Synthesis of methyl α-D-glucopyranosyl-(1→4)-α-D-galactopyranoside and methyl α-D-xylo-hex-4-ulopyranosyl-(1→4)-α-D-galactopyranoside

Article abstract of DOI:10.1016/S0008-6215(01)00044-1

The syntheses of methyl α-D-glucopyranosyl-(1→4)-α-D-galactopyranoside (1) and methyl α-D-xylo-hex-4-ulopyranosyl-(1→4)-α-D-galactopyranoside (4) are reported. The keto-disaccharide 4 is of interest in our design, synthesis, and study of pectate lyase inhibitors. The key step in the syntheses was the high-yielding, stereospecific formation of methyl 4,6-O-benzylidene-2′,3′-di-O-benzyl-α-D-glucopyranosyl- (1→4)-2,3,6-tri-O-benzyl-α-D-galactopyranoside (15), which was accomplished by reacting 2,3-di-O-benzyl-4,6-O-benzylidene-D-glucopyranosyl trichloroacetimidate (10) with methyl 2,3,6-tri-O-benzyl-α-D-galactopyranoside (14) in the presence of a catalytic amount of tert-butyldimethylsilyl trifluoromethane sulfonate (TMSOTF). Compound 15 was either hydrogenolyzed to yield disaccharide 1 or treated with NaBH₃CN-HCl in 1:1 tetrahydrofuran-ether to yield methyl 2,3,6-tri-O-benzyl-α-D-glucopyranosyl-(1→4)-2,3,6-tri-O-benzyl- α-D-galactopyranoside (2). The free 4′-OH of compound 2 was oxidized to a carbonyl group by a Swern oxidation, and the protecting groups were removed by hydrogenolysis to yield keto-disaccharide 4. These synthetic pathways were simple, yet high yielding.

Full text of DOI:10.1016/S0008-6215(01)00044-1

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Carbohydrate Research 331 (2001) 247–253
Synthesis of methyl
a-
D
-glucopyranosyl-(1“4)-a-
D
-galactopyranoside and
methyl a-
D
-xylo-hex-4-ulopyranosyl-
(1“4)-a-D-galactopyranoside
Louis J. Liotta,* Rita D. Capotosto, Rachel A. Garbitt, Brian M. Horan,
Pamela J. Kelly, Andrew P. Koleros, Lisa M. Brouillette, Amy M. Kuhn,
Sonia Targontsidis
Department of Chemistry, Stonehill College, 320 Washington Street, Easton, MA 02357, USA
Received 31 October 2000; accepted 31 January 2001
Abstract
The syntheses of methyl a-
osyl-(1“4)-a- -galactopyranoside (4) are reported. The keto-disaccharide 4 is of interest in our design, synthesis,
and study of pectate lyase inhibitors. The key step in the syntheses was the high-yielding, stereospecific formation of
methyl 4,6-O-benzylidene-2%,3%-di-O-benzyl-a- -glucopyranosyl-(1“4)-2,3,6-tri-O-benzyl-a- -galactopyranoside
(15), which was accomplished by reacting 2,3-di-O-benzyl-4,6-O-benzylidene- -glucopyranosyl trichloroacetimidate
(10) with methyl 2,3,6-tri-O-benzyl-a- -galactopyranoside (14) in the presence of a catalytic amount of tert-
butyldimethylsilyl trifluoromethane sulfonate (TMSOTF). Compound 15 was either hydrogenolyzed to yield disac-
charide 1 or treated with NaBH3CN–HCl in 1:1 tetrahydrofuran–ether to yield methyl 2,3,6-tri-O-benzyl-a-
glucopyranosyl-(1“4)-2,3,6-tri-O-benzyl-a- -galactopyranoside (2). The free 4%-OH of compound 2 was oxidized to
D
-glucopyranosyl-(1“4)-a-
D
-galactopyranoside (1) and methyl a-D-xylo-hex-4-ulopyran-
D
D
D
D
D
D
-
D
a carbonyl group by a Swern oxidation, and the protecting groups were removed by hydrogenolysis to yield
keto-disaccharide 4. These synthetic pathways were simple, yet high yielding. © 2001 Elsevier Science Ltd. All rights
reserved.
