Glycosylation studies on conformationally restricted 3,5-O-(di-tert- butylsilylene)-d-galactofuranosyl trichloroacetimidate donors for 1,2-cis α-d-galactofuranosylation

Article abstract of DOI:10.1016/j.carres.2011.10.004

Conformationally restricted 3,5-O-di-tert-butylsilylene-d-galactofuranosyl trichloroacetimidate donors were synthesized from allyl α-d- galactofuranoside for the construction of 1,2-cis α-d-galactofuranosyl linkages. Glycosylation reactions were performed

Full text of DOI:10.1016/j.carres.2011.10.004

Carbohydrate Research 346 (2011) 2838–2848
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Carbohydrate Research
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Glycosylation studies on conformationally restricted
3,5-O-(di-tert-butylsilylene)-D-galactofuranosyl trichloroacetimidate donors
for 1,2-cis
a-D-galactofuranosylation
⇑
Mariano J. Tilve, Carola Gallo-Rodriguez
CIHIDECAR, Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón II, 1428 Buenos Aires, Argentina
a r t i c l e i n f o
a b s t r a c t
Article history:
Conformationally restricted 3,5-O-di-tert-butylsilylene-
D
-galactofuranosyl trichloroacetimidate donors
-galactofuranosyl
-galactono-1,4-lac-
-mannopyranosyl derivatives. The influence of the temperature and the
reaction solvents was evaluated, as well as the 6-O-substitution pattern of the donor. The higher -selec-
tivities were obtained at ꢀ78 °C in diethyl ether as solvent. 6-O-Acetyl substitution on constrained donor
increased the -selectivity compared to the 6-O-benzyl substitution. Almost no selectivities were
Received 12 September 2011
Received in revised form 3 October 2011
Accepted 4 October 2011
were synthesized from allyl
linkages. Glycosylation reactions were performed with several acceptors, including
tone, -rhamnopyranosyl, and
a-D-galactofuranoside for the construction of 1,2-cis a-D
D
D
D
Available online 12 October 2011
a
Keywords:
a
Glycosylation
Trichloroacetimidate
1,2-cis
Galactofuranose
Solvents effects
Protecting groups
observed in the non-participating solvent CH2Cl2. In contrast, ethereal solvents enhanced the
ity suggesting a participating effect in the reaction intermediate.
a-selectiv-
Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction
saccharides containing
biosynthetic studies.
a-D-Galf units would provide tools for the
It is recognized that the lack of pure and well-defined carbohy-
drates and glycoconjugates constitutes a major obstacle in glycobi-
ology,1,2 in view of the essential role of carbohydrates in biology.3
Synthetic efforts in the oligosaccharide fields have been pursued
mainly focused in the stereoselective preparation of pyranose
derivatives,4,5 whereas studies on stereoselective furanosylation
have been more limited.6–9 Galactofuranose-containing oligosac-
charides have deserved much attention since galactofuranose is
found in many pathogenic microorganisms such as Mycobacterium
tuberculosis, Leishmania, Trypanosoma cruzi and Klebsiella pneumo-
niae, as examples.6–8,10 Due to the xenobiotic nature of galactofura-
nose, its metabolism has been proposed as a potential target for
antimicrobial chemotherapy11 and studies on the biosynthesis
are currently being pursued.12,13 Although Galf is commonly found
Whereas b-
D
-galactofuranosides are readily obtained through
-galac-
neighboring group participation, the synthesis of 1,2-cis
a-D
tofuranosides is more difficult to achieve as a single diastereomer,
as so far, no general method is available for this purpose.4,6,7 The
trichloroacetimidate method for
lowed the synthesis of -Galf-(1?2)-D-galactitol, isolated by
reductive b-elimination from glycoproteins of Clostridium thermo-
a
-galactofuranosylation19 al-
a
-D
cellum and Bacteroides cellulosolvens, by the use of O-(2,3,5,6-tet-
ra-O-benzyl-b-
hexasaccharide repeating unit from a rhizobacteria containing ter-
minal -Galf-(1?2)- -Rha disaccharide was also synthesized
using 1 as donor with 7:1
/b glycosylation ratio.21 More recently,
higher diastereoselectivities have been obtained at low tempera-
ture reaction (ꢀ78 °C) using 2-OH rhamnopyranoside (10:1 /b ra-
tio) and 6-OH mannopyranoside (12.6:1 /b ratio) acceptors
D A
-galactofuranosyl) trichloroacetimidate (1).20
a-D
a-L
a
a
in b-configuration, several examples of
a-D
-Galf-containing oligo-
a
saccharides with 1,2-cis configuration have been established also
in bacteria and fungi.6,7 Interesting examples are the pathogenic
Streptococcus pneumoniae 22F,14 Escherichia coli O16715 and O8516
Salmonella enterica O5317 and O17,16 and Paracoccidioides brasilien-
sis,18 the etiological agent of paracoccidioidomycosis, the most
common systemic mycosis in Latin America. The synthesis of oligo-
derivatives, however, selectivities depended on the acceptor type
and protecting group pattern.22 The thioglycoside method was also
evaluated on galacto and gluco derivatives acceptors, giving better
yields but moderate selectivities which depended also on the
acceptor used.23
The first example of a single diastereomer
tion was reported by the use of the 20-carboxybenzyl (CB) glycoside
method, formerly developed for the construction of 1,2-cis b-
mannosides. The antineoplastic glycosphingolipid agelagalastatin
with -Galf-(1?2)-
-Galf as terminal unit was synthetized.24
a-galactofuranosyla-
D-
⇑
Corresponding author. Tel.: +54 11 4576 3346; fax: +54 11 4576 3352.
E-mail address: cgallo@qo.fcen.uba.ar (C. Gallo-Rodriguez).
a
-D
D
0008-6215/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2011.10.004

M. J. Tilve, C. Gallo-Rodriguez / Carbohydrate Research 346 (2011) 2838–2848
2839
More recently, di- and tetrasaccharide subunits of the cell wall
polysaccharide of Talaromyces flavus were achieved containing
-Galf-(1?2)-Man unit.25
-Galactofuranosides have been synthetized by the 2,3-anhy-
drosugar methodology, formerly developed for the construction of
1,2-cis b-
-Araf linkages.26 In this indirect method, the 2,3-anhy-
dro- -gulofuranosyl thioglycoside or sulfoxide donor reacts with
synthesis of docosasaccharide arabinan motif of mycobacterium
cell wall.42 More recently, a novel method for 1,2-cis b-selective
arabinofuranosylation was developed by the use of 2,3-O-xylyl-
ene-protected Araf thioglycoside donor which allowed the synthe-
sis of an oligosaccharide fragment of mannose-capped
mycobacterial lipoarabinomannan.43
In view of the results obtained with constrained arabinofur-
anosyl donors in selective 1,2-cis glycosylation, and considering
the stereochemical relationship between arabinose and galactose,
the synthesis of a conformationally restricted galactofuranosyl
a-
D
a
-D
D
D
the acceptor by SN2-like displacement, to form a disaccharide
epoxide derivative with a new 1,2-cis glycosidic linkage. After the
stereoselective opening of the epoxide, the desired
is obtained. The use of 2,3-anhydro-5,6-di-O-benzoyl-b-
a
-disaccharide
-gulofur-
D
donor was envisioned for the construction of 1,2-cis a-D-galacto-
anosyl-p-tolyl-(R/S)-sulfoxide as donor allowed the challenging
synthesis of the pentasaccharide repeating unit of varianose, a
polysaccharide produced by the fungus Penicillium varians which
furanosyl linkages. The 3,5-O-di-tert-butylsilylene protecting
group on galactofuranosyl oxocarbenium would favor the en-
trance of the nucleophile acceptor from the ‘inside’ face (a-face)
of the rigid conformer avoiding the eclipsing interactions pro-
duced by a b-face trajectory (Fig. 2). We here present the scope
and limitation of this approach as a contribution to the furanose
glycosylation field.
possesses an internal
a
-Galf unit.27 Glycosylation reaction afforded
one single diastereomer, however, further epoxide opening was
not completely regioselective.
Intense research has been performed to understand the factors
that affect chemical glycosylation mechanism,28–30 however,
mainly focused on glycopyranosyl donors. Stereoselective fur-
anosylation studies are more limited and this could be due to the
flexible ring in which the anomeric effect is less pronounced. Pro-
tecting groups play considerable role in the stereochemical control
of glycosylation reaction and few examples have been described
for 1,2 cis-arabinofuranosylation.31–33
On studying C-glycosylation of five-member ring oxacarbenium
ions, Woerpel et al. had proposed that the nucleophilic attack oc-
curred from inside the envelope (inside attack) in order to avoid
eclipsing interactions. Mixtures were obtained with arabinofura-
nose derivatives due to the stereoelectronic influence of C-2 and
C-3 substituents in trans-relationship, and in conformational equi-
librium.34 Conformationally constrained arabinofuranosyl donors
have been designed which produced highly selective 1,2-cis b-arabi-
nofuranosylation. The introduction of a 3,5-O-di-tert-butylsilylene
2. Results and discussion
Among the glycosylation methods already employed for galacto-
furanosyl linkage construction, the trichloroacetimidate method44
has been extensively used for the synthesis of oligosaccharides of
biological significance.6,7,45–50 In addition, high 1,2-cis selectivities
have been obtained with constrained arabinofuranosyl imidate L-
5 (Fig. 1).40 On the other side, a non participating group was re-
quired in O-2 of the constrained galactofuranosyl donor. For these
reasons, we decided to synthesize O-(2,6-O-benzyl-3,5-O-(di-tert-
butylsilanediyl)-b-
Fig. 2) as conformationally constrained
Several precursors of -galactofuranose have been used to date;
some of them are synthesized in several steps.7,9
D-galactofuranosyl) trichloroacetimidate (7,
D
-galactofuranosyl donor.
D
protecting group in L-arabinofuranosyl thioglycoside derivative L-
2.1. Synthesis of constrained
trichloroacetimidate donor
D-galactofuranosyl
2 (Fig. 1) locked the oxacarbenium intermediate ring in a E3 confor-
mation, directing the attack of the acceptor to the b face, giving rise
to 1,2-cis linkage.35 Glycosylation studies on the enantiomer analog
of 1 (D-3) showed that the activation method of glycosylation was
In this case, the synthesis started with allyl a-D-galactofurano-
side (8)51,52 which is obtained crystalline by direct O-alkylation of
galactose in one step. The anomeric allyl group, orthogonal to the
benzyl and di-tert-butylsilylene protecting groups, would allow
the selective deprotection of the anomeric center and further acti-
vation as the trichloroacetimidate derivative. On the other hand,
selective 2,6-O-protection has been previously described on pente-
crucial for stereoselectivity.36 Moreover,
resulted less selectively than
D
-arabinofuranosylation
L
-arabinofuranosylation.37 The devel-
opment of donor D-336,38 allowed the synthesis of the 22-residue
arabinan oligosaccharide from mycobacterial arabinogalactan and
related compounds.39 Other donors than thioglycoside such as sulf-
oxide L-436 or trichloroacetimidate L-540 also gave high b-selectivi-
ties. Moreover constrained donor L-5 was used in the synthesis of a
hexasaccharide and related fragments of rhamnogalacturonan II, a
highly complex pectic oligosaccharide of the primary cell wall of
higher plants. In this case, the b-anomer was obtained as a single dia-
stereomer whereas 1-thioarabinofuranoside analog L-2 gave a
slightly reduced anomeric selectivity.
nyl
a-D
-galactofuranoside, analog of 8.53 Treatment of 8 with
2.2 equiv of benzoyl chloride in pyridine at ꢀ10 °C gave the 2,6-
di-O-benzoyl derivative 9 in 63% yield (Scheme 1). In the 1H
NMR spectrum, as expected, the H-1 appeared as a doublet with
J1,2 4.8 Hz due to H-1–H-2-cis disposition.20,22 Selective benzoyla-
tion occurred as indicated by the H-2 and H-6a,6b resonances that
shifted 0.94 and 0.74–0.75 ppm downfield, respectively, compared
to the same signals in 8. In the 13C NMR spectrum of 9, the reso-
nances of C-2 and C-4 appeared at 80.2 and 82.7 ppm characteristic
of the galactofuranosyl compounds. On reaction with t-Bu2Si(OTf)2
On the other hand, the conformationally constrained donor D-6
(Fig. 1) with a 3,5-O-tetra-i-propyldisiloxanyllidene protecting
group also gave high b-selectivity41 and it was employed in the
t-Bu
O
OBn
O
OBn
O
O
iPr2Si
R
O
Si
O
t-Bu
t-Bu
t-Bu
Si
O
O
SR
O
STol
iPr2Si
O
OBn
6
D-
2
L- R = SPh
2
D- R=Ph
L-3 R = STol
L-4 R = S(O)Ph
3
D- R=Tol
5
L- R = OC=NHCCl3
Figure 1. Conformationally constrained donors used for 1,2-cis b-Araf linkage construction.

