A new glycosidation method through nitrite displacement on substituted nitrobenzenes

Article abstract of DOI:10.1016/j.carres.2006.11.017

Benzyl, benzoyl, and acetyl protected 1-OH and 1-SH glycoses in the glucose, glucosamine, galactose, mannose, and lactose series react with nitrobenzenes activated by one or two electron withdrawing substituents like nitro and cyano to afford the correspo

Full text of DOI:10.1016/j.carres.2006.11.017

Carbohydrate Research 342 (2007) 440–447
A new glycosidation method through nitrite displacement
on substituted nitrobenzenes
´
*
*
Xavier Alvarez-Mic o´ , Mario J. F. Calvete, Michael Hanack and Thomas Ziegler
Institute of Organic Chemistry, University of Tuebingen, Auf der Morgenstelle 18, 72076 Tuebingen, Germany
Received 4 September 2006; received in revised form 13 November 2006; accepted 15 November 2006
Available online 21 November 2006
Dedicated to the memory of Professor Nikolay K. Kochetkov
Abstract—Benzyl, benzoyl, and acetyl protected 1-OH and 1-SH glycoses in the glucose, glucosamine, galactose, mannose, and lac-
tose series react with nitrobenzenes activated by one or two electron withdrawing substituents like nitro and cyano to afford the
corresponding aryl glycosides in 50–100% yield. The S Ar displacement of nitrite by 1-OH glycoses is reversible and gives predom-
N
inantly the a-glycosides, whereas 1-SH glycoses do not anomerize and afford the b-glycosides. Thus, the prepared dicyanophenyl
gycosides are useful building blocks for the preparation of phthalocyanine-glycoconjugates via template synthesis.
ꢀ
2006 Elsevier Ltd. All rights reserved.
Keywords: Glycosylation; Aryl glycosides; Nucleophilic substitution
1
. Introduction
carbohydrate chemistry today. Although great achieve-
ments in the development of versatile and efficient glyco-
sylation and building block strategies have been made
during the last years, there is still need for more efficient
Carbohydrates habitually exist on cell surfaces as glyco-
proteins or glycolipid conjugates and are engaged in
important functional and structural functions in various
biological recognition processes like for instance, cancer
metastasis, inflammatory response, innate and adaptive
immunity, viral and bacterial infections, and many other
receptor-mediated signalling processes. Moreover, a
large number of natural products require glycosylation
in order to show proper biological performance.
However, the effect of glycosylation on the structure
and function of natural products is not well understood,
mostly due to the lack of efficient synthesis methods to
cover the structural diversity of glycoconjugates re-
quired for answering the distinct role of glycosylation
in biological systems.
Selective glycosidic bond formation in order to gain
chemically well defined oligosaccharides and glycocon-
jugates is probably the most significant challenge of
6
–9
procedures to prepare glycoconjugates.
The basic concepts of glycosylation embrace either
formation of the glycosidic bond through classical Koe-
nigs–Knorr type reactions where the anomeric oxygen
originates from the aglycon or through retention of
the anomeric oxygen via anomeric O-arylation or O-
alkylation reactions. The latter methodology is based
on deprotonation of the anomeric hydroxyl of sugars,
thus, generating an anomeric oxide. Immediate O-aryl-
ation or O-alkylation leads to the glycoside bond. This
method turned out to be extremely important for the
1
,2
3
–5
1
0–12
synthesis of a variety of glycosides.
Nevertheless,
this methodology has limited general applicability to
the synthesis of glycoconjugates.
Recently, we found a novel straightforward and effi-
cient template synthesis of phthalocyanine-glycoconju-
gates from dicyanophenyl glycosides which enabled us
to prepare a series of water soluble phthalocyanines
*
Corresponding authors. Tel.: +49 7071 297 8763; fax: +49 7071 295
44 (T.Z.); e-mail: thomas.ziegler@uni-tuebingen.de
1
3,14
suitable for photodynamic therapy (Chart 1).
For
2
0
008-6215/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2006.11.017

ꢀ
X. Alvarez-Mic o´ et al. / Carbohydrate Research 342 (2007) 440–447
441
1
4
Chart 1. Synthesis of phthalocyanine-glycoconjugates from dicyanophenyl glycosides.
further studies on phthalocyanine-glycoconjugates, we
needed a versatile route to dicyanophenyl glycosides
for which we present a novel preparation through nucleo-
philic nitrite displacement of nitrobenzenes by anomeric
glycosyl oxides (O-arylation of sugars).
coses with 3,4-dicyanophenol also failed (experimental
details not shown here).
Next, we turned our efforts to the nucleophilic dis-
placement of nitrite from activated substituted benzenes
2 (Scheme 1), a method that has already been widely
2
9
used for the synthesis of oxoaryl phthalonitriles. Base
promoted direct anomeric O- or S-arylation of several
2,4,5,6-tetra-O-benzyl, benzoyl, and acetyl protected
hexopyranoses and 1-thio-hexopyranoses 1 to give aryl
glycosides 3 was carried out either with NaH or
K CO (Table 1). NaH as the base resulted in signifi-
2
. Results and discussion
Base promoted direct anomeric O-arylation of protected
sugars has been investigated by several authors.
1
5–18
2
3
These methods take advantage of the excellent leaving
group character of fluoride in substituted, fluorinated
nitro- or dinitrobenzenes, resulting in fairly good yields
of mainly b-O-aryl glycosides. However, similar O-aryl-
ations of glycoses by nitrite substitution on nitrobenz-
enes are not described in the literature yet.
cantly shorter reaction times, compared to K CO as
2 3
the base (approximately 1 h vs 10–12 h).
The main products in the case of 3a–c were the respec-
tive a-anomers independent from the base. Similar unex-
pected results were also observed previously in anomeric
O-arylations and were attributed to the formation of the
thermodynamically favored a-anomers during reversible
S Ar reactions in polar aprotic solvents like Me SO or
In general, nucleophilic displacement of a nitro group
from an activated aromatic substrate can be effectively
achieved by a variety of strong nucleophiles under dipo-
N
2
1
5
DMF in the presence of a base. No such thermody-
namic equilibration can take place in case of thionucleo-
philes 1d and 1f, respectively, and thus resulting in the
exclusive formation of the b-linked products 3d and 3f
(Table 1, entries 4 and 6).
1
9–21
lar aprotic conditions. For example, alcoholates,
thiolates,
1
9,22
19
and sulfinates efficiently effect displace-
ment of a nitrite group from carbonyl, nitro, cyano, sul-
fone, and aryl activated substrates in DMF, Me SO, or
2
1
9–23
HMPA at room temperature.
