An approach to stereoselective preparation of 3-C-glycosylated d- and l-glucals

Article abstract of DOI:10.1016/j.carres.2009.11.025

An approach to stereoselective synthesis of α- or β-3-C-glycosylated l- or d-1,2-glucals starting from the corresponding α- or β-glycopyranosylethanals is described. The key step of the approach is the stereoselective cycloaddition of chiral vinyl ethers

Full text of DOI:10.1016/j.carres.2009.11.025

Carbohydrate Research 345 (2010) 352–362
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Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
An approach to stereoselective preparation of 3-C-glycosylated D- and L-glucals
*
ˇ
Kamil Parkan, Lukáš Werner, Zuzana Lövyová, Eva Prchalová, Ladislav Kniezo
Department of Chemistry of Natural Compounds, Institute of Chemical Technology, Technická 5, 166 28 Prague 6, Czech Republic
a r t i c l e i n f o
a b s t r a c t
Article history:
An approach to stereoselective synthesis of a- or b-3-C-glycosylated L- or D-1,2-glucals starting from the
Received 7 October 2009
Accepted 18 November 2009
Available online 4 December 2009
corresponding
stereoselective cycloaddition of chiral vinyl ethers derived from both enantiomers of mandelic acid.
The preparation of 1,5-anhydro-4,6-di-O-benzyl-2,3-dideoxy-3-C-[(2,3,4,6-tetra-O-benzyl-b- -glucopyr-
anosyl)methyl]- -arabino-hex-1-enitol, 1,5-anhydro-4,6-di-O-benzyl-2,3-dideoxy-3-C-[(2,3,4,6-tetra-O-
benzyl-b- -glucopyranosyl)methyl]- -arabino-hex-1-enitol, and 1,5-anhydro-4,6-di-O-benzyl-2,3-dide-
a- or b-glycopyranosylethanals is described. The key step of the approach is the
D
L
Keywords:
D
D
C-Disaccharides
Glucal derivatives
Stereoselective synthesis
oxy-3-C-[(2,3,4-tri-O-benzyl-
a
-
L-fucopyranosyl)methyl]-
D-arabino-hex-1-enitol serves as an example of
this approach.
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
from a
-glucopyranosylethanal.3 Later, we found that the stereose-
lectivity of the key step in our synthesis, namely the cycloaddition
of substituted oxadiene with ethyl vinyl ether, can be markedly in-
creased by the use of chiral vinyl ethers, the high stereoselectivity
of the cycloaddition being influenced neither by the configuration
of the starting monosaccharide nor by the character of the protect-
ing group used.4 This procedure enables a facile stereoselective
Glycoproteins on the cell surface form specific ligands that are
recognized by receptors on the surface of other cells or by surface
receptors of pathogenic microorganisms. These processes mediate
a variety of biological events that range from cell to cell interaction
(signaling and recognition), host–pathogen interactions, immune
responses, and cancer metastasis. A key player in these communi-
cations is the structure of the oligosaccharide portion of glycopro-
teins synthesized in the endoplasmatic reticulum and Golgi’s
apparatus of the cell.1 Cell surface carbohydrate–receptor binding
events can be investigated with synthetic oligosaccharides, glyco-
conjugates, and their analogues. In the study of these processes,
an important role can also be played by C-disaccharides, which
nominally preserve the structural information of natural disaccha-
rides but are chemically as well as enzymatically non-hydrolyz-
able. Moreover, the synthesized C-disaccharides can also be
utilized in another way. Their attachment as non-hydrolyzable
disaccharide mimetics, mimicking the structure of natural saccha-
ride epitopes to suitable dendrimers or to a suitable peptide chain,
may lead to the preparation of therapeutically useful glycoconju-
gates or vaccines, neither of which will be hydrolyzed by ubiqui-
tous glycosidases in the organism. It is therefore important to
look for stereoselective methods for the synthesis of precursors
for a simple preparation of glycoconjugates containing non-hydro-
lyzable disaccharide mimetics. Such precursors may be derivatives
of 1,5-anhydro-2,3-dideoxy-arabino-hex-1-enitol (1,2-glucal).2
In our previous study, we described a short and efficient synthe-
preparation of a series of
and 2 (Fig. 1) containing any monosaccharide (at least
a
-C-(1?3)-disaccharide derivatives 1
-glucose,
-fucose) at the non-reducing end and
-2-deoxyarabinohexopyranose at the reducing end (e.g.,
D
D
-galactose,
- or
D-mannose, or L
D
L
see Ref. 5). Moreover, the range of compounds obtainable by this
method can be further extended to include the corresponding b-
C-(1?3)-disaccharides 3 and 4 because it is known that in the
presence of amines or other bases, the starting
a-pyranosyletha-
nals easily undergo epimerization to the corresponding b-pyrano-
sylethanals.6 Thus, from a single starting compound such as
a-pyranosylpropene, one can prepare pure a-pyranosylethanal,
which is either converted to two diastereoisomeric C-(1?3)-disac-
charides 1 and 2, or epimerized to give pure b-pyranosylethanal
which affords further two diastereoisomeric C-(1?3)-disaccha-
rides 3 and 4 (For recent synthesis of other C-(1?3)-disaccharides,
see Ref. 19).
In the present study, we would like to show that C-(1?3)-disac-
charides 1–4, obtained by this approach, can easily be transformed
further to derivatives of
hex-1-enitol ( - or -glucal) 5–8. So far, only the preparation of a
similar -galactal has been described in the literature, namely a
C-linked analogue of b- -galactopyranosyl-(1?3)-
-galactal.2c
D- or L-1,5-anhydro-2,3-dideoxy-arabino-
D
L
D
sis of
a-C-(1?3)-disaccharides in which
D
-glucopyranose was
D
D
linked to an
L
- or -2-deoxyarabino-hexopyranose moiety starting
D
1,2-Glucals are extremely useful intermediates in the synthesis of
saccharide derivatives and they enable one- or two-step stereose-
lective preparation of gluco-7 or mannopyranosylglycosides,8 gly-
cosides of glucosamine9, or mannosamine,10 as well as some of
* Corresponding author. Tel.: +420 220 444 265; fax: +420 220 444 422.
E-mail address: Ladislav.Kniezo@vscht.cz (L. Kniezo).
ˇ
0008-6215/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2009.11.025

K. Parkan et al. / Carbohydrate Research 345 (2010) 352–362
353
O
O
OR
OR
RO
RO
O
O
OR1
RO
RO
O
O
1
5
6
RO
RO
O
O
O
RO
RO
OR1
O
RO
RO
RO
RO
O
2
OR
OR
O
O
O
O
OR1
RO
RO
O
RO
RO
O
O
3
4
7
8
RO
O
RO
RO
RO
RO
OR1
O
O
RO
RO
O
= protected D-gluco, D-galacto, D-manno or L-fuco
RO
Figure 1. Synthetic route to 3-C-glycosylated glucals.
C-glycosides.11 One can envisage that these or similar reactions
may also be utilized for attachment of - or b-C-(1?3)-disaccha-
ride mimetics 5–8 to an oligosaccharide, peptide, or lipid moiety,
either by glycosidic or by C–C bonding, thus enabling the synthesis
of various stable, non-hydrolyzable, glycoconjugates.
As the starting compound for the preparation of C-(1?3)-disac-
charides 9 and 10, containing the b- -glucopyranosyl moiety, we
employed a mixture of tetra-O-acetyl- - and tetra-O-acetyl-b-
glucopyranosylpropenes 12a,b in the ratio of about 6:1 (Scheme
1), obtained by reaction of allyltrimethylsilane with peracetylated
glucose in boiling acetonitrile (Scheme 1). Deacetylation and ben-
a
D
a
D-
zylation afforded a mixture of tetra-O-benzyl-
zyl-b- -glucopyranosylpropenes which on ozonolysis afforded a
mixture of tetra-O-benzyl- - and tetra-O-benzyl-b- -glucopyrano-
sylethanals 13a,b in the same ratio as in the starting 12a,b. The
epimerization of protected -glucopyranosylethanals to the cor-
a- and tetra-O-ben-
2. Results and discussion
D
a
D
As examples of this approach, we now report the preparation of
C-substituted
bond in which the b-
lene bridge to C-3 of
1-enitol, and of C-substituted
bond in whichthe
L
-glucal 9 or
D
-glucal 10, mimicking the b-glycoside
-glucopyranosyl moiety is linked by a methy-
- or -1,5-anhydro-2,3-dideoxy-arabino-hex-
-glucal 11, mimicking the -glycoside
-L-fucopyranosyl moiety is linked bya methylene
a
-D
D
responding b-diastereoisomers has been hitherto described only in
two cases. Zhou et al. described epimerization of methanolic solu-
L
D
D
a
tion of 2-O-acetyl-3,4,6-tri-O-benzyl-
by a mixture of MeONa/Zn(OAc)2 (Ref. 6a) or by MeONa alone
(Ref. 6b) however, in both of these cases, the b- -glucopyranosy-
a-D-glucopyranosylethanal
a
bridge to C-3 of
D-1,5-anhydro-2,3-dideoxy-arabino-hex-1-enitol.
D
lethanal formed was not isolated instead, it was in situ reduced
OBn
to the corresponding alcohol. Dondoni et al.6d described an alterna-
OBn
OBn
tive method of epimerization of tetra-O-benzyl-
anosylethanal using -proline in a microwave reactor. Although
the arising tetra-O-benzyl-b- -glucopyranosylethanal was isolated,
a-D-glucopyr-
O
BnO
BnO
O
BnO
BnO
O
L
BnO
D
BnO
BnO
O
BnO
the reaction was performed only in a small vial with 0.4 mmol of
the aldehyde. We have found that epimerization of larger amounts
of the aldehyde can advantageously be performed using a 1% meth-
anolic solution of K2CO3; in this way, in a single batch, a mixture of
BnO
9
10
BnO
OBn
tetra-O-benzyl-a- and tetra-O-benzyl-b-
D-glucopyranosylethanals
13a,b afforded pure tetra-O-benzyl-b-
D
-glucopyranosylethanal
OBn
O
CH3
OR
13b in an amount greater than 10 g. This product in a subsequent
Wittig reaction with ((2-thiazolylcarbonyl)-methylen)triphenyl-
phosphorane 14 (Ref. 13) afforded substituted oxadiene 15 as the
sole product. Unlike the case of similar and previously prepared
substituted oxadienes,3–5 the H-2 proton signal in the 1H NMR
O
RO
11

354
K. Parkan et al. / Carbohydrate Research 345 (2010) 352–362
N
Ph3P
O
S
OAc
O
OBn
OBn
14
O
O
O
AcO
AcO
BnO
BnO
BnO
BnO
i
ii
iii
AcO
O
BnO
BnO
13b
13a,b
12a,b
OBn
6´
4´
5´
O
O
COOMe
1´´
4
1´
2´
BnO
BnO
3
5
2
O
COOMe
3´
BnO
S
Ph
(R)-16
O
6
Ph
N
OBn
17
N
S
O
BnO
BnO
iv
S
BnO
N
O
O
COOMe
OBn
15
O
O
O
COOMe
BnO
BnO
Ph
(S)-16
BnO
Ph
18
Scheme 1. Stereoselective synthesis of 17 and 18. Reagents and conditions: (i) (a) MeONa/MeOH, rt, 20 h; (b) NaH, BnBr, Bu4NI, THF, 50 °C, 2 h, then rt 15 h; (c) O3, CH2Cl2,
ꢀ78 °C, 2 h; (d) Me2S, NaHCO3, rt, 2 days; (ii) 1% K2CO3/MeOH, rt, 2 days; (iii) 14, CHCl3, 50 °C, 30 h; (iv) (R)-16 or (S)-16, Eu(fod)3 (6 mol %), CH2Cl2, rt, 3 days.
spectrum of compound 15 was not overlapping with the aromatic
proton signals and from its coupling constant (J2,3 = 15.6 Hz) we
were able to directly assign trans-configuration of the C@C bond.