2840
M. J. Tilve, C. Gallo-Rodriguez / Carbohydrate Research 346 (2011) 2838–2848
H2
t-Bu
t-Bu
+
CCl3
NH
HO
O
O
O
O
Si
BnO
O
Si
O
H1 C1
O2
O
C3
C4
t-Bu
t-Bu
O
O
HO
HO
O
OH
BnO
OBn
BnO
Nu
Nu
7
8
inside attack
Figure 2.
t-Bu
t-Bu
HO
HO
O
O
O
Si
O
BzCl (2.2 eq)
(tBu)2Si(OTf)2
O
O
OBz
HO
HO
BzO
O
OBz
O
OH
DMAP,C5H5N
0 ºC - r.t.
C5H5N, -10 ºC
63%
HO
BzO
8
9
10
84%
t-Bu
t-Bu
t-Bu
t-Bu
O
O
0.5 M MeONa
MeOH
O
O
BnBr (2.6 eq)
Si
Si
Ac2O, C5H5N, 0 ºC
96%
O
O
O
O
NaH, DMF,
0 ºC 10 min
OBn
OH
84%
RO
12
HO
11
R = H (89%)
R = Bn (3%)
13
+
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
CCl3
O
O
Si
O
O
Cl3CCN, DBU
PdCl2
Si
O
O
Si
O
OH
NH
O
MeOH, r.t.
72%
O
Cl2CH2, -10 ºC
87%
O
O
OBn
OBn
OBn
AcO
AcO
AcO
15
16
β/α 16:1
14
Scheme 1. Synthesis of constrained D-galactofuranosyl trichloroacetimidate donor 16.
in pyridine, catalyzed by DMAP afforded the conformationally re-
stricted silylene derivative 10 (84%). Analysis of the coupling con-
stants in the 1H NMR spectrum of 10 indicated that a furanose
conformation change occurred. Whereas J1,2 remained almost un-
changed (5.0 Hz) compared to the precursor 9, the large coupling
constants (J2,3 9.1 and J3,4 9.8 Hz) in constrained derivative 10 are
in agreement with almost trans-diaxial relationship between H-2
and H-3, and between H-3 and H-4. In the 13C NMR spectrum of
10, the C-4 and C-2 resonances appeared at 74.7 and 77.2 ppm,
respectively, almost 6 ppm and 3 ppm upfield shifted compared
to the same signals in 9. In the arabinofuranosyl series, the fura-
nose ring of thioglycoside donor D-3 (Fig. 1) adopts a nearly perfect
E4 envelope conformation as indicated by X-ray studies.38 Interest-
ingly, constrained 3,5-O-benzylidene analogous of D-3, also adopts
the same E4 conformation.36
In order to introduce a non-participating group in O-2, benzoyl
groups of 10 were removed by treatment with sodium methoxide
in methanol to give 11 in 84% yield. Next step was the 2,6-di-O-
benzylation of 10. On treatment with 2.6 equiv of benzylbromide
and 2.6 equiv of NaH in DMF at 0 °C, 2,6-di-O-benzyl derivative
13 was obtained in very low yield (2%) together with 2-O-benzyl
derivative 12 (31%) and low migrating decomposition by-products
(data not shown). 2-O-Benzyl substitution in 12 was confirmed by
standard acetylation to give 14. In the 1H NMR spectrum of 14, the
H-6a and H-6b resonated 0.5 ppm downfield shifted compared to
the same signals in 12 confirming the acetylation in O-6. A careful
TLC analysis of the benzylation reaction showed that the 2-O-ben-
zyl derivative 12 was rapidly formed as the main product (5–
10 min) followed by decomposition as shown by the low migrating
by-products. Other milder conditions were assayed. The replace-
ment of DMF by THF as solvent described for the arabinofuranosyl
counterpart36 was not successful for the galactofuranosyl com-
pound. Moreover, by the use of nBu4NI as catalyst or activation
with Ag2O instead of NaH37 the desired 2,6-di-O-benzyl derivative
13 was not obtained at all. In these cases, TLC revealed a mixture of
2-O-benzyl derivative 12 together with low migrating decomposi-
tion by-products. These results showed that primary 6-OH is less
reactive than secondary 2-OH, and this could be attributed to steric
factors provided by tert-butyl groups on silyl atom. At this point,
we decided to optimize the synthesis of 2-O-benzyl derivative 12
by reduction of the reaction time in order to avoid decomposition.
The best results were obtained by reaction of 11 with an excess of
benzyl bromide (2.6 equiv) in DMF at 0 °C, followed by addition of
NaH (2.6 equiv) and careful quenching of the reaction after 10 min.
In this case, 12 was obtained in 89% yield together with 2,6-di-O-
benzyl derivative 13 in 3% yield. On the other hand, attempts to
benzylate the 6-O-position of 12 by reaction of benzyl trichloro-
acetimidate and TMSOTf54 was also unsuccessful, for that reason
12 was finally acetylated by standard conditions to give 13 in
96% yield.

M. J. Tilve, C. Gallo-Rodriguez / Carbohydrate Research 346 (2011) 2838–2848
2841
In order to activate the anomeric center via trichloroacetimi-
date, removal of the anomeric function of 14 was performed by
reaction with PdCl2 in methanol52 to afford 15 in 72% yield as an
H-1 signal (d 5.40). In the 13C NMR spectrum, the C-1 appeared
at 98.8 ppm confirming the -configuration. It is interesting to
note that by employing 2,3,5,6-tetra-O-benzyl- ,b- -galactofur-
a
a
D
anomeric mixture in 2:13
of the anomeric protons at d 5.30 (J1,2 3.5 Hz, b anomer) and 5.26
(J1,2 = 5.7 Hz,
anomer) in the 1H NMR spectrum. Removal of pal-
ladium by washing the reaction with water instead of filtering was
required to avoid decomposition. On the other hand, allyl isomer-
ization with hydrogen activated [Ir(COD)(Ph2MeP)2]PF6 complex in
CH2Cl2 of 13, followed by hydrolysis with p-toluensulfonic acid in
CH2Cl2 of the vinyl glycoside did not improve the yield.55 Treat-
ment of 15 with acetonitrile and DBU gave imidate 16 in 16:1 b/
a
/b ratio, as indicated by the integration
anosyl trichloroacetimidate (1), the flexible equivalent of imidate
16, and in the same reaction conditions, the corresponding cyclo-
a
hexyl glycoside was obtained in a similar ratio (2.0:1
Considering that a moderate diastereoselectivity favoring the
a
/b ratio).22
a-
anomer was obtained at ꢀ78 °C, we next evaluated 16 with several
acceptors. Based on our experience in the aldonolactone strategy
for the synthesis of galactofuranose-containing oligosaccha-
rides,46,48 we first used 2,3,5-tri-O-benzoyl-
D-galactono-1,4-lac-
tone (19)57 as acceptor. In this condition, disaccharide 20 was
obtained as an inseparable mixture in 87% yield (entry 2, method
C). After HPLC separation and full characterization of the anomers,
a
anomeric ratio as indicated by the integration of the anomeric
signals at 6.33 (H-1a anomer, J1,2 4.6 Hz) and 6.20 ppm (H-1b ano-
mer, J 2.7 Hz) in the 1H NMR spectrum. Imidate 16 could be stored
at ꢀ20 °C for several weeks.
20
a
and 20b were assigned on the basis of the 1H and 13C NMR
spectra. Whereas the H-10 signal of 20
a
appeared as a doublet (d
5.06) with a coupling constant of 5.1 Hz, the J1,2 for the same signal
of 20b (d 4.96) was smaller (2.9 Hz). On the other hand, in the 13C
2.2. Glycosylation reactions
NMR spectra of 20
101.5 (C-10) and 107.3 (C-10) ppm, respectively. Analysis of the
1H NMR spectrum of the crude reaction indicated a 1.3:1
/b ratio
shown by the integration of H-4 signal compared to the integra-
tion of superimposed H-40b and H-10b signals. We next evaluated
3,4-di-O-benzyl-
-rhamnopyranoside58 (21) as acceptor which
a and 20b, the anomeric carbons appeared at
Once 16 was in hand, the next step was the evaluation of the
a
conformationally locked donor for
a-galactofuranosylation. All
a
reactions were performed employing 1 equiv of donor (0.04 M)
and 1.2 equiv of acceptor using standard trichloroacetimidate acti-
vation conditions (TMSOTf 0.3 equiv and 4 Å molecular sieves). For
a-L
is precursor of the disaccharide present in S. pneumoniae 22F.14
Unexpectedly, reaction of 21 with constrained imidate 16 at
ꢀ78 °C in CH2Cl2 (method C, entry 3) gave only the b diastereomer
22b (66% yield) as indicated by the H-10 signal at d 5.28 (J1,2 3.1 Hz)
in the 1H NMR spectrum and the C-10 signal at 108.7 ppm in the 13C
NMR spectrum. Interestingly, the opposite selectivity was obtained
on reaction of 21 with the flexible tetra-O-benzyl trichloroacetim-
all cases, the diastereomeric a/b ratio of the products of glycosyla-
tion was determined from the 1H NMR spectrum of the crude reac-
tion mixture by integration of the signals of each diastereomer and
comparison with pure isolated isomers. The
a/b ratio was con-
firmed by weighting the isolated and b products after purifica-
a
tion by column chromatography when possible.
The first solvent of choice was the non-participating CH2Cl2,
idate analog 1 to give the corresponding disaccharide in 10:1
a/b
previously used in selective
a-arabinofuranosylation with con-
ratio.22
strained donors of Figure 1. We first evaluated the influence of
the temperature in glycosylation reactions with cyclohexanol as
acceptor. When the reaction was performed at ꢀ10 °C (Table 1,
method A, entry 1), unexpectedly, only the 1,2-trans b-isomer
17b was obtained as a single diasteromer in low yield (29%). The
13C NMR spectrum of 17b showed the anomeric C-1 resonance at
104.9 ppm indicating a b-configuration, whereas in the 1H NMR
spectrum, the anomeric H-1 appeared at 5.06 ppm as a doublet
with a small coupling constant (J1,2 3.2 Hz), however, larger com-
pared to flexible b-galactofuranosyl derivatives (ꢁ1 Hz).22,45–49
The transposition by-product 6-O-acetyl-2-O-benzyl-3,5-O-(di-
2.3. Influence of the 6-O-substitution on galactofuranosyl
constrained donor
Taking into consideration these unexpected results obtained
with constrained galactofuranosyl trichloroacetimidate donor 16
compared to the constrained D-arabinofuranosyl analogs (Fig. 1),
we speculated that the 6-O-acetyl group may contribute as a re-
mote participating group29,59 suggested by preliminary molecular
modeling calculations on the corresponding oxacarbenium ion.
The acetyl group on quasi-axial hydroxymethyl group oriented to
the electrophilic positive carbon. For that reason, we synthesized
the 6-O-benzyl analog of 16, O-(2,6-O-benzyl-3,5-O-(di-tert-buty-
tert-butylsilylene)-1-N-trichloroacetyl-a-D-galactofuranosylamine
(18) was also obtained (35%) suggesting that donor 16 is very reac-
tive probably due to the arming silylene group. N-Glycosyl trichlo-
roacetamides as by-products of glycosylation have been obtained
on reaction with low nucleophilic or sterically hindered accep-
tors.4,20,44,48,56 In the 1H NMR spectrum of 18, the H-1 appeared
lsilanediyl)-b-D-galactofuranosyl) trichloroacetimidate (7), starting
from 13 previously obtained as a by-product of the benzylation
reaction (Scheme 1). Treatment of 13 with PdCl2 in methanol gave
23 in 82% yield (Scheme 2). Subsequent activation of the anomeric
center with Cl3CCN and DBU gave the b-trichloroacetimidate 7 as a
single isomer.
as a triplet with a J1,2 of 7.0 Hz suggesting a
a-configuration con-
firmed by the H-1–H-4 correlation in the NOESY experiment.