Furthermore, nitrite
For 1e (Table 1, entry 5), the obtained product was
also the b-anomer 3e, probably due to the fact that
although 1e is an O-nucleophile, it is sterically hindered
by the presence of the bulky phthalimido group at posi-
tion 2 which, furthermore, strongly promotes the forma-
tion of the b-anomeric linkage. Anomeric mixtures were
separated by preparative HPLC for determining the
anomeric ratio and all anomers were unambiguously
assigned by NMR spectroscopy, which showed the
typical vicinal coupling constants between H-1 and
H-2 significant for the presence of a- or b-anomers
(see Section 3).
is comparable to fluoride regarding its nucleofugicity
2
4
in S Ar reaction.
N
First, we tried to prepare 3,4-dicyanophenyl glucose
derivatives 3 by classical Koenigs–Knorr type glycosyl-
ation reactions of 3,4-dicyanophenol with penta-O-ace-
2
5
tyl-glucose under activation with BF –etherate and
3
2
6
p-toluenesulfonic acid, respectively, or by TMS–tri-
flate activation of 2,3,4,5-tetra-O-benzoyl-D-glucose tri-
chloroacemidate. However, none of these methods
were successful. Similarly, Mitsunobu-type conditions
for condensing various anomerically unprotected gly-
2
7
2
8

ꢀ
442
X. Alvarez-Mic o´ et al. / Carbohydrate Research 342 (2007) 440–447
Scheme 1. Synthesis of dicyanophenyl carbohydrate derivatives.
Table 1. Reactions between 1a–f and 4-nitrophthalonitrile 2a
no reaction took place whereas at elevated temperatures
decomposition of the starting materials occurred. Solely
NaH as the base gave the desired substitution products
at room temperature (Table 2).
The significantly lower anomeric selectivity for O-aryl-
ations with less activated nitrobenzenes 2b and 2c
Entry Conditions
Product Yield (%) Ratio a:b
1
2
3
4
5
6
DMF, NaH, 1 h
3a
, 15 h 3b
, 15 h 3c
, 15 h 3d
, 15 h 3e
, 15 h 3f
99
99
99
99
50
99
9:1
10:1
10:1
0:1
0:1
0:1
DMF, K
DMF, K
DMF, K
DMF, K
DMF, K
2
2
2
2
2
CO
CO
CO
CO
CO
3
3
3
3
3
(
Table 2, entries 1, 2, 4, and 5) can be explained in terms
of a slower equilibration between the a- and b-anomer
compared to the phthalodinitrile aglycon under similar
reaction conditions. In case of the mannose nucleophile
1h, only a-anomers 4c and 5c were found due to the ste-
ric effect in mannose.
In summary, anomeric O-arylation of partially pro-
tected glycoses by nucleophilic nitrite substitution on
nitrobenzenes is a practical alternative to similar O-aryl-
ations using fluorobenzenes when the benzene moiety is
Additionally, we investigated this efficient glycosyl-
ation method for other substrates as well, namely o-dini-
trobenzene 2b and p-nitrobenzonitrile 2c (Scheme 2).
Due to the nucleophilicity of the carbohydrate moieties,
we expected that the nitrite-substitution would also
work well in the case of substituted phenyl compounds
having only one additional electron withdrawing group.
However, S Ar reactions in DMF using K CO or
activated for S
Ar reactions by at least two electron
N
N
2
3
DBU as base failed completely. At room temperature,
withdrawing groups. The anomeric selectivity for nucleo-
Scheme 2. Synthesis of nitrophenyl and cyanophenyl carbohydrate derivatives.

3.2. 3,4-Dicyanophenyl 2,3,4,6-tetra-O-benzyl-D
pyranoside (3a)
-gluco-
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X. Alvarez-Mic o´ et al. / Carbohydrate Research 342 (2007) 440–447
443
Table 2. Reaction of 1a, 1g, 1h with 2b and 2c and NaH in DMF for
15 h at rt
Entry
Product
Yield (%)
Ratio a:b
1
2
3
4
5
6
4a
4b
4c
5a
5b
5c
94
92
89
82
84
84
3:1
3:1
1:0
3:1
3:1
1:0
NaH (280 mg, 7 mmol, 60% suspension in oil) was
added at rt to a stirred soln of 2,3,4,6-tetra-O-benzyl-
30
D-glucopyranose 1a (3.80 g, 7.0 mmol) and 4-nitro-
phthalonitrile 2a (1.33 g, 7.7 mmol) in dry DMF
(
25 mL) under argon. The mixture was stirred for 2 h.
At the end of this period, the reaction was poured into
water (200 mL) and CH Cl (100 mL). The aq layer
All reactions were carried out using DMF as a solvent and NaH as a
base (reaction time 15 min).
2
2
was extracted with CH Cl (3 · 50 mL). The combined
2
2
organic layers were washed with water (3 · 50 mL).
After drying (Na SO ), filtration, and removal of the
2
4
philic displacement of nitrite is comparable to the nucleo-
philic displacement of fluoride.
solvent, the crude product was purified by chromatogra-
phy on silica gel (10:1 toluene–acetone) to give 3a; 4.63 g
(
99%; a/b = 9:1).
2
D
0
a-Anomer: Colorless oil; ½aꢀ +132.7 (c 1.0, CHCl3);
1
3. Experimental
H NMR (250 MHz, CDCl ): d 3.51–3.59 (m, 1H, H-
3
6a), 3.64–3.83 (m, 5H, H-2, H-3, H-4, H-5, H-6b),
3
.1. General methods
4.08–4.18 (dd, 1H, J3–4 8.6, J3–2 9.4 Hz, H-3), 4.38–
4
.65 (m, 4H, H–CH ), 4.81–4.93 (m, 3H, H–CH ),
2
2
1
13
H and C NMR spectra were recorded with Bruker
AC 300F, Avance 400 or DRX 500 spectrometers at
5.03 (d, 1H, J 10.8 Hz, H–CH ), 5.37 (d, 1H, J
3.4 Hz, H-1), 7.23–7.44 (m, 20H, H–Ar, H-2 , H-6 ),
2
1–2
0
0
3
00, 400, or 500 MHz and 75, 100.6, or 126 MHz,
7.11–7.17 (m, 2H, H–Ar), 7.66 (d, 1H, J
0
0
8:6 Hz, H-
5
–6
0
13
respectively. Chemical shifts in CDCl are reported in
5 ); C NMR (62.9 MHz, CDCl ): d 67.9 (C-6), 71.9
3
3
d (ppm) relative to tetramethylsilane (TMS) as internal
standard. Coupling constants J are reported in hertz.