Cycloaddition reaction of 15 with both enantiomers of methyl
(ethenyloxy)(phenyl)acetate, (R)-16 and (S)-16 (Refs. 4,12), stere-
oselectively afforded two different products: 17 and 18 (the first
was an oil whereas the second was a crystalline compound, mp
67–68 °C), with almost identical NMR spectra. In both cases, NOE
experiments confirmed the cis-relation of substituents at C-2 and
C-4 in the dihydropyran ring. Therefore, similar to previous
cases,3–5 compounds 17 and 18 are two diastereoisomers of the
same relative but different absolute configuration of the newly
arisen dihydropyran ring. Unfortunately, the crystalline diastereo-
isomer 18 did not afford any crystals suitable for X-ray analysis;
however, since our previous paper4 confirmed that neither the con-
figuration of the saccharide substituent nor the character of the
protecting groups in the starting oxadiene affects the selectivity
of cycloaddition with chiral vinyl ethers (R)-16 and (S)-16, in this
case we can assume with a great deal of certainty that vinyl ether
(R)-16 afforded cycloadduct 17 with configuration 2S,4S, and vinyl
ether (S)-16 afforded cycloadduct 18 with configuration 2R,4R on
the dihydropyran ring.
pure
b-diastereoisomeric mixture by crystallization from isopropyl
alcohol instead of ethyl acetate, and the desired -stereoisomer,
a-L-fucopyranosylprop-2-ene was isolated from the a- and
a
mp 157–158 °C (Ref. 14, mp 153 °C), was obtained in high purity
after a single crystallization. Similar to the preceding case, fuco-
pyranosylethanal 19 was converted into substituted oxadiene 20.
Its cycloaddition reaction with vinyl ether (S)-16 afforded
cycloadduct 21 as the sole product (Scheme 2). Judging from anal-
ogy with previous results,4,5 we can assume that the configuration
at the newly arisen dihydropyran ring almost certainly is 2R,4R.
The obtained cycloadducts 17, 18, and 21 were converted to the
final L- or D-glucal derivatives 9 or 10 and 11 as described in
Scheme 3. For reasons described in our previous paper,5 we first re-
duced the ester group. For protection of the arising primary alcohol
we used two ways: the alcohol, prepared by reduction of the ester
group of cycloadduct 17, was methylated by the formation of com-
pound 22, and the alcohol, prepared from cycloadduct 18 or 21,
was benzylated to compounds 23 or 24. Both protection proce-
dures were equivalent giving the same yields of the protected
products. The known transformation of the thiazole ring to an alde-
hyde group3–5,15 afforded compounds 25–27, which on hydrobora-
tion and simultaneous reduction of the aldehyde group, followed
by benzylation of the arising hydroxyl goups,3,5 yielded C-(1?3)-
disaccharides 28–30 as the sole reaction products. As confirmed
by the coupling constants in the 1H NMR spectra, in all the synthe-
sized compounds, the new pyranose has the 2-deoxy-arabino-
In the preparation of substituted
-fucopyranosyl moiety, we started from tri-O-benzyl-
pyranosylethanal 19, which, in turn, was prepared from
D
-glucal 11, containing the
-fuco-
-fucose
a-
L
a-L
L
according to Ref. 14. The procedure was slightly modified, in that
BnO
OBn
BnO
S
BnO
OBn
OBn
N
OBn
O
CH3
OBn
OBn
O
O
N
CH3
CH3
O
i
ii
O
COOMe
O
S
O
Ph
19
20
21
Scheme 2. Stereoselective synthesis of 21. Reagents and conditions: (i) 14, CHCl3, 50 °C, 30 h; (ii) (S)-16, Eu(fod)3 (6 mol %), CH2Cl2, rt, 3 days.

K. Parkan et al. / Carbohydrate Research 345 (2010) 352–362
355
OBn
S
O
N
OMe
BnO
BnO
OBn
O
BnO
S
O
O
O
Ph
R
N
Ph
β-D-glucopyranosyl
23, R = tetra-O-benzyl-
22
24, R = tri-O-benzyl-
α-L-fucopyranosyl
i
OBn
O
O
OMe
BnO
BnO
OBn
O
O
O
BnO
O
R
Ph
Ph
O
26, R = tetra-O-benzyl-
β
-D-glucopyranosyl
25
27, R = tri-O-benzyl-
α
-L-fucopyranosyl
ii
OBn
OBn
R
OBn
O
O
BnO
BnO
OMe
O
BnO
O
BnO
O
BnO
Ph
BnO
Ph
29, R = tetra-O-benzyl-
β-D-glucopyranosyl
28
30, R = tri-O-benzyl- -L-fucopyranosyl
α
iii
OBn
OBn
R
O
BnO
BnO
O
BnO
BnO
BnO
O
SPh
SPh
BnO
32a,b, R = tetra-O-benzyl-
β-D-glucopyranosyl
33a,b, R = tri-O-benzyl- -L-fucopyranosyl
α
31a,b
iv
9
10 from 32a,b
11 from 33a,b
Scheme 3. Synthesis of 9–11. Reagents and conditions: (i) (a) MeOTf, MeCN, rt, 15 min; (b) NaBH4, MeOH, rt, 15 min; (c) AgNO3, MeCN/H2O, rt, 20 min; (ii) (a) Me2SꢁBH3, THF,
rt, 16 h; (b) NaOH, H2O2, rt, 30 min; (c) NaH, BnBr, Bu4NI, THF, 40 °C, 15 min, then rt 14 h; (iii) PhSH, BF3ꢁEt2O, CH2Cl2, ꢀ78 °C, then to rt 2 h; (iv) (a) NBS, moist acetone (1%
H2O), ꢀ15 °C, 1 h, exclusion of light; (b) Ms2O, s-collidine, CH2Cl2, 0 °C, 4 h.
hexopyranose configuration (compound 28: J1,2ax = 9.6 Hz, J3,4
=
3. Conclusion
J4,5 = 9.1 Hz, compound 29: J3,4 = J4,5 = 9.1 Hz, and compound 30:
J1,2ax = 11.7 Hz, J3,4 = J4,5 = 9.6 Hz). The reaction of thiophenol with
disaccharides 28–30 afforded anomeric mixtures of thioglycosides
In conclusion, using the three selected examples, we have dem-
onstrated that from an
lectively prepare a 3-C-glycosylated
starting
-pyranosylpropenes are easily available compounds4,14,18
that, on ozonolysis, can be transformed in a single step to -pyr-
a- or b-pyranosylethanal one can stereose-
31a,b, 32a,b, and 33a,b (in a ratio a:b of about 3:1). The mixtures
D
- or -glucal. In general, the
L
of anomeric thioglycosides were subjected to a reaction with
N-bromosuccinimide in aqueous acetone under the formation of
b-C-(1?3)-disaccharides with a free OH group in the anomeric
position16 and the compounds obtained were, without isolation,
reacted with methanesulfonic anhydride in the presence of s-colli-
a
a
anosylethanals which, after epimerization, can be converted to
pure b-pyranosylethanals.6 We have shown that the configuration
of the starting monosaccharide does not affect the stereoselectivity
of the individual steps of the synthesis, therefore, one can assume
that this approach may be used for preparation of any of the substi-
dine.17 In this way, we obtained the substituted
L- glucal 9 or D-glu-
cals 10 and 11 as the sole reaction products.

356
K. Parkan et al. / Carbohydrate Research 345 (2010) 352–362
tuted glucals 5–8, depicted in Figure 1. Substituted glucals, obtain-
able by this method, may then serve as useful intermediates, for
the synthesis of either various (1?3)-disaccharide mimetics using
reactions described in the literature,7–11 or non-hydrolyzable gly-
in dry THF (400 ml), to this solution we added 11.8 g (296.7 mmol)
of 60% suspension of NaH in mineral oil and the reaction mixture
was stirred at room temperature for 1 h. Then, tetrabutylammo-
nium iodide (4.56 g; 12.3 mmol) was added, followed by dropwise
addition of benzyl bromide (35.3 ml; 296.7 mmol), the reaction
mixture was heated at 50 °C for 2 h, and then stirred at room tem-
perature for another 15 h. The excess hydride was decomposed by
the addition of MeOH (5 ml), the solvent was evaporated, and the
residue was partitioned between CH2Cl2 and H2O. The organic
phases were combined, dried, stripped of solvent, and the residue
was chromatographed on silica gel (light petroleum/ethyl acetate
coprotein or glycolipid epitopes containing
a- or b-pyranosyl-
(1?3)-pyranosyl structural motifs.
4. Experimental
4.1. General
The melting points are uncorrected. TLC was performed on
HF254 plates (Merck), detection utilized either UV light or spray-
ing with Ce(SO4)2 solution (5 g) in 10% H2SO4 (500 ml), and sub-
sequent heating. Flash column chromatography was performed
12:1?9:1). This yielded 19.5 g (70%) of a mixture of
a and b perb-
enzylated glucopyranosylprop-2-enes; Rf = 0,35 (light petroleum/
ethyl acetate 9:1). ESIMS m/z: calcd for (C37H40O5): 564.7. Found,
565.8 [M+H]+. The mixture obtained was dissolved in dry dichloro-
methane (150 ml) and, after addition of anhydrous MeOH (30 ml)
and cooling to ꢀ78 °C, it was ozonized. After 2 h, the solution
turned blue permanently and the reaction was terminated by pass-
ing nitrogen through the mixture for 5 min. Then NaHCO3 (4 g) (to
prevent an acetalization), followed by dimethyl sulfide (25.4 ml;
345 mmol), was added successively and the stirred mixture was al-
lowed to warm to room temperature. After stirring the mixture for
2 days at room temperature, the NaHCO3 was filtered off, the sol-
vent was evaporated, and the residue was chromatographed on a
silica gel (light petroleum/ethyl acetate, 10:1). This yielded
14.48 g (74%) of a mixture of aldehydes 13a,b; Rf = 0.18 (light
petroleum/ethyl acetate, 6:1) in 6:1 ratio (integration of 1H NMR
on a silica gel (Merck, 100–160 lm) in solvents which had been
distilled prior to use. Optical rotations were measured at 25 °C
on a JASCO DIP-370 spectropolarimeter. 1H and 13C NMR spectra
were taken on
a Bruker DRX 500 Avance spectrometer at
500.132 MHz (1H NMR) and at 125.767 MHz (13C NMR) using tet-
ramethylsilane as an internal standard. 1H and 13C NMR signal
assignments were confirmed by 2D COSY and HMQC when neces-
sary. NOE connectivities were obtained using 1D 1H DPFGSE-NOE
experiments. Mass spectra and HPLC were performed on
a
250 ꢂ 4.6 mm column packed with 5
l
m Supelco BDS Hypersil
C-18, mobile phase of MeOH/water, using an HP 1100 instrument
equipped with a gradient pump, a column thermostat and, in
addition to a UV detector, an Agilent G1956B single quadrupole
system as an MS detector.
aldehyde group signals; a-diastereoisomer as t at 9.65 ppm, b-dia-
stereoisomer as t at 9.69 ppm). The mixture of aldehydes 13a,b
(14 g; 24.7 mmol) was dissolved in a 1% methanolic solution of
K2CO3 (270 ml) and stirred at room temperature. According to 1H
NMR, after 2 days, the reaction mixture was already completely
4.2. (2,3,4,6-Tetra-O-acetyl-a-D-glucopyranosyl)-prop-2-ene
(12a) and (2,3,4,6-tetra-O-acetyl-b-D-glucopyranosyl)-prop-2-
ene (12b)
free of a-diastereoisomer 13a. The reaction was quenched by neu-
tralization with acetic acid, the solvent was evaporated, and the
residue was partitioned between CH2Cl2 and a saturated NaCl solu-
tion. The organic phase was dried, the solvent evaporated, and the
residue chromatographed on a silica gel (light petroleum/ethyl
acetate 9:1?5:1), affording 10.9 g (78%) of pure aldehyde 13b,
Allyltrimethylsilane (16.3 ml; 100 mmol) and BF3ꢁEt2O (13.2
ml; 100 mmol) were added to a solution of 1,2,3,4,6-penta-O-acet-
yl-a-D-glucopyranose (10 g; 25.64 mmol) in dry CH3CN (160 ml).