By lowering the temperature reaction to ꢀ40 °C (method B, en-
try 1), the
a
-product was now also obtained. Analysis of the crude
However, on reaction of 7 with cyclohexanol at ꢀ78 °C, the sep-
reaction by 1H NMR spectroscopy showed 17 in 1.3:1
established by the integration of H-2 signal and the superim-
posed signals of H-1b and H-1 . Purification on column chroma-
tography gave pure 17b (31%) and a second fraction of 17
slightly impurified with the transposition byproduct 18 in 10:1
a/b ratio,
arable glycosides 24aand 24b were obtained in 1:1 a/b ratio as indi-
a
cated by the integration of the anomeric hydrogen in the 1H NMR
spectrum of the crude reaction (entry 5, method C). No transposition
a
a
by-product was obtained in this case. No selectivity for the a-ano-
mer was obtained in this glycosylation reaction compared to the
previous one, concluding that no remote participation is exerted
by the acetyl group in O-6 of 16. Stereoelectronic effects are involved
in the sense that the electron withdrawing group such as acetyl fa-
17a/18 ratio as shown by integration of the anomeric protons in
the 1H NMR spectrum. When the reaction was conducted at
ꢀ78 °C (method C), the analysis of the crude reaction mixture
showed 17 in 1.7:1
a/b ratio and no signals of transposition by
vors the a-anomer on 3,5-O-silylene galactofuranosyl donor. The
product 18. Purification of the crude gave 17b (27%) and pure
17 (48%). The configuration of the anomeric center of 17 was
established by the coupling constant (J1,2 5.0 Hz) observed for
hydroxymethyl and the protecting group pattern on O-6 strongly
influenced the stereochemical course of the glycosylation, com-
pared to the D-arabinofuranosyl counterpart.
a
a

2842
M. J. Tilve, C. Gallo-Rodriguez / Carbohydrate Research 346 (2011) 2838–2848
Table 1
Glycosylation reactions with silylene donors 16 and 7 (methods A–E)
t-Bu
t-Bu
t-Bu
Si
ROH
CCl
O
O
t-Bu
O
O
3 A, B, C, D or E
Si
O
OR
NH
O
O
TMSOTf
MS4Å
OBn
OBn
RO
RO
16 R = Ac
7
R = Bn
(A) Cl2CH2, -10 ºC; (B) Cl2CH2, -40 ºC; (C) Cl2CH2, -78ºC
(D) CH3CN, -40 ºC; (E) Et2O, -78 ºC
Entry
Donor
t-Bu
Acceptor
Product
Method
a
/ba (yield)b
t-Bu
A
B
C
D
E
Only b (29%) (17 35%)d
1.3:1 (71%) (17 4%)d,e
CCl3
NH
t-Bu
t-Bu
Si
O
O
OBn
O
O
Si
O
1.7:1 (75%)
2.0:1 (33%)
3.6:1 (70%)
O
O
O
OBn
1
Cyclohexanol
AcO
AcO
17
16
β:α 16:1
C
E
1.3:1 (87%)c
4.5:1 (70%)c
BzO
BzO
O
O
O
O
t-Bu
t-Bu
BzO
O
BzO
HO
O
Si
O
OBz
O
OBz
2
O
19
OBn
AcO
20
O
C
E
Only b (66%)
1.1:1 (66%)
H3C
BnO
H3C
BnO
O
O
BnO
BnO
O
t-Bu
OH
O
t-Bu
3
21
Si
O
O
OBn
AcO
22
OBz
t-Bu
Si
OBz
O
t-Bu
O
O
BzO
BzO
O
OBn
OMe
4
E
7.7:1 (95%)
O
25
AcO
OBz
O
BzO
BzO
OMe
26
C
E
1.0:1 (94%)
2.0:1 (71%)
t-Bu
Si
t-Bu
Si
CCl3
NH
t-Bu
O
O
t-Bu
O
OBn
O
O
O
O
O
5
Cyclohexanol
OBn
BnO
BnO
24
7
a
b
c
a
/b ratio established from 1H NMR (500 MHz) spectrum of the crude and confirmed by weights of isolated
Yield of isolated products (combined yield of the - and b- -isomers).
/b unseparable mixture.
% of 6-O-acetyl-2-O-benzyl-3,5-O-(di-tert-butylsilanediyl)-1-N-trichloroacetyl-
Calculated from the unseparable mixture of 18 and anomer.
a and b products.
a
D
a
d
e
a-D-galactofuranosylamine (18) also recovered.
a
2.4. Influence of the solvent
(Fig. 1) and with the flexible tetra-O-benzyl galactofuranosyl
trichloroacetimidate 1 were achieved using the non participating
solvent CH2Cl2. It is accepted that acetonitrile favors the 1,2-trans
We next evaluated the influence of the solvent system with low
expectation, considering that the best results favoring the 1,2-cis
b-glycosylation products in
D
-gluco- and
D-galactopyranose deriva-
glycosylation product with constrained
D
-arabinofuranosyl donors
tives through the formation of an a-nitrilium ion (nitrile effect)

M. J. Tilve, C. Gallo-Rodriguez / Carbohydrate Research 346 (2011) 2838–2848
2843
t-Bu
t-Bu
t-Bu
Si
t-Bu
t-Bu
CCl3
NH
O
O
t-Bu
O
Si
O
Cl3CCN, DBU
PdCl2
O
O
Si
O
OH
O
MeOH, r.t.
82%
O
OBn
O
Cl2CH2, 0ºC
80%
O
OBn
OBn
BnO
BnO
BnO
23
13
7
Scheme 2. Synthesis of constrained D-galactofuranosyl thrichloroacetimidate donor 7.
which is further displaced by the acceptor.29,44 Glycosylation of 16
with cyclohexanol in acetonitrile (ꢀ40 °C, method D, entry 1) gave
3. Conclusions
17 in 2.0:1 a/b ratio, slightly better compared to that obtained with
On the basis of the stereochemical relationship between arabi-
nose and galactose, and considering the influence of the 3,5-O-silyl-
ene group as 1,2-cis-directing glycosylation group on
arabinofuranose donors derivatives, we have performed glycosyla-
CH2Cl2 at ꢀ78 °C (method C) but in very low yield. To our surprise,
when the reaction was carried in diethyl ether as solvent at ꢀ78 °C
(method E), glycoside 17 was obtained in 3.6:1
a/b ratio (70%).
Same
even better than it was obtained using the flexible imidate 1 in
ethyl ether (2.4:1 /b) in the same
/b) or CH2Cl2 at ꢀ78 °C (2.0:1
reaction conditions.22 Moreover, reaction of 6-O-benzyl con-
strained imidate 7 with cyclohexanol gave 24 in 2:1 /b ratio (en-
try 5, method E) whereas no selection was observed in CH2Cl2.
With these results, evaluation of method E on acceptors 19 and
21 were also conducted.
a/b ratio was obtained with THF as solvent. This ratio was
tion studies on the galactofuranose counterpart. 3,5-O-Silylene-
galactofuranosyl constrained trichloroacetimidate donors for 1,
2-cis -galactofuranosylation were synthesized from allyl -galac-
tofuranoside. The presence of the 3,5-O-silylene-group was not
determinant for the -diastereoselection since almost no -selec-
tivities were obtained in CH2Cl2 as solvent. However, modest to
high selectivities toward the -anomer were achieved using dieth-
D-
a
a
a
D
a
a
a
a
ylether as solvent at ꢀ78 °C suggesting a participating effect in the
On reaction of imidate 16 with lactone 19 the a/b ratio of disac-
reaction intermediate. Moreover, 6-O-acetyl substitution on con-
charide 20 increased from 1.3:1 to 4.5:1 by changing the solvent
from CH2Cl2 to ethyl ether (entry 2, method E). On the other hand,
the reaction with rhamnosyl acceptor 21 gave disaccharide 22 in
strained donor increased the
a-selectivity compared to the 6-O-
benzyl substitution. /b ratio of the glycosylation products strongly
a
depended on the acceptor employed. The solvent effects on con-
1.1:1
was obtained in CH2Cl2 at ꢀ78 °C (method C). We also evaluated
methyl 2,3,4-tri-O-benzoyl-
-mannopyranoside60 25 as acceptor
because it is a precursor of the disaccharide constituent of P. brasil-
iensis. In this case, disaccharide 26 was obtained in 95% yield in
a/b ratio (entry 3, method E), whereas only the b anomer
strained galactofuranosyl trichoroacetimidate are the opposite to
those exerted on the flexible 2,3,5,6-tetra-O-benzyl-D-galactofur-
anosyl trichoroacetimidate and this fact could be due to the change
in the conformation on the oxacarbenium intermediate.
The development of conformationally constrained arabinofur-
anosyl donors allowed the synthesis of challenging and biologically
relevant oligosaccharides with 1,2-cis linkages. However, stereose-
lectivity strongly depended on the activation method of glycosyla-
tion, as well as on the acceptor.36,61 In this sense, other methods of
glycosylation such as the thioglycoside method should be evalu-
ated on 3,5-O-silylene constrained galactofuranosyl donor and this
is currently being pursued in our laboratory to bring a better
understanding to the furanose glycosylation field.
a-D
7.7:1
nals corresponding to H-10 of the
mer in the 1H NMR spectrum of the crude reaction. Compounds
26 and 26b were easily purified by column chromatography. By
the use of the flexible imidate 1, the corresponding disaccharide
was obtained in 1.5:1 /b ratio in the same solvent and in 12.6:1
/b ratio in CH2Cl2, however in moderate yield (63%).22 This disac-
charide was obtained also by the carbobenzoxy method of glyco-
sylation in 8:1
/b ratio without characterization data.25
Compound 16 could be considered a good precursor for -Galf-
(1-6)- -Man linkage construction, with a galactofuranosyl moiety
that could be further functionalized.
It is intriguing why diethylether increased the selectivity to-
ward the -product in all cases when the 3,5-O-silylene moiety
locks the conformation of the galactofuranosyl ring. In the pyra-
nose counterpart, diethylether increases the -anomeric selectiv-
ity apparently by the formation of diethyl oxonium ion
a/b ratio (entry 4) as indicated by the integration of the sig-
a-anomer and H-1 of the b-ano-
a
a
a
a
a-D
4. Experimental
D
4.1. General methods
a
TLC was performed on 0.2 mm Silica Gel 60 F254 aluminium-
supported plates. When TEA was added to the solvent system, a
previous TLC elution was performed. Detection was effected by
exposure to UV light or by spraying with 5% (v/v) sulfuric acid in
EtOH and charring. Column chromatography was performed on Sil-
ica Gel 60 (230–400 mesh). High-performance liquid chromatogra-
phy (HPLC) was performed using Thermo Separation (Spectra
a
a
intermediate which adopts a b-configuration probably by steric
factors, although reverse anomeric effect has been also consid-
ered.4,5,44 We may speculate that ethyl ether could participate
from the b-face which is further displaced by the nucleophile
Series P100) with
a
Beckman ultrasphere ODS (5 lm,
leading to the
a-product. On the other hand, activation was per-
250 ꢂ 10 mm), employing a variable wavelength UV detector at a
rate of 3.00 mL/min in 9:1 acetonitrile/H2O. Melting points are
uncorrected. Optical rotations were measured at 25 °C. NMR spec-
tra were recorded at 500 MHz (1H) and 125.8 MHz (13C) or, at
200 MHz (1H) and 50.3 MHz (13C). 1H and 13C NMR spectra assign-
ments were supported by homonuclear COSY and HSQC-DEPT
experiments. High resolution mass spectra (HRMS) were recorded
on a BRUKER micrOTOF-Q II electrospray ionization mass spec-
trometer. Optical rotations were measured with a path length of
1 dm at 25 °C.
formed by TMSOTf, thus, a covalent triflate intermediate could
be involved. On activation of constrained arabinofuranosyl do-
nors D-3 and L-4, a triflate intermediate in 1,2-trans configura-
tion was identified by low variable temperature 1H NMR
studies. If this were the case, after a b-triflate formation in galac-
tofuranosyl constrained donor, the nucleophilic displacement of
the acceptor should provide the
a-glycoside, at least in non
participating solvents such as CH2Cl2. Mechanism of glycosyla-
tion of furanoses deserves more investigation because many
aspects remain unclear.

2844
M. J. Tilve, C. Gallo-Rodriguez / Carbohydrate Research 346 (2011) 2838–2848
4.2. Allyl 2,6-di-O-benzoyl-
a
-
D
-galactofuranoside (9)
-galactofuranoside52 (8, 1.18 g,
water and the residue was purified by column chromatography
(5:1 hexane–EtOAc) to afford 11 (3.41 g, 84%) as a colorless syrup:
Rf = 0.45 (2:1 hexane–EtOAc); [
+137.1 (c 1, CHCl3); 1H NMR
To a stirred solution of allyl
a-
D
a]
D
5.36 mmol) in dry pyridine (36 mL), cooled at ꢀ15 °C, benzoyl
chloride (1.4 ml, 12.1 mmol) was added during 3 h. After 3 h of
stirring, ice (20 g) was added and the stirring was continued for
1 h. The resulting mixture was diluted with water (30 mL) and
then extracted with CH2Cl2 (3 ꢂ 70 mL). The organic layer was
sequentially washed with 2.5 M HCl (70 mL), saturated aq NaHCO3
(70 mL), water (3 ꢂ 70 mL), dried (Na2SO4), filtered, and concen-
trated. Column chromatography of the mixture (8:1 toluene–
EtOAc) gave syrupy 9 (1.45 g, 63%): Rf = 0.76 (9:1 CH2Cl2–MeOH),
(CDCl3, D2O 500 MHz) d 5.90 (dddd, 1H, J = 17.2, 10.4, 6.2, 5.7 Hz,
CH@CH2), 5.30 (dq, 1H, J = 17.2, 1.5 Hz, CH@CHaH), 5.25 (dq, 1H,
J = 10.3, 1.2 Hz, CH@CHbH), 5.02 (d, 1H, J = 5.4 Hz, H-1), 4.46 (m,
1H, H-5), 4.25 (t, 1H, J = 9.5 Hz, H-3), 4.24 (ddt, J = 12.7, 5.7,
1.4 Hz, OCHaHCH@), 4.11 (ddt, J = 12.7, 6.2, 1.2 Hz, OCHbHCH@),
4.07 (dd, 1H, J = 8.8, 5.5 Hz, H-2), 4.06 (dd, 1H, J = 9.5, 6.7 Hz, H-
4), 3.82 (dd, 1H, J = 11.6, 5.9 Hz, H-6a), 3.71 (dd, 1H, J = 11.6,
6.6 Hz, H-6b), 1.05, 1.02 (2s, 18H, 2(CH3)3C); 13C NMR (CDCl3,
128.5 MHz) d 133.3 (CH@CH2), 118.5 (CH@CH2), 99.9 (C-1), 76.0
(C-4), 75.2 (C-2), 74.6 (C-3), 73.2 (C-5), 70.2 (OCH2CH@), 62.6 (C-
6); 27.2, 27.1 ((CH3)3C); 21.7, 20.7 (2(CH3)3C).