Assignment of signals was made by first order inspection
of the spectra and by H H-, C H-COSY, HMQC, or
NOESY experiments, respectively. MS spectra were re-
corded with Bruker Autoflex (MALDI-TOFMS) and
Bruker Apex II FT-ICR (FABMS) instruments. Specific
optical rotations [a] were recorded with a Perkin–Elmer
polarimeter Model 341 at 589 nm (Na-D) for solns in
(C-5), 73.5, 74.0, 75.3, 75.9 (C–CH ), 76.9 (C-2), 79.5
2
0
(C-4), 81.6 (C-3), 96.3 (C-1), 108.9 (C-4 ), 115.0 (C-
0
0
0
0
0
3 CN), 115.4 (C-4 CN), 117.5 (C-3 ), 121.4 (C-2 , C-
1
1
13
1
6 ), 127.81, 127.87, 127.91, 127.95, 128.0, 128.2,
128.46, 128.48, 128.5, 128.6 (C-2Ar, C-3Ar, C-4Ar),
0
135.2 (C-5 ), 137.5, 137.7, 137.8, 138.5 (C-1Ar), 159.7
0
+
(C-1 ); MALDI-TOFMS: m/z 689.4 [M+Na] . Anal.
Calcd for C H N O : C, 75.66; H, 5.74; N, 4.20;
4
2
38
2
6
Found: C, 75.95; H, 5.76; N, 4.30.
1
CHCl at 20 ꢁC if not stated otherwise. Elemental anal-
b-Anomer (minor byproduct): H NMR (250 MHz,
3
yses were performed with a Hekatech CHNS analysator
Euro EA 300. Melting points were determined on a
B u¨ chi SMP-20 instrument. GC was performed with
Varian/Chrompack CP 9000 and CP 9001 instruments
using Chirasil-b-Cyclodextrin columns. TLC was per-
formed on Macherey & Nagel Silica Gel SIL G/UV254
plates. Spots were detected by visual inspection of the
plates under UV light, by charring with H SO (5% in
CDCl ): d 3.58–3.78 (m, 6H, H-2, H-3, H-4, H-5, H-
3
6), 4.42–4.59 (m, 3H, H–CH ), 3.78–4.95 (m, 5H, H–
2
CH ), 5.01 (d, 1H, J
7.8 Hz, H-1), 7.13–7.43 (m,
2
1–2
0
0
22H, H–Ar, H-2 , H 6 ), 7.59 (d, 1H, J
0
0
8:6 Hz, H-
5
–6
0
13
5 ); C NMR (62.9 MHz, CDCl ): d 68.4 (C-6), 73.5,
3
75.1, 75.3 (C–CH ), 75.5 (C-5), 75.8 (C–CH ), 77.3 (C-
2
2
0
2), 81.7 (C-4), 84.5 (C-3), 100.7 (C-1), 109.1 (C-4 ),
0
0
0
115.0 (C-3 CN), 115.4 (C-4 CN), 117.4 (C-3 ), 121.1
2
4
0
0
EtOH), with KMnO (5% in water) and with I , respec-
(C-2 ), 121.7 (C-6 ), 127.5, 127.7, 127.8, 127.9, 128.0,
128.44, 128.47, 128.5, 128.8, 128.9 (C-2Ar, C-3Ar, C-
4
2
tively. Preparative column chromatography was per-
formed by eluting compounds with various mixtures of
solvents from glass columns of various sizes filled with
Macherey & Nagel Silica Gel S (0.032–0.063 mm). Solns
in organic solvents were dried with Na SO , filtered,
0
4Ar), 135.2 (C-5 ), 137.7, 137.8, 138.1 (C-1Ar), 159.9
0
+
(C-1 ); MALDI-TOFMS: m/z 689.4 [M+Na] .
3.3. 3,4-Dicyanophenyl 2,3,4,6-tetra-O-benzoyl-D-gluco-
pyranoside (3b)
2
4
and concentrated with a rotary evaporator. Anomeric
ratios were determined by HPLC on a Sykam system
using an Grom Saphir Si; 5 lm; 250 · 6 mm column.
The eluents used were n-heptane and EtOAc. Reverse
phase HPLC was performed on a Waters apparatus
K CO (5.60 g, 40.2 mmol) was added at rt to a stirred
2
3
3
1
soln of 2,3,4,6-tetra-O-benzoyl-D-glucopyranose
1b
(4.00 g, 6.7 mmol) and 4-nitrophthalonitrile 2a (1.28 g,
7.4 mmol) in dry DMF (25 mL). The mixture was stirred
overnight. At the end of this period, the mixture was
using
a
GROM SIL 120 ODS-4HE; 10 lm;
2
50 · 20 mm column.

ꢀ
444
X. Alvarez-Mic o´ et al. / Carbohydrate Research 342 (2007) 440–447
0
0
2:5; 8:6 Hz, H-5 ); C NMR (62.9 MHz, CDCl3):
5 –6
13
poured into water (200 mL) and CH Cl (100 mL). The
J
0
2
2
aq layer was extracted with CH Cl (3 · 50 mL). The or-
d 20.4 (C–CH ), 61.4 (C-6), 67.8 (C-4), 69.1 (C-5), 69.4
2
2
3
0
ganic layer was washed with water (3 · 50 mL). After
(C-3), 69.9 (C-2), 94.6 (C-1), 109.9 (C-4 ), 114.7 (C-
0
0
0
0
drying (Na SO ), filtration, and removal of the solvent,
3 CN), 115.1 (C-4 CN), 117.8 (C-3 ), 121.1 (C-6 ),
2
4
0
0
0
the crude product was purified by chromatography on
silica gel (10:1 toluene–acetone) to give 4.80 g (99%;
a/b, 9:1) of 3b.
121.5 (C-2 ), 135.4 (C-5 ), 158.9 (C-1 ), 169.4, 169.9,
170.0, 170.3 (C–CO); MALDI-TOFMS: m/z 497.23
+
[M+Na] . Anal. Calcd for C H N O : C, 55.70; H,
2
2
22
2
10
a-Anomer: white solid; mp 174–174.5 ꢁC (n-heptane-
4.67; N 5.90. Found: C, 55.50; H, 4.63; N,5.57.