Keywords: a- -Glucopyranosides; Trichloroacetimidate in a-glycoside formation; Keto-disaccharides
D
1. Introduction
plants.1–3 These enzymes cleave internal glyco-
sidic bonds in polygalacturonic acid or low-
methylesterified pectins by a b-elimination
reaction to yield oligomers that contain 4,5-
unsaturated sugars at their nonreducing ends.
Using this b-elimination mechanism as a
guide, we are currently in the process of de-
signing and synthesizing compounds that will
specifically inhibit pectate lyases. As part of
Pectate lyases are a family of isoenzymes
that constitute the major component of a
complex mixture of cell-wall degrading en-
zymes produced and secreted by plant patho-
gens that cause diseases involving maceration
and killing of parenchymatous tissues in many
our study, we synthesized methyl a-
pyranosyl-(1“4)-a- -galactopyranoside (1),
and the selectively deprotected derivative of 1,
D
-gluco-
* Corresponding author. Tel.: +1-508-5651043; fax: +1-
508-5651469.
E-mail address: lliotta@stonehill.edu (L.J. Liotta).
D
0008-6215/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(01)00044-1

248
L.J. Liotta et al. / Carbohydrate Research 331 (2001) 247–253
methyl 2,3,6-tri-O-benzyl-a-
D
-glucopyranosyl-
reductive
addition.
amination
and
nucleophilic
(1“4)-2,3,6-tri-O-benzyl-a-
D
-galactopyran-
oside (2), as well as the corresponding 4%-
ketoderivatives 3 and 4.
2. Results and discussion
The most challenging aspect of this synthe-
An earlier synthesis of 1 using a thiogly-
coside coupling has been reported. In this
method the glycosidic bond formation gave
37% of the a isomer and 32% of the b isomer.4
In addition the synthesis of the selectively
protected galactoside required the use of envi-
ronmentally toxic mercuric chloride in the for-
mation of a metal chelate.5 More recently an
enzymatic synthesis of 1 using dextransucrase
was reported.6 However, this study indicated
that methyl galactopyranoside was an ineffi-
cient glucose acceptor for reactions catalyzed
by this enzyme.
The work described herein not only pro-
vides an efficient, stereoselective synthesis of
disaccharide 1, but would allow also for this
disaccharide to be incorporated into more
complex molecules. By using the selectively
deprotected disaccharide 2, the larger
oligosaccharide-containing substructure 1 at-
tached by its 4%-hydroxyl group could be syn-
thesized. Likewise the keto groups of
structures 3 and 4 allow for a wide range of
selective chemistry at the 4%-position, including
sis was creating the (1“4)-a- -glycosidic
linkage with high selectivity. For this glyco-
sidic bond formation we employed
trichloroacetimidate coupling between 2,3-di-
O - benzyl - 4,6 - O - benzylidiene - - glucopyra-
nosyl trichloroacetimidate (10) and methyl
D
a
D
2,3,6 - tri - O - benzyl - a -
D
- galactopyranoside
(14).7 The trichloroacetimidate 10 was synthe-
sized in five steps from glucose in 31% overall
yield as illustrated in Scheme 1. The synthesis
of 2,3-di-O-benzyl-4.6-O-benzylidene- -glu-
D
copyranose (9) was as previously described,8
with the only improvement being the use of
anhydrous formic acid as the catalyst for ben-
zylidene acetal formation9 as opposed to the
more common anhydrous ZnCl2. The conver-
sion of glucopyranose derivative 9 into the
trichloroacetimidate 10 was based on a proce-
dure for similar glucopyaranoses.7 Improve-
ments to the literature procedure were in the
area of purification of the trichloroacetimi-
date. Firstly, centrifugation of the reaction
instead of filtration was used to remove the
K2CO3. Secondly, the addition of triethy-
lamine to the chromatography solvent vastly
improved the stability of the trichloroacetimi-
date on silica gel. These changes improved the
yield of the trichloroacetimidate 10 from
about 60 to 87%.
The selectively protected galactopyranoside
14 was synthesized from methyl a- -galac-
D
Scheme 1.

L.J. Liotta et al. / Carbohydrate Research 331 (2001) 247–253
249
as the catalyst for the benzylidene acetal for-
mation. In both this synthesis and the synthe-
sis of 10 above, using anhydrous formic as the
catalyst for benzylidene acetal formation gave
much higher yields than the traditional cata-
lyst. In addition, the reactions with formic
acid were faster (30 min compared to 2 days)
and more easily purified.
