Synthesis of a cyanoethylidene derivative of 3,6-anhydro-d-galactose and its application as glycosyl donor

Article abstract of DOI:10.1016/j.carres.2006.09.015

Starting from 1,2,4-tri-O-acetyl-3,6-anhydro-α-d-galactopyranose, 4-O-acetyl-3,6-anhydro-1,2-O-(1-cyanoethylidene)-α-d-galactopyranose (7) was synthesized by treatment with cyanotrimethylsilane. Additionally, 3,4-di-O-acetyl-1,2-O-(1-cyanoethylidene)-6-O-

Full text of DOI:10.1016/j.carres.2006.09.015

Carbohydrate Research 342 (2007) 520–528
Synthesis of a cyanoethylidene derivative of
3,6-anhydro-D-galactose and its application as glycosyl donor
Christian Vogel,a,* Galina Morales Torres,a Helmut Reinke,a
Dirk Michalikb and Alice Vossa
aUniversity of Rostock, Institute of Chemistry, Albert-Einstein-Str. 3a, D-18059 Rostock, Germany
bLeibniz-Institut fu¨r Katalyse e.V. an der Universita¨t Rostock, Albert-Einstein-Str. 29a, D-18059 Rostock, Germany
Received 27 June 2006; received in revised form 18 September 2006; accepted 18 September 2006
Available online 23 October 2006
Dedicated to the memory of Professor Nikolay K. Kochetkov
Abstract—Starting from 1,2,4-tri-O-acetyl-3,6-anhydro-a-D-galactopyranose, 4-O-acetyl-3,6-anhydro-1,2-O-(1-cyanoethylidene)-a-
D-galactopyranose (7) was synthesized by treatment with cyanotrimethylsilane. Additionally, 3,4-di-O-acetyl-1,2-O-(1-cyanoethylid-
ene)-6-O-tosyl-a-D-galactopyranose was prepared from the corresponding bromide and both cyanoethylidene derivatives were
used as donors in glycosylation reactions. The coupling with benzyl 2,4,6-tri-O-acetyl-3-O-trityl-b-D-galactopyranoside provided
exclusively the b-linked disaccharides in approximately 30% yield. The more reactive methyl 2,3-O-isopropylidene-4-O-trityl-a-
L-rhamnopyranoside gave with donors 3 and 7 the corresponding disaccharides in nearly 60% yield. Furthermore, the synthesis
of 3,6-anhydro-4-O-trityl-1,2-O-[1-(endo-cyano)ethylidene]-a-D-galactopyranose, which can be used as a monomer for polyconden-
sation reaction is described.
ꢀ 2006 Elsevier Ltd. All rights reserved.
Keywords: 3,6-Anhydro-galactose; Cyanoethylidene derivatives; Glycosylation; X-ray structure
1. Introduction
ride in 70% yield. Unfortunately, the sugar orthoester
5 was not used for a condensation with glycosyl acceptor
bearing a secondary hydroxyl group. In the course of the
further development of this type of glycosylation, in
many cases the trityl-cyanoethylidene condensation
(TCC)4 has been turned out to be superior compared
with the orthoester procedure. Therefore, we now report
the preparation of a 1,2-O-cyanoethylidene 3,6-anhy-
dro-D-galactose derivative (7) utilized as a donor in gly-
cosylation reaction. Furthermore, the synthesis of a
corresponding monomer (20) carrying both cyanoethyl-
idene as well as trityl function on the same molecule is
described.
Pursuing a program directed at the synthesis of oligosac-
charide fragments by the modular design principle,1 we
were interested in elucidating the scope and limitations
of 3,6-anhydro-galactose derivatives subjected to glycos-
ylation reaction. To the best of our knowledge, there
are only two report where applications of this type of
sugar as glycosyl acceptor or donor have been described.
A methyl a-carrabioside has been synthesized via glyco-
sylation of methyl 3,6-anhydro-2-O-benzyl-a-D-galacto-
2
´
pyranoside by Bernabe et al., whereas 4-O-acetyl-3,
6-anhydro-a-D-galactopyranose 1,2-(methyl orthoace-
tate) (5) prepared by Bochkov and Kalinevitch3 was
coupled with 1,2:3,4-di-O-isopropylidene-a-D-galacto-
pyranose to give the corresponding b-linked disaccha-
2. Results and discussion
For the synthesis of the cyanoethylidene 3,6-anhydro
derivative 7 (Scheme 2), two alternative routes have
*
Corresponding author. Tel.: +49 381 6430; fax: +49 381 6412; e-mail:
Christian.vogel@uni-rostock.de
0008-6215/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2006.09.015

C. Vogel et al. / Carbohydrate Research 342 (2007) 520–528
521
been considered. Both pathways started from the acet-
ylated 6-O-tosyl galactosyl bromide 1,5 which was
prepared from 1,2,3,4-tetra-O-acetyl-6-O-tosyl-D-galacto-
pyranose6 according to a procedure reported by Rashid
and Mackie.7
excellent 96% yield (Scheme 2). Surprisingly, the stereo-
selectivity of the reaction was low since an exo–endo
mixture in a ratio of 1.0:1.5 was observed. X-ray and
1H NMR studies were employed to address the absolute
configuration of the cyano group in compound 7. In 1H
spectra the proton signal for the methyl group of the
exo-cyano derivative 7exo (S-configuration) appeared at
d 1.91 ppm downfield shifted in comparison to those
from the methyl group of 7endo (R-configuration) at d
1.79 ppm.9
Following Bochkov’s route,3 bromide 1 was con-
verted into orthoester 2 (Scheme 1), which was then sub-
sequently cyclized to the 3,6-anhydro derivative 4 by
treatment with sodium methoxide (Scheme 2). Acetyla-
tion of compound 4 provided derivative 5, whereas
treatment of the orthoester structure 4 with AcOH and
acetic anhydride in pyridine led to an a/b-mixture
(6:1) of the simple 3,6-anhydro triacetate 6, which is
surprisingly not described in the literature yet. Because
attempted preparations of the corresponding bromide
under various conditions failed, presumably due to the
low stability of the pyranose ring under acidic condi-
tions,5 the 1,2-O-cyanoethylidene function was intro-
duced by a procedure reported by Utimoto et al.8 The
treatment of compound 6 with trimethylsilyl cyanide
and stannous chloride in dry MeCN provided the
desired 3,6-anhydro cyanoethylidene derivative 7 in
Finally, the X-ray diffraction studies (Fig. 1) estab-
lished the structure of compound 7exo and confirmed
the 1C4 conformation of this condensed and bridged
pyranose ring.
In parallel, an alternative route for the synthesis of
compound 7 via the cyanoethylidene derivative 3
(Scheme 1) was investigated. The treatment of bromide
1 with carefully powdered potassium cyanide, tetra-n-
butylammonium bromide in dry MeCN10 provided the
exo/endo mixture of 3 in 96% yield. Both diastereomers
could be separated by flash chromatography. Owing
to the observed values for methyl groups of 3exo
[d 1.83 ppm, C(CN)CH3] and 3endo [d 1.76 ppm,
C(CN)CH3], the configurations of the 1,2-cis-fused five
member rings could be described as having endo- and
exo-cyano-ethylidene groups, respectively.
Unfortunately, all attempts to convert compound 3
into a three-ring system (7) were unsuccessful (Scheme
2). Obviously, the cyano group is not stable enough
under basic conditions essential for the formation of
the 3,6-anhydro structure. Nevertheless, intermediate 3
represents also a suitable glycosyl donor for the intro-
duction of a galacto-3,6-anhydro moiety into oligosac-
charides as shown in Schemes 4 and 5.