The mixture was refluxed for 2.5 h and then another portion of
allyltrimethylsilane (16.3 ml; 100 mmol) and BF3ꢁEt2O (13.2 ml;
100 mmol) was added. This procedure was then repeated twice
at 2.5 h intervals, so that the total amount of allyltrimethylsilane
added was 65.2 ml (400 mmol) and the total amount of BF3ꢁEt2O
was 52.8 ml (400 mmol). Two hours after the last addition, the
reaction mixture was cooled to room temperature, diluted with
CH2Cl2 (350 ml), and washed with 1 M NaOH to persisting alkaline
reaction of the aqueous phase. The organic layer was dried over
MgSO4 and the solvent was evaporated. Chromatography of the
residue (PE/AcOEt = 4:1) afforded a mixture of two diastereoiso-
meric products 12a,b (6.87 g; 72%), Rf = 0.63 (PE/AcOEt 2:1) in
Rf = 0.3 (light petroleum/ethyl acetate 3:1). [
a
]
D
ꢀ2.3 (c 0.70,
CHCl3); 1H NMR (CDCl3): 2.54 (ddd, 1H, J2a,2b = 16.2 Hz,
0
J2a,1 = 7.9 Hz, J2a,CHO = 2.5 Hz, H-2a), 2.69 (ddd, 1H, J2b,2a = 16.2 Hz,
0
0
0
0
0
J2b,1 = 4.3 Hz, J2b,CHO = 2.5 Hz, H-2b), 3.33 (dd, 1H, J2 ,1 = J2 ,3
=
9.1 Hz, H-20), 3.47 (ddd, 1H, J5 ,4 = J5 ,6a = 9.6 Hz, J5 ,6b = 2.9 Hz,
0
0
0
0
0
0
H-50), 3.62–3.70 (m, 3H, H-40, H-6a , H-6b ), 3.73 (dd, 1H, J3 ,2
=
0
0
0
0
J3 ,4 = 9.1 Hz, H-30), 3.81 (ddd, 1H, J1 ,2 = 9.1 Hz, J1 ,2a = 7.9 Hz,
0
0
0
0
0
J1 ,2b = 4.3 Hz, H-10), 4.45–4.96 (m, 8H, 4 ꢂ CH2Ph), 7.10–7.40 (m,
0
20H, 4 ꢂ C6H5), 9.69 (t, J = 2.5 Hz, CHO). 13C NMR (CDCl3): 45.9
(C-2), 68.6 (C-60), 74.4 (C-10), 73.4, 74. 9, 74.9, 75.4 (4 ꢂ CH2Ph),
78.2 (C-40), 79.1 (C-50), 81.1 (C-20), 87.0 (C-30), 127.5–128.4
(4 ꢂ C6H5), 137.5, 137.9, 137.9, 138.3 (4 ꢂ ipso C6H5), 200. 0
(CHO). ESIMS m/z: calcd for (C36H38O6): 566.7. Found, 567.4
[M+H]+. Anal. Calcd for C36H38O6: C, 76.30; H, 6.76. Found: C,
76.42; H, 6. 88.
the ratio a
:b = 6:1 (integration of H-10 signals in 1H NMR spectrum;
diastereoisomer
a as ddd at 4.20 ppm, diastereoisomer b as ddd at
3.50 ppm).
4.3. (2,3,4,6-Tetra-O-benzyl-b-D-glucopyranosyl)-ethanal (13b)
4.4. (E)-4-(2,3,4,6-Tetra-O-benzyl-b-D-glucopyranosyl)-1-
A 0.1 M solution of MeONa in MeOH was added dropwise to a
mixture of compounds 12a,b (23 g; 61.76 mmol) in MeOH
(500 ml) to allow the alkaline reaction to persist and the reaction
mixture was stirred at room temperature. After 20 h, no starting
compound was detected (TLC) in the reaction mixture which was
then neutralized with Dowex 50 (5 g) and filtered. Evaporation of
the solvent and chromatography on a silica gel (chloroform/MeOH
(thiazol-2-yl)-but-2-en-1-one (15)
Ylide 14 (Ref. 13; 13.7 g, 35.3 mmol) was added to a solution
of aldehyde 13b (10 g, 17.6 mmol) in CHCl3 (50 ml) and the mix-
ture was heated at 50 °C. After 30 h the reaction mixture did not
show an aldehyde proton signal (9.69 ppm) in the 1H NMR spec-
trum. The solvent was evaporated and the residue chromato-
graphed on a silica gel (light petroleum/ethyl acetate 5:1?3:1)
affording 9.42 g (79%) of compound 15; Rf = 0.3 (light petro-
5:1) afforded 11 g (87%) of a mixture of
a and b D-glucopyranosyl-
prop-2-enes, Rf = 0.4 (chloroform/MeOH 5:1). ESIMS m/z: calcd for
(C9H16O5): 204.2. Found, 205.7 [M+H]+. The obtained mixture of
leum/ethyl acetate 3:1). [
(CDCl3): 2.56 (ddd, 1H, J4a,4b = 15.3 Hz, J4a,1 = 7.8 Hz, J4a,3 = 6.2 Hz,
a
]
ꢀ3.79 (c 1.08, CHCl3); 1H NMR
D
D-glucopyranosylprop-2-enes (10.1 g; 49.4 mmol) was dissolved

K. Parkan et al. / Carbohydrate Research 345 (2010) 352–362
357
0
H-4a), 2.85 (ddd, 1H, J4b,4a = 15.3 Hz, J4b,1 = 5.7 Hz, J4b,3 = 3.4 Hz,
4.7. Methyl (S)-2-phenyl-2-((2R,4R)-4-((2,3,4,6-tetra-O-benzyl-
b- -glucopyranosyl)methyl-6-(thiazol-2-yl)-3,4-dihydro-2H-
pyran-2-yl)oxy)acetate (18)
H-4b), 3.36 (dd, 1H, J3 ,4 = J4 ,5 = 9.1 Hz, H-40), 3.41–3.51 (m, 2H,
H-10, H-50), 3.62–3.76 (m, 4H, H-60a, H-60b, H-20, H-30), 4.50–
4.98 (m, 8H, 4 ꢂ CH2Ph), 7.10–7.42 (m, 21H, 4 ꢂ C6H5, H-3) 7.43
(d, J2,3 = 15.6 Hz, H-2), 7.64 (d, 1H, J = 3.0 Hz, CH-thiazole) 7.97
(d, 1H, J = 3.0 Hz, CH-thiazole). 13C NMR (CDCl3): 35.2 (C-4),
68.7 (C-60), 73.5, 75.0, 75.1, 75.5 (4 ꢂ CH2Ph), 77.8 (C-10), 78.4
(C-30), 79.1 (C-50), 81.5 (C-40), 87.2 (C-20), 126.2 (C-3), 126.4
(CH-thiazole), 127.5–128.5 (20 ꢂ C6H5), 137.9, 138.1, 138.2,
138.5 (4 ꢂ ipso C6H5), 144.6 (CH-thiazole), 147.4 (C-2), 168.2
(C-thiazole), 181.4 (C-1). ESIMS m/z: calcd for (C41H41NO6S):
675.8. Found, 693.7 [M+NH4]+. Anal. Calcd for C41H41NO6S: C,
72.86; H, 6.11. Found: C, 72.83; H, 6.17.
D
0
0
0
0
According to the same procedure described for the preparation
of compound 17, compound 15 (3.51 g; 5.2 mmol) and chiral vinyl
ether (S)-16 (Refs. 4,12) (2.5 g, 13.0 mmol) afforded 3.65 g (81%) of
compound 18, mp 67–68 °C (ethyl acetate/light petroleum).
Rf = 0.32 (light petroleum/ethyl acetate 6:1). [
a
]
+56.9 (c 0.048,
D
CHCl3). 1H NMR (CDCl3): 1.76 (ddd, 1H, J1a ,1b = 14. 6 Hz,
00
00
J1a ,4 = 10.3 Hz, J1a ,1 = 5.0 Hz, H-1a00); 1.83 (ddd, 1H, J3ax,3eq
13.5 Hz, J3ax,4 = 8.0 Hz, J2,3ax = 7.3 Hz, H-3ax); 1.96 (ddd, 1H,
=
00
00
0
J1a ,1b = 14.6 Hz, J1b ,4 = 10.3 Hz, J1b ,1 = 2.5 Hz, H-1b00); 2.33 (ddd,
1H, J3ax,3eq = 13.5 Hz, J3eq,4 = 6.7 Hz, J2,3eq = 1.8 Hz, H-3eq); 2.85 (m,
1H, H-4); 3.25 (m, 1H, J = 8.7 Hz, H-40); 3.35–3.43 (m, 2H, H-50,
H-10); 3.61–3.79 (m, 4H, H-20, H-30, H-60a, H-60b); 3.72 (s, 3H,
PhCHCOOCH3); 4.53–4.67, 4.78–4.92 (m, 8H, 4 ꢂ PhCH2); 5.39
(dd,1H, J2,3ax = 7.3 Hz, J2,3eq = 1.8 Hz, H-2); 5.52 (s, 1H,
PhCHCOOCH3); 5.98 (d, 1H, J4,5 = 3.2 Hz, H-5); 7.10–7.43 (m, 25H,
5 ꢂ C6H5) 7.45 (1H, J = 3.2 Hz, CH-thiazole); 7.75 (d, 1H, J = 3.2 Hz,
CH-thiazole). 13C NMR (CDCl3): 27.7 (C-4); 32.95 (C-3); 37.9 (C-
100); 52.4 (CH–COOCH3); 69.0 (C-60); 73.6, 74.9, 75.2, 75.5
(4 ꢂ PhCH2); 77.1 (C-10); 77.7 (CH–COOCH3); 78.4 (C-30); 79.0 (C-
50); 82.7 (C-40); 87.2 (C-20); 98.9 (C-2); 106.5 (C-5); 118.5 (CH-thi-
azole); 127.3–128.6 (25 ꢂ C6H5); 136.1, 138.0, 138.2, 138.3, 138.6
(5 ꢂ ipso C6H5); 143.2 (CH-thiazole); 143.4 (C-6); 164.1 (C-thia-
zole); 171.0 (CH–COOCH3). ESIMS m/z: calcd for (C52H53NO9S):
868.1. Found, 869.6 [M+H]+. Anal. Calcd for C52H53NO9S: C, 71.95;
H, 6.15. Found: C, 71.99; H, 6.12.