The t-butyldimethylsilyl trifluoromethane-
sulfonate catalyzed coupling of 10 and 14 gave
the protected a-disaccharide 15 in 90% yield
and its b isomer 16 in 9% yield (Scheme 3). As
described by Wegmann and Schmidt,7 the
high yield and stereoselectivity are as expected
for a glycosidic bond formation taking place
in ether as opposed to the more common
dichloromethane, particularly with a weakly
reactive glycosyl acceptor such as galactopyra-
noside 14. The a isomer was verified by the
Scheme 2.
1
presence of a doublet in the H NMR at 4.94
ppm with a coupling constant of 4.2 Hz,
corresponding to the anomeric hydrogen on
the glucopyranoside. In addition, the 13C
NMR had a peak at 100.39 ppm correspond-
ing to the anomeric carbon of the a configura-
tion.11 The b isomer was verified by the
presence of a 13C NMR peak at 103.49 ppm
for the anomeric carbon11 and the absence of
a peak corresponding to the anomeric proton
of the a isomer, since the anomeric proton of
the b isomer was obscured by the benzyl
protons.
Scheme 3.
Disaccharide 15 was deprotected by hy-
drogenolysis (H2, Pd/C) to give the desired
methyl a-
D
-glucopyranosyl-(1“4)-a- -galac-
D
topyranoside (1) in 91% yield. Disaccharide 1
had identical physical and spectral characteris-
tics as those previously reported.11 Alterna-
tively, treatment of disaccharide 15 with
NaBH3CN and HCl in THF–ether resulted in
the selectively deprotected derivative 2 in 63%
yield (Scheme 4). The selective deprotection
was verified by the loss of the benzylidene
proton peak at 5.52 ppm and the appearance
of two doublets at 4.38 and 4.22 ppm corre-
sponding to the hydrogens of the 6%-O-benzyl
ether. The structure of compound 2 was also
supported by the disappearance of the benzyl-
idene peak at 99.0 ppm in the 13C NMR
spectrum and the appearance of an OꢀH
stretch at 3350–3600 cm−1 in the IR
spectrum.
Scheme 4.
topyranoside (11) in three steps in 56% overall
yield as illustrated in Scheme 2. This synthesis
was as previously described10 except anhy-
drous formic acid was used instead of ZnCl2

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L.J. Liotta et al. / Carbohydrate Research 331 (2001) 247–253
The 4-hydroxyl group of compound 2 was
Dichloromethane was distilled from CaH2.
Trichloroacetonitrile was distilled from P2O5.
Anhyd K2CO3 was dried at 60 °C for 2 days in
a vacuum oven before use. All other solvents
and reagents were used without further purifi-
cation. The 2,3-di-O-benzyl-4,6-O-benzyli-
oxidized under Swern conditions (DMSO, ox-
alyl chloride, Et3N) giving ketone 3 in 87%
yield (Scheme 4).12 Both the IR spectrum
(CꢁO stretch at 1730 cm−1) and the 13C NMR
spectrum (new CꢁO carbon at 205.0 ppm)
verified the success of this reaction. In addi-
tion, the H-4% proton of compound 2 was no
longer observed, and the H-3% and H-5% peaks
both shifted downfield. H-3% was observed as a
doublet at 4.35 ppm, while H-5% was part of a
multiplet at ꢀ4.7 ppm. A small amount of
material (ꢀ11%), which has tentatively been
identified as the compounds resulting from
isomerization a to the carbonyl group, has
also been isolated. The benzyl protecting
groups were removed from compound 3 by
catalytic hydrogenolysis (H2, Pd/C) giving the
desired keto-disaccharide 4 in quantitative
yield. Preliminary proton NMR studies indi-
cated that over time, isomerization occurs at
C-3% and C-5% and that H-3% and H-5% exchange
with deuterium (75% exchange in 2.5 days).
The overall yield of disaccharide 1 was 51%
from the starting methyl galactopyranoside
11, while that of the keto-disaccharide 4 was
31%. Compounds 2 and 3, the potential inter-
mediates to more elaborate compounds, were
produced in 35 and 31% overall yields, respec-
tively. Thus, the described work provides a
high-yielding synthesis of these biochemically
important compounds.
dene-D-glucopyranose (9) was prepared as
previously described.8 Likewise, the methyl-
2,3,6-tri-O-benzyl-a, -galactopyranoside (14)
D
was prepared as previously described.10 In
both syntheses, the 4,6-benzylidene acetal
derivatives were prepared using anhyd formic
acid as the catalyst.