b-Anomer (minor byproduct): H NMR (250 MHz,
2
0
1
1
EtOAc); ½aꢀ +98.4 (c 1.0, CHCl3);
H
NMR
D
(
250 MHz, CDCl ): d 4.38–4.58 (m, 3H, H-5, H-6),
CDCl ): d 2.02 s, 2.05 s, 2.09 s (12H, H–CH ), 3.89–
3
3
3
5
5
.44–5.52 (d, 2H, J2–1 3.7, J2–3 10.1 Hz, H-2), 5.71–
.76 (dd, 1H, J4–5 9.6, J4–3 9.9 Hz, H-4), 6.14 (d, 1H,
3.97 (m, 1H, H-5), 2.17–2.24 (m, 2H, H-6), 5.02–5.31
(m, 4H, H-1, H-2, H-3, H-4), 7.25–7.30 (dd, 1H, J
0
0
6 –2
0
J1–2 3.4 Hz, H-1), 6.27–6.39 (dd, 1H, J3–4 9.9, J3–2
1
2
2.5, J
0
0
8:6 Hz, H-6 ), 7.38 (d, 1H, J
0
0
2:5 Hz, H-
C NMR
6 –5
2 –6
0
0
13
0.1 Hz, H-3), 7.27–7.65 (m, 15H, H-2Ar, H-4Ar, H-
2 ), 7.72 (d, 1H, J
0
0
8:6 Hz, H-5 );
5
–6
0
0
0
13
, H-5 , H-6 ), 7.83–7.98 (m, 8H, H-3Ar); C NMR
(62.9 MHz, CDCl ): d 20.52 (C–CH ), 61.87 (C-6),
3 3
(
5
1
62.9 MHz, CDCl ): d 62.6 (C-6), 68.9 (C-4), 69.7 (C-
67.90 (C-2), 70.79 (C-4), 72.25 (C-3), 72.76 (C-5),
3
0
0
0
), 69.72 (C-3), 71.1 (C-2), 94.4 (C-1), 109.7 (C-4 ),
97.98 (C-1), 110.08 (C-4 ), 114.90 (C-3 CN), 115.06 (C-
0
0
0
0 0 0 0
4 CN), 117.70 (C-3 ), 121.09 (C-2 ), 121.77 (C-6 ),
14.6 (C-3 CN), 115.0 (C-4 CN), 117.7 (C-3 ), 120.9
0
0
0
0
(
1
C-2 ), 121.7 (C-6 ), 128.2, 128.3, 128.4, 128.54, 128.59,
28.6, 128.7, 129.1 (C-1Ar, C-3Ar), 129.5, 129.7, 129.9
135.21 (C-5 ), 159.26 (C-1 ), 169.06, 169.31, 170.03,
170.37 (C–CO); MALDI-TOFMS: m/z 497.23
+
(
5
C-2Ar), 133.5, 133.7, 133.8, 133.9 (C-4Ar), 135.3 (C-
[M+Na] .
0
0
), 158.6 (C-1 ), 165.3, 165.6, 165.75, 165.76 (C–CO);
+
FABMS: m/z 723.1 [M+Na] . Anal. Calcd for
C H N O : C, 69.80; H, 4.18; N, 3.88. Found: C,
3.5. 3,4-Dicyanophenyl 2,3,4,6-tetra-O-acetyl-1-thio-b-D-
glucopyranoside (3d)
4
2
30
2
10
6
9.90; H, 4.20; N, 3.79.
b-Anomer (minor byproduct): H NMR (250 MHz,
CDCl ): d 4.39–4.57 (m, 2H, H-5, H-6a), 4.64–4.71
1
Treatment of 2,3,4,6-tetra-O-acetyl-1-thio-D-glucopyra-
3
2
nose 1d (4.00 g, 11.0 mmol) and 2a (3.23 g, 18.7 mmol)
as described for 3b afforded 3d (5.48 g; 100%); white
3
(
dd, 1H, J6b–5 2.5, J6b–6a 11.8 Hz, H-6b), 5.56 (d, 1H,
J1–2 7.2 Hz, H-1), 5.69–5.82 (m, 2H, H-2, H-4), 5.94–
powder;
mp
164–165 ꢁC
(n-heptane–EtOAc);
2
0
1
6
.03 (t, 1H, J
9.1 Hz, H-3), 7.20–7.64 (m, 15H,
½aꢀ ꢁ51.0 (c 0.5, CHCl ); H NMR (250 MHz, CDCl ):
3
–2/3–4
0
D
3
3
0
0
H-2 , H-5 , H-6 , H-3Ar, H-4Ar), 8.82–8.99 (m, 8H,
d 1.98 s, 2.02 s, 2.06 s, 2.12 s (12H, H–CH ), 3.78–3.86
3
1
3
H-2Ar); C NMR (62.9 MHz, CDCl ): d 62.7 (C-6),
(m, 1H, H-5), 4.18–4.23 (m, 2H, H-6), 4.82 (d, 1H,
3
6
1
8.9 (C-4), 71.3 (C-2), 72.2 (C-3), 73.3 (C-5), 98.2 (C-
J1–2 10 Hz, H-1), 4.92–5.08 (m, 2H, H-2, H-4), 5.20–
5.30 (dd, 1H, J3–4 9.1, J3–4 9.3 Hz, H-3), 7.67–7.71 (dd,
0
0
0
), 109.9 (C-4 ), 114.7 (C-3 CN), 115.1 (C-4 CN), 117.6
0
0
0
0
(
(
C-3 ), 121.2 (C-2 ), 121.6 (C-6 ), 128.4, 128.6, 128.7
C-3Ar), 129.1 (C-1Ar), 129.6, 129.7, 129.8, 129.9 (C-
1H, J5
0
0
1, J
0
0
0
8:4 Hz, H-5 ), 7.71–7.76 (dd, 1H,
–2
5 –6
0
J6
J2
0
0
2, J
0
8.4 Hz, H-6 ), 7.86–7.88 (dd, 1H, J
2 Hz, H-2 ); C NMR (62.9 MHz, CDCl ): d
0
0
1,
–2
6 –5
2 –5
0
0
13
2
Ar), 133.5, 133.6, 133.8 (C-4Ar), 135.1 (C-5 ), 159.1
0
0
–6
3
0
(
C-1 ), 164.9, 165.2, 165.6, 165.8 (C–CO); FABMS:
20.5, 20.7, 20.8 (C–CH ), 61.9 (C-6), 67.8 (C-4), 69.4
3
+
0
m/z 723.1 [M+1] .
(C-2), 73.4 (C-3), 76.4 (C-5), 83.9 (C-1), 114.3 (C-4 ),
0
0
0
1
14.9 (C-3 CN), 115.0 (C-4 CN), 116.5 (C-3 ), 133.3
0
0
0
0
3.4. 3,4-Dicyanophenyl 2,3,4,6-tetra-O-acetyl-D-gluco-
pyranoside (3c)
(C-5 ), 134.9 (C-2 ), 135.0 (C-6 ), 140.88 (C-1 ), 169.1,
169.3, 169.9, 170.5 (C–CO); MALDI-TOFMS: m/z
+
5
13.24 [M+Na] . Anal. Calcd for C H N O S: C,
2
2
22
2
9
3
1
Treatment of 2,3,4,6-tetra-O-acetyl-D-glucopyranose
53.87; H, 4.52; N, 5.71; S, 6.54. Found: C, 53.86; H,
4.73; N, 5.33; S, 6.24.
