Synthesis of fully protected α-l-fucopyranosyl-(1→2)-β-d- galactopyranosides with a single free hydroxy group at position 2′, 3′ or 4′ using O-(2-naphthyl)methyl (NAP) ether as a temporary protecting group

Article abstract of DOI:10.1016/j.tetasy.2004.11.056

Perbenzylated methyl α-l-fucopyranosyl-(1→2)-β-d- galactopyranosides having a single free OH group at position C-2′, C-3′ or C-4′ have been synthesized. Methyl 3,4,6-tri-O-benzyl- β-d-galactopyranoside was glycosylated either with phenyl 3,4-di-O-benzyl-2

Full text of DOI:10.1016/j.tetasy.2004.11.056

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 16 (2005) 83–95
Synthesis of fully protected
a-L-fucopyranosyl-(1!2)-b-D-galactopyranosides with a single free
hydroxy group at position 20, 30 or 40 using
O-(2-naphthyl)methyl (NAP) ether as a temporary protecting group
a
Zoltan B. Szabo, Aniko Borbas, Istvan Bajza and Andras Liptak
a
a
a,b,
*
´
´
´
´
´
´
´
aUD-HAS Research Group for Carbohydrates, PO Box 55, H-4010 Debrecen, Hungary
´
Department of Biochemistry, Faculty of Sciences, University of Debrecen, Egyetem ter 1, H-4032 Debrecen, Hungary
b
Received 13 October 2004; accepted 23 November 2004
Available online 21 December 2004
This article is dedicated to the memory of the outstanding chemist and excellent colleague Christian Pedersen
Abstract—Perbenzylated methyl a-L-fucopyranosyl-(1!2)-b-D-galactopyranosides having a single free OH group at position C-20,
C-30 or C-40 have been synthesized. Methyl 3,4,6-tri-O-benzyl-b-D-galactopyranoside was glycosylated either with phenyl 3,4-di-O-
benzyl-2-O-(2-naphthyl)methyl-, phenyl 2,4-di-O-benzyl-3-O-(2-naphthyl)methyl- or phenyl 2,3-di-O-benzyl-4-O-(2-naphthyl)-
methyl-1-thio-b-L-fucopyranoside. The 2-ONAP ether functioned well as a non-participating group. The yields of the glycosylation
reactions, promoted by NIS/TfOH, were above 80% and the stereoselectivity was 8:1 to 10:1 in favour of the a-anomers. The 2-
ONAP ether was obtained by (2-naphthyl)methylation, the 3-ONAP and the 4-ONAP ethers were prepared either by hydrogenolysis
of the 3,4-O-(2-naphthyl)methylene acetals of b-L-fucopyranoside or by tin acetal-mediated alkylations. The latter procedure
afforded higher yields. The ONAP ethers from the disaccharides were removed by oxidative cleavage with DDQ.
ꢀ 2004 Elsevier Ltd. All rights reserved.
1. Introduction
from the slime mould Dictyostelium discoideum, have
unequivocally confirmed that complex O-glycosylation
can take place in the cytoplasm of a eukaryote.2 The
pentasaccharide is linear, and the rough structure can
be described by the following abbreviated form:
Hex ! Hex ! Fuc ! Hex ! HexNAc. The attachment
site was verified by Edman degradation and proved to
be hydroxyproline. After methanolysis, the aminosugar
HexNAc was identified as GlcNAc. Exoglycosidase
digestion of glycopeptide Skp1 and MALDI-TOF MS
analysis of the digestum suggested the following penta-
saccharide structure: a-D-Galp-(1!6)-a-D-Galp-(1!?)-
a-L-Fucp-(1!2)-b-D-Galp-(1!3)-b-D-GlcpNAc-(1 !
Hy pro).2 It is worth mentioning that in the meantime a
b-D-Galp-(1!6)-b-D-Galp-(1! structure was also pro-
posed for the non-reducing disaccharide end, and the
outer b-D-Galp-(1!6)-b-D-Galp-(1!?)-L-Fuc cap struc-
ture has not been found elsewhere. It is also interesting
to note that the core trisaccharide, a-L-Fucp-(1!2)-b-D-
Galp-(1!3)-b-D-GlcpNAc is equivalent to blood group
H (type 1) expressed by mammalian cells.5
Skp1 is a 21 kD protein, a subunit of the SCF-E3 ubiq-
uitin ligases and other protein complexes in the nucleus
and cytoplasm of yeast and mammalian cells.1 In Dictyo-
stelium it is partially modified by a complex, unusual
pentasaccharide O-linked to hydroxyproline 143.2,3
Since glycoproteins play extremely important biological
roles, the biosynthesis of hundreds of glycoproteins are
known. These investigations suggested that protein gly-
cosylation occurred exclusively on extracellular or lume-
nal polypeptides. Today it is well known that a huge
number of glycosylated proteins are located in the nuclear
and cytoplasmic compartment in the cell.4 It seems very
probable that complex glycosylation can occur in these
compartments,5–7 too. Recently, structural investiga-
tions of the cytoplasmic protein called Skp1, isolated
*
Corresponding author. Tel.: +36 52 512900x2256; fax: +36 52
512913; e-mail: liptaka@tigris.klte.hu
0957-4166/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2004.11.056