2,3-Di-O-benzyl-4,6-O-benzylidene- -glu-
D
copyranosyl trichloroacetimidate (10).—To a
stirring solution of glucopyranose 9 (3.0 g,
6.70 mmol) in CH2Cl2 (225 mL) were added
sequentially anhyd K2CO3 (33 g, 23 mmol)
and CCl3CN (33 mL, 329 mmol). The reaction
was stirred under N2 for 16 h at rt. The
reaction mixture was centrifuged to remove
the K2CO3. The K2CO3 pellet was washed
with CH2Cl2 (2×100 mL). The washes were
combined with the original CH2Cl2 superna-
tant and evaporated to an oil. This oil was
purified by chromatography eluting the
column with 100:5:1 CH2Cl2–CH3CN–tri-
ethylamine to give trichloroacetimidate 10
(3.44 g, 87%) and recovered starting material
9 (332 mg, 11%). 10: Rf 0.8 (100:5:1 CH2Cl2–
CH3CN–triethylamine); IR (neat): 3330 cm−1
(NꢀH stretch), 3000–3100 cm−1 (ar CꢀH
stretch), 2850–2990 cm−1 (satd CꢀH stretch),
1
1670 cm−1 (CꢁN stretch); H NMR (CDCl3):
l 8.72 (s, 0.5 H, b-NH), 8.61 (s, 0.5 H, a-NH),
7.53–7.21 (m, 15 H, Ar), 6.43 (d, 0.5 H, J1,2
3.7 Hz, a-H-1), 5.93 (d, 1 H, J1,2 7.4 Hz,
b-H-1), 5.57 (s, 1 H, PhCH), 4.96–4.73 (m, 4
H, 2×PhCH2O), 4.41 (dd, 0.5 H, J5,6a 5.0,
J6b,6a 10.3 Hz, b-H-6a), 4.31 (dd, 0.5 H, J5,6a
5.0, J6b,6a 10.3 Hz, a-H-6a), 4.12 (t, 0.5 H,
J2,3,4 9.3 Hz, b-H-3), 4.03 (dt, 0.5 H, J4,5,6b 10.0
Hz, b-H-5), 3.88–3.61 (m, 4 H, H-2, a-H-3,
H-4, a-H-5, H-6b). 13C NMR (CDCl3): l
161.7, 161.4, 138.9, 138.7, 138.3, 138.2, 137.5,
137.5, 129.4, 128.7, 128.7, 138.6, 128.4, 128.3,
128.2, 128.1, 128.1, 128.0, 126.4, 126.4, 101.6,
98.6, 95.0, 81.8, 81.5, 81.3, 81.0, 79.0, 78.4,
75.6, 75.6, 75.4, 73.7, 69.1, 69.0, 67.0, 65.4;
Anal. Calcd for C29H28Cl3NO6: C, 58.75; H,
4.76; N, 2.36. Found: C, 59.13; H, 4.65; N,
2.25.
3. Experimental
General methods.—Optical rotations were
measured with a Perkin–Elmer 141 polarime-
ter. NMR spectra were recorded with a
Bruker 300 MHz Aspect 3000 spectrometer.
NMR spectra were run in either CDCl3 using
tetramethylsilane (TMS) as an internal stan-
dard or in D2O using 3-(trimethylsi-
lyl)propanoate (TSP) as the internal standard.
Column chromatography was performed on
,
KP-Sil™ silica gel (32–63 mm, 60 A) using
Biotage prepacked columns and the Biotage
Flash 12i+40i™ chromatography system. IR
spectra were obtained on a Perkin–Elmer
1310 IR spectrometer. Diethyl ether was dis-
tilled from sodium benzophenone ketyl.