00
00
00
00
0
4.5. (E)-4-(2,3,4-Tri-O-benzyl-a-L-fucopyranosyl)-1-(thiazol-2-
l)-but-2-en-1-one (20)
Similar to the preceding experiment, aldehyde 19 (Ref. 14; 6.2 g,
13.5 mmol) and ylide 14 (11.5 g; 29.7 mmol) afforded 5.74 g (75%)
of compound 20; Rf = 0.6 (light petroleum/ethyl acetate 3:1). [a]
D
ꢀ43.0 (c 0.74, CHCl3); 1H NMR (CDCl3): 1.30 (d, 3H, J = 6.5 Hz,
CH3), 2.55 (m, 1H, H-4b), 2.68 (m, 1H, H-4a), 3.74–3.84 (m, 3H,
H-20, H-30, H-40), 3.96 (m, 1H, H-50), 4.23 (m, 1H, H-10), 4.46–4.80
(m, 6H, 3 ꢂ CH2Ph), 7.21–7.40 (m, 17H, 3 ꢂ C6H5, H-2, H-3), 7.58
(d, 1H, J = 2.9 Hz, CH-thiazole), 7.95 (d, 1H, J = 2.9 Hz, CH-thiazole).
13C NMR (CDCl3): 15.0 (C-60), 31.7 (C-4), 68.8, 69.6 (C-10, C-50), 72.1,
72.5, 72.9 (3 ꢂ PhCH2), 76.3, 75.5, 74.1 (C-20, C-30, C-40), 125.1 (C-3),
126.1 (CH-thiazole), 128.3–127.3 (3 ꢂ C6H5), 137.9, 138.3, 138.4
(3 ꢂ ipso C6H5), 144.5 (CH-thiazole), 148.1 (C-2), 168.1 (C-thiazole),
181.1 (C-1). ESIMS m/z: calcd for (C34H35NO5S): 569.7. Found,
587.2 [M+NH4]+. Anal. Calcd for C34H35NO5S: C, 71.68; H, 6.19.
Found: C, 71.51; H, 6.22.
4.8. Methyl (S)-2-phenyl-2-(((2R, 4R)-4-((2,3,4-tri-O-benzyl-a-L-
fucopyranosyl)methyl)-6-(thiazol-2-yl)-3,4-dihydro-2H-pyran-
2-yl)oxy)acetate (21)
4.6. Methyl (R)-2-phenyl-2-((2S, 4S)-4-((2,3,4,6-tetra-O-benzyl-
b-D-glucopyranosyl)methyl-6-(thiazol-2-yl)-3,4-dihydro-2H-
pyran-2-yl)oxy)acetate (17)
According to the same procedure described for the preparation
of compound 17, compound 20 (4.9 g; 8.6 mmol) and chiral vinyl
ether (S)-16 (Refs. 4,12) (3.3 g; 17.2 mmol) afforded 4.93 g (75%)
of compound 21. Rf = 0.3 (light petroleum/ethyl acetate 2:1). [a]
D
ꢃ0 (c 3.24, CHCl3). 1H NMR (CDCl3): 1.22 (d, 3H, J = 6.4 Hz, CH3);
Eu(fod)3 (0.46 g, 0.44 mmol) was added to a solution of com-
pound 15 (5 g, 7.3 mmol) and chiral vinyl ether (R)-16 (Refs.
4,12) (3.6 g, 18.4 mmol) in dichloromethane (200 ml) and the reac-
tion mixture was stirred at room temperature. After 3 days, the
mixture did not contain (TLC) any starting compound 15. Evapora-
tion of solvent and chromatography of the residue on silica gel
(light petroleum/ethyl acetate 7:1) afforded 5.1 g (79%) of com-
00
00
00
00
0
1.59 (ddd, 1H, J1a ,1b = 14.2 Hz, J1a ,4 = 9.6 Hz, J1a ,1 = 2.8 Hz, H-
1a00); 1.87 (ddd, 1H, J3ax,3eq = 13.7 Hz, J3ax,4 = 6.9 Hz, J2,3ax = 6.0 Hz,
00
00
00
0
00
H-3ax); 2.06 (ddd, 1H, J1b ,1a = 14.2 Hz, J1b ,1 = 11.6 Hz, J1b ,4
=
6.0 Hz, H-1b00); 2.26 (ddd, 1H, J3eq,3ax = 13.7 Hz, J3eq,4 = 6.8 Hz,
J3eq,2 = 2.2 Hz, H-3eq); 2.59 (m, 1H, H-4); 3.65 (s, 3H, PhCH-
COOCH3); 3.69–3.81 (m, 4H, H-20, H-30, H-40, H-50); 4.15 (ddd, 1H,
J1 ,1b = 11.6 Hz, J1 ,2 = 6.0 Hz, J1 ,1a = 2.8 Hz, H-10) 4.48–4.79 (m,
6H, 3 ꢂ PhCH2); 5.43 (dd, 1H, J2,3ax = 6.0 Hz, J2,3eq = 2.2 Hz, H-2);
5.49 (s, 1H, PhCHCOOCH3); 6.00 (d, 1H, J4,5 = 3.7 Hz, H-5); 7.20–
7.45 (m, 21H, 4 ꢂ C6H5, CH-thiazole); 7.74 (d, 1H, J = 3.2 Hz, CH-thi-
pound 17; Rf = 0.35 (light petroleum/ethyl acetate 6:1). [a]
D
0
00
0
0
0
00
+96.7 (c 0.54, CHCl3). 1H NMR (CDCl3): 1.75 (ddd, 1H, J1a ,1b
=
00
00
14.2 Hz, J1 a,4 = 10.1 Hz, J1a ,1 = 4.6 Hz, H-1a00); 1.81 (ddd, 1H,
J3ax,3eq = 13.3 Hz, J3ax,4 = 8.0 Hz, J2,3ax = 7.3 Hz, H-3ax); 1.96 (ddd,
00
00
0
1H, J1a ,1b = 14.2 Hz, J1b ,4 = 10.1 Hz, J1b ,1 = 2.1 Hz, H-1b00); 2.34
(ddd, J3ax,3eq = 13.3 Hz, J3eq,4 = 6.4 Hz, J2,3eq = 2.1 Hz, H-3eq); 2.85
(m, 1H, H-4); 3.25 (t, 1H, J = 8.8 Hz, H-40); 3.36–3.43 (m, 2H,
H-50, H-10); 3.62–3.78 (m, 4H, H-20, H-30, H-60a, H-60b); 3.73
(s, 3H, PhCHCOOCH3); 4.52–4.68, 4.78–4.93 (m, 8H, 4 ꢂ PhCH2);
5.38 (dd, 1H, J2,3ax = 7.3 Hz, J2,3eq = 2.1 Hz, H-2); 5.52 (s, 1H,
PhCHCOOCH3); 5.99 (d, 1H, J4,5 = 3.2 Hz, H-5); 7.14–7.44 (m, 25H, 5 ꢂ
C6H5), 7.45 (d, 1H, J = 3.2 Hz, CH-thiazole), 7.75 (d, 1H, J = 3.2 Hz, CH-
13
azole). C NMR (CDCl3): 15.0 (C-60); 27.2 (C-4); 31.8 (C-3); 32.5
00
00
00
00
0
(C-100); 52.2 (CH–COOCH3); 68.2 (C-10); 68.2 (C-50); 72.9, 76.6,
77.1 (3 ꢂ PhCH2); 75.8 75.8, 76.9, 77.3 (CH–COOCH3, C-40, C-30,
C-20); 98.0 (C-2); 106.5 (C-5); 118.2 (CH-thiazole); 127.1–128.4
(4 ꢂ C6H5); 136.1, 138.1, 138.4, 138.6 (4 ꢂ ipso C6H5); 142.7 (C-
6); 143.1 (CH-thiazole); 163.9 (C-thiazole); 170.7 (CH–COOCH3).
ESIMS m/z: calcd for (C45H47NO8S): 761.9. Found, 763.1 [M+H]+.
Anal. Calcd for C45H47NO8S: C, 70.94; H, 6.22. Found: C, 70.89; H,
6.32.
13
thiazole). C NMR (CDCl3): 27.7 (C-4); 33.0 (C-3); 37.9 (C-100); 52.4
(CH–COOCH3); 69.0 (C-60); 73.6, 74.9, 75.2, 75.5 (4 ꢂ PhCH2); 77.1
(C-10); 77.7 (CH–COOCH3); 78.4 (C-30); 79.0 (C-50); 82.67 (C-40);
87.2 (C-20); 98.9 (C-2); 106.6 (C-5); 118.53 (CH-thiazole); 127.3–
128.6 (25 ꢂ C6H5); 136.1, 138.0, 138.2, 138.3, 138.6 (5 ꢂ ipso C6H5);
143.1 (CH-thiazole); 143.4 (C-6); 164.1 (C-thiazole); 171.0 (CH–
COOCH3). ESIMS m/z: calcd for (C52H53NO9S): 868.0. Found, 869.0
[M+H]+. Anal. Calcd for C52H53NO9S: C, 71.95; H, 6.15. Found: C,
72.01; H, 6.18.
4.9. (2S,4S)-2-[(2R)-2-Methoxy-1-phenylethoxy]-4-[(2,3,4,6-
tetra-O-benzyl-b-D-glucopyranosyl)methyl]-6-(thiazol-2-yl)-
3,4-dihydro-2H-pyran (22)
Lithium aluminum hydride (0.5 g; 13.8 mmol) was added
portionwise to a solution of compound 17 (4.01 g, 4.61 mmol) in
tetrahydrofuran (200 ml), pre-cooled to 0 °C, and the reaction

358
K. Parkan et al. / Carbohydrate Research 345 (2010) 352–362
mixture was stirred at room temperature for 2 h. After cautious
addition of 1 M solution of NaOH (10 ml), the salts were removed
by filtration, washed with ethyl acetate, and the solvent was evap-
orated. The residue was partitioned between ethyl acetate and
water, the organic layer was dried and taken down, and the residue
was chromatographed through a short silica gel column in light
petroleum/ethyl acetate (5:1). The obtained alcohol (3.8 g,
Rf = 0.35 in light petroleum/ethyl acetate 2:1, m/z 841.6 [M+H]+)
was dissolved in tetrahydrofuran (250 ml) and the solution was
stirred with potassium tert-butoxide (1.4 g, 12.5 mmol) at room
temperature for 15 min, the mixture was then treated with methyl
iodide (1.04 ml, 16.6 mmol) and stirred at room temperature for
15 h. After the addition of saturated aqueous NH4Cl (100 ml), the
reaction mixture was concentrated in vacuo and the residue was
partitioned between dichloromethane and a saturated solution of
NH4Cl. The organic layer was dried, the solvent evaporated, and
the residue chromatographed on silica gel in light petroleum/ethyl
acetate (6:1) affording 2.95 g (75%) of compound 22; Rf = 0.71
acetate/light petroleum), Rf = 0.5 (light petroleum/ethyl acetate
4:1). [
+33.8 (c 1.03, CHCl3). 1H NMR (CDCl3): 1.75–1.85 (m,
2H, H-1a00, H-3ax); 2.07 (m, 1H, H-1b00); 2.20 (m, 1H, H-3eq); 2.84
a
]
D
(m, 1H, H-4); 3.29 (dd, 1H, J3 ,4 = J4 ,5 = 8.9 Hz, H-40); 3.35–3.46
(m, 2H, H-10, H-50); 3.57 (dd, 1H, J = 11.0 Hz, J = 3.7 Hz,
PhCHCH2aOBn); 3.60–3.71 (m, 3H, PhCHCH2bOBn, H-30, H-60a);
3.71–3.77 (m, 2H, H-60b, H-20); 4.45–4.92 (m, 10H, 5 ꢂ PhCH2);
4.95 (dd, 1H, J = 8.0 Hz, J = 3.7 Hz, PhCHCH2OBn), 5.46 (dd, 1H,
J2,3ax = 6.9 Hz, J2,3eq = 1.6 Hz, H-2); 5.94 (d, 1H, J4,5 = 3.0 Hz, H-5);
7.12 (d, 1H, J = 3.2 Hz, CH-thiazole); 7.13–7.40 (m, 30H,
6 ꢂ C6H5); 7.66 (d, J = 3.2 Hz, CH-thiazole). 13C NMR (CDCl3): 27.4
(C-4); 32.7 (C-3); 37.7 (C-100); 69.0 (C-60); 73.5, 73.5, 74.9, 75.0,
75.3 (5 ꢂ PhCH2); 75.5 (PhCHCH2OBn) 76.9 (C-10); 78.5 (C-30);
79.0 (C-50), 81.7 (PhCHCH2OBn); 82.8 (C-40); 87.2 (C-20); 101.2
(C-2); 105.4 (C-5); 118.5 (CH-thiazole); 126.6–128.4 (30 ꢂ C6H5);
138.0, 138.2, 138.3, 138.6, 139.8, 139.8 (6 ꢂ ipso C6H5); 142.7
(CH-thiazole); 143.6 (C-6); 164.5 (CH-thiazole). ESIMS m/z: calcd
for (C58H59NO8S): 930.2. Found, 948.3 [M+NH4]+. Anal. Calcd for
C58H59NO8S: C, 74.89; H, 6.39. Found: C, 74.97; H, 6.56.