[a
]
D
+40.9 (c 1, CHCl3); 1H NMR (CDCl3, 500 MHz) d 8.08–7.42
(m, 10H, aromatic), 5.85 (dddd, 1H, J = 17.2, 10.4, 5.8, 5.4 Hz,
CH@CH2), 5.37 (d, 1H, J = 4.8 Hz, H-1), 5.28 (dq, 1H, J = 17.2,
1.4 Hz, HC@CHaH), 5.18 (dq, 1H, J = 10.4, 1.4 Hz, HC@CHbH), 5.11
(dd, 1H, J = 7.3, 4.8 Hz, H-2), 4.82 (dd, 1H, J = 7.3, 6.4 Hz, H-3),
4.49 (dd, 1H, J = 11.4, 6.4 Hz, H-6a), 4.41 (dd, 1H, J = 11.4, 5.8 Hz,
H-6b), 4.27 (ddt, 1H, J = 13.1, 5.4, 1.4 Hz, OCHaH-CH@), 4.22 (dd,
1H, J = 6.2, 3.4 Hz, H-4), 4.11 (ddt, 1H, J = 13.1, 5.8, 1.4 Hz,
OCHbH-CH@), 4.08 (m, 1H, H-5); 13C NMR (CDCl3, 125.8 MHz) d
167.0, 166.6 (COPh); 133.6, 133.1, 129.9, 129.8, 129.7, 129.0,
128.5, 128.4 (aromatic); 133.1 (CH@CH2), 118.2 (CH@CH2), 100.0
(C-1), 82.7 (C-4), 80.8 (C-2), 73.5 (C-3), 69.9 (OCH2-CH@), 69.3
(C-5), 65.4 (C-6). Anal. Calcd for C23H24O8: C, 64.48; H, 5.65. Found:
C, 64.21; H, 5.48.
Anal. Calcd for C17H32O6Si: C, 56.64; H, 8.95. Found: C, 56.36; H,
9.06.
4.5. Allyl 2-O-benzyl-3,5-O-(di-tert-butylsilanediyl)-a-D-
galactofuranoside (12)
To a solution of 11 (1.23 g, 3.41 mmol) in dry DMF (30 mL)
cooled to 0 °C was added BnBr (1.05 mL, 8.80 mmol) followed by
NaH (dispersion in oil 60% , 350 mg, 8.75 mmol) with stirring. After
10 min of stirring, ice (5 g) was added. The reaction mixture was
rapidly diluted with CH2Cl2 (250 mL), washed with water
(3 ꢂ 70 mL), dried (Na2SO4), filtered and concentrated. Column
chromatography (12:1 toluene–EtOAc) of the residue afforded a
first fraction of syrupy allyl 2,6-di-O-benzyl-3,5-O-(di-tert-buty-
4.3. Allyl 2,6-di-O-benzoyl-3,5-O-(di-tert-butylsilanediyl)-a-D-
galactofuranoside (10)
lsilanediyl)-
hexane–EtOAc);
a
-
D
-galactofuranoside (13, 0.053 g, 3%): Rf = 0.74 (2:1
[a]
D
+73.7 (c 0.6, CHCl3); 1H NMR (CDCl3,
To a stirred solution of 9 (5.68 g, 13.3 mmol) and DMAP (85 mg,
0.70 mmol) in dry pyridine (40 mL), cooled to 0 °C, (tBu)2Si(OTf)2
(5.0 mL, 15.3 mmol) was added during 3.5 h. The mixture was al-
lowed to reach room temperature and after 1 h of stirring, the reac-
tion was quenched by addition of MeOH (2 mL). The resulting
solution was coevaporated with toluene to dryness. Column chro-
matography (toluene) of the residue gave 10 (6.37 g, 85%) as a syr-
200 MHz) 7.47–7.25 (m, 5H, aromatic), 5.88 (dddd, J = 16.6, 10.6,
6.0, 5.6 Hz, CH@CH2), 5.23 (dd, J = 16.6, 1.4 Hz, CH@CHaH), 5.16
(dd, J = 10.6, 1.2 Hz, CH@CHbH), 4.87 (d, 1H, J = 5.2 Hz, H-1), 4.82,
4.74 (2d, 2H, J = 12.4 Hz, 4.65–4.55 (m, 3H, H-5, CH2Ph), 4.49 (t,
1H, J = 9.3 Hz, H-3), 4.12 (dd, J = 12.8, 5.2 Hz OCHaHCH@), 3.99–
3.91 (m, 2H, H-4, OCHbHCH@), 3.87 (dd, 1H, J = 9.1, 5.2 Hz, H-2),
3.86 (dd, 1H, J = 10.2, 3.4 Hz, H-6a), 3.75 (dd, 1H, J = 10.2, 7.6 Hz,
H-6b), 1.03, 1.00 (2s, 18H, 2(CH3)3C)); 13C NMR (CDCl3,
up. Rf = 0.66 (hexane–EtOAc 2:1); [a]
D +157.8 (c 1, CHCl3); 1H NMR
(CDCl3, 500 MHz) d 8.12–7.42 (m, 10H, aromatic), 5.64 (dddd, 1H,
J = 17.3, 10.5, 6.0, 5.3 Hz, CH@CH2), 5.40 (d, 1H, J = 5.0 Hz, H-1),
5.08 (dd, 1H, J = 9.1, 5.0 Hz, H-2), 5.05 (dq, 1H, J = 17.3, 1.7 Hz,
HC@CHaH), 4.97 (dq, 1H, J = 10.5, 1.5 Hz, HC@CHbH), 4.91 (t, 1H,
J = 9.5 Hz, H-3), 4.81 (dt, 1H, J = 3.9, 6.8 Hz, H-5), 4.71 (dd, 1H,
J = 11.9, 3.9 Hz, H-6a), 4.53 (dd, 1H, J = 11.9, 6.7 Hz, H-6b), 4.21
(dd, 1H, J = 9.8, 6.8 Hz, H-4), 4.09 (ddt, 1H, J = 13.7, 5.3, 1.5 Hz,
OCHaH-CH@), 3.91 (ddt, 1H, J = 13.7, 6.0, 1.4 Hz, OCHbH-CH@),
1.07, 1.04 (2s, 18H, 2(CH3)3C); 13C NMR (CDCl3, 125.8 MHz) d
166.5, 166.3 (COPh), 133.5 (CH@CH2); 133.2, 132.9, 130.2, 129.8
(ꢂ2), 129.6, 128.4, 128.3 (aromatic); 117.2 (CH@CH2), 98.8 (C-1),
77.2 (C-2), 74.7 (C-4), 72.1 (C-3), 72.0 (C-5), 69.6 (OCH2-CH@),
64.7 (C-6); 27.2, 27.1 ((CH3)3C); 21.7, 20.8 ((CH3)3C); HRMS (ESI)
m/z calcd for C31H41O8Si (M+H+) 569.2571, found 569.2567.
50.3 MHz)
d
138.0, 137.7
,
134.0, 128.3, 128.2 (ꢂ2), 128.0,
127.7,127.6 (aromatics), 117.7 (CH@CH2), 99.1 (C-1), 80.5, 75.5,
73.8, 73.7, 71.9, 70.0, 68.9, 27.3, 27.2 ((CH3)3C), 21.5, 20.6
((CH3)3C); HRMS (ESI) m/z Calcd for C31H44NaO6Si [M+Na]+
563.2805. Found: [M+Na]+ 563.2799.
The second fraction gave syrupy 12 (1.36 g, 89%): Rf = 0.55 (2:1
hexane–EtOAc); [a]
D +84.5 (c 1, CHCl3); 1H NMR (CDCl3, 500 MHz)
d 7.43–7.25 (m, 5H, aromatic), 5.90 (dddd, J = 17.2, 10.4, 6.3, 5.5 Hz,
CH@CH2), 5.30 (dq, J = 17.2, 1.5 Hz, CH@CHaH), 5.21 (dq, J = 10.4,
1.2 Hz, CH@CHbH), 4.92 (d, 1H, J = 5.1 Hz, H-1), 4.84, 4.76 (2d,
2H, J = 12.3 Hz, CH2Ph), 4.62 (t, 1H, J = 9.4 Hz, H-3), 4.44 (q, 1H,
J = 6.3 Hz, H-5), 4.16 (ddt, J = 12.9, 5.5, 1.4 Hz, OCHaHCH@), 4.05
(ddt, J = 12.9, 6.3, 1.2 Hz, OCHbHCH@), 4.03 (dd, 1H, J = 9.6,
6.5 Hz, H-4), 3.92 (dd, 1H, J = 9.1, 5.1 Hz, H-2), 3.86 (m, 1H, H-
6a), 3.75 (m, 1H, H-6b), 2.28 (t, J = 6.8 Hz, OH), 1.06, 1.01 (2s,
18H, 2(CH3)3C)); 13C NMR (CDCl3, 128.5 MHz) d 137.7 (Ar); 133.8
(CH@CH2); 128.3, 128.2, 127.5 (aromatics), 118.1 (CH@CH2), 99.8
(C-1), 80.3 (C-2), 76.1 (C-4), 73.5 (C-5), 73.3 (C-3), 71.9 (CH2Ph),
69.8 (OCH2CH@), 62.9 (C-6), 28.0, 27.2 ((CH3)3C), 21.6, 20.8
((CH3)3C).
4.4. Allyl 3,5-O-(di-tert-butylsilanediyl)-a-D-galactofuranoside
(11)
To
a externally cooled (0 °C) flask containing 10 (6.37 g,
11.2 mmol) was added cooled 0.5 M NaOMe in MeOH (75 mL) with
stirring and the mixture was sonicated to complete dissolution
(2 min). The solution was stirred for 3 h at 0 °C, and then warmed
to rt over 0.5 h. After cooling at 0 °C, the reaction was quenched
and neutralized with cold 10% m/v HCl (14 mL). The mixture was
then extracted with CH2Cl2 (3 ꢂ 80 ml) and the combined organic
layer was successively washed with saturated aq NaHCO3
(50 mL), water (3 ꢂ 70 mL), dried (Na2SO4), filtered, and concen-
trated. Methyl benzoate was eliminated by co-evaporation with
Anal. Calcd for C24H38O6Si: C, 63.97; H, 8.50. Found: C, 63.91; H,
8.72.
4.6. Allyl 6-O-acetyl-2-O-benzyl-3,5-O-(di-tert-butylsilanediyl)-
a-D-galactofuranoside (14)
To a solution of 12 (1.56 g, 3.46 mmol) in dry pyridine cooled at
0 °C was added dropwise acetic anhydride (15 mL) with stirring.

M. J. Tilve, C. Gallo-Rodriguez / Carbohydrate Research 346 (2011) 2838–2848
2845
After 1.5 h, the reaction mixture was allowed to reach room tem-
perature and the stirring continued for 1 h. The reaction was
cooled at 0 °C, quenched with MeOH and concentrated in vacuum.
Purification of the residue by column chromatography (15:1 hex-
ane–EtOAc) afforded 14 (1.64 g, 96%) as a syrup: Rf 0.67 (2:1 hex-
J = 12.0, 3.6 Hz, H-6a), 4.36 (dd, 1H, J = 10.3, 6.6 Hz, H-4), 4.33
(dd, 1H, J = 12.0, 7.2 Hz, H-6b), 4.22 (dd, 1H, J = 6.6, 2.7 Hz, H-2),
2.09 (s, 3H, CH3CO), 1.06, 1.02 (2s, 18H, 2(CH3)3C). 13C NMR (CDCl3,
128.5 MHz) d 170.8 (CH3CO), 160.9 (C@NH); 137.2, 128.4, 127.8
(aromatic); 104.1 (C-1), 91.0 (CCl3), 87.1 (C-2), 76.9 (C-3), 76.4
(C-4), 72.2 (CH2Ph), 70.7 (C-5), 64.0 (C-6), 27.1, 27.0 (2(CH3)3C),
21.6, 20.7 (2(CH3)3C), 20.9 (CH3CO).
ane–EtOAc); ½a D
ꢃ
+77.2 (c 1, CHCl3); 1H NMR (CDCl3, 500 MHz) d
7.44–7.28 (m, 5H, aromatic), 5.89 (dddd, 1H, J = 17.2, 10.3, 6.4,
5.4, Hz, CH@CH2), 5.29 (dq, 1H, J = 17.2, 1.6 Hz, CH@CHaH), 5.19
(ddt, 1H, J = 10.3, 1.6, 1.3 Hz, CH@CHbH), 4.91 (d, 1H, J = 5.1 Hz,
H-1), 4.83, 4.78 (2d, 2H, J = 12.3 Hz, CH2Ph), 4.65 (t, 1H, J = 9.4 Hz,
H-3), 4.56 (dt, 1H, J = 6.6, 3.5 Hz, H-5), 4.36 (dd, 1H, J = 11.9,
6.6 Hz, H-6a), 4.27 (dd, 1H, J = 11.9, 3.6 Hz, H-6b), 4.17 (dddd, 1H,
J = 12.8, 5.3, 1.6, 1.3 Hz, OCHaHCH@), 3.98 (ddt, 1H, J = 12.8, 6.4,
1.3 Hz, OCHbHCH@), 3.98 (dd, 1H, J = 9.9, 6.7, Hz, H-4), 3.89 (dd,
1H, J = 5.1, 9.1 Hz, H-2), 2.09 (s, 3H, CH3CO), 1.07, 1.01 (2s, 18H,
2(CH3)3C); 13C NMR (CDCl3, 128.5 MHz) d 170.8 (CH3CO), 137.8
(Ar), 133.9 (CH@CH2); 128.3 (Ar), 128.1 (Ar), 127.7 (Ar), 117.9
(CH@CH2), 99.2 (C-1), 80.3 (C-2), 75.4 (C-4), 73.8 (C-3), 71.9 (C-
5), 71.7 (CH2Ph), 69.1 (OCH2CH@), 64.3 (C-6), 27.2, 27.1
(2(CH3)3C), 21.7 (CH3CO), 21.0, 20.7 (2(CH3)3C).