1
c (6.0 g, 17.0 mmol) and 2a (3.23 g, 18.7 mmol) as de-
scribed for 3b afforded 8.06 g (100%; a/b = 10:1) of 3c.
a-Anomer: white solid; mp 159–160 ꢁC (n-heptane-
3.6. 3,4-Dicyanophenyl 3,4,6-tri-O-acetyl-2-desoxy-2-
phthalimido-b-D-glucopyranoside (3e)
2
0
1
EtOAc); ½aꢀ +202.0 (c 1, CHCl3);
H
NMR
D
(
(
250 MHz, CDCl ): d 2.01 s, 2.02 s, 2.03 s, 2.04 s
3
12H, H–CH ), 3.91–4.06 (m, 2H, H-5, H-6a), 4.15–
Treatment of 3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-
3
3
1
4
5
.24 (dd, 1H, J6b–5 4.9, J6b–6a 12.3 Hz, H-6b), 5.02–
.07 (dd, 1H, J2–1 3.5, J2–3 10.1 Hz, H-2), 5.08–5.18
D-glucopyranose 1e (6.5 g, 15.0 mmol) and 2a (3.23 g,
18.7 mmol) as described for 3b afforded 3e (4.25 g;
50%); white powder; mp 102–103 ꢁC (n-heptane–EtOAc);
(
dd, 1H, J4–3 9.6, J4–5 10.1 Hz, H-4), 5.57–5.67 (dd,
2
D
0
1
1
3
H, J3–4 9.6, J3–2 10.1 Hz, H-3), 5.81 (d, 1H, J1–2
½aꢀ +74.9 (c 1, CHCl ); H NMR (250 MHz, CDCl ): d
3
3
.5 Hz, H-1), 7.38–7.45 (dd, 1H, J
0
0
2:5, J
0
0
8:6 Hz,
1.87 s, 2.05 s, 2.12 s (H–CH ), 4.03–4.15 (m, 1H, H-5),
6
–2
6 –5
3
0
0
H-6 ), 7.53 (d, 1H, J2
0
0
2:5 Hz, H-2 ), 7.75 (d, 1H,
2.16–4.31 (m, 2H, H-6), 4.56–4.65 (dd, 1H, J2–1 8.8,
–6

ꢀ
X. Alvarez-Mic o´ et al. / Carbohydrate Research 342 (2007) 440–447
445
1–2
J2–3 10.6 Hz, H-2), 5.15–5.25 (dd, 1H, J4–3 9.1, J4–5
0.1 Hz, H-4), 5.78–5.88 (dd, 1H, J3–4 9.1, J3–2 10.6 Hz,
H-3), 6.11 (d, 1H, J1–2 8.8 Hz, H-1), 4.18–4.24 (dd, 1H,
(dd, 1H, J
9.6, J1-SH 9.8 Hz, H-1), 4.86 (d, 1H, J
1–2
0
0
1
7.9 Hz, H-1 ), 5.31–5.45 (m, 2H, H-2, H-3 ), 5.65–5.81
(m, 3H, H-3, H-2 , H-4 ), 7.09–7.60 (m, 21H, H-3Ar,
0 0
0
13
J
2
0
0
2, J
0
0
8:8 Hz, H-6 ), 7.33 (d, 1H, J
0
0
2 Hz, H-
H-4Ar), 7.84–8.02 (m, 14H, H-2Ar);
C NMR
6
0
–2
6 –5
2 –6
0
0
), 7.65 (d, 1H, J5
0
0
8:8 Hz, H-5 ), 7.72–7.79 (m, 2H,
(62.9 MHz, CDCl ): d 61.0 (C-6 ), 62.5 (C-6), 67.5 (C-
–6
3
1
3
0
0
0
0
H-3Ar, H-4Ar), 7.80–7.88 (m, 2H, H-2Ar, H-6Ar);
NMR (62.9 MHz, CDCl ): d 20.3, 20.6, 20.7 (C–CH ),
4.1 (C-2), 61.9 (C-6), 68.4 (C-4), 70.3 (C-3), 72.8 (C-
), 95.3 (C-1), 110.0 (C-4 ), 114.9 (C-3 CN), 115.1 (C-
CN), 117.6 (C-3 ), 121.4 (C-2 ), 121.7 (C-6 ), 123.9
C-2Ar, C-5Ar), 131.1 (C-1Ar, C-6Ar), 134.7 (C-3Ar,
C-4Ar), 135.1 (C-5 ), 159.1 (C-1 ), 169.37, 170.02,
70.43 (C–CO); MALDI-TOFMS: m/z 584.32
M+Na] . Anal. Calcd for C H N O : C, 59.89; H,
28 23 3 10
C
4 ), 69.9 (C-2 ), 71.4 (C-5 ), 71.8 (C-3 ), 73.7 (C-3),
74.1 (C-2), 75.7 (C-4), 77.5 (C-5), 78.9 (C-1), 100.9 (C-
3
3
0
5
5
4
1 ), 128.2, 128.4, 128.51, 128.55, 128.6 (C-3Ar), 129.5,
0
0
129.64, 129.67, 129.7, 129.9, 129.9 (C-1Ar, C-2Ar),
133.2, 133.4, 133.5 (C-4Ar), 164.8, 165.2, 165.3, 165.5,
165.9 (C–CO); MALDI-TOFMS: m/z 1109.65
0
0
0
0
(
0
0
+
[M+Na] . Anal. Calcd for C H O S: C, 67.39; H,
6
1
50 17
1
[
4
4.64; S, 2.95. Found: C, 67.41; H, 4.68; S, 2.80.
+
0
0
0
0
.13; N, 7.48. Found: C, 59.95; H, 4.18; N, 7.28.