AcO
AcO
AcO
AcO
OTs
OTs
O
O
AcO
O
Br
O
1
2
OMe
AcO
AcO
OTs
O
O
O
Next, a galacto-configurated glycosyl acceptor carry-
ing a trityl ether function at the 3-O-position (10) was
synthesized. Selective tritylation of benzyl 2,6-di-O-acet-
yl-b-D-galactopyranoside (8)11 with tritylium perchlor-
ate in the presence of 2,4,6-collidine led to the 3-O-trityl
CN
3
Scheme 1. Synthesis of cyanoethylidene glycosyl donor 3 by the
treatment of bromide 1 with sodium cyanide and tetrabutylammonium
bromide in dry MeCN.
OAc
O
O
O
2
O
O
RO
AcO
O
OAc
OMe
4: R = H
5: R = Ac
6
O
O
3
O
AcO
O
CN
7
Scheme 2. Synthesis of 4-O-acetyl-3,6-anhydro-1,2-O-(1-cyanoethylidene)-a-D-galactopyranose (7) by the treatment of the corresponding triacetate 6
with cyanotrimethylsilane.

522
C. Vogel et al. / Carbohydrate Research 342 (2007) 520–528
AcO
AcO
AcO
O
OTs
OAc
O
O
3
10
+
OBn
AcO
AcO
13
RO
O
OR
O
7
10
+
OBn
O
RO
O
RO
Figure 1. An ORTEP diagram of compound 7exo
.
OR
14: R = Ac
15: R = H
derivative 9 (72%, Scheme 3). Acetylation (Ac2O/pyr-
idine) catalyzed by N,N-dimethyl-4-aminopyridine gave
then the full protected trityl ether 10 in 81% yield.
HMBC correlation between H-3 of the pyranose ring
and the quaternary carbon atom of the trityl group con-
firms its position at O-3. An alternative route to glycosyl
acceptor 10 started from compound 8 via cyclic ortho-
ester 11, which was treated without further structural
characterization with aq AcOH to form triacetate 12
in 75% overall yield. The structure of compound 12 is
in accordance with the NMR spectra as well as the data
from literature.12 Finally, tritylation under conditions
described above gave acceptor 10 in 75% yield. Alto-
gether this pathway is a little favourable in comparison
with the route via intermediate 9.
Scheme 4. Two alternative routes for the synthesis of b-(1!3)-linked
3,6-anhydro-D-galactopyranosyl-D-galactopyranoside 15.
observed by the use of 3,6-anhydro donor 7 (32% yield
of 14). The NMR data secure the b-linkage between
galactose moieties in compound 13. Thus, the stereo-
chemistry of the glycosidic linkage was assigned based
3
0
0
on the large vicinal coupling constants J1 ;2 ¼ 8:0 Hz
1
in the H NMR and on the resonances of C-10 at d
101.2 in the 13C NMR spectra of 13. Determination of
the stereochemistry at the anomeric centre of the an-
hydro residue in disaccharide 14 is not a simple task
because the 1C4 conformation of this ring system
resulted in small coupling constants for both a- and b-
linked glycosides. But, the observed coupling constant
with a value almost zero argued for a trans-glycosidic
linkage.
Besides 10, the rhamnose derivative 1613 was used as a
model compound for a glycosyl acceptor (Scheme 5).
The following synthesis of disaccharides was carried
out in the presence of tritylium perchlorate in dichloro-
methane using vacuum technique under the standard
conditions of the TCC.13
The coupling of the 6-O-tosyl donor 3 with acceptor
10 gave the expected b-(1!3)-linked disaccharide 13 in
28% isolated yield (Scheme 4). A similar outcome was
The final evidence for this assessment was given by the
transformation of the 6-O-tosyl residue in disaccharide
13 into a 3,6-anhydro structure. The deacetylation of
´
compounds 13 and 14 under Zemplen conditions, but,
in the case of disaccharide 13 with a 10-fold excess of
sodium methoxide and extended reaction time compared
to 14, provided the same deesterified 3,6-anhydro deriv-
ative 15.
RO
TrO
HO
HO
OAc
OAc
Next, condensation of the cyanoethylidene derivatives
3 and 7 with rhamnosyl acceptor 16 provided quite
better results and both disaccharides 17 and 18 were
O
O
OBn
OBn
OAc
OAc
1
obtained in approximately 60% yield. The H and 13C
8
9: R = H
NMR spectra of 17 and 18 were fully consistent with
the assigned structures. The b-stereochemistry of the
glycosidic linkage between galactose residue and rham-
nose in disaccharide 17 was evident from the large cou-
10: R = Ac
O
AcO
HO
EtO
OAc
OAc
O
1
3
0
0
pling constant J1 ;2 ¼ 7:8 Hz in the H NMR spectra.
The signal for C-10 of compound 17 appeared in the
anomeric region at d 100.3. The coupling constant at
the anomeric centre for the 3,6-anhydro residue of com-
pound 18 was zero and indicates a trans-glycosidic
linkage.
O
O
OBn
OBn
OAc
OAc
11
12
Scheme 3. Synthesis of galacto-configurated glycosyl acceptor 10 by
two alternative routes.

C. Vogel et al. / Carbohydrate Research 342 (2007) 520–528
523
OMe
AcO
AcO
OMe
OTs
O
O
+
O
3
TrO
O
O
AcO
O
O
O
17
16
OMe
O
O
+
O
7
16
O
O
O
AcO
OAc
18
Scheme 5. Two alternative routes for the synthesis of b-(1!4)-linked 3,6-anhydro-D-galactopyranosyl-L-rhamnopyranoside 18.
O
O
O
O
O
O
TrO
HO
7endo
O
O
NC
NC
20
19
Scheme 6. Synthesis of 3,6-anhydro-4-O-trityl-1,2-O-[1-(endo-cyano)ethylidene]-a-D-galactopyranose (20) as a potential monomer for polyconden-
sation reactions.
1
The treatment of tosyl derivative 17 with sodium
methoxide, followed by acetylation provided disaccha-
ride 18 in 65% yield. Again, the stereochemistry of the
anomeric centre of the 3,6-anhydro-galactopyranosyl
residue was confirmed by an alternative synthetic route.
In summary it may be said that the supply of suitable
glycosyl donors based on 3,6-anhydro-galactose until
now is limited, but, the cyanoethylidene derivative 7,
which was obtained in an excellent yield provide b-
linked disaccharides in moderate yields as these first
experiments have shown. It is worth noting that we also
synthesized monomer 20 for application in polyconden-
sation reactions based on the same principle. For this
purpose, compound 7 was deacetylated by treatment
with 0.28 M methanolic hydrochloric acid (19), and sub-
sequently tritylated with tritylium perchlorate (Scheme
6).
