI MS: m/z 783.3524 [M + Na]+, calcd for C43H56O10Si
783.3643.
3-Azidopropyl 2-O-Benzyl-3,5-O-(di-tert-butylsilanediyl)-â-L-
arabinofuranosyl-(1f6)-2-O-benzoyl-4-O-benzyl-3-O-(9-fluorenyl-
methoxycarbonyl)-â-D-galactopyranoside (21). Rf ) 0.47 (hexane/
EtOAc, 3/1). 1H NMR (500 MHz, CDCl3): δ 8.08 (d, J ) 7.5 Hz, 2H,
Ar), 7.72 (t, J ) 7.0 Hz, 2H, Ar), 7.57 (t, J ) 7.5 Hz, 1H, Ar), 7.50-
7.28 (m, 15H, Ar), 7.24 (t, J ) 7.5 Hz, 1H, Ar), 7.13 (m, 2H, Ar),
5.71 (t, J ) 10.0, 8.0 Hz, 1H), 5.04 (dd, J ) 10.5, 3.0 Hz, 1H), 4.91
(d, J ) 5.5 Hz, 1H, H-1′), 4.86 and 4.77 (AB, J ) 12.5 Hz, 2H, PhCH2),
4.80 and 4.61 (AB, J ) 12.0 Hz, 2H, PhCH2), 4.59 (d, J ) 8.0 Hz,
1H, H-1), 4.38 (t, J ) 9.5 Hz, 1H), 4.33 (m, 2H), 4.20 (t, J ) 10.5, 8.5
Hz, 1H), 4.16 (br s, 1H), 4.11 (t, J ) 7.5 Hz, 1H), 3.96 (m, 3H), 3.82
(m, 3H), 3.67 (m, 1H), 3.55 (m, 1H), 3.24 (m, 2H, CH2CH2N3), 1.76
t
t
(m, 2H, CH2CH2N3), 1.09 (s, 9H, Bu), 1.03 (s, 9H, Bu). 13C NMR
(75 MHz, CDCl3): δ 165.1, 154.5, 143.2, 142.8, 141.2, 141.1, 137.9,
137.7, 133.2, 129.7, 129.6, 128.4, 128.3, 128.2, 128.0, 127.8, 127.72,
127.66, 127.1, 127.0, 125.2, 124.9, 119.9, 101.4 (C-1), 101.1 (C-1′),
80.5, 78.7, 77.7, 75.0, 73.7, 73.6, 73.1, 71.8, 70.15, 70.11, 68.3, 66.6,
66.1, 47.9, 46.4, 28.9, 27.5, 27.1, 22.5, 20.0. MALDI HR-MS: m/z
1064.4761 [M + Na]+, calcd for C58H67N3O13Si 1064.4443.
3-Azidopropyl 2-O-Benzoyl-4,6-O-benzylidene-3-O-(9-fluorenyl-
methoxycarbonyl)-â-D-galactopyranosyl-(1f6)-2,3,4-tri-O-benzoyl-
â-D-galactopyranoside (25). A mixture of the glycosyl donor 22 (602
mg, 0.88 mmol), the acceptor 23 (436 mg, 0.76 mmol), and powdered
4 Å molecular sieves (0.9 g) in CH2Cl2 (14 mL) was stirred at room
temperature for 30 min and then cooled to -20 °C. NIS (260 mg, 1.16
mmol), followed by a solution of AgOTf (100 mg, 0.39 mmol) in
toluene (0.8 mL), was added. The reaction mixture was warmed slowly
to room temperature, stirred for 20 min, and then quenched by the
addition of pyridine. The suspension was diluted with EtOAc (50 mL)
and filtered through a pad of Celite, and the filtrate was washed
successively with 10% Na2S2O3 (8 mL) and brine (10 mL). The organic
layer was dried (MgSO4) and concentrated in vacuo to give a residue,
9
J. AM. CHEM. SOC. VOL. 128, NO. 36, 2006 11955

A R T I C L E S
Zhu et al.