0
0
0
0
(light petroleum/ethyl acetate 2:1). [a]
+48.8 (c 0.86, CHCl3). 1H
D
NMR (CDCl3): 1.74–1.84 (m, 2H, H-1a00, H-3ax); 2.03 (m, Hz, 1H,
H-1b00); 2.23 (m, 1H, H-3eq); 2.85 (m, 1H, H-4); 3.29 (dd, 1H,
4.11. (2R,4R)-2-[(2S)-2-Benzyloxy-1-phenylethoxy]-4-(2,3,4-tri-
J3 ,4 = J4 ,5 = 8.7 Hz, H-40); 3.37 (s, 3H, PhCHCH2OCH3); 3.32–3.44
(m, 2H, H-10, H-50); 3.47 (dd, 1H, J = 10.8 Hz, J = 3.7 Hz, PhCHCH2a
OCH3); 3.57 (dd, 1H, J = 10.5 Hz, J = 8.5 Hz, H-60a); 3.65–3.78 (m,
4H, H-30, PhCHCH2bOCH3, H-60b, H-20); 4.54–4.68 (m, 4H, 2 ꢂ
PhCH2); 4.76–4.95 (m, 4H, 2 ꢂ PhCH2); 4.91 (m, 1H, PhCHCH2
OCH3); 5.42 (dd, 1H, J2,3ax = 7.3 Hz, J2,3eq = 1.8 Hz, H-2); 5.91 (d,
1H, J4,5 = 3.0 Hz, H-5); 7.12 (d, 1H, J = 3.2 Hz, CH-thiazole); 7.13–
7.44 (m, 25H, 5 ꢂ C6H5); 7.66 (d, J = 3.2 Hz, CH-thiazole). 13C
NMR (CDCl3): 27.6 (C-4); 32.9 (C-3); 37.8 (C-100); 59.3
(PhCHCH2OCH3); 69.0 (C-60); 73.4, 73.5, 74.9, 75.3, 75.5 (4 ꢂ
PhCH2, PhCHCH2OCH3); 76.8 (C-10); 78.5 (C-30); 79.0 (C-50); 81.5
(PhCHCH2OCH3); 82.8 (C-40); 87.2 (C-20); 101.3 (C-2); 105.4
(C-5); 118.5 (CH-thiazole); 126.1–128.4 (25 ꢂ C6H5); 138.0, 138.2,
138.2, 138.6, 139.8 (5 ꢂ ipso C6H5); 142.8 (CH-thiazole); 143.7
(C-6); 164.4 (C-thiazole). ESIMS m/z: calcd for (C52H55NO8S):
854.1. Found, 872.4 [M+NH4]+. Anal. Calcd for C52H55NO8S: C,
73.13; H, 6.49. Found: C, 73.23; H, 6.56.
O-benzyl-a-L-fucopyranosyl)methyl]-6-(thiazol-2-yl)-3,4-
dihydro-2H-pyran (24)
0
0
0
0
Using the same procedure as described for the preparation of
compound 23, compound 21 (4.27 g; 5.6 mmol) was converted to
compound 24 (2.65 g; 69%), Rf = 0.65 (light petroleum/ethyl ace-
tate 9:1). [
a
]
ꢀ20.8 (c 1.26, CHCl3). 1H NMR (CDCl3): 1.27 (d, 3H,
D
J = 6.2 Hz, CH3), 1.62 (m, 1H, H-1a00), 1.78 (m, 1H, H-3ax), 2.08
(ddd, 1H, J1b ,1a = 14.6 Hz, J = 9.6 Hz, J = 5.0 Hz, H-1b00), 2.22
(m,1H, H-3eq), 2.60 (m, 1H, H-4), 3.60 (dd, 1H, J = 11.00,
J = 3.7 Hz, PhCHCH2aOBn), 3.65–3.90 (m, 5H, H-20, H-30, H-40, H-50,
PhCHCH2bOBn), 4.20 (m, 1H, H-10), 4.42–4.80 (m, 8H, 4 ꢂ CH2Ph),
4.98 (1H, J = 8.3 Hz, J = 3.7 Hz, PhCHCH2OBn), 5.49 (dd, 1H,
J2,3ax = 6.9 Hz, J2,3eq = 1.8 Hz, H-2), 5.92 (d, 1H, J5,4 = 3.2 Hz, H-5),
7.05 (d, 1H, J = 3.2 Hz, CH-thiazole), 7.13–7.38 (m, 25H, 5 ꢂ C6H5),
7.08 (d, 1H, J = 3.2 Hz, CH-thiazole).13C NMR (CDCl3): 15.6 (C-60),
27.3 (C-4), 32.2 (C-3), 32.3 (C-100), 68.2, 68.3 (C-10, C-50), 72.8,
72.9, 73.0, 73.2 (4 ꢂ PhCH2), 74.7 (PhCHCH2OBn), 75.9, 76.7, 76.9
(C-20, C-30, C-40), 80.8 (PhCHCH2OBn), 100.7 (C-2), 105.3 (C-5),
118.3 (CH thiazole), 126.4–128.2 (5 ꢂ C6H5), 138.0, 138.1, 138.4,
138.6, 139.5 (5 ꢂ ipso C6H5), 142.7 (CH tiazol), 143.4 (C-6), 164.2
(thiazole C-2). ESIMS m/z: calcd for (C51H53NO7S): 823.4. Found,
824.3 [M+H]+. Anal. Calcd for C51H53NO7S: C, 74.34; H, 6.48. Found:
C, 74.53; H, 6.59.
00
00
4.10. (2R,4R)-2-[(2S)-2-Benzyloxy-1-phenylethoxy]-4-[(2,3,4,6-
tetra-O-benzyl-b-D-glucopyranosyl)methyl]-6-(thiazol-2-yl)-
3,4-dihydro-2H-pyran (23)
Lithium aluminum hydride (0.5 g, 22.14 mmol) was added por-
tionwise under argon to a solution of compound 18 (6.41 g,
7.38 mmol) in tetrahydrofuran (250 ml), pre-cooled to 0° C, and
the reaction mixture was stirred at room temperature for 2 h. After
cautious addition of 1 M solution of NaOH (10 ml), the salts were
removed by filtration, terahydrofuran was evaporated and the res-
idue was partitioned between ethyl acetate and water. The organic
layer was dried, the solvent evaporated and the residue was sub-
jected to flash chromatography through a short column of silica
gel in light petroleum/ethyl acetate (5:1). The obtained alcohol
(5.248 g, Rf = 0.4 in light petroleum/ethyl acetate = 4:1, m/z 839.6
[M+H]+) was dissolved in tetrahydrofuran (300 ml) and the solu-
tion was stirred at room temperature for 1 h with a 60% suspension
of NaH v mineral oil (1 g, 41.6 mmol). Then benzyl bromide
(2.23 ml, 18.7 mmol) and tetrabutylammonium iodide (0.58 g,
1.56 mmol) were added, the reaction mixture was heated at
40 °C for 20 min and then stirred at room temperature for 14 h.
MeOH (5 ml) was added, the solvent was evaporated in vacuo
and the residue partitioned between dichloromethane and a satu-
rated solution of NaHCO3. The organic layer was dried, the solvent
was taken down and the residue was chromatographed on a silica
gel in light petroleum/ethyl acetate (6:1). This procedure yielded
5.07 g (74%) of compound 23, mp 107–108 °C (from ethyl
4.12. (2S,4S)-2-[(2R)-2-Methoxy-1-phenylethoxy]-4-[(2,3,4,6-
tetra-O-benzyl-b-D-glucopyranosyl)methyl]-6-formyl-3,4-
dihydro-2H-pyran (25)
Molecular sieves (4 Å; 3.5 g) were added to a solution of com-
pound 22 (2.8 g, 3.28 mmol) in acetonitrile (40 ml), and methyl tri-
flate (0.48 ml, 4.26 mmol) was added dropwise. After stirring at
room temperature for 15 min, MeOH (5 ml) was added and the sol-
vent was evaporated in vacuo. The residue was treated with MeOH
(40 ml) and then NaBH4 (0.37 g, 9.83 mmol) was added in portions.
After stirring at room temperature for 15 min, acetone (8 ml) was
added, the reaction mixture was filtered through a supercel and
the filtrate was evaporated in vacuo. The residue was dissolved
in acetonitrile (40 ml) and a solution of AgNO3 (1.11 g, 6.56 mmol)
in water (4.4 ml) was added under vigorous stirring. After stirring
for 10 min, phosphate buffer (30 ml, pH 7) was added and after
10 min, the acetonitrile was evaporated in vacuo and the residue
was partitioned between dichloromethane and a phosphate buffer
(pH 7). The organic phase was dried, the solvent evaporated, and
the residue flash-chromatographed through a short silica gel

K. Parkan et al. / Carbohydrate Research 345 (2010) 352–362
359
column in light petroleum/ethyl acetate (4:1). This resulted in a
yield of 1.83 g (70%) of crystalline aldehyde 25, mp 113–114 °C
(ethyl acetate/light petroleum), Rf = 0.3 (light petroleum/ethyl ace-
PhCHCH2OBn), 5.60 (d, 1H, J = 2.7 Hz, H-2), 5.90 (d, 1H, J = 4.6 Hz,
H-5), 7.10–7.40 (m, 25H, 5 ꢂ C6H5), 8.85 (s, 1H, CHO). 13C NMR
(CDCl3): 15,6 (C-60), 28.0 (C-4), 31.1 (C-100), 30.9 (C-3), 67.9 (C-50),
70.3 (C-10), 72.9, 73.0, 73.1, 73.4 (4 ꢂ PhCH2), 74.3 (PhCHCH2OBn),
76.5 (C-40), 76.8 (C-30), 77.3 (C-20), 78.9 (PhCHCH2OBn), 98.0 (C-2),
126.5–128.3 (5 ꢂ C6H5, C-5), 138.0, 138.2, 138.4, 138.6, 139.2
(5 ꢂ ipso C6H5), 148.3 (C-6), 186.3 (CHO). ESIMS m/z: calcd for
(C49H52O8): 768.9. Found, 787.1 [M+NH4]+. Anal. Calcd for
C49H52O8: C, 76.54; H, 6.82. Found: C, 76.73; H, 7.01.