3.8. 3,4-Dicyanophenyl 2,3,6,2 ,3 ,4 ,6 -hepta-O-benzyl-1-
thio-b-lactoside (3f)
0
0
0
0
3
(
.7. 2,3,6,2 ,3 ,4 ,6 -Hepta-O-benzoyl-1-thio-b-lactose
1f)
0
0
0
0
Treatment of 2,3,6,2 ,3 ,4 ,6 -hepta-O-benzoyl-1-thio-b-
lactose 1f (10.0 g, 9.2 mmol) and 2a (1.61 g, 9.3 mmol)
as described for 3b afforded 3f (11.0 g; 100%); white
A soln of lactose (6.50 g, 19 mmol) in pyridine (60 mL)
was heated at 80 ꢁC for 30 min, and on cooling, benzoyl
chloride (30 mL, 258 mmol) was added dropwise. The
reaction mixture was heated for another 2 h at 80 ꢁC
and cooled to rt. Water (10 mL) was added and after
2
0
solid; mp 134–135 ꢁC (n-heptane–EtOAc); ½aꢀ +20.6 (c
D
1
0.5, CHCl ); H NMR (250 MHz, CDCl ): d 3.64–3.84
3
3
0
0
(m, 2H, H-6 ), 3.92–4.03 (m, 2H, H-5, H-5 ), 4.12–4.21
(dd, 1H, J4–3 9.4, J4–5 9.6 Hz, H-4), 4.45–4.54 (dd,
1H, J6a–5 4.9, J6a–6b 12.3 Hz, H-6a), 4.63–4.71 (dd, 1H,
1
0 min, the mixture was poured into ice water
(
(
500 mL). The aq phase was extracted with CH Cl2
3 · 100 mL). The combined organic phases were
J6b–5 1.7,
J
12.3 Hz, H-6b), 4.90 (d, 1H,
2
6b–6a
0
J1
0
0
7:9 Hz, H-1 ), 4.99 (d, 1H, J
9.9 Hz, H-1),
–2
1–2
0
0
washed with 2 M HCl (3 · 50 mL), satd aq NaHCO3
soln (1 · 50 mL) and water (1 · 50 mL), dried (Na SO ),
filtrated, and concentrated. The intermediate octa-O-
benzoyl-lactose was used without further purification
for the next step. A soln of crude 1,2,3,6,2 ,3 ,4 ,6 -
4.34–4.45 (m, 2H, H-2, H-3 ), 4.67–4.76 (m, 2H, H-2 ,
0
H-4 ), 4.80–4.89 (t, 1H, J
9.4 Hz, H-3), 7.09–7.60
2
4
H2/H5
00 00 00
(m, 24H, H-3Ar, H-4Ar, H-2 , H-5 , H-6 ), 7.84–8.02
1
3
(m, 14H, H-2Ar); C NMR (62.9 MHz, CDCl ): d
3
0
0
0
0
0 0 0
60.9 (C-6 ), 62.1 (C-6), 67.5 (C-4 ), 69.9 (C-2 ), 70.0 (C-
0 0
2), 71.5 (C-5 ), 71.7 (C-3 ), 73.5 (C-3), 75.8 (C-4), 77.6
octa-O-benzoyl-lactose (19 mmol) in CH Cl (50 mL)
2
2
0 00
(C-5), 83.9 (C-1), 101.1 (C-1 ), 114.2 (C-4 ), 114.6 (C-
was treated with 33% HBr in AcOH (20 mL) at rt for
h. The soln was cooled in an ice-bath, diluted with
CH Cl (100 mL), washed sequentially with ice-cold
00
00
00
2
3 CN), 114.9 (C-4 CN), 116.2 (C-3 ), 128.3, 128.4,
128.5, 128.6, 128.7 (C-3Ar), 128.8, 129.2, 129.4 (C-
1Ar), 128.5, 129.6, 129.7, 129.92, 129.98 (C-2Ar),
2
2
water (50 mL), ice-cold, satd soln of NaHCO3
(
filtrated, and then concentrated. The intermediate hep-
ta-O-benzoyl-lactosyl bromide was used without further
00
2 · 50 mL) and ice-cold water (50 mL), dried (Na SO ),
133.2, 133.3, 133.4, 133.5, 133.6, 133.7, 133.8 (C-5 ,
C-4Ar), 135.3 (C-6 ), 135.4 (C-2 ), 140.4 (C-1 ), 164.8,
165.1, 165.19, 165.22, 165.4, 165.6 (C–CO); MALDI-
2
4
0
0
00
00
0
0
0
0
+
purification for the next step. A soln of 2,3,6,2 ,3 ,4 ,6 -
TOFMS: m/z 1235.92 [M+Na] . Anal. Calcd for
hepta-O-benzoyl-a-lactosyl bromide and thiourea
C H N O S: C, 68.31; H, 4.32; N, 2.31; S, 2.64.
6
9
52
2
17
(
1.90 g, 25 mmol) in anhyd acetone (200 mL) was boiled
Found: C, 68.02; H, 4.29; N, 2.23; S, 2.56.
under reflux for 7 h, cooled, and the acetone was evap-
orated under diminished pressure. The residue was stir-
red with CH Cl (100 mL) and an aq soln of K S O
7
3.9. 2-Nitrophenyl 2,3,4,6-tetra-O-benzyl-D-glucopyrano-
side (4a)
2
2
2
2
(
5.60 g in 100 mL water) at reflux overnight. After cool-
ing, the organic layer was separated and washed with
water (25 mL). After drying (Na SO ), filtration, and re-
Treatment of 1a (1.0 g, 1.85 mmol), NaH (88 mg) and 2b
(0.34 g, 2.2 mmol) as described for 3a afforded 4a
(1.22 g; 94%; a/b 3:1).
2
4
moval of the solvent, the crude product was purified by
chromatography on silica gel (10:1 toluene–acetone) to
give 1f (12.47 g; 60%); white solid; mp 129–130 ꢁC (n-
2
0
1
a-Anomer: ½aꢀ +120.1 (c 1, CHCl3); H NMR
D
(250 MHz, CDCl ): d 3.52–3.58 (dd, 1H, J
2, J6a–6b
6a–5
3
2
D
0
1
heptane–EtOAc); ½aꢀ ꢁ69.8 (c 0.5, CHCl ); H NMR
11 Hz, H-6a), 3.67–3.78 (m, 3H, H-2, H-4, H-6b),