MAT’ (Dr. Kernchen Co.). H NMR spectra (500.13
and 250.13 MHz) and 13C NMR spectra (125.8 and
62.8 MHz) were recorded on Bruker instruments
AVANCE 500 and AC 250, with CDCl3 or Me2SO-d6
as solvents. The calibration of spectra was carried out
on solvent signals (CDCl3: d1H = 7.25, d13C = 77.0;
Me2SO-d6: d1H = 2.50, d13C = 39.7). The H and 13C
NMR signals were assigned by DEPT and two-dimen-
1
sional H,1H COSY, H,1H NOESY and H,13C corre-
lation spectra (HMBC and HSQC). The mass spectra
were recorded on an AMD 402/3 spectrometer (AMD
Intectra GmbH). Elemental analysis was performed on
a Leco CHNS-932 instrument. For the X-ray structure
determination of compound 7exo, an X8Apex system
1
1
1
˚
with CCD area detector was used (k = 0.71073 A,
graphite monochromator). The structure was solved by
direct methods (Bruker-SHELXTL). The refinement calcu-
lations were done by the full-matrix least-squares meth-
od of Bruker SHELXTL, Vers.5.10, Copyright 1997,
Bruker Analytical X-ray Systems. All non-hydrogen
atoms were refined anisotropically. The hydrogen atoms
were put into theoretical positions and refined using the
riding model. CCDC 610435 contains the supplemen-
tary crystallographic data for this paper. These data
can be obtained free of charge via http://www.ccdc.
cam.ac.uk/conts/retrieving.html (or from the CCDC,
12 Union Road, Cambridge CB2 1EZ, UK; fax: +44
3. Experimental
3.1. General methods
Melting points were determined with a Boetius micro-
heating plate BHMK 05 (Rapido, Dresden) and are
uncorrected. Optical rotations were measured for solns
in a 2-cm cell with an automatic polarimeter ‘GYRO-

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C. Vogel et al. / Carbohydrate Research 342 (2007) 520–528
1223 336033; e-mail: deposit@ccdc.cam.ac.uk): All
washing solns were cooled to ꢀ5 ꢁC. The NaHCO3 and
NaCl solns were saturated. Trityl perchlorate was ob-
tained and purified as described in Ref. 4. All reactions
were monitored by TLC (Silica Gel 60, F254, E. Merck
KGaA). The following solvent systems (v/v) were used:
(A1) 1:2, (A2) 1:1, (A3) 2:1, (A4) 5:1 petroleum ether–
EtOAc; (B1) 1:3, (B2) 1:1 toluene–EtOAc; (C1) 3:1
CHCl3–MeOH; (E1) 5:1:1 toluene–heptane–EtOH. The
spots were made visible by spraying with methanolic
10% H2SO4 soln and charring them for 3–5 min with
a heat gun. The detection of benzyl derivatives was
effected by UV fluorescence. Preparative flash chromato-
graphy was performed by elution from the columns of
slurry-packed Silica Gel 60 (E. Merck, 63–200 or 40–
63 lm). All solvents and reagents were purified and
dried according to standard procedures.14 After a classi-
cal work-up of the reaction mixtures, the organic layer
as a rule, were dried over MgSO4, and then concentrated
under diminished pressure (rotary evaporator).
250.13 MHz):
d
7.79–7.72, 7.38–7.31 (2m, 4H,
3
SO2C6H4CH3), 5.69 (d, 1H, J1,2 4.6 Hz, H-1), 5.47
3
3
(dd, 1H, J4,5 2.5 Hz, H-4), 5.32 (dd, 1H, J3,4 3.05 Hz,
3
H-3), 4.36 (dd, 1H, J2,3 7.5 Hz, H-2), 4.32 (dd, 1H,
3J5,6a 6.2 Hz, H-5), 4.16–4.03 (m, 2H, H-6a,6b), 2.45
(s, 3H, SO2C6H4CH3), 2.08, 2.05 (2s, 6H, 2 · CH3CO),
1.76 [s, 3H, CH3(CN)C]; 13C NMR (CDCl3,
62.8 MHz): d 169.46, 169.42 (2 · CH3CO), 145.38,
132.24, 130.02, 128.01 (SO2C6H4CH3, two signals are
isochronic), 117.39 [CH3(CN)C], 98.68 [CH3(CN)C],
98.49 (C-1), 76.26 (C-2), 69.65, 69.39 (C-3, C-5), 65.78
(C-6), 65.76 (C-4), 26.81 [CH3(CN)C], 21.67 (CH3C6H4),
20.55, 20.47 (2 · CH3CO). Anal. Calcd for C20H23NO10S
(469.46): C, 51.17; H, 4.94; N, 2.98; S, 6.83. Found: C,
51.33; H, 5.16; N, 3.07; S, 6.54.
3.3. 1,2,4-Tri-O-acetyl-3,6-anhydro-D-galactopyranose
(6)
3,6-Anhydro-1,2-O-(1-methoxyethylidene)-a-D-galacto-
pyranose (4)3 (880 mg, 4 mmol) was dissolved in aq
90% AcOH (20 mL) at ambient temperature, and kept
for 30 min under these conditions. After concentration,
the residue was dissolved in dry pyridine (10 mL) and
freshly distilled Ac2O (6 mL) was added dropwise un-
der an atmosphere of argon at 0 ꢁC. After stirring for
2 h at room temperature (TLC, solvent B2), the mix-
ture was poured into ice water (100 mL). The aq layer
was extracted with CHCl3 (2 · 50 mL), the combined
extracts were washed successively with ice water
(2 · 50 mL), aq NaHCO3 (2 · 50 mL) and ice water
(2 · 50 mL), dried and concentrated. Traces of pyridine
were removed by evaporation with repeated addition of
toluene. The crude material was purified by column
chromatography (solvent B2) to yield 6 (976 mg, 84%,
6:1 ratio of the a,b anomers) as a colourless syrup:
Rf 0.52 (solvent B2); 1H NMR of 6a (CDCl3,
3.2. 3,4-Di-O-acetyl-1,2-O-[1-(exo-,endo-cyano)ethyl-
idene]-6-O-tosyl-a-D-galactopyranose (3)
The heterogeneous mixture of freshly prepared 2,3,4-tri-
O-acetyl-6-O-tosyl-a-D-galactopyranosyl bromide (1)6
(1.042 g, 2.2 mmol), carefully powdered sodium cyanide
(650 mg, 13.3 mmol) and tetrabutylammonium bromide
(299 mg, 0.9 mmol) in dry MeCN (6 mL) was vigorously
stirred at room temperature for 15 h in the dark (TLC,
solvent A3). The mixture was then diluted with CHCl3
(60 mL), washed with water (7 · 20 mL), passed through
a bed of silica gel and concentrated. The residue was then
subjected to column chromatography (gradient EtOAc–
toluene 30!60%) to yield 3 (96%), separated into frac-
tions containing pure exo-isomer (470 mg), an exo-,
endo-mixture (231 mg) and pure endo-isomer (198 mg).
The exo-isomer had: mp: 98–100 ꢁC (from EtOAc–
3
250.13 MHz): d 6.12 (d, 1H, J1,2 2.9 Hz, H-1), 5.44
25
3
3
heptane); ½aꢁD +65 (c 1.0, CHCl3); Rf 0.49 (solvent
(d, 1H, J4,5 1.8 Hz, H-4), 5.21 (dd, J2,3 5.5 Hz,
A3); 1H NMR (CDCl3, 250.13 MHz): d 7.79–7.72,
H-2), 4.50 (br, 1H, H-5), 4.46 (d, 1H, H-3), 4.28 (d,
3
2
3
7.38–7.31 (2m, 4H, SO2C6H4CH3), 5.76 (d, 1H, J1,2
1H, J6a,b 10.6 Hz, H-6a), 4.03 (dd, 1H, J5,6a 3.1 Hz,
H-6b), 2.17, 2.07, 2.06 (3s, 9H, 3 · CH3CO); 13C
NMR of 6a (CDCl3, 62.8 MHz): d 169.72, 169.54,
168.46 (CH3CO), 87.83 (C-1), 76.71 (C-2), 75.92,
72.78 (C-3, C-5), 69.45 (C-6), 69.27 (C-4), 20.87,
20.70 (3 · CH3CO, one signal is isochronic). Anal.