(m, 2H), 2.48 (m, 2H, CH2CH2N3), 2.16, 2.01, 1.97 (3 × s, 9H), 1.54
(m, 1H), 1.45 (m, 1H). 13C NMR (75 MHz, CDCl3): δ 206.3, 172.2,
170.2, 169.3, 165.4, 165.3, 165.2, 164.8, 154.4, 143.1, 142.8, 141.1,
141.0, 137.7, 137.4, 133.4, 133.2, 133.1, 130.0, 129.7, 129.64, 129.55,
129.2, 129.0, 128.8, 128.5, 128.4, 128.2, 128.1, 127.9, 127.73, 127.70,
127.6, 127.02, 126.99, 125.0, 124.9, 119.8, 101.3, 101.1, 100.8 (three
anomeric carbons), 77.3, 75.1, 75.0, 73.7, 73.3, 73.2, 72.9, 72.1, 71.6,
70.0, 69.8, 69.6, 68.9, 68.5, 66.4, 66.1, 62.3, 47.7, 46.4, 37.8, 29.7,
28.6, 27.7, 20.71, 20.66. MALDI HR-MS: m/z 1610.5524 [M + Na]+,
calcd for C87H85N3O26 1610.5421.
concentrated in vacuo and the residue was purified by flash column
chromatography (hexane/EtOAc, 2/1 f 1/1) to afford 30 (69 mg, 80%)
as a white amorphous solid, which was used directly in the next step
without further identification: Rf ) 0.21 (hexane/EtOAc, 1.5/1).
MALDI HR-MS: m/z 1652.4940 [M + Na]+, calcd for C87H99N3O26-
Si 1652.6286. The coupling of the glycosyl donor 3 (19 mg, 40 µmol)
and the acceptor 30 (26 mg, 16 µmol) was performed as described for
29 to give the pentasaccharide 31 (28 mg, 89%) as a white amorphous
solid: Rf ) 0.61 (hexane/EtOAc, 1.4/1). [R]25D ) -175.9° (c 0.7, CH2-
1
Cl2). H NMR (500 MHz, CDCl3): δ 8.03 (t, J ) 7.0 Hz, 4H, Ar),
7.94 (d, J ) 8.0 Hz, 2H, Ar), 7.75 (d, J ) 7.5 Hz, 2H, Ar), 7.61 (t, J
) 7.5 Hz, 1H, Ar), 7.56 (t, J ) 7.5 Hz, 1H, Ar), 7.52 (t, J ) 7.5 Hz,
1H, Ar), 7.48-7.22 (m, 29H, Ar), 5.79 (d, J ) 3.0 Hz, 1H), 5.63 (dd,
J ) 10.0, 8.0 Hz, 1H), 5.57 (t, J ) 10.0 Hz, 1H), 5.46 (dd, J ) 10.5,
3.0 Hz, 1H), 5.28 (dd, J ) 10.0, 8.0 Hz, 1H), 5.07 (d, J ) 11.0 Hz,
1H), 5.03 (d, J ) 5.0 Hz, 1H, H-1′′′), 4.93 (dd, J ) 10.5, 3.0 Hz, 1H),
4.85 and 4.70 (AB, J ) 12.0 Hz, 2H), 4.83 (d, J ) 8.0 Hz, 1H, H-1),
4.80 and 4.75 (AB, J ) 12.5 Hz, 2H), 4.61 (q-like, J ) 12.0 Hz, 2H),
4.58 (d, J ) 8.0 Hz, 1H, H-1′), 4.53 (d, J ) 9.0 Hz, 1H), 4.52 (d, J )
7.5 Hz, 1H, H-1′′), 4.39 (br s, 1H), 4.37 (d, J ) 4.0 Hz, 1H, H-1′′′′),
4.33 (m, 1H), 4.20 (t, J ) 9.0 Hz, 1H), 4.05 (m, 2H), 4.00-3.89 (m,
5H), 3.85 (br s, 1H), 3.80 (d-like, J ) 10.0 Hz, 1H), 3.74-3.59 (m,
7H), 3.53 (m, 2H), 3.40 (m, 2H), 3.26 (m, 1H), 3.06 (m, 2H), 1.93,
1.91 (2 × s, 6H), 1.53 (m, 1H), 1.45 (m, 1H), 1.11, 1.03, 0.92, 0.88 (4
× s, 36H). 13C NMR (125 MHz, CDCl3): δ 170.1, 169.5, 165.4, 165.32,
165.27, 164.8, 138.8, 138.4, 137.83, 137.79, 133.4, 133.2, 133.1, 132.9,
130.4, 130.0, 129.8, 129.7, 129.6, 129.3, 129.2, 128.9, 128.5, 128.4,
128.31, 128.29, 128.26, 128.24, 128.19, 128.0, 127.9, 127.72, 127.66,
127.5, 127.2, 101.5, 101.23, 101.20, 101.16, 100.2 (five anomeric
carbons), 80.5, 80.2, 80.0, 78.8, 78.2, 74.9, 74.6, 74.0, 73.9, 73.7, 73.5,
73.43, 73.36, 73.1, 72.8, 71.7, 71.6, 71.2, 69.9, 69.0, 68.34, 68.28, 67.9,
67.6, 66.2, 66.1, 47.8, 28.7, 27.6, 27.4, 27.1, 27.0, 22.6, 22.3, 20.8,
20.7, 20.1, 19.9. MALDI HR-MS: m/z 2014.8250 [M + Na]+, calcd
for C107H129N3O30Si2 2014.8200.