4.9. 2,6-O-Benzyl-3,5-O-(di-tert-butylsilanediyl)-a,b-D-
galactofuranose (23)
To
a
solution of allyl 2,6-di-O-benzyl-3,5-O-(di-tert-buty-
-galactofuranoside 13 (120 mg, 0.22 mmol) in
lsilanediyl)-
a-D
MeOH (2.7 mL), PdCl2 (27 mg, 0.15 mmol) was added at rt and
the reaction mixture was sonicated until dissolution of the palla-
dium salt (20 s). The mixture was covered from light exposure
and stirred. After 2 h of stirring, CH2Cl2 (10 mL) was added and
the mixture was washed with water (2 ꢂ 10 mL), dried (Na2SO4),
filtered, and concentrated at room temperature. The crude product
was purified by column chromatography (7:1 hexane–EtOAc) to af-
ford 23 as a colorless syrup (90 mg, 82%): Rf = 0.31 (4:1 hexane–
Anal. Calcd for C26H40O7Si: C, 63.38; H, 8.18. Found: C, 63.29; H,
8.24.
EtOAc); [
a
]
D
+22.0 (c 0.4, CHCl3); 1H NMR (CDCl3, 200 MHz) d
7.49–7.19 (m, 10H, aromatic), 5.29 (t, 1H, J = 3.0 Hz, H-1), 4.83–
4.51 (m, 5H, 2 PhCH2, H-5); 4.30 (mAB, 2H, H-3, H-4), 3.90 (dd,
1H, J = 3.2, 6.2 Hz, H-2), 3.72 (dd, 1H, J = 3.4, 10.2 Hz, H-6a), 3.61
(dd, 1H, J = 7.2, 10.2 Hz, H-6b), 2.94 (d, 1H, J = 3.4 Hz, OH); 1.03,
1.02 (2s, 18H, 2(CH3)3C). 13C NMR (CDCl3, 50.3 MHz) d 138.1,
137.6, 128.4 (ꢂ2), 128.0, 127.9, 127.8, 127.6 (arom.); 101.3 (C-1),
88.9 (C-2), 77.2 (C-3), 75.2, 73.6, 72.7, 72.0, 70.0, 27.2, 27.1
(2(CH3)3C); 21.6, 20.7 (2(CH3)3C); HRMS (ESI) Calcd for
4.7. 6-O-Acetyl-2-O-benzyl-3,5-O-(di-tert-butylsilanediyl)-D-
galactofuranose (15)
To a solution of 14 (876 mg, 1.78 mmol) in MeOH (8 mL), PdCl2
(150 mg, 0.85 mmol) was added at rt and the reaction mixture was
sonicated until dissolution of the palladium salt (20 s) and covered
from light exposure. After 2.5 h of stirring, CH2Cl2 (40 mL) was
added and the mixture was washed with water (2 ꢂ 50 mL), dried
(Na2SO4), filtered, and concentrated. The crude product was puri-
fied by column chromatography (4:1 hexane–EtOAc) to afford syr-
C
28H40NaO6Si [M+Na]+ 523.2492. Found: [M+Na]+ 523.2503.
4.10. O-(2,6-O-Benzyl-3,5-O-(di-tert-butylsilanediyl)-b-D-
galactofuranosyl) trichloroacetimidate (7)
upy 15 (584 mg, 72%) as 2:13
hexane–EtOAc); [
D +19.7 (c 1, CHCl3); 1H NMR (CDCl3, 500 MHz)
data for the b anomer, diagnostic signal for the anomer is given d
7.41–7.27 (m, 5H, aromatic), 5.30 (t, 1H, J = 3.5 Hz, H-1), 5.26 (dd,
0.15H, J = 8.1, 5.7 Hz, H-1 anomer), 4.79, 4.67 (2d, 2H,
a/b anomeric mixture: Rf = 0.48 (2:1
a]
a
To a stirred solution of 23 (75 mg, 0.15 mmol) and trichloroace-
tonitrile (110 l, 1.10 mmol) in CH2Cl2 (5 mL) cooled to 0 °C, DBU
(11.5 l, 0.077 mmol) was slowly added. After 40 min of stirring,
l
a
l
J = 11.9 Hz, CH2Ph), 4.64–4.58 (m, 1H, H-5), 4.36 (dd, 1H, J = 10.1,
6.6 Hz, H-4), 4.32–4.29 (m , 3H, H-3, H-6a, H-6b), 3.94 (dd, 1H,
J = 6.6, 3.1 Hz, H-2), 3.12 (d, 1H, J = 3.5 Hz, OH), 2.09 (s, 3H, CH3CO),
1.06, 1.02 (2s, 18H, 2(CH3)3C); 13C NMR (CDCl3, 128.5 MHz) data
the solution was concentrated under reduced pressure at rt, and
the dark brown residue was purified by column chromatography
(20:1 hexane–EtOAc) to give 7 as a colorless syrup (77 mg, 80%).
Compound 7 could be stored at ꢀ20 °C for 1 month. Rf = 0.68
(4:1:0.05 hexane–EtOAc–TEA); 1H NMR (CDCl3, 500 MHz) d 8.60
(s, 1H, NH), 7.49–7.19 (m, 10H, aromatic), 6.19 (d, 1H, J = 2.6 Hz,
H-1), 4.78, 4.65 (2d, 2H, J = 11.8 Hz, CH2Ph), 4.64, 4.55 (2d, 2H,
J = 12.2 Hz, CH2Ph), 4.70–4.60 (m, 1H, H-5), 4.40 (dd , 1H, J = 10.0,
6.0, Hz, H-3), 4.31 (dd, 1H, J = 10.0, 6.2 Hz, H-4), 4.20 (dd, 1H,
J = 6.4, 2.6 Hz, H-2), 3.77 (dd, 1H, J = 10.2, 3.0 Hz, H-6a), 3.66 (dd,
1H, J = 10.2, 7.3 Hz, H-6b), 1.04, 1.01 (2s, 18H, 2(CH3)3C). 13C
NMR (CDCl3, 128.5 MHz) d 137.3, 128.4 (ꢂ2), 128.0, 127.9, 127.6
(aromatic); 104.2 (C-1), 87.5 (C-2), 76.6, 73.6, 72.5, 72.3, 69.8;
27.2 (2(CH3)3C); 21.6, 20.7 (2(CH3)3C).
for the b anomer, diagnostic signal for the
170.9 (CH3CO); 137.6, 128.5, 128.4 (ꢂ2), 128.2, 128.1, 127.9 (ꢂ2),
127.8 (aromatic); 101.4 (C-1), 95.2 (C-1 ), 88.6 (C-2), 77.0 (C-3),
a anomer is given d
a
75.0 (C-4), 72.0 (CH2Ph), 71.0 (C-5), 64.3 (C-6), 27.1, 27.0
(2(CH3)3C), 21.6, 20.8 (2(CH3)3C), 21.0 (CH3CO).
Anal. Calcd for C23H33O7Si: C, 61.03; H, 8.02. Found: C, 61.03; H,
8.15.
4.8. O-(6-O-Acetyl-2-O-benzyl-3,5-O-(di-tert-butylsilanediyl)-
a,b-D-galactofuranosyl) trichloroacetimidate (16)
To a stirred solution of 15 (237 mg, 0.52 mmol) and trichloro-
acetonitrile (380 l, 3.79 mmol) in CH2Cl2 (20 mL) cooled to 0 °C,
DBU (35 l, 0.23 mmol) was slowly added. After 40 min of stirring,
the solution was concentrated under reduced pressure at rt, and
the dark brown residue was purified by column chromatography
(15:1 toluene–EtOAc) to give syrupy 16 (270 mg, 87%) as a 1:16
4.11. General procedures for glycosylation reactions
l
l
4.11.1. Method A
To a solution of trichloroacetimidate donor (1 equiv) and the
acceptor (1.2 equiv) in anhyd CH2Cl2 (3.0 mL/0.04 M of donor)
was added activated powdered 4 Å molecular sieves (150 mg),
and the mixture was vigorously stirred at room temperature under
argon. After 5 min, the mixture was cooled to ꢀ10 °C, TMSOTf
(0.3 equiv) was added and the stirring continued for 40 min. The
reaction was monitored by TLC, and quenched by the addition of
triethylamine (0.3 equiv) after total disappearance of the donor.
The mixture was diluted with CH2Cl2 (5 mL) and filtered. The
a
/b mixture. Compound 16 was stable for 1 month at ꢀ20 °C.
Rf = 0.61 (6:1:0.05 toluene–EtOAc–TEA); 1H NMR (CDCl3,
500 MHz) data for the b anomer, diagnostic signal for the anomer
is given d 8.61 (s, 1H, NH), 7.40–7.28 (m, 5H, aromatic), 6.33 (d,
0.06H, J = 4.6 Hz, H-1 anomer), 6.20 (d, 1H, J = 2.7 Hz, H-1b ano-
a
a
mer), 4.78, 4.68 (2d, 2H, J = 12.0 Hz, CH2Ph), 4.67 (dt, 1H, J = 6.9,
3.6 Hz, H-5), 4.42 (dd , 1H, J = 10.3, 6.6, Hz, H-3), 4.38 (dd, 1H,

2846
M. J. Tilve, C. Gallo-Rodriguez / Carbohydrate Research 346 (2011) 2838–2848
filtrate was concentrated and the residue was purified by silica gel
column chromatography, as indicated in each case.
4.5, Hz, H-6a), 4.33 (dd, 1H, J = 10.0, 6.7 Hz, H-3), 4.23 (dd, 1H,
J = 11.8, 6.8 Hz, H-6b), 4.15 (t, 1H, J = 7.0 Hz, H-2), 3.91 (dd, 1H,
J = 10.0, 6.7 Hz, H-4), 2.06 (s, 3H, CH3CO), 1.07, 1.02 (2s, 18H,
2(CH3)3C). 13C NMR (CDCl3, 128.5 MHz) d 170.9 (CH3CO), 161.8
(NHC@O); 136.6, 128.5, 128.2, 127.8 (aromatic); 79.9 (C-2), 79.5
(C-1), 76.7 (C-3), 74.0 (C-4), 72.3 (CH2Ph), 70.8 (C-5), 63.5 (C-6);
27.2, 27.1 (2(CH3)3C); 21.7, 21.0 (2(CH3)3C); 20.7 (CH3CO); NOESY
H-1–H-4; HRMS (ESI) Calcd for C25H37Cl3NO7Si [M+H]+ 596.1405.
Found: [M+H]+ 596.1417.
a
/b ratio was established from the 1H NMR spectrum of the
crude reaction, and then corroborated by weights of isolated
a
and b products (Table 1).
4.11.2. Method B
Same procedure described for method A was followed at
ꢀ40 °C.
Method B: Compound 16 (43 mg, 0.072 mmol) and cyclohexanol
4.11.3. Method C
Same procedure described for method A was followed at
ꢀ78 °C.
(9.0 lL, 0.086 mmol) gave 12 mg of 17b (31%), and 17 mg of 17a
(40%) and 18 (4%) as a 10:1 mixture according to 1H NMR spectrum.
Method C: Compound 16 (65 mg, 0.109 mmol) and cyclohexanol
(13.6
(48%).
Method D: Compound 16 (60 mg, 0.101 mmol) and cyclohexanol
lL, 0.131 mmol) gave 16 mg of 17b (27%), and 28 mg of 17a
4.11.4. Method D
Same procedure described for method A was followed, using
anhyd CH3CN as solvent at ꢀ40 °C.
(12.6
l
L, 0.121 mmol) gave 6 mg of 17b (11%), and 12 mg of 17
a
(22%).
4.11.5. Method E
Same procedure described for method A was followed at
ꢀ78 °C, using anhyd diethylether as solvent.