3.89–3.95 (m, 1H, H-5), 4.17–4.27 (dd, 1H, J3–2 9.1,
3
0
(
250 MHz, CDCl ): d 3.68–3.76 (m, 2H, H-6 ), 3.80–
.91 (m, 2H, H-5, H-5 ), 4.20–4.30 (dd, 1H, J
3
0
3
9.4,
J3–4 9.3 Hz, H-3), 4.4 (d, 1H, J 12 Hz, H–CH ), 4.47–
4
–3
2
J4–5 9.8 Hz, H-4), 4.47–4.60 (m, 2H, H-6), 4.68–4.77
4.64 (m, 3H, H–CH ), 4.77–4.91 (m, 3H, H–CH ),
2
2

ꢀ
446
X. Alvarez-Mic o´ et al. / Carbohydrate Research 342 (2007) 440–447
1
5
.00 (d, 1H, J 11 Hz, H–CH ), 5.46 (d, 1H, J 3.5 Hz,
b-Anomer (minor byproduct): H NMR (250 MHz,
2
1–2
H-1), 7.02–7.11 (ddd, 1H, J4
0
0
1:2,
J
0
0
7:4,
CDCl ): d 3.53–3.70 (m, 2H, H-6), 3.76–3.78 (m, 1H,
H-5), 4.10–4.15 (dd, 1H, J3–4 3.9, J3–2 7.6 Hz, H-3),
–6
4 –5
3
0
0
J4
0
0
8:4 Hz, H-4 ), 7.13–7.37 (m, 21H, H-6 , H-2Ar,
–3
H-3Ar, H-4Ar), 7.38–7.45 (ddd, 1H, J5
0
0
1:7,
4.29–4.61 (m, 9H, H-2, H-2, H–CH ), 4.69 (d, 1H, J
–3
2
0
J5
J3
0
0
7:4,
J
0
0
9:1 Hz, H-5 ), 7.80–7.84 (dd, 1H,
8:4 Hz, H-3 ); C NMR (62.9 MHz,
11.8 Hz, H–CH ), 5.66 (1H, J
1.2 Hz, H-1), 7.04–
–4
5 –6
2
1–2
0
13
0
0
0
1:7, J
0
0
7.11 (ddd, 1H, J
0
0
1 Hz, J
0
0
7:1, J
0
0
8:1 Hz, H-4 ),
–5
3 –4
4 –6
4 –5
4 –3
CDCl ): d 68.2 (C-6), 71.9 (C-5), 73.4, 73.5, 74.9, 75.9
7.12–7.43 (m, 22H, H-2Ar, H-3Ar, H-4Ar), 7.78–7.82
3
0
13
(
C–CH ), 77.1 (C-4), 79.8 (C-2), 81.5 (C-3), 96.9 (C-1),
(dd, 1H, J
0
0
1:7, J 8:1 Hz, H-3 );
0 0
C NMR
2
3 –5
3 –4
0
0
0
1
17.1 (C-6 ), 121.8 (C-4 ), 125.4 (C-3 ), 127.6, 127.7,
(62.9 MHz, CDCl ): d 70.5 (C-6), 72.2, 72.5, 73.4, 75.5
3
1
27.8, 128.9, 128.1, 128.3, 128.4, 128.5 (C-2Ar, C-3Ar,
(·2) (C–CH ) (C-5), 82.1 (C-4), 82.3 (C-3), 88.5 (C-2),
2
0
0
0
0
C-4Ar), 133.8 (C-5 ), 137.7, 138.2, 138.3, 138.7 (C-1Ar),
1
106.4 (C-1), 119.4 (C-6 ), 122.2 (C-4 ), 125.5 (C-3 ),
127.5, 127.6, 127.7, 127.8, 127.9, 128.0, 128.1, 128.33,
128.37, 128.36, 128.39, 128.4 (C-2Ar, C-3Ar, C-4Ar),
0
0
40.8 (C-2 ), 149.9 (C-1 ); MALDI-TOFMS: m/z 684.6
+
[
M+Na] . Anal. Calcd for C H NO : C, 72.60; H,
40 39 8
0
5
.94; N, 2.12. Found: C, 72.98; H, 5.84; N, 2.09.
133.7 (C-5 ), 137.3, 137.6, 138.1, 138.2 (C-1Ar), 141.3
1
0
0
b-Anomer (minor byproduct): H NMR (250 MHz,
(C-2 ), 149.8 (C-1 ); MALDI-TOFMS: m/z 684.0
+
CDCl ): d 3.55–3.87 (m, 6H, H-2, H-3, H-4, H-5, H-
[M+Na] .
3
6
), 4.45–4.58 (m, 3H, H–CH ), 4.77–4.85 (m, 3H, H–
2
CH ), 4.97 (d, 1H, J 11 Hz, H–CH ), 5.04 (d, 1H, J
3.11. 2-Nitrophenyl 2,3,4,6-tetra-O-benzyl-a-D-manno-
pyranoside (4c)
2
2
1
7
4
1 Hz, H–CH ), 5.11 (d, 1H, J
.50 (m, 23H, H-4 , H-5 , H-6 , H-2 Ar, H-3 Ar, H-
7 Hz, H-1), 7.15–
1–2
2
0
0
0
0
13
Ar), 7.83 (d, 1H, J3
0
0
7:9 Hz, H-3 );
C NMR
Treatment of 1h (0.5 g, 0.92 mmol), NaH (44 mg) and 2b
(0.17 g, 1.1 mmol) as described for 3a afforded 4c
–4
(
62.9 MHz, CDCl ): d 68.9 (C-6), 73.5 (C-5), 75.1,
3
2
D
0
1
7
5.2, 75.5, 75.8 (C–CH ), 77.5 (C-2), 81.6 (C-4), 84.6
(0.53 g; 89%); ½aꢀ +59.7 (c 1, CHCl3); H NMR
2
0
0
(
C-3), 100.9 (C-1), 117.1 (C-6 ), 122.0 (C-4 ), 125.4
(250 MHz, CDCl ): d 3.66–3.71 (dd, 1H, J
2.2,
6a–5
3
0
(
C-3 ), 127.7, 127.8, 127.9, 128.0, 128.3, 128.4, 128.5
J6a–5 10.8 Hz, H-6a), 3.73–3.80 (dd, 1H, J6b–5 4.9, J6b–5
(
1
6
C-2Ar, C-3 Ar, C-4 Ar), 133.9, 137.8, 137.9, 138.4 (C-
11.1 Hz, H-6b), 3.89–4.13 (m, 4H, H-2, H-3, H-4, H-
0
0
Ar), 140.5 (C-2 ), 150.1 (C-1 ); MALDI-TOFMS: m/z
5), 4.46 (d, 1H, J 11.8 Hz, H–CH ), 4.52 (d, 1H, J
2
+
84.6 [M+Na] .
11.1 Hz, H–CH ), 4.60 (d, 1H, J 11.8 Hz, H–CH ),
2
2
3
.67–4.75 (m, 3H, H–CH ), 4.81 (d, 1H, J 12.1 Hz, H–
2
3.10. 2-Nitrophenyl 2,3,4,6-tetra-O-benzyl-D-galacto-
pyranoside (4b)
CH ), 4.89 (d, 1H, J 11.1 Hz, H–CH ), 5.57 (d, 1H,
2 2
J1–2 2.0 Hz, H-1), 7.04–7.12 (ddd, 1H, J
0
0
1:7,
4 –6
0
J4
0
0
6:7, J
0
0
8:1 Hz, H-4 ), 7.16–7.45 (m, 22H, H-
–5
4 –3
Treatment of 1g (0.5 g, 0.92 mmol), NaH (44 mg) and 2b
2Ar, H-3Ar, H-4Ar), 7.78–7.83 (dd, 1H, J
0
0
1:4,
3 –5
0
13
(
(
0.17 g, 1.1 mmol) as described for 3a afforded 4b
0.55 g; 92%; a/b 3:1).