3-Azidopropyl 2,3-Di-O-acetyl-4-O-benzyl-6-O-levulinoyl-â-D-ga-
lactopyranosyl-(1f6)-[2-O-benzyl-3,5-O-(di-tert-butylsilanediyl)-â-
L-arabinofuranosyl-(1f3)]-2-O-benzoyl-4-O-benzyl-â-D-galactopy-
ranosyl-(1f6)-2,3,4-tri-O-benzoyl-â-D-galactopyranoside (29). Et3N
(2.4 mL) was added to a solution of 27 (157 mg, 99 µmol) in CH2Cl2
(12 mL). After it was stirred at room temperature for 18 h, the reaction
mixture was concentrated in vacuo and the residue was purified by
flash column chromatography (hexane/EtOAc, 1/1 f 1/2) to furnish
28 (111 mg, 82%) as a white foam, which was used directly in the
next step without further identification: Rf ) 0.28 (hexane/EtOAc,
1/1.2). MALDI HR-MS: m/z 1388.5251 [M + Na]+, calcd for
C72H75N3O24 1388.4741. A mixture of the thioglycoside 3 (76 mg, 0.16
mmol) and the sugar alcohol 28 (111 mg, 81 µmol) in CH2Cl2 (10
mL) was stirred at room temperature in the presence of 4 Å molecular
sieves (500 mg) for 30 min and then cooled to -30 °C. NIS (48 mg,
0.21 mmol), followed by a solution of AgOTf (28 mg, 0.1 mmol) in
toluene (0.2 mL), was added. The reaction mixture was warmed slowly
to room temperature, stirred for 15 min, and then quenched by the
addition of Et3N. The suspension was diluted with EtOAc (40 mL)
and filtered through a pad of Celite, and the filtrate was washed
successively with 10% Na2S2O3 (8 mL) and brine (10 mL). The organic
layer was dried (MgSO4) and concentrated in vacuo to give a residue,
which was purified by flash column chromatography (hexane/EtOAc,
2/1 f 1/1) to furnish the tetrasaccharide 29 (94 mg, 67%) as a white
1
amorphous solid: Rf ) 0.21 (hexane/EtOAc, 1.5/1). H NMR (500
3-Aminopropyl â-L-Arabinofuranosyl-(1f6)-â-D-galactopyrano-
syl-(1f6)-[â-L-arabinofuranosyl-(1f3)]-â-D-galactopyranosyl-(1f6)-
â-D-galactopyranoside (32). TBAF (75 µL, 1.0 M in THF) and AcOH
(11.0 µL) were added to the solution of the pentasaccharide 31 (25
mg, 12.5 µmol) in THF (3 mL). The reaction mixture was stirred at
room temperature for 26 h, after which the solvent was removed in
vacuo. The reaction residue was dissolved in DCM, washed with water
(2 × 5 mL), and then dried (MgSO4). After filtration and evaporation
of solvent, the residue was dried in vacuo for several hours. Then, it
was dissolved in dry MeOH (6 µL) and treated with NaOMe (10 mg,
30% in MeOH). The reaction mixture was stirred at 50 °C in an oil
bath for 1 h and then neutralized with weakly acidic resin (Amberlite
IRC-50). After filtration and concentration in vacuo, the residue was
purified by silica gel column chromatography (DCM/MeOH, 10/1).