4.11.7. 6-O-Acetyl-2-O-benzyl-3,5-O-(di-tert-butylsilanediyl)-
a
-
D
-galactofuranosyl-2,3,5-tri-O-benzoyl-
D
-galactono-1,4-lactone
) and 6-O-acetyl-2-O-benzyl-3,5-O-(di-tert-butylsilanediyl)-
-galactono-1,4-
(20a
4.11.6. Cyclohexyl 6-O-acetyl-2-O-benzyl-3,5-O-(di-tert-
b-D
-galactofuranosyl-2,3,5-tri-O-benzoyl-
D
butylsilanediyl)-
a-
D-galactofuranoside (17a) and cyclohexyl 6-
lactone (20b)
O-acetyl-2-O-benzyl-3,5-O-(di-tert-butylsilanediyl)-b-
galactofuranoside (17b)
D
-
Compounds 20a and 20b were obtained according to general
procedures (method E) from donor 16 (86 mg, 0.144 mmol) and
2,3,5-tri-O-benzoyl- -galactono-1,4-lactone (19, 85 mg,
0.173 mmol).57 The crude was purified by column chromatography
Compounds 17
procedures (method E) from donor 16 (120 mg, 0.201 mmol) and
cyclohexanol (25 L, 0.241 mmol). The crude was purified by col-
umn chromatography (25:1 hexane–EtOAc) to afford 17b (16 mg,
15%) as a syrup: Rf = 0.53 (15:1 toluene–EtOAc); [
ꢀ28.8 (c 1,
a
and 17b were obtained according to general
D
l
(25:1 toluene–EtOAc) to afford 93 mg of 20a and 20b (70%) in 4.5:1
ratio as indicated by the 1HNMR spectrum. HPLC separation of a
fraction was performed only for identification purposes.
a
]
D
CHCl3); 1H NMR (CDCl3, 500 MHz) d 7.40–7.25 (m, 5H, arom),
5.06 (d, 1H, J = 3.2 Hz, H-1), 4.75, 4.64 (2d, 2H, J = 12.0 Hz, PhCH2),
4.61 (m, 1H, H-5), 4.34 (dd, 1H, J = 3.5, 11.9 Hz, H-6a), 4.28 (dd, 1H,
J = 7.6, 11.9 Hz, H-6b), 4.25 (dd, 1H, J = 6.4, 10.2 Hz, H-3), 4.22 (dd,
1H, J = 6.4, 9.1 Hz, H-4), 3.91 (dd, 1H, J = 3.2, 6.4 Hz, H-2), 3.48 (m,
1H,OCH), 2.09 (CH3CO), 1.88 (m, 2H), 1.71 (m, 2H), 1.52 (m, 1H),
1.42–1.14 (m, 5H); 1.04, 1.01 (2s, 18H, 2(CH3)3C). 13C NMR (CDCl3,
128.5 MHz) d 171.0 (CH3CO); 137.9, 128.3, 127.7, 127.6 (arom.);
104.9 (C-1), 88.3 (C-2), 76.7 ((CH2)5CHO), 76.4 (C-3), 74.7 (C-4);
71.9, 71.2 (PhCH2, C-5); 64.5 (C-6); 33.8, 31.7, 25.6, 24.2, 24.1
((CH2)5CHO); 27.2, 27.0 (2(CH3)3C); 21.6, 20.7 (2(CH3)3C); 21.0
(CH3CO); HRMS (ESI) Calcd for C29H46NaO7Si [M+Na]+ 557.2911.
Found: [M+Na]+ 557.2915.
Compound 20
toluene–EtOAc);
a: tr 17.5 min (9:1 CH3CN–H2O), Rf = 0.25 (15:1
[a]
+51.7 (c 1, CHCl3); 1H NMR (CDCl3,
D
500 MHz) d 8.12–7.25 (m, 20H, arom.), 5.90 (d, 1H, J = 6.4 Hz, H-
2), 5.83 (t, 1H, J = 6.2 Hz, H-3), 5.67 (ddd, 1H, J = 1.9, 5.5, 8.7 Hz,
H-5), 5.06 (d, 1H, J = 5.1 Hz, H-10), 5.01 (dd, 1H, J = 2.0, 6.1 Hz, H-
4), 4.79, 4.69 (2d, 2H, J = 12.2 Hz, PhCH2), 4.58 (t, 1H, J = 9.3 Hz,
H-30), 4.49 (dt, 1H, J = 3.6, 6.6 Hz, H-50), 4.37 (dd, 1H, J = 6.6,
11.9 Hz, H-6b0), 4.06 (dd, 1H, J = 5.6, 10.2 Hz, H-6a), 3.97 (dd, 1H,
J = 6.7, 9.7 Hz, H-40), 3.95 (dd, 1H, J = 5.1, 9.0 Hz, H-20), 3.81 (dd,
1H, J = 8.9, 10.1 Hz, H-6b), 2.06 (s, 3H, CH3CO), 1.04, 1.00 (2s,
18H, 2(CH3)3C); 13C NMR (CDCl3, 128.5 MHz) d 170.9 (CH3CO),
168.9 (C-1); 165.4, 165.1, 164.9 (PhCO); 137.9, 133.8, 133.7,
133.6, 130.1 (ꢂ2), 130.0, 128.9, 128.6, 128.5, 128.4 (ꢂ2), 128.1,
127.7, 127.5 (arom); 101.5 (C-10), 81.1 (C-20), 78.2 (C-4), 75.4 (C-
40), 73.5 (C-30), 73.5 (C-3), 72.6 (C-2), 71.7 (C-50), 71.6 (PhCH2),
69.8 (C-5), 65.8 (C-6), 64.1 (C-60), 27.3, 27.1 (2(CH3)3C), 21.7, 20.8
(2(CH3)3C), 20.9 (CH3CO); HRMS (ESI) Calcd for C50H56NaO15Si
[M+Na]+ 947.3286. Found: [M+Na]+ 947.3244.
Next fraction from the column gave syrupy 17
a (59 mg, 55%):
Rf = 0.45 (15:1 toluene–EtOAc); [
a]
+80.3 (c 1, CHCl3); 1H NMR
D
(CDCl3, 500 MHz) d 7.44–7.24 (m, 5H, arom), 5.05 (d, 1H, J = 5.2 Hz,
H-1), 4.75 (s, 2H, PhCH2), 4.55 (t, 1H, J = 9.3 Hz, H-3), 4.55 (m, 1H,
H-5), 4.32 (dd, 1H, J = 6.7, 11.9 Hz, H-6a), 4.28 (dd, 1H, J = 4.3,
11.9 Hz, H-6b), 3.93 (dd, 1H, J = 6.7, 9.7 Hz, H-4), 3.85 (dd, 1H,
J = 5.3, 9.0 Hz, H-2), 3.44 (m, 1H, OCH), 2.10 (s, 3H, CH3CO), 1.90
(m, 2H), 1.74 (m, 2H), 1.52 (m, 1H), 1.45–1.12 (m, 5H), 1.05, 1.01
(2s, 18H, 2(CH3)3C); 13C NMR (CDCl3, 128.5 MHz) d 170.9 (CH3CO);
138.1, 128.3, 127.8, 127.6 (aromatic); 98.9 (C-1), 80.6 (C-2), 77.6
((CH2)5CHO), 75.0 (C-4), 73.6 (C-3), 72.0 (C-5), 71.5 (PhCH2), 64.5
(C-6); 33.6, 32.0, 25.5, 24.5, 24.3 ((CH2)5CHO); 27.3, 27.1
(2(CH3)3C); 21.6, 20.7 (2(CH3)3C), 21.0 (CH3CO); HRMS (ESI) Calcd
for C29H46NaO7Si [M+Na]+ 557.2911. Found: [M+Na]+ 557.2915.
Method A: Compound 16 (27 mg, 0.045 mmol) and cyclohexanol
Compound 20b: tr 20.0 min (9:1 CH3CN–H2O); Rf = 0.25 (15:1
toluene–EtOAc);
[a
]
D
ꢀ3.0 (c 1, CHCl3); 1H NMR (CDCl3,
500 MHz) d 8.08–7.22 (m, 20H, arom.), 6.06 (d, 1H, J = 5.6 Hz, H-
2), 5.83 (t, 1H, J = 5.4 Hz, H-3), 5.82 (td, 1H, J = 2.6, 6.4 Hz, H-5),
4.98 (dd, 1H, J = 2.6, 5.2 Hz, H-4), 4.96 (d, 1H, J = 2.9 Hz, H-10);
4.63, 4.49 (2d, 2H, J = 11.9 Hz, PhCH2), 4.54 (dt, 1H, J = 4.9 Hz, H-
50), 4.30–4.24 (m, 3H, H-6a0, H-6b0, H-30), 4.19 (dd, 1H, J = 6.8,
10.2 Hz, H-40), 4.02 (dd, 1H, J = 6.5, 10.7 Hz, H-6a), 3.90 (dd, 1H,
J = 2.9, 6.6 Hz, H-20), 3.88 (dd, 1H, J = 6.5, 10.7 Hz, H-6b), 2.09 (s,
3H, CH3CO), 1.03, 0.98 (2s, 18H, 2(CH3)3C). 13C NMR (CDCl3,
128.5 MHz) d 170.9 (CH3CO), 169.0 (C-1); 165.4, 165.2, 165.0
(PhCO); 137.5, 133.9, 133.7, 133.6, 130.1, 130.0 (ꢂ2), 128.9,
128.6, 128.4, 128.3, 127.9, 127.7 (ꢂ2) (arom); 107.3 (C-10), 87.9
(C-20), 79.3 (C-4), 76.9 (C-30), 75.0 (C-40), 74.3 (C-3), 72.3 (C-2),
72.0 (PhCH2), 70.8 (C-5, C-50), 65.8 (C-6), 64.2 (C-60); 27.1, 27.0
(2(CH3)3C); 21.6, 20.7 (2(CH3)3C); 21.0 (CH3CO); HRMS (ESI) Calcd
for C50H56NaO15Si [M+Na]+ 947.3286. Found: [M+Na]+ 947.3250.
(6.5
acetyl-2-O-benzyl-3,5-O-(di-tert-butylsilanediyl)-1-N-trichloro-
acetyl- -galactofuranosylamine (18, 35%) as a syrup: Rf = 0.45
(15:1 toluene–EtOAc); [
+66.0 (c 1, CHCl3); 1H NMR (CDCl3,
lL, 0.054 mmol) gave 7 mg of 17b (29%) and 9.5 mg of 6-O-
a-D
a]
D
500 MHz) d 7.73 (d, 1H, J = 8.0 Hz, NH), 7.38–7.30 (m, 5H, aro-
matic), 5.64 (t, 1H, J = 7.7 Hz, H-1), 4.80, 4.70 (2d, 2H, J = 12.0 Hz,
CH2Ph), 4.65 (dt, 1H, J = 6.7, 4.5 Hz, H-5), 4.41 (dd , 1H, J = 11.8,

M. J. Tilve, C. Gallo-Rodriguez / Carbohydrate Research 346 (2011) 2838–2848
2847
Method C: Compound 16 (112 mg, 0.188 mmol) and 19 (111 mg,
lsilanediyl)-b-
0.033 mmol) and cyclohexanol (4 l
purified by column cromatography (25:1 hexane–EtOAc) to give a
D
-galactofuranosyl) trichloroacetimidate (7, 21 mg,
L, 0.038 mmol). The crude was
0.226 mmol) gave 152 mg of 20
a
and 20b (87%) in 1.3:1 ratio as
indicated by 1H NMR spectrum.
first fraction of syrupy 24b (4.5 mg, 24%): Rf = 0.43 (15:1 hexane–
4.11.8. Allyl 6-O-acetyl-2-O-benzyl-3,5-O-(di-tert-
butylsilanediyl)- -galactofuranosyl-(1?2)-3,4-di-O-benzyl-
-rhamnopyranoside (22 ) and allyl 6-O-acetyl-2-O-benzyl-3,5-
O-(di-tert-butylsilanediyl)-b- -galactofuranosyl-(1?2)-3,4-di-
O-benzyl- -rhamnopyranoside (22b)
Compounds22 and 22b were obtained according to general pro-
cedures (method E) from donor 16 (58 mg, 0.097 mmol) and allyl
3,4-di-O-benzyl-
-rhamnopyranoside (21, 44 mg, 0.114 mmol).58
EtOAc); [
a
]
ꢀ15.5 (c 0.6, CHCl3); 1H NMR (CDCl3, 500 MHz) d
D
a
-
D
a-
7.40–7.26 (m, 10H, aromatic), 5.05 (d, 1H, J = 3.1 Hz, H-1), 4.73,
4.62 (2d, 2H, J = 11.9 Hz, PhCH2); 4.63, 4.56 (2d, 2H, J = 12.2 Hz,
PhCH2), 4.61 (m, 1H, H-5), 4.19 (mAB, 2H, H-3, H-4), 3.90 (dd, 1H,
J = 3.1, 6.6 Hz, H-2), 3.72 (dd, 1H, J = 2.9, 10.3 Hz, H-6a), 3.63 (dd,
1H, J = 7.9, 10.3 Hz, H-6b), 3.48 (m, 1H, OCH), 1.87 (m, 2H), 1.71
(m, 2H), 1.51 (m, 1H), 1.39–1.12 (m, 5H); 1.02, 1.01 (2s, 18H,
2(CH3)3C); 13C NMR (CDCl3, 128.5 MHz) d 138.2, 137.9, 128.3,
127.9, 127.8, 127.7, 127.6 (arom.); 104.8 (C-1), 88.7 (C-2), 76.9 (C-
3), 76.2 ((CH2)5CHO), 74.9 (C-4), 73.6 (PhCH2), 73.0 (C-5), 72.0
(PhCH2), 70.1 (C-6); 33.8, 31.7, 29.7, 25.6, 24.2, 24.1 ((CH2)5CHO);
27.2, 27.1 (2(CH3)3C); 21.6, 20.7 (2(CH3)3C); HRMS (ESI) Calcd for
C34H50NaO6Si [M+Na]+ 605.3274. Found: [M+Na]+ 605.3257.