tate, 3:1). [
a
]
ꢀ19.0 (c 0.19, CHCl3), 1H NMR (CDCl3): 1.70 (ddd,
D
1H, J1a ,1b = 13.8 Hz, J = 10.2 Hz, J = 4.6 Hz, H-1a00); 1.92 (ddd, 1H, J
3ax,3eq = 14.0 Hz, J3ax,4 = 9.2 Hz, J2,3ax = 4.6 Hz, H-3ax); 2.03 (ddd,
1H, J3ax,3eq = 14.0 Hz, J3eq,4 = 7.3 Hz, J2,3eq = 2.6 Hz, H-3eq); 2.20
00
00
(ddd, 1H, J1a ,1b = 13.8 Hz, J = 8.7 Hz, J = 2.2 Hz, H-1b00); 2.73 (m,
00
00
1H, H-4); 3.28 (dd, 1H, J3 ,4 = J4 ,5 = 9.2 Hz, H-40); 3.32 (s, 3H,
PhCHCH2OCH3); 3.37–3.47 (m, 3H, H-10, H-50, PhCHCH2aOCH3);
3.50 (dd, 1H, J = 10.54 Hz, J = 8.25 Hz, PhCHCH2bOCH3); 3.63 (dd,
0
0
0
0
4.15. (2R)-2-Methoxy-1-phenylethyl 2,3-dideoxy-3-C-[(2,3,4,6-
1H, J2 ,3 = J3 ,4 = 9.2 Hz, H-30); 3.66 (dd, 1H, J = 10.54 Hz, J = 4.6 Hz,
H-60a); 3.69–3.75 (m, 2H, H-60b, H-20); 4.51–4.95 (m, 8H, 4 ꢂ
PhCH2); 4.90 (m, 1H, PhCHCH2OCH3); 5.49 (dd, 1H, J2,3ax = 4.6 Hz,
J2,3eq = 2.6 Hz, H-2); 5.87 (d, 1H, J5,4 = 4.1 Hz, H-5); 7.16–7.37 (m,
25H, 5 ꢂ C6H5); 8.79 (s, 1H, CHO). 13C NMR (CDCl3): 27.7 (C-4);
31.4 (C-3); 36.9 (C-100); 59.2 (CHCH2OCH3); 69.2 (C-60); 73.5, 75.0,
75.2, 75.6, 77.2 (4 ꢂ PhCH2, PhCHCH2OCH3); 77.5 (C-10); 78.6 (C-
30), 78.9 (C-50); 79.8 (PhCHCH2OCH3); 82.6 (C-40); 87.2 (C-20);
98.8 (C-2); 126.6 (C-5); 127.5–128.5 (25 ꢂ C6H5); 138.0, 138.1,
138.2, 138.5, 139.3 (5 ꢂ ipso C6H5); 148.7 (C-6); 186.3 (CHO).
ESIMS m/z: calcd for (C50H54O9): 799.0. Found, 817.1 [M+NH4]+.
Anal. Calcd for C50H54O9: C, 75.16; H, 6.81. Found: C, 75.23; H, 6.93.
tetra-O-benzyl-b-
arabinohexopyranoside (28)
D
-glucopyranosyl)methyl]-4,6-di-O-benzyl-b-L-
0
0
0
0
A
2 M solution of BH3ꢁMe2S in tetrahydrofuran (3.94 ml,
7.88 mmol) was added dropwise to a solution of aldehyde 25
(1.8 g, 2.23 mmol) in tetrahydrofuran (40 ml) pre-cooled to 0 °C,
and the reaction mixture was stirred at room temperature for
16 h. Then, a 30% NaOH solution (4 ml) and 30% H2O2 (4 ml) were
added in succession. The mixture was stirred at room temperature
for 30 min and partitioned between dichloromethane and a satu-
rated NaCl solution. The organic phase was dried, the dichloro-
methane evaporated in vacuo, and the residue was dissolved in
tetrahydrofuran (60 ml). After addition of a 60% suspension of
NaH in mineral oil (0.72 g, 30.03 mmol), the mixture was stirred
at room temperature for 1 h. Benzyl bromide (1.04 ml, 9.01 mmol)
and tetrabutylammonium iodide (0.21 g, 0.56 mmol) were added
and the reaction mixture was heated at 40 °C for 15 min. After stir-
ring at room temperature for 14 h, MeOH (5 ml) was added, the
solvent was evaporated in vacuo, and the residue was partitioned
between dichloromethane and a saturated solution of NaHCO3.
The organic layer was dried, the solvent removed in vacuo, and
the residue chromatographed on silica gel in light petroleum/ethyl
acetate (5:1) to give 1.69 g (75%) of compound 28, Rf = 0.35 (light
4.13. (2R,4R)-2-[(2S)-2-Benzyloxy-1-phenylethoxy]-4-[(2,3,4,6-
tetra-O-benzyl-b-D-glucopyranosyl)methyl]-6-formyl-3,4-
dihydro-2H-pyran (26)
Using the same procedure as described for the preparation of
compound 25, compound 23 (3.39 g; 3.64 mmol) was converted to
aldehyde 26, (2.36 g; 74%), Rf = 0.5 (light petroleum/ethyl acetate,
3:1). [
a]
ꢀ83.8 (c 0.66, CHCl3). 1H NMR (CDCl3): 1.70 (ddd, 1H,
D
J1a ,1b = 13.8 Hz, J = 10.3 Hz, J = 5.7 Hz, H-100a); 1.94 (m, 1H, J3ax,3eq
=
00
00
14.2 Hz, J3ax,4 = 9.6 Hz, J3ax,2 = 4.6 Hz, H-3ax); 2.03 (m, 1H,
J3eq,3ax = 14.2 Hz, J3eq,4 = 6.4 Hz, J3eq,2 = 2.8 Hz Hz, H-3eq); 2.24 (ddd,
petroleum/ethyl acetate, 3:1). [
a]
ꢀ6.3 (c 0.19, CHCl3). 1H NMR
D
1H, J1b ,1a = 13.8 Hz, J = 8.7 Hz, J = 2.1 Hz, H-100b); 2.73 (m, 1H, H-
(CDCl3): 1.34 (m, 1H, H-2ax), 1.45 (m, 1H, H-1a00), 1.71 (m, 1H, H-
3), 2.04 (m, 1H-1b00), 2.12 (m, 1H, H-2eq), 3.12 (m, 1H, H-10), 3.17
(m, 1H, H-5), 3.29 (dd, 1H, J3,4 = J4,5 = 9.1 Hz, H-4), 3.34 (s, 3H,
PhCHCH2OCH3), 3.32–3.40 (m, 2H, PhCHCH2aOCH3, H-40), 3.47–
3.56 (m, 2H, PhCHCH2bOCH3, H-50), 3.58 (m, 1H, H-6a); 3.58-
3.68 (m, 4H, H-60a, H-30, H-20, H-60a), 3.71 (m, 1H, H-6b), 4.30–
4.92 (m, 12H, 6 ꢂ CH2Ph), 4.75 (dd, 1H, J1,2ax = 9.6 Hz,
J1,2eq = 1.60 Hz, H-1), 4.84 (m, 1H, PhCHCH2OCH3) 7.15–7.40 (m,
00
00
4); 3.30 (dd, 1H, J3 ,4 = J4 ,5 = 9.2 Hz, H-40); 3.36–3.47 (m, 2H, H-10,
H-50); 3.50–3.58 (m, 2H, PhCHCH2aOBn, H-60a); 3.63 (dd, 1H,
0
0
0
0
J2 ,3 = J3 ,4 = 9.1 Hz, H-30); 3.66–3.74 (m, PhCHCH2bOBn, H-60b, H-
20); 4.43–4.93 (m, 10H, 5 ꢂ PhCH2); 4.94 (dd, 1H, J = 7.6 Hz,
J = 4.1 Hz, PhCHCH2OBn); 5.55 (dd, 1H J2,3ax = 4.6 Hz, J2,3eq = 2.8 Hz,
H-2); 5.89 (d, 1H, J5,4 = 4.1 Hz, H-5); 7.10–7.39 (m, 30H, 6 ꢂ C6H5);
8.82 (s, 1H, CHO). 13C NMR (CDCl3): 27.6 (C-4); 31.1 (C-3); 36.8 (C-
100); 69.1 (C-60); 73.3, 73.4, 74.8, 74.9, 75.2 (5 ꢂ PhCH2); 75.6
(PhCHCH2OBn); 77.4 (C-10); 78.5 (C-30), 78.8 (C-50); 80.1
(PhCHCH2OBn); 82.5 (C-40); 87.2 (C-20); 98.8 (C-2); 126.5 (C-5);
127.3–128.4 (6 ꢂ C6H5); 137.9, 138.0, 138.1, 138.3, 138.4, 139.2
(5 ꢂ ipso C6H5); 148.7 (C-6); 186.4 (CHO). ESIMS m/z: calcd for
(C56H58O9): 875.1. Found, 893.6 [M+NH4]+. Anal. Calcd for
C56H58O9: C, 76.86; H, 6.68. Found: C, 76.82; H, 6.75.
0
0
0
0
13
35H, 7 ꢂ C6H5). C NMR (CDCl3): 34.5 (C-100), 35.8 (C-2), 36.0 (C-
3), 59.2 (PhCHCH2OCH3), 69.0, 69.3 (C-60, C-6), 70.3, 73.4, 73.5,
73.6, 75.0, 75.1, 75.5 (PhCHCH2OCH3, 6 ꢂ CH2Ph), 75.4 (C-50),
77.9 (C-4), 78.0 (C-10), 78.6 (C-30), 78.7 (C-5), 79.0 (PhCHCH2OMe),
82.6 (C-40), 87.3 (C-20), 101.8 (C-1), 126.7–128.5 (35 ꢂ C6H5), 138.1,
138.2, 138.3, 138.4, 138.5, 138.6, 140.3 (7 ꢂ ipso C6H5). ESIMS m/z:
calcd for (C64H70O10): 999.2. Found, 1000.6 [M+H]+. Anal. Calcd for
C64H70O10: C, 76.93; H, 7.06. Found: C, 77.25; H, 6.98.