Calcd for C12H16O8 (288.25): C, 50.00; H, 5.59. Found:
C, 50.23; H, 5.73.
3
5.0 Hz, H-1), 5.35 (dd, 1H, J4,5 2.1 Hz, H-4), 4.94
3
(dd, 1H, J3,4 3.7 Hz, H-3), 4.30–4.25 (m, 2H, H-2,
H-5), 4.15–4.00 (m, 2H, H-6a,6b), 2.45 (s, 3H,
SO2C6H4CH3), 2.05 (s, 6H, 2 · CH3CO, one signal is
isochronic), 1.83 [s, 3H, CH3(CN)C]; 13C NMR (CDCl3,
62.8 MHz): d 169.74, 169.46 (2 · CH3CO), 145.31,
132.25, 129.96, 128.02 (SO2C6H4CH3, two signals are
isochronic), 116.65 [CH3(CN)C], 98.65 (C-1), 97.41
[CH3(CN)C], 72.74 (C-2), 70.63, 69.42 (C-3, C-5),
65.95 (C-6), 64.98 (C-4), 25.72 [CH3(CN)C], 21.66
(SO2C6H4CH3), 20.56, 20.40 (2 · CH3CO). Anal. Calcd
for C20H23NO10S (469.46): C, 51.17; H, 4.94; N, 2.98; S,
6.83. Found: C, 51.07; H, 5.11; N, 2.48; S, 6.43.
3.4. 4-O-Acetyl-3,6-anhydro-1,2-O-[1-(exo-,endo-cyano)-
ethylidene]-a-D-galactopyranose (7)
Trimethylsilyl cyanide (0.9 mL, 6.8 mmol) and stannous
chloride (68.0 mg, 0.36 mmol) were added to a stirred
soln of compound 6 (667 mg, 2.3 mmol) in dry MeCN
(8 mL) under argon at room temperature. After stirring
23
The syrup endo-isomer had: ½aꢁD +61.6 (c 1.0,
CHCl3); Rf 0.35 (solvent A3); 1H NMR (CDCl3,

C. Vogel et al. / Carbohydrate Research 342 (2007) 520–528
525
3
for 6 h (TLC, solvent B1), the mixture was diluted with
CHCl3 (50 mL). The organic layer was washed with
water (5 · 20 mL), concentrated and toluene was
coevaporated several times from the residue. Column
chromatography (gradient EtOAc–toluene 30!60%)
furnished compound 7 in 96% yield, separated into frac-
tions containing pure exo-isomer (105 mg) as colourless
needles, an exo-, endo-mixture (292 mg) and pure endo-
isomer (168 mg) as colourless crystals.
(ddd, 1H, J4,5 1.2 Hz, H-5), 2.51 (br, 1H, H-4), 2.29
(br, 1H, OH-4), 2.00, 1.95 (2s, 6H, 2 · CH3CO); 13C
NMR (CDCl3, 125.8 MHz):
d
170.50, 169.64
(2 · CH3CO), 144.19, 137.23, 128.85, 128.29, 127.95,
127.66, 127.65, 127.47 [C6H5CH2, C(C6H5)3, 16 signals
are isochronic], 99.69 (C-1), 87.70 [C(C6H5)3], 74.26
(C-3), 71.46 (C-5), 70.42 (C-2), 69.90 (C6H5CH2),
67.09 (C-4), 62.78 (C-6), 21.14, 20.80 (2 · COCH3).
Anal. Calcd for C36H36O8 (596.67): C, 72.47; H, 6.08.
Found: C, 72.52; H, 6.21.
The exo-isomer had: mp 105–109 ꢁC (from EtOAc–
23
1
heptane); ½aꢁD +10.5 (c 1.0, CHCl3); H NMR (CDCl3,
3
250.13 MHz): d 5.62 (d, 1H, J1,2 3.2 Hz, H-1), 5.38 (d,
1H, 3J4,5 1.8 Hz, H-4), 4.54–4.49 (m, 2H, H-2, H-3), 4.47
3.6. Benzyl 2,4,6-tri-O-acetyl-3-O-trityl-b-D-galacto-
pyranoside (10)
2
(br, 1H, H-5), 4.08 (d, 1H, J6a,b 10.5 Hz, H-6b), 4.00
(dd, 1H, J5,6a 3.0 Hz, H-6a), 2.08 (s, 3H, CH3CO),
3
1.91 [s, 3H, CH3(CN)C]; 13C NMR (CDCl3,
62.8 MHz): d 169.52 (CH3CO), 116.45 [CH3(CN)C],
101.68 [CH3(CN)C], 96.48 (C-1), 79.53 (C-2), 76.38
(C-5), 75.38 (C-3), 71.92 (C-4), 71.01 (C-6), 25.98
[CH3(CN)C], 20.79 (CH3CO). Anal. Calcd for
C11H13NO6 (255.22): C, 51.77; H, 5.13; N, 5.49. Found:
C, 51.72; H, 5.15; N, 5.34.
Via 9. Compound 9 (466 mg, 0.8 mmol) was added to a
soln
of
N,N-dimethyl-4-aminopyridine
(94 mg,
0.8 mmol) in Ac2O (5 mL) and pyridine (4 mL). The
reaction mixture was then kept for 24 h under argon
at room temperature (TLC, solvent A4). After adding
EtOH (3 mL) at 0 ꢁC stirring was continued for further
20 min at ambient temperature. The reaction mixture
was then diluted with CHCl3 (50 mL) and poured into
ice water. The phases were separated, and the aqueous
phase was extracted with CHCl3 (2 · 25 mL). The com-
bined organic soln was successively washed with ice
water (2 · 50 mL), aq NaHCO3 (2 · 50 mL), ice water
(2 · 50 mL), dried and concentrated. Traces of pyridine
were removed by evaporation with repeated addition of
toluene. The residue was purified by column chromato-
graphy (solvent A4) to yield 9 (405 mg, 81%) as a light-
yellow syrup.
The endo-isomer had: mp 112–114 ꢁC (from EtOAc–
23
1
heptane); ½aꢁD +8.7 (c 1.0, CHCl3); H NMR (CDCl3,
3
250.13 MHz): d 5.64 (d, 1H, J1,2 3.2 Hz, H-1), 5.50
(d, 1H, J4,5 1.8 Hz, H-4), 4.65–4.53 (m, 2H, H-3, H-
5), 4.36 (dd, 1H, J2,3 5.0 Hz, H-2), 4.12 (d, 1H, J6a,b
3
3
2
3
10.5 Hz, H-6b), 4.07 (dd, 1H, J5,6a 3.0 Hz, H-6a), 2.08
(s, 3H, CH3CO), 1.79 [s, 3H, CH3(CN)C]; 13C NMR
(CDCl3, 62.8 MHz):
d
169.31 (CH3CO), 117.42
[CH3(CN)C], 101.62 [CH3(CN)C], 97.65 (C-1), 80.55
(C-2), 75.85 (C-5), 75.76 (C-3), 72.56 (C-4), 70.12 (C-
6), 26.54 [CH3(CN)C], 20.81 (CH3CO). Anal. Calcd
for C11H13NO6 (255.22): C, 51.77; H, 5.13; N, 5. 49.
Found: C, 51.75; H, 5.20; N, 5.31.