L.J. Liotta et al. / Carbohydrate Research 331 (2001) 247–253
251
3000–3100 cm−1 (ar CꢀH stretch), 2850–2990
Methyl 2,3-di-O-benzyl-4,6-O-benzylidene-
-glucopyranosyl-(1“4)-2,3,6-tri-O-ben-
zyl-h- -galactopyranoside (15).—Glucosyl-
1
cm−1 (satd CꢀH stretch); H NMR (CDCl3):
h-
D
l 7.56–7.18 (m, 30 H, Ar), 5.59 (s, 1 H,
PhCH), 5.10 (d, 1 H, J 9.6 Hz, 0.5×
PhCH2O), 5.09 (d, 1 H, J 9.6 Hz, 0.5×
PhCH2O), 4.93 (d, 1 H, J 12.0 Hz,
0.5×PhCH2O), 4.91 (d, 1 H, J 11.5 Hz, 0.5×
PhCH2O), 4.83–4.72 (m, 4 H, PhCH2O, H-1,
H-1%), 4.66 (d, 1 H, J 11.8 Hz, 0.5×PhCH2O),
4.63 (d, 1 H, J 11.9 Hz, 0.5×PhCH2O), 4.56
(d, 1 H, J 11.9 Hz, 0.5×PhCH2O), 4.40 (d, 1
H, J 12.2 Hz, 0.5×PhCH2O), 4.27 (m, 1 H,
H-4), 4.25 (dd, 1 H, J5%,6e% 5.0, J6e%,6a% 10.5 Hz,
H-6e%), 4.01–3.97 (m, 3 H, H-5, H-6a, H-6b),
3.80–3.63 (m, 5 H, H-2, H-3, H-3%, H-4%,
H-6a%), 3.50 (t, 1 H, J1%,2%,3% 8.0 Hz, H-2%), 3.45
(s, 3 H, OCH3), 3.34 (ddd, J4%,5% 10.0, J5%,6a% 10.0
D
trichloroacetimidate 10 (2.76 g, 4.65 mmol)
and the 4-O-deprotected galactoside 14 (1.34
g, 2.88 mmol) were dissolved in Et2O (63 mL).
While the reaction was stirred at rt under N2,
tert-butyldimethylsilyl
trifluoromethanesul-
fonate (0.355 mL, 1.55 mmol) was added by
syringe. After stirring for 2.5 h at rt, the
reaction was quenched by adding excess solid
NaHCO3. The reaction was washed with satd
aq NaHCO3 (65 mL). The NaHCO3 layer was
subsequently extracted with Et2O (3×75 mL).
The ether layers were combined, dried over
Na2SO4, decanted, and evaporated to an oil.
The oil was chromatographed through silica
gel eluting with a solvent gradient of 40:30:1–
40:30:4 CH2Cl2–hexane–EtOAc resulting in
the a-disaccharide 15 (2.32 g, 90%) and the
b-disaccharide 16 (0.23 g, 9%). 15: [h]D28
+49.6° (c 2.7, CH2Cl2); Rf 0.33 (40:30:3
CH2Cl2 –hexane–EtOAc); IR (neat): 3000–
3100 cm−1 (Ar CꢀH stretch), 2850–2990
13
Hz, H-5%); C NMR (CDCl3): l 139.2, 139.1,
139.0, 138.8, 138.7, 137.7, 129.3, 128.8, 128.7,
128.6, 128.6, 128.6, 128.5, 128.4, 128.3, 128.2,
128.1, 128.1, 128.0, 127.9, 127.8, 127.7, 127.7,
126.4, 103.5, 101.5, 99.0, 82.7, 81.9, 81.1, 78.9,
77.4, 75.3, 75.0, 74.0, 74.0, 73.8, 73.7, 70.3,
69.7, 69.1, 66.1, 55.7.
1
cm−1 (satd CꢀH stretch); H NMR (CDCl3):
Preparation of methyl h-
(1“4)-h- -galactopyranoside (1).—Protected
D
-glucopyranosyl-
l 7.37–7.17 (m, 30 H, Ar), 5.52 (s, 1 H,
PhCH), 4.95 (d, 1 H, J 10.7 Hz, 0.5×
PhCH2O), 4.94 (d, 1 H, J1%,2% 4.2 Hz, H-1%),
4.88 (d, 1 H, J 12.2 Hz, 0.5×PhCH2O), 4.87
(d, 1 H, J 11.8 Hz, 0.5×PhCH2O), 4.79 (s, 2
H, PhCH2O), 4.76 (non-first order ABq, 2 H,
PhCH2O), 4.69 (d, 1 H, J 11.8 Hz, 0.5×
PhCH2O), 4.69 (d, 1 H, J1,2 3.4 Hz, H-1), 4.32
(dd, 1 H, J5%,6e% 4.8, J6e%,6a% 9.9 Hz, H-6e%), 4.25
(non-first order ABq, 2 H, PhCH2O), 4.07 (m,
1 H, H-4), 4.01 (t, 1 H, J2%,3%,4% 9.3 Hz, H-3%),
3.95 (dd, 1 H, J5,6a 3.4, J6a,6b 10.3 Hz, H-6a),
3.92–3.82 (m, 2 H, H-5, H-5%), 3.81 (dd, 1 H,
J5,6b 4.9 Hz, H-6b), 3.61 (t, 1 H, J3%,4%,5% 9.5 Hz,
H-4%), 3.57 (dd, 1 H, J5%,6b% 3.7 Hz, H-6b),
3.53–3.46 (m, 3 H, H-3, H-2, H-2%), 3.36 (s, 3
D
disaccharide 15 (0.171 g, 0.191 mmol) was
dissolved in reagent-grade alcohol (6 mL).