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Z. B. Szabo et al. / Tetrahedron: Asymmetry 16 (2005) 83–95
84
The most delicate question connected with the structure
of the pentasaccharide of Skp1 is the branching point of
the a-L-Fucp residue. To help answering this question
we decided to synthesize the partially protected three
a-L-Fucp-(1!2)-b-D-Galp disaccharides carrying sepa-
rately a free OH group at position 20-, 30- and 40, which
could be the building blocks for the preparation of the
desired pentasaccharides.
authors did not observe any formation of the b-
anomers.
Recently, it was reported that the (2-naphthyl)methyl
(NAP) ethers were excellent protecting groups in carbo-
hydrate chemistry11–14 and these ethers could be gener-
ated by the hydrogenolysis of dioxane15,16 and
dioxolane-type (2-naphthyl)methylene acetals.15,17 To
extend the use of the NAP ethers to the syntheses of
fucose-containing oligosaccharides we decided to pre-
pare phenyl 3,4-di-O-benzyl-2-O-(2-naphthyl)methyl-1-
thio 7, phenyl 2,4-di-O-benzyl-3-O-(2-naphthyl)methyl-
1-thio 13 and phenyl 2,3-di-O-benzyl-4-O-(2-naph-
thyl)methyl-1-thio-b-L-fucopyranoside 14 and use them
as glycosyl donors.
2. Results and discussion
2.1. Preparation of the NAP ethers via (2-naphthyl)-
methylene acetal derivatives
Since in the planned disaccharides the galactopyrano-
side unit has a b-anomeric configuration we selected
Treatment of peracetylated L-fucopyranose with thio-
phenol in the presence of BF3ÆEt2O has been described
by Hasegawa and co-workers.18 In our case the ratio
of the a:b anomers 2 was 15:85, as determined by
methyl
3,4,6-tri-O-benzyl-b-D-galactopyranoside
1
(Fig. 1) as a model acceptor compound. For the synthe-
sis of 1 a published procedure8 was followed. To con-
struct a 1,2-cis-L-fucopyranosyl glycosidic bond, a
non-participating group at position two is necessary,
which is a benzyl or a substituted benzyl in most cases.
The real break-through in the syntheses of the a-L-fuco-
pyranosyl unit-containing oligosaccharides occurred in
1975 when Lemieux9 introduced the in situ anomeriza-
tion reaction of a peracetylated a-glycosyl bromide into
the more reactive b-anomer. This methodology worked
successfully also in the case of 2,3,4-tri-O-benzyl-a-L-
fucopyranosyl bromide and the Lewis A blood-group
antigenic determinant was synthesized. Nowadays,
perbenzylated thio-glycosides compete with the Lemieux
method and it is especially true for the synthesis of the a-
L-fucopyranoside-containing oligosaccharides. Since the
thioglycosides are more stable than the glycosyl bro-
mides they have been used regularly over the last 5–6
years. We selected therefore the derivatives of phenyl
1-thio-b-L-fucopyranoside. In search of 20-hydroxy-,
30-hydroxy- and 40-hydroxy otherwise fully protected