Via 12. Trityl perchlorate (1.9 g, 5.5 mmol) and 2,4,6-
collidine (0.9 mL, 6.5 mmol) were added to a soln of 12
(1.7 g, 4.3 mmol) in CH2Cl2 (32 mL). After stirring for
20 min at ambient temperature, an additional amount
of 2,4,6-collidine (0.4 mL, 3.2 mmol) and trityl perchlo-
rate (0.86 g, 2.6 mmol) was added and stirring was con-
tinued for 1 h (TLC, solvent A3). The reaction mixture
was then diluted with CHCl3 (200 mL) and the organic
layer was washed with water (3 · 60 mL), dried and con-
centrated. The residue was purified by column chroma-
tography (solvent A3) to give 10 (2.06 g, 75%) as a light-
3.5. Benzyl 2,6-di-O-acetyl-3-O-trityl-b-D-galactopyran-
oside (9)
Trityl perchlorate (0.96 g, 2.8 mmol) and 2,4,6-collidine
(0.5 mL, 3.6 mmol) were added in portions to a soln of
benzyl 2,6-di-O-acetyl-b-D-galactopyranoside
(8)11
(528 mg, 1.5 mmol) in CH2Cl2 (10 mL). After stirring
for 15 min at room temperature under argon (TLC, sol-
vent A3), the mixture was diluted with CHCl3 (60 mL)
and the organic layer was washed with water
(3 · 30 mL), dried and concentrated. The residue was
purified by column chromatography (solvent A3) to af-
ford 9 (638 mg, 72%) as an amorphous colourless solid:
21
yellow syrup: ½aꢁD ꢂ9.7 (c 1.0, CHCl3); Rf 0.25 (solvent
A3); 1H NMR (CDCl3, 250.13 MHz): d 7.44–7.34, 7.33–
3
7.20 (2m, 20H, C6H5,CH2C6H5), 5.50 (dd, 1H, J2,3
2
9.9 Hz, H-2), 4.84, 4.53 (2d, 2H, J 12.4 Hz, CH2C6H5),
3
4.30 (d, 1H, H-4), 4.19 (d, 1H, J1,2 7.9 Hz, H-1), 3.90
3
(m, 2H, H-6a,6b), 3.62 (dd, 1H, J3,4 3.2 Hz, H-3),
21
mp 204–205 ꢁC; ½aꢁD ꢂ26.5 (c 1.0, CHCl3); Rf 0.55 (sol-
3.21 (m, 1H, H-5), 2.20, 2.00, 1.80 (3s, 9H, 3 · CH3CO);
13C NMR (CDCl3, 62.8 MHz): d 170.29, 169.94, 169.80
(3 · CH3CO), 144.09, 137.03, 129.06, 128.32, 127.74,
127.69, 127.62, 127.35 [C6H5CH2, C(C6H5)3, 16 signals
are isochronic], 100.17 (C-1), 87.85 [C(C6H5)3], 72.61
(C-3), 71.32 (C-5), 70.52 (C-2), 70.22 (C6H5CH2),
69.53 (C-4), 62.29 (C-6), 21.21, 21.09, 20.68
1
vent A3); H NMR (CDCl3, 500.13 MHz): d 7.48, 7.32–
3
7.23 (2m, 20H, C6H5, CH2C6H5), 5.46 (dd, 1H, J2,3
2
9.8 Hz, H-2), 4.83, 4.55 (2d, 2H, J 12.3 Hz, CH2C6H5),
3
2
4.24 (d, 1H, J1,2 7.9 Hz, H-1), 4.16 (dd, 1H, J6a,b
3
3
11.4 Hz, J5,6a 6.9 Hz, H-6a), 4.01 (dd, 1H, J5,6b
6.0 Hz, H-6b), 3.71 (dd, 1H, J3,4 3.2 Hz, H-3), 3.21
3

526
C. Vogel et al. / Carbohydrate Research 342 (2007) 520–528
(3 · CH3CO). Anal. Calcd for C38H38O9 (638.70): C,
71.46; H, 6.00. Found: C, 71.42; H, 6.06.
fied by column chromatography (gradient EtOAc–tolu-
ene 30!60% with 1% Et3N).
3.9. Benzyl 2,3,4-tri-O-acetyl-6-O-tosyl-b-D-galactopyr-
anosyl-(1!3)-2,4,6-tri-O-acetyl-b-D-galactopyranoside
(13)
3.7. Benzyl 2,4,6-tri-O-acetyl-b-D-galactopyranoside (12)
Triethyl orthoacetate (5 · 2.6 mL, total 71 mmol) and
anhyd p-toluenesulfonic acid (2 · 88 mg, total
0.94 mmol) were added in portions to a stirred soln of
compound 8 (5.047 g, 11.9 mmol) in abs CH2Cl2
(83 mL) at room temperature. After stirring for 2 h
(TLC, solvent A1, Rf 0.54), Et3N (40 mL) and CH2Cl2
(300 mL) were successively added and the organic layer
was washed with water (2 · 150 mL), dried and concen-
trated. The residue (11) was dissolved in aq 80% AcOH
(40 mL), and the reaction mixture was kept for 10 min at
room temperature (TLC, solvent A1), diluted then with
toluene (50 mL) and evaporated. After repeated coeva-
poration with solvent E1 (4 · 60 mL) crystalline com-
pound 12 (3.5 g, 75%) was obtained: mp 130–133 ꢁC
Reagents: CED glycosyl donor 3 (115 mg, 0.24 mmol);
trityl ether glycosyl acceptor 10 (171 mg, 0.27 mmol);
initiator trityl perchlorate (9 mg, 0.024 mmol); disaccha-
ride 13 (57 mg, 28%): mp 73–75 ꢁC (amorphous white
22
solid); ½aꢁD ꢂ21.9 (c 1.0, CHCl3); Rf 0.24 (solvent A2);
1H NMR (CDCl3, 500.13 MHz): d 7.75, 7.37–7.26
3
(2m, 9H, CH2C6H5, SO2C6H4CH3), 5.41 (d, 1H, J3,4
3
3.5 Hz, H-4), 5.29 (d, 1H, J3 ;4 3:5 Hz, H-40), 5.24
0
0
(dd, 1H, 3J2,3 10.0 Hz, H-2), 5.02 (d, 1H,
J2 ;3 10:5 Hz, H-20), 4.89–4.86 (m, 2H, H-30,
3
0
0
CH2C6H5), 4.60 (d, 1H, 2J 12.5 Hz, CH2C6H5), 4.51
3
(d, 1H, J1 ;2 8:0 Hz, H-10), 4.40 (d, 1H, J1,2 8.2 Hz,
H-1), 4.20–4.05 (m, 3H, H-6a,6b, H-6a0), 3.94–3.86 (m,
2H, H-50, H-6b0), 3.85 (dd, 1H, H-3), 3.81 (m, 1H,
3
0
0
22
(from diisopropyl ether), lit.12 mp 133 ꢁC; ½aꢁD ꢂ46.2
(c 1.0, CHCl3), lit.12 [a]D ꢂ40 (c 0.82, CHCl3); Rf 0.24
3J5,6a = 3J5,6b 6.3 Hz, J4,5 0.8 Hz, H-5), 2.45 (s, 3H,
3
1
(solvent A1); H NMR (CDCl3, 250.13 MHz): d 7.37–
SO2C6H4CH3), 2.12, 2.07, 2.04, 2.03, 1.99, 1.93 (6s,
18H, CH3CO); 13C NMR (CDCl3, 125.8 MHz): d
170.52, 170.12, 170.03, 170.00, 169.19, 168.97
(6 · CH3CO), 145.29, 136.87, 132.42, 130.02, 128.43,
127.93, 127.90, 127.74 (C6H5CH2, SO2C6H4CH3, four
signals are isochronic), 101.17 (C-10), 99.41 (C-1),
75.64 (C-3), 71.32 (C-5), 71.11 (C-50), 71.02 (C-2),
70.39 (C-30), 70.30 (C6H5CH2), 69.22 (C-4), 68.33 (C-
20), 66.77 (C-40), 66.62 (C-60), 62.10 (C-6), 21.63
(SO2C6H4CH3), 20.88, 20.75, 20.63, 20.51, 20.45, 20.43
(6 · COCH3). Anal. Calcd for C38H46O19S (838.83): C,
54.41; H, 5.53; S, 3.82. Found: C, 54.18; H, 5.57; S, 3.80.