J3
0
0
8:1 Hz, H-3 ); C NMR (62.9 MHz, CDCl ): d
69.1 (C-6), 72.7, 73.2 (C–CH ), 73.3 (C-5, C–CH ),
74.4 (C-4), 74.8 (C-2), 75.0 (C–CH ), 79.6 (C-3), 98.3
2
(C-1), 118.7 (C-6 ), 122.3 (C-4 ), 125.4 (C-3 ), 127.5,
127.6, 127.7, 127.8, 127.9, 128.1, 128.2, 128.3, 128.4,
128.5 (C-2Ar, C-3Ar, C-4Ar), 134.1 (C-5 ), 138.1,
138.2 (·2), 138.4 (C-1Ar), 140.7 (C-2 ), 149.7 (C-1 );
MALDI-TOFMS: m/z 684.0 [M+Na] . Anal. Calcd
–4
3
2
2
20
1
a-Anomer: ½aꢀ +129 (c 0.75, CHCl3); H NMR
D
0
0
0
(
250 MHz, CDCl ): d 3.42–3.54 (m, 2H, H-6), 3.99 (br
3
s, 1H, H-4), 4.07–4.15 (dd, 1H, J5–6a 6.4, J5–6b 6.9 Hz,
H-5), 4.17–4.25 (m, 2H, H-2, H-3), 4.27–4.39 (m, 2H,
H–CH ), 4.30 (d, 1H, J 11.6 Hz, H–CH ), 4.37 (d, 1H,
0
0
+
0
2
2
J 11.8 Hz, H–CH ), 4.56 (d, 1H, J 11.3 Hz, H–CH ),
2
2
4
1
1
7
.63 (d, 1H, J 12.3 Hz, H–CH ), 4.78 (d, 1H, J
for C H NO : C, 72.60; H, 5.94; N, 2.12. Found: C,
73.02; H, 5.96; N, 2.11.
2
40 39
8
1.6 Hz, H–CH ), 4.82–4.92 (m, 2H, H–CH ), 4.96 (d,
2
2
H, J 11.3 Hz, H–CH ), 5.56 (d, 1H, J1–2 2.2 Hz, H-1),
2
.00–7.07 (ddd, 1H, J4
0
0
0:9, J
0
0
7:2, J 8:1 Hz,
0 0
3.12. 4-Cyanophenyl 2,3,4,6-tetra-O-benzyl-D-glucopyr-
anoside (5a)
–6
4 –5
4 –3
0
H-4 ), 7.12–7.43 (m, 22H, H-2Ar, H-3Ar, H-4Ar),
0
13
7
.78–7.84 (dd, 1H, J3
0
0
1:7, J
0 0
8:1 Hz, H-3 );
C
–5
3 –4
NMR (62.9 MHz, CDCl ): d 68.6 (C-6), 71.2 (C-5),
Treatment of 1a (0.5 g, 0.92 mmol), NaH (44 mg) and 2c
(0.17 g, 1.1 mmol) as described for 3a afforded 5a
(0.48 g; 82%) as an inseparable anomeric mixture; a/b
3
7
7
3.2, 73.5, 73.6, 74.9 (C–CH ), 75.2 (C-4), 76.1 (C-2),
2
0
0
8.6 (C-3), 97.2 (C-1), 117.0 (C-6 ), 121.5 (C-4 ), 125.4
0
13
(
C-3 ), 127.55, 127.58, 127.61, 127.63, 127.73, 127.74,
3:1 (determined by NMR). Representative C NMR
1
28.21, 128.26, 128.29, 128.31, 128.39 (C-2Ar, C-3Ar,
signals for a and b isomers.
a-Anomer: C NMR (62.9 MHz, CDCl ): d 68.1 (C-
0
13
C-4Ar), 133.8 (C-5 ), 137.8, 138.51, 138.54, 138.6 (C-
1
6
3
0
0
Ar), 140.7 (C-2 ), 150.1 (C-1 ); MALDI-TOFMS: m/z
6), 71.3 (C-5), 77.1 (C-4), 79.6 (C-2), 81.8 (C-3), 95.4 (C-
+
0
0
0
0
0
84.0 [M+Na] . Anal. Calcd for C H NO : C, 72.60;
1), 105.6 (C-4 ), 117.2 (C-2 , C-6 ), 133.9 (C-3 , C-5 ),
4
0
39
8
0
H, 5.94; N, 2.12. Found: C, 73.05; H, 5.97; N, 2.10.
159.9 (C-1 ).

ꢀ
X. Alvarez-Mic o´ et al. / Carbohydrate Research 342 (2007) 440–447
447
1
3
b-Anomer: C NMR (62.9 MHz, CDCl ): d 68.7 (C-
Deutsche Forschungsgemeinschaft and the Fonds der
Chemischen Industrie.
3
6
(
5
), 75.3 (C-5), 77.5 (C-2), 81.8 (C-4), 84.6 (C-3), 100.7
0 0 0 0
C-1), 105.9 (C-4 ), 117.2 (C-2 , C-6 ), 133.9 (C-3 , C-
0
0
+
), 160.3 (C-1 ); MALDI-TOFMS: m/z 663.9 [M+Na] .
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pyranoside (5c)
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20
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0.49 g; 84%); slightly yellow oil; ½aꢀ +80.8 (c 0.75,
D
1
CHCl ); H NMR (250 MHz, CDCl ): d 3.59–3.66
3
3
(
dd, 1H, J6a–5 3.9, J6a–5 12.5 Hz, H-6a), 3.70–3.80 (m,
1
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2
4
H, H-5, H-6b), 3.91–3.95 (t, 1H, J2–1/2–3 3.9 Hz, H-2)
.01–4.13 (m, 2H, H-3, H-4), 4.43 (d, 1H, J 11.8 Hz,
H–CH ), 4.51 (d, 1H, J 10.5 Hz, H–CH ), 4.59 (d, 1H,
J 11.8 Hz, H–CH ), 3.67–4.90 (m, 5H, H–CH ), 5.58
2
2
2
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2
(
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–2
0 0
2 –3 /6 –5
1
.9 Hz, H-2 , H-6 ), 7.13–7.40 (m, 20H, H-2Ar, H-3Ar,
8.9 Hz, H-3 , H-5 );
NMR (62.9 MHz, CDCl ): d 68.8 (C-6), 72.6 (C–CH ),
2.9 (C-5), 73.1, 73.3 (C–CH ), 74.4 (C-4), 74.5 (C-2),
5.1 (C–CH ), 79.6 (C-3), 96.5 (C-1), 105.6 (C-4 ),
17.1 (C-2 , C-6 ), 127.5, 127.6, 127.71, 127.75, 127.83,
27.87, 127.9, 128.3, 128.4, 128.5 (C-2Ar, C-3Ar, C-
Ar), 133.9 (C-3 , C-5 ), 137.9, 138.1, 138.2 (·2) (C-
Ar), 159.3 (C-1 ); MALDI-TOFMS: m/z 663.9
M+Na] . Anal. Calcd for C H NO : C, 76.73; H,
.13; N, 2.18. Found: C, 76.81; H, 6.14; N, 2.18.
0
0
13
H-4Ar), 7.52 (d, 2H, J3
0
0
0
0
C
–4 /5 –6
2
3
2
3
7
7
1
1
4
1
2
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2
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2
Acknowledgements
1
We thank the following colleagues for their support of
this work: K. Albert and his crew for recording the
NMR spectra; K.-P. Zeller and his crew for recording
mass spectra and A. Just for performing the elemental
analyses. This work was financially supported by the
9
4
2. Matta, K. L.; Girotra, R. N.; Barlow, J. J. Carbohydr.
Res. 1975, 43, 101–109.