4.14. (2R,4R)-2-[(2S)-2-Benzyloxy-1-phenylethoxy]-4-[(2,3,4-
tri-O-benzyl-
a
-L
-fucopyranosyl)methyl]-6-formyl-3,4-dihydro-
4.16. (2S)-2-Methoxy-1-phenylethyl 2,3-dideoxy-3-C-[(2,3,4,6-
2H-pyran (27)
tetra-O-benzyl-b-
D-glucopyranosyl)methyl]-4,6-di-O-benzyl-b-
D-arabinohexopyranoside (29)
Using the same procedure as described for the preparation of
compound 25, compound 24 (2.65 g; 3.22 mmol) was converted
to aldehyde 27 (1.79 g; 72%), Rf = 0.65 (light petroleum/ethyl ace-
Using the same procedure as described for the preparation of
compound 28, aldehyde 26 (2.36 g, 2.7 mmol) was converted to
compound 29 (2.21 g; 76%), Rf = 0.4 (light petroleum/ethyl acetate,
tate, 2:1). [
a
]
ꢀ21.2 (c 0.79, CHCl3). 1H NMR (CDCl3): 1.12 (d,
D
3H, J = 6.3 Hz, CH3), 1.72 (m, 1H, H-1a00), 1,95 (m, 1H, H-3ax), 2.01
3:1). [
a
]
D ꢀ45.24 (c 1.25, CHCl3). 1H NMR (CDCl3): 1.36 (m, 1H, H-
(ddd, 1H, J3eq,3ax = 14.2 Hz, J3eq,4 = 7.3 Hz, J3eq,2 = 2.7 Hz, H-3eq),
2ax), 1.48 (m, 1H, H-100a), 1.83 (m, 1H, H-3) 2.05 (m, 1H-2eq), 2.14
(m, 1H, H-100a), 3.14 (m, 1H, H-10), 3.19 (m, 1H, H-5), 3.29 (dd,
1H, J3,4 = J4,5 = 9.1 Hz, H-4), 3.37 (m, 2H, PhCHCHaOBn, H-40), 3.47
(m, 1H, H-50), 3.54 (m, 1H, H-6a), 3.58–3.74 (m, 6H, H-60a,
PhCHCHbOMe, H-6b, H-30, H-20, H-60b), 4.42–4.92 (m, 14H,
7 ꢂ CH2Ph) 4.79 (m, 1H, H-1), 4.92 (m, 1H, PhCHCH2OBn), 4.73–
2.12 (ddd, 1H, J1b ,1a = 14.2 Hz, J = 9.6 Hz, J = 6.9 Hz, H-1b00), 2.46
(m, 1H, H-4), 3.56 (m, 1H, H-50), 3.57 (dd, J = 11.00 Hz, J = 3.7 Hz,
PhCHCH2aOBn), 3.63 (m, 1H, H-40), 3.64–3.70 m (m, 2H, H-20,
PhCHCH2bOBn), 3.85 (m, 1H, H-30), 4.15 (m, 1H, H-10), 4.43–4.83
(m, 8H, 4 ꢂ O-CH2-Ph), 4.98 (dd, J = 8.3 Hz, J = 3.7 Hz, 1H,
00
00

360
K. Parkan et al. / Carbohydrate Research 345 (2010) 352–362
4.93 (m, 6H, H-1, 2 ꢂ CH2Ph,) 7.14–7.41 (m, 40H, 8 ꢂ C6H5). 13C
NMR (CDCl3): 34.4 (C-100), 35.8 (C-2), 35.9 (C-3), 69.0, 69.3 (C-60,
C-6), 73.2, 73.3, 73.4, 73.6, 74.6, 74.9, 75.1, 75.5, (PhCHCH2OCH3,
7 ꢂ CH2Ph), 75.5 (C-50), 78.0 (C-4), 78.5 (C-10), 79.0 (C-30), 79.3
(C-5), 79.4 (PhCHCH2OBn), 82.5 (C-40), 87.3 (C-20), 101.8 (C-1),
126.8–128.4 (40 ꢂ C6H5), 138.1, 138.2, 138.2, 138.3, 138.4, 138.5,
138.6, 140.3 (8 ꢂ ipso C6H5). ESIMS m/z: calcd for (C64H70O10):
1075.3. Found, 1076.1 [M+H]+. Anal. Calcd for C70H74O10: C,
78.19; H, 6.94. Found: C, 78.38; H, 7.21.
Minor b-diastereoisomer 31b: 1H NMR, 4.75 (dd, J1,2ax = 11.7 Hz,
J1,2eq = 1.6 Hz, H-1). Further signals were overlapped by those of
the major diastereoisomer.
4.19. Phenyl-1-thio 2,3-dideoxy-3-C-[(2,3,4,6-tetra-O-benzyl-b-
D
-glucopyranosyl)methyl]-4,6-di-O-benzyl-
pyranoside (32a) and phenyl-1-thio 2,3-dideoxy-3-C-[(2,3,4,6-
tetra-O-benzyl-b- -glucopyranosyl)methyl]-4,6-di-O-benzyl-b-
-arabinohexopyranoside (32b)
a-D-arabinohexo-
D
D
4.17. (2S)-2-Methoxy-1-phenylethyl 2,3-dideoxy-3-C-[(2,3,4-tri-
Using the same procedure as described for the preparation of
O-benzyl-
arabinohexopyranoside (30)
a
-
L
-fucopyranosyl)methyl]-4,6-di-O-benzyl-b-
D
-
compounds 31a,b, compound 29 2.1 g (1.95 mmol) was converted
to a mixture of thioglycosides 32a,b (1.72 g; 92%), Rf = 0.45 (light
petroleum/ethyl acetate, 3:1).
Using the same procedure as described for the preparation of
compound 28, aldehyde 27 (1.79 g, 2.33 mmol) was converted to
compound 30 (1.63 g; 72%), Rf = 0.65 (light petroleum/ethyl ace-
Major a
-diastereoisomer 32a: 1H NMR (CDCl3): 1.49 (m, 1H, H-
1a00), 1.86 (m, 1H, H-2ax), 1.98 (m, 1H, H-1b00), 2.16 (m, 1H, H-2eq),
2.41 (m, 1H, H-3), 3.15–3.32 (m, 3H, H-10, H-4, H-50), 3.32–3.39 (m,
1H, H-40), 3.51 (m, 1H, H-6a), 3.57–3.71 (m, 4H, H-30, H-6b, H-5, H-
20), 3.75 (m, 1H, H-60a), 3.83 (m, 1H, H-60b), 4.37–4.97 (m, 12H,
6 ꢂ CH2Ph), 5.61 (d, 1H, J1,2 = 5.1 Hz, H-1), 7.14–7.53 (m, 35H,
tate, 9:1). [
a
]
ꢀ11.5 (c 0.41, CHCl3). 1H NMR (CDCl3): 1.14 (d,
D
3H, J = 6.4 Hz, CH3), 1.2–1.4 (m, 2H, H-100b, H-2ax), 1.82 (m, 1H,
H-3), 2.2 (m, 2H, H-100a, H-2eq), 3.18 (dd, 1H, J3,4 = J4,5 = 9.6 Hz, H-
4), 3.35 (m, 1H, H-5), 3.52–3.59 (m, 2H, H-6a, H-40, H-30), 3.60–
3.69 (m, 4H, H-50, PhCHCH2aOBn, H-6b), 3.72 (dd, 1H, J = 11.9 Hz,
J = 3.7 Hz,, PhCHCH2bOBn), 3.95 (m, 1H, H-20), 4.12 (ddd, 1H,
J = 12.4 Hz, J = 7.8 Hz, J = 3.2 Hz, H-10), 4.3–4.75 (m, 12H,
6 ꢂ CH2Ph), 4.82 (dd, 1H, J1,2ax = 11.7 Hz, J1,2eq = 7.4 Hz, H-1), 4.93
(dd, 1H, J = 3.7 Hz, J = 7.7 Hz, PhCHCH2OBn), 7.1–7.4 (m, 35H,
13
7 ꢂ C6H5). C NMR (CDCl3): 33.4 (C-100), 34.0 (C-3), 34.2 (C-2),
69.0, 69.3 (C-60, C-6), 72.1, 72.8, 73.4, 74., 75.2, 75.7, (6 ꢂ CH2Ph),
75.6 (C-50), 78.3 (C-4), 79.0 (C-10), 79.2 (C-30), 80.0 (C-5), 82.5 (C-
40), 84.8 (C-1), 87.4 (C-20), 126.2–128.7 (35 ꢂ C6H5), 138.0, 138.0,
138.1, 138.2, 138.2, 138.3, 138.6, (7 ꢂ ipso C6H5). ESIMS m/z: calcd
for (C61H64O8S): 957.2. Found, 973.5 [M+NH4]+.
13
7 ꢂ C6H5). C NMR (CDCl3): 16.1 (C-60), 28.0 (C-100), 35.4 (C-2),
Minor b-diastereoisomer 32b: 1H NMR, 4.75 (dd, J1,2ax = 11.5 Hz,
J1,2eq = 1.7 Hz, H-1). Further signals were overlapped by those of
the major diastereoisomer.
35.7 (C-3), 67.2 (C-50), 67.3 (C-10), 69.2 (C-6), 72.8, 72.9, 73.0,
73.3, 73.8, 74.3, (6 ꢂ PhCH2), 74.6 (PhCHCH2OBn), 76.6 (C-40),
76.7 (C-30), 76.8 (C-20), 78.1 (C-5), 78.5 (C-4), 79.3 (PhCHCH2OBn),
101.6 (C-1), 126.7–128.3 (7 ꢂ C6H5), 138.1, 138.3, 138.4, 138.5,
138.6, 138.7, 140.1 (7 ꢂ ipso C6H5). ESIMS m/z: calcd for
(C63H68O9): 969.2. Found, 987.5 [M+NH4]+. Anal. Calcd for
C63H68O9: C, 78.07; H, 6.94. Found: C, 78.56; H, 7.46.
4.20. Phenyl-1-thio 2,3-dideoxy-3-C-[(2,3,4-tri-O-benzyl-
fucopyranosyl)methyl]-4,6-di-O-benzyl-
arabinohexopyranoside (33a) and phenyl-1-thio 2,3-dideoxy-3-
C-[(2,3,4-tri-O-benzyl- -fucopyranosyl)methyl]-4,6-di-O-
benzyl-b- -arabinohexopyranoside (33b)
a-L-
a-D-
a
-L
D
4.18. Phenyl-1-thio 2,3-dideoxy-3-C-[(2,3,4,6-tetra-O-benzyl-b-
D
-glucopyranosyl)methyl]-4,6-di-O-benzyl-
ranoside (31a) and phenyl-1-thio 2,3-dideoxy-3-C-[(2,3,4,6-
tetra-O-benzyl-b- -glucopyranosyl)methyl]-4,6-di-O-benzyl-b-
arabinohexopyranoside (31b)
a
-
L
-arabinohexopy-
Using the same procedure as described for the preparation of
compounds 31a,b, compound 30 (1.63 g; 1.68 mmol) was con-
verted to a mixture of thioglycosides 33a,b, (1.1 g; 83%). Rf = 0.55
(light petroleum/ethyl acetate, 3:1).
D
L-
Major
1a00), 1.22 (d, 3H, J = 6.4 Hz, CH3), 1.76 (m, 1H, H-2ax), 2.12 (m, 1H,
H-3), 2.15–2.27 (m, 2H, H-1b00, H-2eq), 3.35 (dd, 1H, J3,4
a
-diastereoisomer 33a: 1H NMR (CDCl3): 1.11 (m, 1H, H-
BF3ꢁEt2O (0.31 ml, 2.4 mmol) and thiophenol (0.82 ml, 8.0
mmol) were added in an inert atmosphere to a solution of
compound 28 (1.6 g, 1.60 mmol) in dichloromethane (100 ml),
pre-cooled to ꢀ78° C. The stirred reaction mixture was allowed
to warm spontaneously to room temperature and after 2 h, the
reaction was quenched by cautious addition of aqueous NaHCO3.
The reaction mixture was partitioned between dichloromethane
and a saturated NaHCO3 solution, the combined organic phases
were dried and the residue was chromatographed on a silica gel
(light petroleum/ethyl acetate 7:1) affording 1.36 g (89%) of a mix-
=
J4,5 = 9.6 Hz, H-4), 3.48 (m, 1H, H-5), 3.57–3.65 (m, 3H, H-6a, H-
40, H-30), 3.66–3.78 (m, 2H,, H-50, H-6b), 3.91 (m, 1H, H-20), 4.06
(m, 1H, H-10), 4.42–4.86 (m, 12H, 6 ꢂ CH2Ph), 5.61 (dd, 1H,
J = 1 Hz, J = 5.0 Hz, H-1), 7.12–7.54 (m, 35H, 6 ꢂ C6H5). 13C NMR
(CDCl3): 15.9 (C-60), 29.6 (C-100), 33.8 (C-3), 35.0 (C-2), 67.7 (C-50),
67.7 (C-10), 69.2 (C-6), 72.7, 72.8, 73.2, 74.3, 75.7 (5 ꢂ PhCH2),
76.6 (C-40), 76.7 (C-30), 76.8 (C-20), 78.6 (C-5), 81.2 (C-4), 84.7 (C-
1), 126.6–127.3 (6 ꢂ C6H5), 137.9, 138.3, 138.5, 138.6, 138.8,
140.2 (6 ꢂ ipso C6H5). ESIMS m/z: calcd for (C54H58O7S): 850.4.