3
7.26 (m, 5H, CH2C6H5), 5.31 (dd, 1H, J3,4 3.8 Hz,
3
3J4,5 1.0 Hz, H-4), 5.04 (dd, 1H, J2,3 10.0 Hz, H-2),
2
4.89, 4.62 (2d, 2H, J 12.5 Hz, CH2C6H5), 4.47 (d, 1H,
3J1,2 8.0 Hz, H-1), 4.22–4.10 (m, 2H, H-3, H-5), 3.84–
3.75 (m, 2H, H-6a,6b), 2.67 (br, 1H, OH), 2.14, 2.07
(2s, 9H, 3 · CH3CO, one signal is isochronic); 13C
NMR (CDCl3, 62.8 MHz): d 171.12, 170.93, 170.50
(3 · CH3CO),
136.80,
128.40,
127.96,
127.76
(C6H5CH2, two signals are isochronic), 99.41 (C-1),
72.69 (C-3), 71.34 (C-5), 70.98 (C-2), 70.63
(C6H5CH2), 69.66 (C-4), 61.91 (C-6), 20.91, 20.73,
20.70 (3 · CH3CO). Anal. Calcd for C19H24O9
(396.39): C, 57.57; H, 6.10. Found: C, 57.85; H, 6.23.
3.10. Benzyl 3,6-anhydro-2,4-di-O-acetyl-b-D-galacto-
pyranosyl-(1!3)-2,4,6-tri-O-acetyl-b-D-galactopyran-
oside (14)
3.8. General procedure of glycosylations
The CED glycosyl donor (3 or 7) together with 10 mol %
excess of trityl ether glycosyl acceptor (10 or 16) dis-
solved in dry NO2Me (1 mL/mmol) and trityl perchlor-
ate (10 mol % of the amount of CED glycosyl donor)
likewise dissolved in dry NO2Me (1 mL/0.1 mmol) were
placed in separate limbs of a turning-fork-shaped tube,
and both solns were freeze-dried. NO2Me was then dis-
tilled (0.133 Pa) from CaH2 into the limb containing the
sugar derivatives, and lyophilization was repeated fol-
lowed by drying of the residuals for several hours.
CH2Cl2 was distilled (0.133 Pa) from CaH2 into the tube
and the solns were mixed and kept overnight at room
temperature in the dark. The bright yellow coloured
reaction mixture was treated with 1:1 MeOH–pyridine
(0.05 mL/mmol), and the decolourized soln was diluted
with CHCl3 and washed with water. The organic phase
was dried and evaporated. The crude material was puri-
Reagents: CED glycosyl donor 7 (226 mg, 0.88 mmol);
trityl glycosyl acceptor 10 (623 mg, 0.97 mmol); initiator
trityl perchlorate (30 mg, 0.08 mmol); disaccharide 14
(177 mg, 32%): mp 61–63 ꢁC (amorphous white solid);
22
½aꢁD ꢂ36.6 (c 1.1, CHCl3); Rf 0.33 (solvent A2); 1H
NMR (CDCl3, 500.13 MHz): d 7.34–7.26 (m, 5H,
3
CH2C6H5), 5.42 (d, 1H, J3,4 3.5 Hz, H-4), 5.26 (dd,
3
3
0
0
1H, J2,3 10.0 Hz, H-2), 5.18 (d, 1H, J4 ;5 1:8 Hz, H-
40), 4.89 (d, 1H, J2 ;3 4:7 Hz, H-20), 4.88, 4.61 (2d,
3
0
0
2
2H, J 12.5 Hz, CH2C6H5), 4.66 (s, 1H, H-10), 4.41 (d,
3
1H, J1,2 8.0 Hz, H-1), 4.32 (br, 1H, H-50), 4.28 (d,
1H, H-30), 4.23 (d, 1H, J6a0;6b 10:0 Hz, H-6a0), 4.14
2
0
(m, 2H, H-6a,6b), 3.81–3.76 (m, 3H, H-3, H-5, H-6b0),
2.17, 2.08, 2.07, 2.05, 2.03 (5s, 15H, CH3CO); 13C
NMR (CDCl3, 125.8 MHz): d 170.48, 170.37, 169.86,
169.63, 169.41 (5 · CH3CO), 136.89, 128.41, 127.90,
127.78 (C6H5CH2, two signals are isochronic), 99.67

C. Vogel et al. / Carbohydrate Research 342 (2007) 520–528
527
3
3
(C-1), 99.67 (C-10), 76.23 (C-3), 76.17 (C-30), 75.42 (C-
50), 73.22 (C-20), 73.22 (C-40), 71.34 (C-5), 70.38 (C-60),
70.35 (C6H5CH2), 70.25 (C-2), 67.91 (C-4), 62.14 (C-
6), 20.89, 20.84, 20.84, 20.78, 20.74 (5 · COCH3). Anal.
Calcd for C29H36O5 (624.59): C, 55.77; H, 5.8. Found:
C, 55.64; H, 5.75.
1H, J3 ;4 3:4 Hz, H-30), 4.87 (d, 1H, J1 ;2 7:8 Hz, H-
0
0
0
0
3
10), 4.83 (d, 1H, J1,2 0.8 Hz, H-1), 4.07 (dd, 1H,
J6a0;6b 10:0 Hz, J5 ;6a0 6:6 Hz, H-6a0), 4.05 (dd, 1H,
2
3
0
0
3J2,3 5.7 Hz, H-2), 4.00 (dd, 1H, J3,4 7.3 Hz, H-3),
3
4.00 (dd, 1H, J6a0;6b 10:0 Hz, J5 ;6b 6:2 Hz, H-6b0),
2
3
0
0
0
3
3.89 (m, 1H, H-50), 3.56 (dq, 1H, J5,6 6.2 Hz, H-5),
3
3.47 (dd, 1H, J4,5 10.0 Hz, H-4), 3.34 (s, 3H, OCH3),
3.11. Benzyl 3,6-anhydro-b-D-galactopyranosyl-(1!3)-b-
2.44 (s, 3H, SO2C6H4CH3), 2.04, 2.03, 1.95 (3s, 9H,
CH3CO), 1.47, 1.31 [2s, 6H, C(CH3)2], 1.23 (d, 3H, H-
6); 13C NMR (CDCl3, 125.8 MHz): d 169.98, 169.94,
169.65 (3 · CH3CO), 145.21, 132.33, 129.98, 127.99
(SO2C6H4CH3, two signals are isochronic), 109.37
[C(CH3)2], 100.28 (C-10), 97.83 (C-1), 80.15 (C-4),
77.98 (C-3), 75.94 (C-2), 70.69 (C-50), 70.64 (C-30),
68.92 (C-20), 67.00 (C-40), 66.19 (C-60), 63.78 (C-5),
54.80 (OCH3), 27.96, 26.29 [2 · C(CH3)2], 21.64
(SO2C6H4CH3), 20.79, 20.51, 20.50 (3 · COCH3),
17.54 (C-6). Anal. Calcd for C29H40O15S (660.68): C,
52.72; H, 6.10; S, 4.85. Found: C, 52.68; H, 6.24; S, 4.40.