Pd/C (ca. 20 mg, 10%) was added to the
solution. The reaction was flushed with H2,
then stirred at rt under an H2 atmosphere for
16 h. The mixture was filtered through a plug
of Celite on glass wool. The residue was rinsed
with EtOH (3×1.5 mL). The filtrate and
rinses were combined and evaporated to dry-
ness. The resulting white solid was dissolved
in water (5 mL) and washed with CH2Cl2
(2×3 mL). The CH2Cl2 extracts were com-
bined and extracted once with water (1 mL).
The water fractions were combined and evap-
orated to dryness giving disaccharide 1 (62
13
H, OCH3); C NMR (CDCl3): l 138.8, 138.5,
mg, 91%) as an amorphous powder. 1: [h]D26
26
138.3, 138.2, 137.7, 128.7, 128.4, 128.4, 128.3,
128.3, 128.2, 128.1, 128.0, 127.9, 127.7, 127.6,
127.5, 127.5, 127.5, 127.3, 126.0, 101.0, 100.4,
99.0, 82.8, 79.6, 79.1, 77.7, 77.2, 75.1, 74.3,
74.2, 73.4, 72.9, 72.8, 69.2, 68.9, 68.0, 63.0,
55.3; Anal. Calcd for C55H58O11: C, 73.81; H,
6.53. Found: C, 73.73; H, 6.54.
+195.6° (c 1.03, water), lit.6 +116.1°; [h]
578
+203.2° (c 1.03, water), lit.4 +210°; Rf 0.55
(1:1 CH2Cl2–CH3OH); IR (Nujol): 3100–3600
cm−1 (OꢀH stretch), 2850–2990 cm−1 (satd
1
CꢀH stretch); H NMR (D2O): l 4.93 (d, 1 H,
J1%,2% 3.8 Hz, H-1%), 4.90 (d, 1 H, J1,2 2.9 Hz,
H-1), 4.12 (dt, 1 H, J4%,5 10.2, J5%,6% 3.3 Hz,
H-5%), 4.06 (m, 1 H, H-4), 4.03–3.79 (m, 7 H,
H-2, H-3, H-5, H-6a, H-6b, H-6a%, H-6b%),
16: [h]2D8 +29.4° (c 2.3, CH2Cl2); Rf 0.20
(40:30:3 CH2Cl2–hexane–EtOAc); IR (neat):

252
L.J. Liotta et al. / Carbohydrate Research 331 (2001) 247–253
128.2, 127.8, 127.7, 127.7, 127.7, 127.6,127.5,
127.4, 127.3, 127.3, 99.5, 98.8, 81.6, 80.0, 77.7,
76.5, 75.1, 75.0, 73.6, 73.4, 73.3, 72.9, 72.7,
71.6, 70.2, 69.2, 69.0, 68.0, 55.2; Anal. Calcd
for C55H60O11: C, 73.64; H, 6.74. Found: C,
73.52; H, 6.62.
3.74 (t, 1 H, J2%,3%,4% 9.8 Hz, H-3%), 3.55 (dd, 1
H, H-2%), 3.46 (t, 1 H, H-4%), 3.43 (s, 3 H,
OCH3); C NMR (D2O): l 103.0, 102.3, 81.4,
75.5, 74.8, 74.6, 74.0, 72.1, 71.8, 71.1, 63.3,
62.9, 58.0; Anal. Calcd for C13H24O11: C,
43.82; H, 6.79. Found: C, 43.3; H, 6.36.