L
a
D
a-L
a
a-L
The crude was purified by column chromatography (40:1 toluene–
EtOAc) to afford 25 mg of 22b (31%) as a syrup: Rf = 0.38 (15:1 tolu-
ene–EtOAc); [
a
]
D
ꢀ40.6 (c 1, CHCl3); 1H NMR (CDCl3, 500 MHz) d
7.37–7.20 (m, 15H, aromatic), 5.82 (dddd, 1H, J = 5.3, 6.2, 10.3,
17.2 Hz, CH@CH2), 5.28 (d, 1H, J = 3.1 Hz, H-10), 5.22 (dq, 1H,
J = 1.6, 17.2 Hz, CH@CHaH), 5.13 (dq, 1H, J = 1.3, 10.3 Hz, CH@CHbH),
4.91, 4.53 (2d, 2H, J = 10.7 Hz, PhCH2), 4.76, 4.61 (2d, 2H, J = 10.6 Hz,
PhCH2), 4.74, 4.64 (2d, 2H, J = 12.1 Hz, PhCH2), 4.71 (d, 1H, J = 1.6 Hz,
H-1), 4.54 (m, 1H, H-50), 4.36 (dd, 1H, J = 3.8, 11.9 Hz, H-6a0), 4.30 (m,
2H, H-40, H-30), 4.26 (dd, 1H, J = 7.3, 11.9 Hz, H-6b0), 4.10 (dd, 1H,
J = 3.1, 6.6 Hz, H-20), 4.09 (ddt, 1H, J = 1.7, 5.0, 12.9 Hz, OCHH-
CH@CH2), 3.98 (dd, 1H, J = 3.3, 9.5 Hz, H-3), 3.88 (ddt, 1H, J = 1.3,
6.2, 12.9 Hz, OCHH-CH@CH2), 3.82 (dd, 1H, J = 1.6, 3.3 Hz, H-2),
3.69 (dq, 1H, J = 6.4, 9.5 Hz, H-5), 3.56 (t, 1H, J = 9.5 Hz, H-4), 2.08
(s, 3H, CH3CO), 1.30 (d, 3H, J = 6.4 Hz, H-6); 1.04, 1.00 (2s, 18H,
2(CH3)3C). 13C NMR (CDCl3, 128.5 MHz) d 170.9 (CH3CO); 138.4,
138.3, 137.5, 128.3, 128.2, 128.0 (ꢂ2), 127.6, 127.3 (aromatic);
133.7 (CH2CH@CH2), 117.4 (CH2CH@CH2), 108.7 (C-10), 96.9 (C-1),
88.2 (C-20), 80.3 (C-3), 80.0 (C-4), 78.8 (C-2), 77.0 (C-30), 75.3
(PhCH2), 75.1 (C-40), 73.3 (PhCH2), 71.9 (PhCH2), 71.0 (C-50), 67.8
(C-5), 67.7 (CH2CH@CH2), 64.2 (C-60); 27.2, 27.0 (2(CH3)3C); 21.0
(CH3CO); 21.6, 20.7 (2(CH3)C); 17.9 (C-6); HRMS (ESI) Calcd for
Next fraction from the column gave 24
Rf = 0.29 (15:1 hexane–EtOAc); [
a as a syrup (9 mg, 71%):
a
]
D
+57.6 (c 0.7, CHCl3); 1H NMR
(CDCl3, 500 MHz) d 7.40–7.26 (m, 10H, arom.), 5.00 (d, 1H,
J = 5.2 Hz, H-1), 4.73 (s, 2H, PhCH2), 4.60 (s, 2H, PhCH2), 4.59
(ddd, 1H, J = 2.7, 6.4, 8.7 Hz, H-5), 4.40 (t, 1H, J = 9.3 Hz, H-3),
3.90 (dd, 1H, J = 6.6, 9.7 Hz, H-4), 3.82 (dd, 1H, J = 5.2, 9.0 Hz, H-
2), 3.71 (dd, 1H, J = 2.9, 10.4 Hz, H-6a), 3.58 (dd, 1H, J = 8.6,
10.4 Hz, H-6b), 3.40 (m, 1H, OCH), 1.86 (m, 1H), 1.81–1.66 (m,
3H), 1.53 (m, 1H), 1.35–1.08 (m, 5H); 1.03, 1.00 (2s, 18H,
2(CH3)3C); 13C NMR (CDCl3, 128.5 MHz) d 138.1, 138.0, 128.3
(ꢂ2), 128.1, 127.9, 127.7, 127.6 (arom.); 98.7 (C-1), 80.8 (C-2),
77.3 ((CH2)5CHO), 75.1 (C-4), 73.9 (C-5), 73.7 (PhCH2, C3), 71.6
(PhCH2), 70.0 (C-6); 33.7, 31.9, 25.5, 24.5, 24.4 ((CH2)5CHO); 27.3
(2(CH3)3C); 21.5, 20.6 (2(CH3)3C); HRMS (ESI) Calcd for
C
34H50NaO6Si [M+Na]+ 605.3274. Found: [M+Na]+ 605.3297.
Method C: Compound 7 (20 mg, 0.031 mmol) and cyclohexanol
(3.9
lL, 0.037 mmol) gave 8.5 mg of 24b (47%) and 8.5 mg of 24a
C
46H62NaO11Si [M+Na]+ 841.3959. Found: [M+Na]+ 841.3954.
Next fraction from the column gave syrupy 22 (28 mg, 35%):
Rf = 0.35 (15:1 toluene–EtOAc); [
+5.4 (c 1, CHCl3); 1H NMR
(47%).
a
a]
4.11.10. Methyl 6-O-acetyl-2-O-benzyl-3,5-O-(di-tert-
butylsilanediyl)- -galactofuranosyl-(1?6)-2,3,4-tri-O-
benzoyl- -mannopyranoside (26 ) and methyl 6-O-acetyl-2-
O-benzyl-3,5-O-(di-tert-butylsilanediyl)-b- -galactofuranosyl-
(1?6)-2,3,4-tri-O-benzoyl- -mannopyranoside (26b)
Compounds 26 and 26b were obtained according to general
procedure (method E) from 16 (40 mg, 0.067 mmol) and methyl
D
(CDCl3, 500 MHz) d 7.4–7.2 (m, 15H, arom.), 5.80 (m, 1H, CH@CH2),
5.19 (dq, 1H, J = 1.6, 17.3 Hz, CH@CHaH), 5.19 (d, 1H, J = 4.9 Hz, H-
10), 5.13 (dq, 1H, J = 1.6, 10.4 Hz, HC@CHbH), 4.98, 4.54 (2d, 2H,
J = 10.7 Hz, PhCH2), 4.78 (s, 2H, PhCH2), 4.75, 4.64 (2d, 2H,
J = 12.0 Hz, PhCH2), 4.69 (d, 1H, J = 1.9 Hz, H-1), 4.59 (m, 1H, H-50),
4.58 (t, 1H, J = 9.0 Hz, H-30), 4.38 (dd, 1H, J = 6.9, 11.9 Hz, H-6a0),
4.32 (dd, 1H, J = 4.3, 11.9 Hz, H-6b0), 4.08 (ddt, 1H, J = 1.6, 5.5,
13.1 Hz, CHHCH@CH2), 4.00 (dd, 1H, J = 3.1, 9.1 Hz, H-3), 3.97 (dd,
1H, J = 6.7, 9.7 Hz, H-40), 3.91 (dd, 1H, J = 1.9, 2.9 Hz, H-2), 3.90 (dd,
J = 4.9, 8.8 Hz, H-20), 3.88 (ddt, 1H, J = 1.4, 6.0, 13.1 Hz, CHHCH@CH2),
3.66 (dq, 1H, J = 6.2, 9.4 Hz, H-5), 3.56 (t, 1H, J = 9.1 Hz, H-4), 2.01 (s,
3H, CH3CO), 1.26 (d, 3H, J = 6.2 Hz, H-6), 1.05, 1.04 (2s, 18H,
2(CH3)3C). 13C NMR (CDCl3, 128.5 MHz) d 170.8 (CH3CO), 138.6,
138.0, 128.3 (ꢂ2), 128.2, 127.9, 127.8, 127.6, 127.5 (aromatic);
134.0 (CH2CH@CH2), 117.0 (CH2CH@CH2), 101.3 (C-10), 97.5 (C-1),
81.2 (C-20), 80.3 (C-4), 78.4 (C-3), 76.2 (C-2), 75.2 (C-40), 74.9
(PhCH2), 74.0 (C-30), 73.0 (PhCH2), 72.0 (C-50), 71.7 (PhCH2), 68.1
(C-5), 67.7 (CH2CH@CH2), 64.3 (C-60); 27.2, 27.0 (2(CH3)3C); 20.9
(CH3CO); 21.7, 20.7 (2(CH3)C); 17.81 (C-6); HRMS (ESI) Calcd for
a-D
a
-
D
a
D
a
-D
a
2,3,4-tri-O-benzoyl-
a-
D-mannopyranoside
(25,
40 mg,
0.079 mmol).60 The crude was purified by column chromatography
(15:1 toluene–EtOAc) to give 7 mg of syrupy 26b (11%): Rf = 0.61
(6:1 toluene–EtOAc); [
a]
ꢀ46.5 (c 0.6, CHCl3); 1H NMR (CDCl3,
D
500 MHz) d 8.10–7.23 (m, 20H, arom.), 5.86 (dd, 1H, J = 3.3,
10.0 Hz, H-3), 5.81 (t, 1H, J = 10.0 Hz, H-4), 5.65 (dd, 1H, J = 1.8,
3.3 Hz, H-2), 5.00 (d, 1H, J = 3.1 Hz, H-10), 4.96 (d, 1H, J = 1.8 Hz,
H-1), 4.72, 4.63 (2d, 2H, J = 11.8 Hz, PhCH2), 4.56 (dt, 1H, J = 3.6,
7.3 Hz, H-50), 4.29 (dd, 1H, J = 3.8, 11.9 Hz, H-6a0), 4.27–4.22 (m,
3H, H-6b0, H-5, H-30), 4.20 (dd, 1H, J = 6.5, 10.2 Hz, H-40), 3.91
(dd, 1H, J = 3.1, 6.7 Hz, H-20), 3.87 (dd, 1H, J = 2.7, 11.5 Hz, H-6a),
3.72 (dd, 1H, J = 6.7, 11.5 Hz, H-6b), 3.49 (s, 3H, CH3O), 2.07 (s,
3H, CH3CO); 1.03, 0.97 (2s, 18H, 2(CH3)3C); 13C NMR (CDCl3,
128.5 MHz) d 170.9 (CH3CO); 165.5 (ꢂ2), 165.4 (PhC@O); 137.8,
133.5, 133.4, 133.1, 129.9, 129.8, 129.7, 129.1, 128.6, 128.5, 128.3
(ꢂ2), 127.8, 127.7 (arom.); 107.8 (C-10), 98.4 (C-1), 88.0 (C-20),
74.9 (C-40), 72.0 (PhCH2), 71.0 (C-50), 70.4 (C-2), 70.1 (C-3), 70.0
(C-30, C-5), 68.1 (C-6), 67.5 (C-4), 64.3 (C-60), 55.3 (CH3O); 27.1,
27.0 (2(CH3)3C); 21.6, 20.6 (2(CH3)3C); 21.0 (CH3CO); HRMS (ESI)
C
46H62NaO11Si [M+Na]+ 841.3959. Found: [M+Na]+ 841.3945.
Method C: Compound 16 (103 mg, 0.173 mmol) and 21 (80 mg,
0.208 mmol) gave 94 mg of 22b (66%).
4.11.9. Cyclohexyl 2,6-di-O-benzyl-3,5-O-(di-tert-
butylsilanediyl)-a-D-galactofuranoside (24a) and cyclohexyl
2,6-di-O-benzyl-3,5-O-(di-tert-butylsilanediyl)-b-
D
-
Calcd for
963.3612.
C
51H60NaO15Si [M+Na]+ 963.3599. Found: [M+Na]+
galactofuranoside (24b)
Compounds24
a
and 24b were obtained according to general pro-
Next fraction from the column gave syrupy 26a (53 mg 84%):
cedures (method E) from O-(2,6-O-benzyl-3,5-O-(di-tert-buty-
Rf = 0.55 (6:1 toluene–EtOAc); [
a]
ꢀ29.8 (c 1, CHCl3); 1H NMR
D

2848
M. J. Tilve, C. Gallo-Rodriguez / Carbohydrate Research 346 (2011) 2838–2848
21. Ghosh, S.; Misra, A. K. Tetrahedron: Asymmetry 2010, 21, 2755–2761.
22. Gola, G.; Tilve, M. J.; Gallo-Rodriguez, C. Carbohydr. Res. 2011, 346,
1495–1502.