MALDI HR-MS: m/z 1234.4219 [M + Na]+, calcd for C59H77N3O24
1234.4897. Pd/C (10%, 1.5 times the weight of the starting material)
was added to a solution of the protected azido pentasaccharide in
pyridine under an atmosphere of Ar. After evacuation, the flask was
placed under an atmosphere of H2. The reaction mixture was stirred
for 18 h until TLC analysis. Hexane/EtOAc (1/1, v/v), CHCl3/CH3OH
(9/1, v/v), and i-PrOH/28% NH4OH (95/5, v/v) indicated completion
of the reaction. The mixture was filtered through a polytetrafluoroethene
(PTFE) syringe filter (diameter 25 mm, pore size 0.2 mm), which was
further washed with pyridine. The solvents were coevaporated with
toluene. The residue was dried in vacuo for several hours. Matrix-
assisted time-of-flight (MALDI-TOF) MS and NMR spectroscopy
confirmed the reduction of the azido groups. Pd(OH)2 (Degussa type,
Aldrich, 2.0 times the weight of the starting material) was added to
the material obtained above and dissolved in a mixture of t-BuOH,
AcOH, and H2O (5/10/1, v/v/v, 2-5 mL) under Ar. The mixture was
placed under an atmosphere of H2 and stirred overnight. TLC analyses
i-PrOH/28% NH4OH (95/5, v/v) and i-PrOH/H2O/28% NH4OH (30/
MHz, CDCl3): δ 8.01 (t, J ) 7.0 Hz, 4H, Ar), 7.92 (d, J ) 7.5 Hz,
2H, Ar), 7.72 (d, J ) 7.5 Hz, 2H, Ar), 7.59 (t, J ) 7.5 Hz, 1H, Ar),
7.54 (t, J ) 7.0 Hz, 1H, Ar), 7.50 (t, J ) 7.5 Hz, 1H, Ar), 7.46-7.19
(m, 24H, Ar), 5.76 (d, J ) 3.0 Hz, 1H), 5.61 (dd, J ) 10.5, 8.0 Hz,
1H), 5.55 (t, J ) 9.0 Hz, 1H), 5.44 (dd, J ) 10.0, 3.5 Hz, 1H), 5.30
(dd, J ) 10.0, 8.0 Hz, 1H), 5.05 (d, J ) 11.0 Hz, 1H), 5.02 (d, J ) 5.0
Hz, 1H, H-1′′′), 4.95 (dd, J ) 10.5, 3.0 Hz, 1H), 4.78 (d, J ) 12.5 Hz,
1H), 4.72 and 4.68 (AB, J ) 12.0 Hz, 2H), 4.58-4.49 (m, 4H), 4.42
(d, J ) 8.0 Hz, 1H), 4.19 (m, 2H), 4.14 (dd, J ) 11.0, 7.0 Hz, 1H),
4.05 (dd, J ) 7.5, 3.0 Hz, 1H), 3.98 (dd, J ) 11.0, 3.0 Hz, 1H), 3.94
(d, J ) 2.5 Hz, 1H), 3.89 (m, 2H), 3.84 (br s, 1H), 3.79 (dd, J ) 10.0,
2.0 Hz, 1H), 3.72-3.64 (m, 4H), 3.53 (t, J ) 6.0 Hz, 1H), 3.49 (dt, J
) 10.0, 5.0 Hz, 1H), 3.38 (m, 2H), 3.24 (m, 1H), 3.03 (m, 2H), 2.67
(m, 2H), 2.47 (t, J ) 6.5 Hz, 2H), 2.15, 1.99, 1.92 (3 × s, 9H), 1.50
(m, 1H), 1.42 (m, 1H), 0.90, 0.87 (2 × s, 18H). 13C NMR (75 MHz,
CDCl3): δ 206.4, 172.2, 170.3, 169.4, 165.4, 165.3, 165.2, 164.8, 138.6,
137.7, 137.5, 133.4, 133.2, 133.1, 132.9, 130.3, 130.0, 129.73, 129.70,
129.6, 129.2, 129.1, 128.8, 128.5, 128.4, 128.33, 128.27, 128.2, 128.0,
127.9, 127.7, 127.3, 101.5, 101.1, 101.0, 100.3 (four anomeric carbons),
80.1, 80.0, 78.2, 75.1, 74.6, 73.8, 73.74, 73.70, 73.3, 73.1, 72.0, 71.7,
71.5, 71.2, 69.8, 69.7, 69.0, 68.4, 67.9, 67.7, 66.1, 62.3, 47.8, 37.8,
29.8, 28.6, 27.7, 27.4, 27.0, 22.3, 20.8, 20.7, 19.9. MALDI HR-MS:
m/z 1750.8198 [M + Na]+, calcd for C92H105N3O28Si 1750.6654.