13
Methyl 2,3,6-tri-O-benzyl-h-
ulopyranosyl-(1“4)-2,3,6-tri-O-benzyl-h-
galactopyranoside (3).—A solution
D-xylo-hex-4-
Methyl 2,3,6-tri-O-benzyl-h-
osyl-(1“4)-2,3,6-tri-O-benzyl-h-
D
-glucopyran-
D
of
-
D
-galacto-
pyranoside (2).—To benzylidene-protected
disaccharide 15 (2.02 g, 2.26 mmol) was added
dimethyl sulfoxide (410 mL, 5.77 mmol) in
CH2Cl2 (1.5 mL) was added dropwise to a
solution of oxalyl chloride (193 mL, 2.21
mmol) in CH2Cl2 (6 mL) that had been pre-
cooled to −60 °C. The resulting reaction mix-
ture was stirred under N2 at −60 °C for 10
min. The 4-unprotected disaccharide 2 (1.088
g, 1.21 mmol) was dissolved in CH2Cl2 (3
mL). The resulting solution was added drop-
wise to the −60 °C reaction mixture. After 15
min at −60 °C, triethylamine (2 mL, 14.3
mmol) was added, and the reaction was al-
lowed to warm to rt. The reaction mixture was
diluted with water (200 mL) and extracted
with CH2Cl2 (4×175 mL). The CH2Cl2 ex-
tracts were combined, dried over Na2SO4, de-
canted and evaporated to a viscous oil. The
oil was chromatographed through silica gel
eluting with 4:1 hexane–EtOAc, yielding the
desired keto-disaccharide 3 (0.94 g, 87%). 3:
[h]2D9 +100.8° (c 3.70, CH2Cl2); Rf =0.55 (2:1
hexane–EtOAc); IR (neat): 3000–3100 cm−1
(ar CꢀH stretch), 2850–2990 cm−1 (satd CꢀH
,
3 A molecular sieves, followed by 1 M
NaBH3CN in THF (31 mL, 3.1 mmol,
Aldrich). The mixture was stirred at rt under
N2 while 1 M HCl in ether (33 mL, 3.3 mmol,
Aldrich) was added dropwise. When the addi-
tion was complete, the reaction mixture was
decanted and the sieves and flask rinsed with
1:1 CH2Cl2–water (2×60 mL). The rinse and
reaction solutions were combined, and the
CH2Cl2 was removed. The aqueous layer was
extracted with CH2Cl2 (50 mL). The combined
CH2Cl2 extracts were washed with satd aq
NaHCO3 (100 mL). The NaHCO3 wash was
subsequently extracted with CH2Cl2 (50 mL).
The CH2Cl2 fractions were combined, dried
over Na2SO4, decanted and evaporated to a
yellow oil. The oil was chromatographed
through silica gel, eluting with 5:9:2 CH2Cl2–
hexane–EtOAc, yielding the desired disaccha-
ride 2 (1.27 g, 63%). 2: [h]2D9 +73.1° (c 2.86,
CH2Cl2); Rf 0.38 (5:9:2 CH2Cl2–hexane–
EtOAc); IR (neat): 3350–3600 cm−1 (OꢀH
stretch), 3000–3100 cm−1 (ar CꢀH stretch),
2850–2990 cm−1 (satd CꢀH stretch); 1H
NMR (CDCl3): l 7.37–7.17 (m, 30 H, Ar),
4.99 (d, 1 H, J1%,2% 3.3 Hz, H-1%), 4.92 (d, 1 H,
J 11.2 Hz, 0.5×PhCH2O), 4.85 (d, 1 H, J
12.2 Hz, 0.5×PhCH2O), 4.78 (d, 1 H, J 11.3
Hz, 0.5×PhCH2O), 4.77 (d, 1 H, J 11.9 Hz,
0.5×PhCH2O), 4.75–4.64 (m, 5 H, 2×
PhCH2O, H-1), 4.38 (d, 1 H, J 12.2 Hz,
0.5×PhCH2O), 4.25 (non-first order ABq, 2
H, PhCH2O), 4.22 (d, 1 H, J 12.3 Hz, 0.5×
PhCH2O), 4.19–4.10 (m, 1 H, H-5%), 4.08 (m,
1 H, H-4), 3.98–3.73 (m, 6 H, H-2, H-3, H-5,
H-6a, H-3%, H-6a%), 3.53–3.46 (m, 2 H, H-6b,
H-6b%), 3.36 (s, 3 H, OCH3), 3.33–3.27 (m, 1
H, H-4%), 3.16 (dd, 1 H, J1%,2% 3.9, J2%,3% 10.2 Hz,