23. Guelin, M.; Ferrieres, V.; Plusquellec, D. Eur. J. Org. Chem. 2000, 1423–1431.
24. Lee, Y. J.; Lee, B.-Y.; Jeon, H. B.; Kim, K. S. Org. Lett. 2006, 8, 3971–3974.
25. Baek, J. Y.; Joo, Y. J.; Kim, K. S. Tetrahedron Lett. 2008, 49, 4734–4737.
26. Bai, Y.; Lowary, T. L. J. Org. Chem. 2006, 71, 9658–9671.
27. Bai, Y.; Lowary, T. L. J. Org. Chem. 2006, 71, 9672–9680.
28. Mydock, L. K.; Demchenko, A. V. Org. Biomol. Chem. 2010, 8, 497–510.
29. Bohé, L.; Crich, D. C.R. Chim. 2011, 14, 3–16.
(CDCl3, 500 MHz) d 8.12–7.14 (m, 20H, arom.), 5.89 (dd, 1H, J = 3.5,
10.0 Hz, H-3), 5.72 (t, 1H, J = 10.1 Hz, H-4), 5.68 (dd, 1H, J = 1.7,
3.5 Hz, H-2), 5.04 (d, 1H, J = 1.7 Hz, H-1), 4.90 (d, 1H, J = 4.9 Hz,
H-10); 4.80, 4.72 (2d, 2H, J = 12.4 Hz, PhCH2); 4.62 (t, 1H,
J = 9.4 Hz, H-30), 4.56 (m, 1H, H-50), 4.46 (dd, 1H, J = 7.6, 12.0 Hz,
H-6a0), 4.33 (ddd, 1H, J = 2.0, 7.9, 10.1 Hz, H-5), 4.25 (dd, 1H,
J = 3.8, 12.0 Hz, H-6b0), 4.00 (dd, 1H, J = 6.6, 9.7 Hz, H-40), 3.95
(dd, 1H, J = 7.9, 10.8 Hz, H-6a), 3.90 (dd, 1H, J = 4.9, 9.0 Hz, H-20),
3.60 (dd, 1H, J = 2.0, 10.8 Hz, H-6b), 3.51 (s, 3H, CH3O), 1.91 (s,
3H, CH3CO); 1.02, 0.99 (2s, 18H, 2(CH3)3C). 13C NMR (CDCl3,
128.5 MHz) d 170.5 (CH3CO); 165.6, 165.5, 165.4, (PhCO); 137.9,
133.4, 133.3, 133.0, 129.9, 129.8, 129.7, 129.5, 129.2, 129.0,
128.5, 128.4, 128.2(x2), 128.0, 127.7 (aromatic); 100.0 (C-10),
98.1 (C-1), 80.5 (C-20), 75.6 (C-40), 73.4 (C-30), 72.0 (C-50), 71.7
(PhCH2), 70.6 (C-2), 70.1 (C-3), 69.5 (C-5), 67.7 (C-4), 67.2 (C-6),
64.3 (C-60), 55.1 (CH3O); 27.2, 27.0 (2(CH3)3C); 21.6, 20.7
(2(CH3)3C); 20.6 (CH3CO).
30. Crich, D. Acc. Chem. Res. 2010, 43, 1144–1153.
31. Manabe, S.; Ito, Y. Curr. Bioact. Compd. 2008, 4, 258–281.
32. Walvoort, M. T. C.; Dinkelaar, J.; van den Bos, L. J.; Lodder, G.; Overkleeft, H. S.;
Codée, J. D. C.; van der Marel, G. A. Carbohydr. Res. 2010, 345, 1252–1263.
33. Guo, J.; Ye, X.-S. Molecules 2010, 15, 7235–7265.
34. (a) Smith, D. M.; Tran, M. B.; Woerpel, K. A. J. Am. Chem. Soc. 2003, 125, 14149–
14152; (b) Larsen, C. H.; Ridgway, B. H.; Shaw, J. T.; Smith, D. M.; Woerpel, K. A.
J. Am. Chem. Soc. 2005, 127, 10879–10884.
35. Zhu, X.; Kawatkar, S.; Rao, Y.; Boons, G.-J. J. Am. Chem. Soc. 2006, 128, 11948–
11957.
36. Crich, D.; Pedersen, C. M.; Bowers, A. A.; Wink, D. J. J. Org. Chem. 2007, 72,
1553–1565.
37. Wang, Y.; Maguire-Boyle, S.; Dere, R. T.; Zhu, X. Carbohydr. Res. 2008, 343,
3100–3106.
38. Nacario, R. C.; Lowary, T. L.; McDonald, R. Acta Crystallogr., Sect. E 2007, 63,
o498–o500.
HRMS (ESI) Calcd for C51H60NaO15Si [M+Na]+ 963.3599. Found:
[M+Na]+ 963.3576.
39. (a) Joe, M.; Bai, Y.; Nacario, R. C.; Lowary, T. L. J. Am. Chem. Soc. 2007, 129, 9885–
9901; (b) Rademacher, C.; Shoemaker, G. K.; Kim, H.-S.; Zheng, R. B.; Taha, H.;
Liu, C.; Nacario, R. C.; Schriemer, D. C.; Klassen, J. S.; Peters, T.; Lowary, T. L. J.
Am. Chem. Soc. 2007, 129, 10489–10502.
40. (a) Rao, Y.; Boons, G.-J. Angew. Chem., Int. Ed. 2007, 46, 6148–6151; (b) Rao, Y.;
Buskas, T.; Albert, A.; O’Neill, M. A.; Hahn, M. G.; Boons, G.-J. ChemBioChem
2008, 9, 381–388.
41. (a) Ishiwata, A.; Akao, H.; Ito, Y. Org. Lett. 2006, 8, 5525–5528; (b) Ishiwata, A.;
Ito, Y. Trends Glycosci. Glycotechnol. 2009, 21, 266–289.
42. Ishiwata, A.; Ito, Y. J. Am. Chem. Soc. 2011, 133, 2275–2291.
43. Imamura, A.; Lowary, T. L. Org. Lett. 2010, 12, 3686–3689.
44. (a) Schmidt, R. R.; Zhu, X. Glycosyl Trichloroacetimidates. In Glycoscience;
Fraser-Reid, B., Tatsuta, K., Thiem, J., Eds.; Springer-Verlag: Berlin Heidelberg,
2008; pp 451–453; (b) Schmidt, R. R.; Kinzy, W. Adv. Carbohydr. Chem. Biochem.
1994, 50, 21–123.
Acknowledgments
This work was supported by grants from the Agencia Nacional
de Promoción Científica y Tecnológica, Universidad de Buenos
Aires and CONICET. C. Gallo-Rodriguez is a research member of
CONICET. M. J. Tilve is a research fellow from CONICET.
Supplementary data
Supplementary data (1H and 13C NMR spectra for new com-
pounds 7, 9–16, 17
a, 17b, 18, 20a, 20b, 22a, 22b, 23, 24a, 24b,
45. Gallo-Rodríguez, C.; Gandolfi-Donadio, L.; de Lederkremer, R. M. Org. Lett. 1999,
1, 245–248.
46. (a) Gandolfi-Donadío, L.; Gallo-Rodriguez, C.; Lederkremer, R. M. J. Org. Chem.
2002, 67, 4430–4435; (b) Gandolfi-Donadío, L.; Gallo-Rodriguez, C.; de
Lederkremer, R. M. J. Org. Chem. 2003, 68, 6928–6934.
47. Gallo-Rodriguez, C.; Gil-Libarona, M. A.; Mendoza, V. M.; Lederkremer, R. M.
Tetrahedon 2002, 58, 9373–9380.
48. Mendoza, V. M.; Kashiwagi, G. A.; De Lederkremer, R. M.; Gallo-Rodriguez, C.
Carbohydr. Res. 2010, 345, 385–396.
49. Gandolfi-Donadío, L.; Santos, M.; de Lederkremer, R. M.; Gallo-Rodriguez, C.
Org. Biomol. Chem. 2011, 9, 2085–2097.
50. (a) Qiao, Y.; Lindner, B.; Zähringer, U.; Truog, P.; Schmidt, R. R. Bioorg. Med.
Chem. 2010, 18, 3696–3702; (b) Splain, R. A.; Kiessling, L. L. Bioorg. Med. Chem.
2010, 18, 3753–3759.
51. Klotz, W.; Schmidt, R. R. Liebigs Ann. Chem. 1993, 683–690.
52. Gola, G.; Libenson, P.; Gandolfi-Donadío, L.; Gallo-Rodriguez, C. Arkivoc 2005,
xii, 234–242.
53. Gelin, M.; Ferrieres, V.; Lefeuvre, M.; Plusquellec, D. Eur. J. Org. Chem. 2003,
1285–1293.
54. (a) Jensen, H. S.; Limberg, G.; Pedersen, C. Carbohydr. Res. 1997, 302, 109–112;
(b) Eckenberg, P.; Groth, U.; Huhn, T.; Richter, N.; Schmeck, C. Tetrahedron
1993, 49, 1619–1624.
55. Wang, P.; Haldar, P.; Wang, Y.; Hu, H. J. Org. Chem. 2007, 72, 5870–5873.
56. (a) Sadozai, K. K.; Nukada, T.; Ito, Y.; Nakahara, Y.; Ogawa, T.; Kobata, A.
Carbohydr. Res. 1986, 157, 101–123; (b) Kinzy, W.; Schmidt, R. R. Liebigs Ann.
Chem. 1987, 407–415; (c) Kobayashi, M.; Yamazaki, F.; Ito, Y.; Ogawa, T.
Carbohydr. Res. 1990, 201, 51–67; (d) Lohman, G. J. S.; Seeberger, P. H. J. Org.
Chem. 2004, 69, 4081–4093.
57. Du Mortier, C.; Varela, O.; de Lederkremer, R. M. Carbohydr. Res. 1989, 189, 79–
86.
58. Westerduin, P.; De Haan, P. E.; Deers, M. J.; van Boom, J. H. Carbohydr. Res. 1988,
180, 195–205.
26 and 26b) associated with this article can be found, in the on-
line version, at doi:10.1016/j.carres.2011.10.004.
a
References
1. Boltje, T. J.; Buskas, T.; Boons, G.-J. Nat. Chem. 2009, 1, 611–622.
2. Stallforth, P.; Lepenies, B.; Adibekian, A.; Seeberger, P. H. J. Med. Chem. 2009, 52,
5561–5577.
3. Essentials of Glycobiology; Varki, A., Cummings, R. D., Esko, J. D., Freeze, H. H.,
Stanley, P., Bertozzi, C. R., Hart, G. W., Etzler, M. E., Eds., 2nd ed.; Cold Spring
Harbor Laboratory Press: New York, 2009.
4. Zhu, X.; Schmidt, R. R. Angew. Chem., Int. Ed. 2009, 48, 1900–1934.
5. Demchenko, A. V. Curr. Org. Chem. 2003, 7, 35–79.
6. Peltier, P.; Euzen, R.; Daniellou, R.; Nugier-Chauvin, C.; Ferrières, V. Carbohydr.
Res. 2008, 343, 1897–1923.
7. Richards, M. R.; Lowary, T. L. ChemBioChem 2009, 10, 1920–1938.
8. Lowary, T. L. Curr. Opin. Chem. Biol. 2003, 7, 749–756.
9. (a) Houseknecht, J. B.; Lowary, T. L. Curr. Opin. Chem. Biol. 2001, 5, 677–682; (b)
Imamura, A.; Lowary, T. L. Trends Glycosci. Glycotechnol. 2011, 23, 134–152.
10. Lederkremer, R. M.; Colli, W. Glycobiology 1995, 5, 547–552.
11. Pedersen, L. L.; Turco, S. J. Cell. Mol. Life Sci. 2003, 60, 259–266.
12. Tam, P.-H.; Lowary, T. L. Curr. Opin. Chem. Biol. 2009, 13, 618–625.
13. Belanova, M.; Dianiskova, P.; Brennan, P. J.; Completo, G. C.; Rose, N. L.; Lowary,
T. L.; Mikusova, K. J. Bacteriol. 2008, 190, 1141–1145.
14. Richards, J. C.; Perry, M. B.; Kniskern, P. J. Can. J. Chem. 1989, 67, 1038–1050.
15. Linnerborg, M.; Wollin, R.; Wildmalm, G. Eur. J. Biochem. 1997, 246, 565–573.
16. Perepelov, A. V.; Li, D.; Liu, B.; Senchenkova, S. N.; Guo, D.; Shashkov, A. S.;
Feng, L.; Knirel, Y. A.; Wang, L. Innate Immun. 2011, 17, 164–173.
17. Perepelov, A. V.; Liu, B.; Senchenkova, S. N.; Shashkov, A. S.; Feng, L.; Knirel, Y.
A.; Wang, L. Carbohydr. Res. 2011, 346, 373–376.
18. Ahrazem, O.; Prieto, A.; San-Blas, G.; Leal, J. A.; Jimenez-Barbero, J.; Bernabé, M.
Glycobiology 2003, 13, 743–747.
19. Gelin, M.; Ferrières, V.; Plusquellec, D. Carbohydr. Lett. 1997, 2, 381–388.
20. Gandolfi-Donadio, L.; Gola, G.; de Lederkremer, R. M.; Gallo-Rodriguez, C.
Carbohydr. Res. 2006, 341, 2487–2497.
59. Baek, J. Y.; Lee, B.-Y.; Jo, M. G.; Kim, K. S. J. Am. Chem. Soc. 2009, 131, 17705–
17713.
60. Ziegler, T.; Kovac, P.; Glaudemans, C. P. J. Carbohydr. Res. 1989, 194, 185–198.
61. Xie, N.; Taylor, C. M. Org. Lett. 2010, 12, 4968–4971.