D-galactopyranoside (15)
Via 13. A methanolic sodium methoxide soln (1.0 M,
0.5 mL) was added to a soln of compound 13 (47 mg,
0.056 mmol) in dry MeOH (5 mL). After stirring for
18 h at room temperature, the reaction mixture was neu-
tralized with IRC-120 (H+) resin, filtered, dried and con-
centrated. Column chromatography (solvent A1) of the
residue gave disaccharide 15 (19 mg, 83%) as a colour-
less syrup.
Via 14. A methanolic sodium methoxide soln (1.0 M,
0.05 mL) was added to a soln of compound 14 (44 mg,
0.07 mmol) in dry MeOH (5 mL). After stirring for 2 h
at ambient temperature, the reaction mixture was neu-
tralized with IRC-120 (H+) resin, filtered and dried
and concentrated. Chromatographically, purification
(solvent A1) of the residue provided 15 (22 mg, 75%)
3.13. Methyl 3,6-anhydro-2,4-di-O-acetyl-b-D-galacto-
pyranosyl-(1!4)-2,3-O-isopropylidene-a-L-rhamno-
pyranoside (18)
Reagents: CED glycosyl donor 7 (51.7 mg, 0.2 mmol);
trityl glycosyl acceptor 16 (100 mg, 0.22 mmol); initiator
trityl perchlorate (7 mg, 0.02 mmol); disaccharide 18
(54 mg, 60%).
22
as a colourless syrup: ½aꢁD ꢂ68.9 (c 0.89, MeOH); Rf
1
0.33 (solvent C1); H NMR (Me2SO-d6, 500.13 MHz):
d
7.40–7.26 (m, 5H, C6H5CH2), 5.33 (d, 1H,
3
3
J2 ;OH 4:7 Hz, OH-20), 5.10 (d, 1H, J4 ;OH 4:0 Hz,
Via 17. A methanolic sodium methoxide soln (1.0 M,
1.25 mL) was added to a soln of compound 17 (245 mg,
0.37 mmol) in dry MeOH (5 mL). After stirring for 18 h
at ambient temperature, the reaction mixture was neu-
tralized with IRC-120 (H+) resin, filtered and dried
and concentrated. Ac2O (2.0 mL) was added dropwise
to a soln of the residue in dry pyridine (5 mL) under
an atmosphere of argon at 0 ꢁC. After stirring for 2 h
at room temperature (TLC, solvent A3), the mixture
was poured into ice water (50 mL). The aqueous layer
was extracted with CHCl3 (2 · 25 mL), the combined ex-
tracts were washed successively with ice water
(2 · 25 mL), aq NaHCO3 (2 · 25 mL) and ice water
(2 · 25 mL), dried and concentrated. Traces of pyridine
were removed by evaporation with repeated additions of
toluene. The crude material was purified by column
chromatography (eluent gradient EtOAc 30!60% in
toluene with 1% Et3N) to yield 18 (108 mg, 65%) as a
0
0
3
OH-40), 5.02 (d, 1H, J2,OH 5.4 Hz, OH-2), 4.80, 4.58
(2d, 2H, J 12.3 Hz, C6H5CH2), 4.68 (s, 1H, H-10),
2
2
0
4.63 (br, 1H, OH-6), 4.43 (d, 1H, J6a0;6b 9:0 Hz, H-
3
6a0), 4.34 (d, 1H, J4,OH 6.8 Hz, OH-4), 4.23 (d, 1H,
3J1,2 7.7 Hz, H-1), 4.12 (br, 1H, H-40), 4.04 (br, 1H,
H-50), 3.89–3.86 (m, 3H, H-4, H-20, H-30), 3.68 (dd,
1H, J6a0;6b 9:0 Hz, J5 ;6b 3:0 Hz, H-6b0), 3.58–3.47
2
3
0
0
0
(m, 3H, H-2, H-6a,6b), 3.35 (m, 1H, J5,6a = 3J5,6b
3
3
3
6.3 Hz, J4,5 1.0 Hz, H-5), 3.31 (dd, 1H, J2,3 9.8 Hz,
3J3,4 3.4 Hz, H-3); 13C NMR (Me2SO-d6, 125.8 MHz):
d 138.28, 128.25, 127.72, 127.45 (C6H5CH2, two signals
are isochronic), 104.39 (C-10), 102.92 (C-1), 81.76 (C-3),
80.94 (C-20), 77.46 (C-50), 75.38 (C-5), 72.77 (C-30),
69.81 (C-40), 69.70 (C-2), 69.53 (C6H5CH2), 69.27 (C-
60), 67.82 (C-4), 60.26 (C-6); MS, CI (m/z): 415 [M]+.
3.12. Methyl 2,3,4-tri-O-acetyl-6-O-tosyl-b-D-galacto-
pyranosyl-(1!4)-2,3-O-isopropylidene-a-L-rhamnopyr-
anoside (17)
21
colourless syrup: ½aꢁD ꢂ57.5 (c 0.8, CHCl3); Rf 0.46 (sol-
vent A3); 1H NMR (CDCl3, 500.13 MHz): d 5.25 (d, 1H,
3
J4 ;5 1:8 Hz, H-40), 5.18 (s, 1H, H-10), 5.03 (d, 1H,
0
0
3
3
J2 ;3 4:8 Hz, H-20), 4.82 (d, 1H, J1,2 0.6 Hz, H-1),
0
0
Reagents: CED glycosyl donor 3 (94 mg, 0.20 mmol) tri-
tyl glycosyl acceptor 1613 (100 mg, 0.22 mmol); initiator
trityl perchlorate (6.9 mg, 0.02 mmol); disaccharide 17
4.40 (m, 1H, H-50), 4.37 (d, 1H, H-30), 4.34 (d, 1H,
2
3
J6a0;6b 9:8 Hz, H-6a0), 4.17 (dd, 1H, J3,4 7.0 Hz, H-3),
0
21
3
(78 mg, 59%): ½aꢁD ꢂ17.4 (c 0.87, CHCl3); Rf 0.27 (sol-
4.06 (dd, 1H, J2,3 5.7 Hz, H-2), 3.88 (dd, 1H,
2
1
3
J6a0;6b 9:8 Hz, J5 ;6b 3:2 Hz, H-6b0), 3.66 (dq, 1H,
0
0
0
vent A3); H NMR (CDCl3, 500.13 MHz): d 7.74, 7.32
(2m, 4H, SO2C6H4CH3), 5.33 (dd, 1H, J4 ;5 1:0 Hz,
3J5,6 6.3 Hz, H-5), 3.55 (dd, 1H, J4,5 9.8 Hz, H-4),
3
3
0
0
H-40), 5.07 (dd, 1H, J2 ;3 10:4 Hz, H-20), 5.00 (dd,
3.34 (s, 3H, OCH3), 2.11, 2.07 (2s, 6H, CH3CO), 1.50,
3
0
0

528
C. Vogel et al. / Carbohydrate Research 342 (2007) 520–528
22
1.30 [2s, 6H, C(CH3)2], 1.33 (d, 3H, H-6); 13C NMR
(CDCl3, 125.8 MHz): d 169.89, 169.55 (2 · CH3CO),
109.35 [C(CH3)2], 98.06 (C-1), 97.24 (C-10), 78.17 (C-
4), 77.88 (C-3), 76.45 (C-30), 75.91 (C-2), 75.36 (C-50),
74.40 (C-20), 73.50 (C-40), 70.54 (C-60), 63.87 (C-5),
54.78 (OCH3), 27.81, 26.28 [2 · C(CH3)2], 20.94, 20.88
(2 · COCH3), 18.15 (C-6). Anal. Calcd for C20H30O11
(446.45): C, 53.81; H, 6.77. Found: C, 53.64; H, 6.36.