H-2%); 13C NMR (CDCl3): l 138.9, 138.8,
138.7, 138.5, 138.1, 138.0, 128.3, 128.3, 128.2,
1
stretch), 1730 cm−1 (CꢁO stretch); H NMR
(CDCl3): l 7.44–7.17 (m, 30 H, Ar), 5.21 (d, 1
H, J1%,2% 3.1 Hz, H-1%), 5.03 (d, 1 H, J 10.9 Hz,
0.5×PhCH2O), 4.82 (d, 1 H, J 11.9 Hz, 0.5×
PhCH2O), 4.79–4.67 (m, 6 H, 2×PhCH2O,
H-1, H-5%), 4.64 (d, 1 H, J 11.9 Hz, 0.5×
PhCH2O), 4.62 (d, 1 H, J 10.9 Hz, 0.5×
PhCH2O), 4.40 (non-first order ABq, 2 H,
PhCH2O), 4.35(d, 1 H, J2%,3% 10.5 Hz, H-3%),
4.27 (s, 2 H, PhCH2O), 4.21 (m, 1 H, H-4),
4.00–3.79 (m, 5 H, H-2, H-3, H-5, H-6a,
H-6a%), 3.53–3.46 (m, 2 H, H-6b, H-6b%), 3.36
(s, 3 H, OCH3), 3.26 (dd, 1 H, H-2%); 13C
NMR (CDCl3): l 205.0, 139.1, 138.8, 138.7,
129.1, 129.0, 128.9, 128.8, 128.7, 128.7, 128.5,
128.4, 128.4, 128.3, 128.2, 128.1, 128.1, 100.1,
99.2, 83.2, 80.3, 78.2, 77.9, 75.7, 75.6, 75.2,
74.7, 74.3, 73.8, 73.7, 73.5, 69.6, 68.2, 68.2,
56.0; Anal. Calcd for C55H58O11: C, 73.81; H,
6.53. Found: C, 73.42; H, 6.52.

L.J. Liotta et al. / Carbohydrate Research 331 (2001) 247–253
253
h-
D
-xylo-Hex-4-ulopyranosyl-(1“4)-h-
D
-
from Research Corporation. This research
was partially supported by the Stonehill Un-
dergraduate Research Experience (SURE)
program. B.M.H. thanks DuPont for an un-
dergraduate summer fellowship (Educational
Aid Grant). P.J.K. thanks Pfizer Central Re-
search for a 1997 Pfizer Undergraduate Sum-
mer Fellowship. A.M.K. and S.T. thank the
Northeastern Section of the ACS for 1995 and
1996 James Flack Norris and Theodore
William Richards Undergraduate Research
Summer Scholarships, respectively. We are
grateful to Providence College for the use of
their polarimeter. We are also indebted to Dr
S.M. Adamus of Providence College for her
valuable comments.
galactopyranoside (4).—Protected keto-disac-
charide 3 (0.163 g, 0.182 mmol) was dissolved
in reagent alcohol (6 mL). Pd/C (ca. 40 mg,
10%) was added to the solution. The reaction
was flushed with H2, then stirred at rt under
an H2 atmosphere for 21 h. The mixture was
filtered through a plug of Celite on glass wool.
The residue was rinsed with EtOH (3×1.5
mL). The filtrate and rinses were combined
and evaporated to dryness. The resulting
white solid was dissolved in water (5 mL) and
washed with CH2Cl2 (2×3 mL). The CH2Cl2
was combined and extracted once with water
(1 mL). The water fractions were combined
and evaporated to dryness giving disaccharide
4 (64 mg, 99.5%) as an amorphous powder. 4:
[h]2D6 +204.8° (c 1.07, water); [h]
+212.7°
26
578
(c 1.07, water); Rf 0.54 (1:1 CH2Cl2–CH3OH);
IR (Nujol): 3100–3600 cm−1 (OꢀH stretch),
2850–2990 cm−1 (satd CꢀH stretch), 1725
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1
cm−1 (CꢁO stretch); H NMR (D2O): l 5.17
(m, 1 H, H-5%) 4.97 (d, 1 H, J1%,2% 3.7 Hz, H-1%),
4.90 (d, 1 H, J1,2 2.5 Hz, H-1), 4.61 (d, 1 H,
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Acknowledgements
This research was supported by an award
.