Found, 868.3 [M+NH4]+.
ture of thioglycosides 31a,b in a ratio
in NMR spectrum). Rf = 0.4 (light petroleum/ethyl acetate, 3.5:1).
Major
-diastereoisomer 31a: 1H NMR (CDCl3): 1.49 (m, 1H, H-
a:b = 3:1 (integration of H-1
a
Minor b-diastereoisomer 33b: 1H NMR, 4.93 (dd, J1,2ax = 9.2 Hz,
J1,2eq = 3.2 Hz, H-1). Further signals were overlapped by those of
the major diastereoisomer.
1a00), 1.84 (m, 1H, H-2ax), 1.96 (m, 1H, H-1b00), 2.18 (m, 1H, H-2eq),
2.40 (m, 1H, H-3), 3.16–3.32 (m, 3H, H-10, H-5, H-4,), 3.35 (m, 1H,
H-40), 3.55 (dd, 1H, J = 9.62 Hz, J = 3.21 Hz, H-6a), 3.59–3.67 (m, 4H,
H-30, H-6b, H-50, H-20), 3.73 (m, 1H, H-60a), 3.83 (dd, 1H, J = 10.9 Hz,
J = 3.2 Hz, H-60b), 4.34–4.93 (m, 12H, 6 ꢂ CH2Ph), 5.60 (d, 1H,
J1,2 = 5.3 Hz, H-1), 7.14–7.53 (m, 35H, 7 ꢂ C6H5). 13C NMR (CDCl3):
33.9 (C-100), 35.3 (C-3), 35.5 (C-2), 69.0, 69.3 (C-60, C-6), 72.1, 72.6,
73.5, 74.9, 75.2, 75.7, (6 ꢂ CH2Ph), 75.6 (C-50), 78.1 (C-4), 78.6 (C-
10), 79.2 (C-30), 80.0 (C-5), 82.5 (C-40), 84.8 (C-1), 87.4 (C-20),
126.1–128.7 (35 ꢂ C6H5), 138.0, 138.1, 138.2, 138.3, 138.3, 138.6,
138.6, (7 ꢂ ipso C6H5). ESIMS m/z: calcd for (C61H64O8S): 957.2.
Found, 973.5 [M+NH4]+.
4.21. 1,5-Anhydro-4,6-di-O-benzyl-2,3-dideoxy-3-C-[(2,3,4,6-
tetra-O-benzyl-b-D-glucopyranosyl)methyl]-L-arabino-hex-1-
enitol (9)
N-Bromosuccinimide (0.06 g, 0.34 mmol) was added to a solu-
tion of anomers 31a,b (0.24 g, 0.25 mmol) in acetone (12 ml) con-
taining 1% water. The reaction mixture was stirred at ꢀ15 °C under
exclusion of light and the reaction course was monitored by TLC
(light petroleum/ethyl acetate 3:1). After 1 h, the reaction mixture

K. Parkan et al. / Carbohydrate Research 345 (2010) 352–362
361
00
00
did not contain the starting compound and the reaction was
quenched by the addition of a NaHCO3 solution to pH 8. After par-
titioning between dichloromethane and aqueous NaHCO3, the or-
ganic phase was dried, the solvent evaporated, and the residue
chromatographed on a short silica gel column in light petroleum/
ethyl acetate (2:1) affording 0.20 g of 2,3-dideoxy-3-C-[(2,3,4,6-
J = 2.8 Hz, H-100b), 2.04 (dt, 1H, J1b ,1a = 14.2 Hz, J = 2.8 Hz, H-100a),
2.39 (dt, 1H, J = 11.00 Hz, J = 1.9 Hz, H-3), 3.48 (dd, 1H,
J3,4 = J4,5 = 9.2 Hz, H-4), 3.54 (m, 1H, H-30), 3.56–3.63 (m, 2H, H-40,
H-50), 3.75–3.87 (m, 3H, H-5, H-6a, H-6b), 3.92 (m, 1H, H-20),
4.11 (ddd, 1H, J = 13.3 Hz, J = 7.8 Hz, J = 3.2 Hz, H-10), 4.47–4.86
(m, 11H, 5 ꢂ CH2Ph, H-2), 6.32 (dd, 1H, J = 2.3 Hz, J = 5.9 Hz, H-1),
13
tetra-O-benzyl-b-
D
-glucopyranosyl)methyl]-4,6-di-O-benzyl-
L
-ara-
7.1–7.45 (m, 25H, 5 ꢂ C6H5). C NMR (CDCl3): 16.0 (C-60), 29.6
bino-hexopyranose (Rf 0.3, light petroleum/ethyl acetate (2:1), m/z
865.7 [M+H]+). The obtained compound (0.23 mmol) was dissolved
in dichloromethane (5 ml) and the solution was treated in an inert
atmosphere at 0 °C with s-collidine (0.415 g, 3.43 mmol) and mesyl
anhydride (0.08 g, 0.458 mmol). The reaction mixture was stirred
at 0 °C and its course was monitored by TLC (light petroleum/ethyl
acetate 3:1). After 4 h, the reaction mixture was partitioned be-
tween dichloromethane and aqueous NaHCO3. The organic phase
was dried, the solvent evaporated, and the residue chromato-
graphed on silica gel in light petroleum/ethyl acetate (7:1?4:1),
affording 0.145 g (64%) of compound 9, Rf = 0.65 (light petro-
(C-100), 35.1 (C-3), 67.4 (C-50), 68.6 (C-6), 69.0 (C-10), 72.8, 73.0,
73.8, 73.5, 74.3 (5 ꢂ PhCH2), 76.7 (C-40), 76.7 (C-20), 76.9 (C-4),
77.8 (C-5), 78.2 (C-30), 101.7 (C-2), 127.3–128.3 (5 ꢂ C6H5), 138.2,
138.3, 138.4, 138.5, 138.8 (5 ꢂ ipso C6H5), 142.4 (C-1). ESIMS m/z:
calcd for (C48H52O7): 740.9. Found, 758.1 [M+NH4]+. Anal. Calcd
for C48H52O7: C, 77.81; H, 7.07. Found: C, 77.95; H, 7.68.
Acknowledgments
This work was supported by the Grant Agency of the Czech
Republic (Grant No. 203/08/1124) and by the Ministry of Education,
Youth and Sport of the Czech Republic (Grant No. 6046137305).
leum/ethyl acetate, 3:1). [
a
]
+35.1 (c 0.43, CHCl3). 1H NMR
D
(CDCl3): 1.50 (m, 1H, H-1a00), 1.76 (ddd, 1H, J1a ,1b = 13.3 Hz,
00
00
J = 10.1 Hz, J = 3.2 Hz, H-1b000), 2.65 (m, 1H, H-3), 3.19 (dd, 1H,
J3 ,4 = J4 ,5 = 8.9 Hz, H-40), 3.30–3.38 (m, 2H, H-10, H-50), 3.44 (dd,
0
0
0
0
References
1H, J3,4 = J4,5 = 8.8 Hz, H-4), 3.56–3.76 (m, 4H, H-30, H-6a , H-6b ,
H-20), 3.77–3.81 (m, 1H, H-6a), 3.82–3.86 (m, 2H, H-5, H-6b),
4.47–4.67 (m, 8H, 4 ꢂ CH2Ph), 4.69 (dd, 1H, J = 5.9 Hz, J = 2.0 Hz,
H-2), 4.75–4.92 (m, 4H, 2 ꢂ CH2Ph), 6.30 (dd, 1H, J = 5.9 Hz,
J = 1.8 Hz, H-1), 7.16–7.38 (m, 30H, 6 ꢂ C6H5). 13C (CDCl3): 34.5
(C-100), 35.3 (C-3), 68.7, 69.0 (C-60, C-6), 73.4, 73.6, 73.8, 74.9,
75.2, 75.6 (6 ꢂ CH2Ph), 76.0, 76.2 (C-40, C-4), 77.9 (C-5), 78.6 (C-
30), 79.1 (C-10), 82.4 (C-50), 87.3 (C-20), 102.1 (C-2), 127.5–128.4
(6 ꢂ C6H5), 138.0, 138.1, 138.2, 138.3, 138.4, 138.6 (6 ꢂ ipso
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848.3 [M+H]+. Anal. Calcd for C55H58O8: C, 77.99; H, 6.90. Found:
C, 78.36; H, 7. 7.06.
0
0
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4.22. 1,5-Anhydro-4,6-di-O-benzyl-2,3-dideoxy-3-C-[(2,3,4,6-
tetra-O-benzyl-b-D-glucopyranosyl)methyl]-D-arabino-hex-1-
enitol (10)
Using the same procedure as described for the preparation of
compound 9, the mixture of compounds 32a,b (1.6 g; 1.11 mmol)
was converted to compound 10 (0.63 g; 67%), Rf = 0.65 (light petro-
leum/ethyl acetate, 3:1). [
a
]
D +7.4 (c 0.99, CHCl3). 1H NMR (CDCl3):
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1.53 (m, 1H, H-100), 1.77 (m, 1H, H-100), 2.67 (m, 1H, H-3), 3.21 (dd,
1H, J3 ,4 = J4 ,5 = 9.0 Hz, H-40), 3.31–3.38 (m, 2H, H-10, H-50), 3.45
0
0
0
0
(dd, 1H, J3,4 = J4,5 = 8.9 Hz, H-4), 3.56–3.74 (m, 4H, H-30, H-6a , H-
0
0
6b , H-20), 3.76–3.82 (m, 1H, H-6a), 3.82–3.88 (m, 2H, H-5, H-6b),
4.37–4.68 (m, 8H, 4 ꢂ CH2Ph), 4.70 (dd, 1H, J = 5.9 Hz, J = 1.6 Hz,
H-2), 4.76–4.95 (m, 4H, 2 ꢂ CH2Ph), 6.32 (dd, 1H, J = 5.9 Hz,
J = 2.0 Hz, H-1), 7.05–7.45 (m, 30H, 6 ꢂ C6H5). 13C (CDCl3): 34.4
(C-100), 35.2 (C-3), 68.6, 68.9 (C-60, C-6), 73.3, 73.4, 73.5, 73.7,
74.9, 75.1, (6 ꢂ CH2Ph), 75.9, 76.1 (C-40, C-4), 77.8 (C-5), 78.5 (C-
30), 79.0 (C-10), 82.3 (C-50), 87.3 (C-20), 102.0 (C-2), 127.4–128.3
(6 ꢂ C6H5), 138.1, 138.2, 138.2, 138.4, 138.3, 138.6 (6 ꢂ ipso
C6H5), 142.4 (C-1). ESIMS m/z: calcd for (C55H58O8): 847.1. Found,
848.3 [M+H]+. Anal. Calcd for C55H58O8: C, 77.99; H, 6.90. Found:
C, 78.29; H, 7.12.
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benzyl-a-L-fucopyranosyl)methyl]-D-arabino-hex-1-enitol (11)
Using the same procedure as described for the preparation of
compound 9, the mixture of compounds 33a,b (0.69 g; 0.81 mmol)
was converted to compound 11 (0.26 g; 67%), Rf = 0.75 (light petro-
leum/ethyl acetate, 3:1). [
(CDCl3): 1.13 (d, 3H, J = 6.4 Hz, CH3), 1.19 (dt, 1H, J1a ,1b = 14.2 Hz,
a
]
ꢀ43.0 (c 0.74, CHCl3). 1H NMR
D
00
00

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