as a colourless syrup: ½aꢁD ꢂ3.7 (c 1.0, CHCl3); Rf 0.28
1
(solvent A4); H NMR (CDCl3, 500.13 MHz): d 7.49–
7.46, 7.35–7.25 (2m, 15H, C6H5), 5.46 (d, 1H, J1,2
3.2 Hz, H-1), 4.56 (d, 1H, J4,5 1.5 Hz, H-4), 4.21 (dd,
3
3
3
1H, J2.3 5.0 Hz, H-2), 4.16 (d, 1H, H-3), 4.10 (dd, 1H,
3J5,6a 3.2 Hz, H-6a), 3.90 (d, 1H, J6a,b 10.1 Hz, H-6b),
3
3.29 (br, 1H, H-5), 1.67 [s, 3H, CH3(CN)C]; 13C NMR
(CDCl3, 125.8 MHz): d 143.69, 128.70, 128.09, 127.48
[C(C6H5)3, 14 signals are isochronic], 117.42 [CH3(CN)C],
101.19 [CH3(CN)C], 97.61 (C-1), 88.14 [C(C6H5)3],
81.18 (C-2), 77.28 (C-5), 77.23 (C-3), 73.15 (C-4), 70.31
(C-6), 26.59 [CH3(CN)C]. Anal. Calcd for C28H25NO5
(455.50): C, 73.83; H, 5.53; N, 3.08. Found: C, 73.54;
H, 5.79; N, 2.89.
3.14. 3,6-Anhydro-1,2-O-[1-(endo-cyano)ethylidene]-
a-D-galactopyranose (19)
Compound 7endo (150 mg, 0.58 mmol) was dissolved in
methanolic HCl (0.28 M, 12.25 mL, prepared by adding
0.25 mL acetyl chloride to 12 mL of ice cold dry MeOH)
and the soln was stirred for 9 h at room temperature
(TLC, solvent A2). The reaction mixture was then neu-
tralized by filtration through a layer of alkaline alumina
and concentrated. The residue was purified by column
chromatography (solvent A2) to furnish compound 19
References
1. For a short review see: Vogel, C.; Nolting, B.; Kramer, S.;
Steffan, W.; Ott, A.-J. Synthesis of pectin fragments by
modular design principle. In Advances in Pectin and
Pectinase Research; Vorhagen, F., Schols, H., Visser, R.,
Eds.; Kluwer Academic: Dordrecht, 2003; pp 209–220.
21
(76 mg, 62%) as a colourless syrup: ½aꢁD +58,7 (c 0.98,
CHCl3); Rf 0.39 (solvent A2); 1H NMR (CDCl3,
250.13 MHz): d 5.62 (d, 1H, 3J1,2 3.2 Hz, H-1), 4.65 (br,
1H, H-4), 4.48–4.43 (m, 2H, H-3, H-5), 4.35 (dd, 1H,
´
2. Parra, E.; Caro, H.-N.; Jimenez-Barbero, J.; Martin-
´
Lomas, M.; Bernabe, M. Carbohydr. Res. 1990, 208, 83– 710
92.
3
3J2,3 5.0 Hz, H-2), 4.14 (dd, 1H, J5,6a 3.1 Hz, H-6a),
3. Bochkov, A. F.; Kalinevitch, V. M. Carbohydr. Res. 1974,
32, 9–14.
4. Kochetkov, N. K.; Betaneli, V. I.; Ovchinnikov, M. V.;
Backinowsky, L. V. Tetrahedron 1981, 37, 149–156.
5. Haworth, W. N.; Jackson, J.; Smith, F. J. Chem. Soc.
1940, 620–632.
2
4.05 (d, 1H, J6a,b 10.5 Hz, H-6b), 2.70 (d, 1H,3J4,OH
4.5 Hz, OH-4), 1.77 [s, 3H, CH3(CN)C]; 13C NMR
(CDCl3, 62.8 MHz): d 117.75 [CH3(CN)C], 101.37
[CH3(CN)C], 97.49 (C-1), 80.81 (C-2), 77.95 (C-5),
77.76 (C-3), 70.43 (C-4), 69.68 (C-6), 26.51 [CH3(CN)C].
Anal. Calcd for C9H11NO5 (213.19): C, 50.70; H, 5.20; N,
6.57. Found: C, 50.45; H, 5.16; N, 6.11.
´
´
6. Gyo¨rgydeak, Z.; Szilagyi, L. Liebigs Ann. Chem. 1987,
235–241.
7. Rashid, A.; Mackie, W. Carbohydr. Res. 1992, 223, 147–
155.
8. Utimoto, K.; Wakabayashi, Y.; Horiie, T.; Inoue, M.;
Shishiyama, Y.; Obayashi, M.; Nozaki, H. Tetrahedron
1983, 39, 967–973.
3.15. 3,6-Anhydro-4-O-trityl-1,2-O-[1-(endo-cyano)ethyl-
idene]-a-D-galactopyranose (20)
´
´
9. Cano, F. H.; Foces-Foces, C.; Bernabe, M.; Jimenez-
Barbero, J.; Martin-Lomas, M.; Penades-Ullate, S. Tetra-
hedron 1985, 41, 3875–3886.
Trityl perchlorate (157 mg, 0.57 mmol), 2,4,6-collidine
(70 lL, 0.52 mmol) and N,N-dimethyl-4-aminopyridine
(16 mg, 0.13 mmol) were added to a soln of compound
19 (50 mg, 0.23 mmol) in dry CH2Cl2 (5 mL). After stir-
ring overnight under an inert atmosphere at room tem-
perature (TLC, solvent A4), the mixture was diluted
with CH2Cl2 (10 mL), and successively washed with cold
aq 15% NaHSO4 (2 · 5 mL), ice water (3 · 5 mL), dried
and concentrated. The residue was purified by column
chromatography (solvent A4) to yield 20 (85 mg, 80%)
10. Betaneli, V. I.; Ovchinnikov, M. V.; Backinowsky, L. V.;
Kochetkov, N. K. Carbohydr. Res. 1979, 68, C11–C13.
11. Levy, A.; Flowers, H. M.; Sharon, N. Carbohydr. Res.
1967, 4, 305–311.
12. Lee, E. E.; Bruzzi, A.; O’Brien, E.; O’Colla, P. S.
Carbohydr. Res. 1974, 35, 103–109.
13. Betaneli, V. I.; Ovchinnikov, M. V.; Backinowsky, L. V.;
Kochetkov, N. K. Carbohydr. Res. 1979, 76, 252–256.
14. Perrin, D. D.; Amarego, W. L. F. Purification of Labo-
ratory Chemicals, 3rd ed.; Pergamon Press: Oxford, 1988.