3-Azidopropyl 2-O-Benzyl-3,5-O-(di-tert-butylsilanediyl)-â-L-ara-
binofuranosyl-(1f6)-2,3-di-O-acetyl-4-O-benzyl-â-D-galactopyrano-
syl-(1f6)-[2-O-benzyl-3,5-O-(di-tert-butylsilanediyl)-â-L-arabino-
furanosyl-(1f3)]-2-O-benzoyl-4-O-benzyl-â-D-galactopyranosyl-
(1f6)-2,3,4-tri-O-benzoyl-â-D-galactopyranoside (31). Hydrazine
acetate (10 mg, 0.11 mmol) was added to a solution of 29 (92 mg, 53
µmol) in a mixture of CH2Cl2 (9 mL) and MeOH (0.9 mL). After it
was stirred at room temperature for 5 h, the reaction mixture was
9
11956 J. AM. CHEM. SOC. VOL. 128, NO. 36, 2006

Stereoselective Introduction of
â
-Arabinofuranosides
A R T I C L E S
10/5, v/v or 30/20/10, v/v) indicated the presence of a single compound.
The mixture was filtered through a PTFE syringe filter (as above) and
further washed with AcOH. The solvents were coevaporated with
toluene. The residue was dried in vacuo for several hours. The recovered
materials were passed through a small amount of Iatrobeads and slowly
eluted with a mixture of i-PrOH and 28% NH4OH. Fractions containing
the products were collected and concentrated in vacuo. The products
were brought to pH 4.5 by the addition of AcOH and freeze-dried to
afford the fully deprotected pentasaccharide 32 (3.5 mg, 34% over four
steps). 1H NMR (500 MHz, CDCl3): δ 5.08 (d, J ) 4.5 Hz, 1H, H-1′′′),
4.93 (d, J ) 4.5 Hz, 1H, H-1′′′′), 4.42 (d, J ) 8.0 Hz, 1H, H-1), 4.37
(d, J ) 7.5 Hz, 1H, H-1′), 4.34 (d, J ) 8.0 Hz, 1H, H-1′′), 4.13-4.02
(m, 5H, H-2′′′, H-2′′′′), 3.99-3.89 (m, 4H), 3.86-3.73 (m, 8H, H-3′′′,
H-3), 3.71-3.65 (m, 3H, H-3′′′′), 3.64-3.51 (m, 6H, H-2, H-3′, H-3′′),
3.46-3.40 (m, 2H, H-2′, H-2′′), 3.07-3.03 (m, 2H, CH2CH2NH2),
1.92-1.88 (m, 2H, CH2CH2NH2). 13C NMR (125 MHz, CDCl3): δ
103.5, 103.4, 103.1, 101.2, 98.9 (five anomeric carbons), 82.0, 78.8,
76.4, 74.6, 73.8, 73.6, 73.4, 73.1, 72.6, 70.9, 70.6, 69.4, 69.3, 69.2,
68.4, 67.3, 67.1, 66.0, 63.2, 62.7, 62.1, 61.4, 61.3, 61.2, 44.8, 27.0.
MALDI HR-MS: m/z 848.3322 [M + Na]+, calcd for C31H55NO24
848.3114.
Computational Methods. All the geometry optimizations were
performed with the Gaussian03 program35 using density functional
theory (B3LYP36-38) and the 6-31G** basis set.39 The figures were
generated using Insight II. The xyz coordinates of all the optimized
structures are given in the Supporting Information.
Acknowledgment. This research was supported by the NSF
(Grant No. DBI 0421683).
Supporting Information Available: Text giving procedures
1
for the preparation of compounds 22-24, figures giving H
NMR spectra of all synthetic compounds, tables giving xyz
coordinates of optimized structures, and a full list of authors
for reference 35. This material is available free of charge via
the Internet at http://pubs.acs.org.
JA0629817
(35) Frisch, G. W.; et al. Gaussian 03, revision C.02; Gaussian, Inc.: Wall-
ingford, CT, 2004.
(36) Becke, A. D. Phys. ReV. A 1988, 38, 3098-3100.
(37) Becke, A. D. J. Chem. Phys. 1993, 98, 5648-5652.
(38) Lee, C. T.; Yang, W. T.; Parr, R. G. Phys. ReV. B 1988, 37, 785-789.
(39) Hariharan, P. C.; Pople, J. A. Theor. Chim. Acta 1973, 28, 213-222.
9
J. AM. CHEM. SOC. VOL. 128, NO. 36, 2006 11957