a-L-fucopyranosyl-(1!2)-b-D-galactopyranoside deriv-
atives in the literature only one report could be found
when Hindsgaul and co-workers10 synthesized octyl 20-
O-methyl-, 30-O-methyl- and 40-O-methyl-a-L-fucopyr-
anosyl-(1!2)-b-D-galactopyranoside and octyl 20,60-
dideoxy-a-L-lyxo-hexopyranosyl-,30,60-dideoxy-a-L-xylo-
hexopyranosyl- and 40,60-dideoxy-a-L-xylo-hexopyrano-
syl-(1!2)-b-D-galactopyranoside disaccharides, which
were used as substrates in enzymatic investigations. In
that case the acceptor was octyl 3,4,6-tri-O-benzyl-b-D-
galactopyranoside and ethyl 3,4-di-O-benzyl-2-O-(p-
methoxy)benzyl-1-thio-b-L-, ethyl 3-O-acetyl-2,4-di-O-
benzyl-1-thio-b-L- and ethyl 4-O-acetyl-2,3-di-O-benz-
yl-1-thio-b-L-fucopyranosides were used as the donors.
The yields were 67%, 71% and 71%, respectively. These
´
HPLC. Zemplen deacetylation of the anomeric mixture
2 resulted in the crystalline b-anomer 3b obtained from
an ethanol–hexane solvent system. The a-anomer 3a was
isolated as a syrup after chromatographic purification.
The overall yield of the three steps was 80% for 3b
(Scheme 1).
OAc
OAc
SH
SPh
OAc
i)
H3C
AcO
O
H3C
AcO
O
+
OAc
OAc
2
α:β = 15:85 (HPLC)
ii)
SPh
H3C
HO
SPh
O
H3C
HO
O
OH
OH
OH
OH
3b (80%)
3a (13%)
Scheme 1. Preparation of phenyl 1-thio-a- and b-L-fucopyranosides.
Reagents and conditions: (i) BF3ÆEt2O, CH2Cl2, overnight, 0 ꢁC; (ii)
NaOMe, MeOH, rt.
Acetalation of 3b with 2,2-dimethoxypropane furnished
the crystalline 4b,33 from an ether–hexane solvent mix-
ture, with a yield of 89%. Naphthylmethylation of 4b
yielded the crystalline compound 5 (96%). Acid hydro-
lysis of the isopropylidene group from 5 afforded the
likewise crystalline 6 with 91% yield. Benzylation of
6 proceeded, again, with high yield (94%) and the new
compound 7, the first required glycosyl donor, was crys-
talline (Scheme 2). The [a]D values given in the literature
for compounds 3b18 and 4b34 were different from the
values measured in our laboratory. To solve this problem
the C-1, H-1 coupling constants for compounds 3a, 3b,
4a and 4b (a and b pairs) were determined on a Bruker
360 MHz apparatus and the specific rotatory values
OBn
BnO
O
BnO
OCH3
OH
1
Figure 1. Structure of the acceptor used.8

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Z. B. Szabo et al. / Tetrahedron: Asymmetry 16 (2005) 83–95
85
SPh
OH
thyl)methylene acetal 9endo (25%, Scheme 3). The third
product having a medium chromatographic mobility
was a so-called mixed acetal: phenyl 2-O-R/S(methoxy-
20-naphthyl)methyl-3,4-O-(endo-2-naphthyl)-methylene-
1-thio-b-L-fucopyranoside 10 (6%) which proved to be a
single diastereomer, but its absolute configuration has
not been determined. Replacement of DMF by CH3CN
in the transacetalization reaction considerably reduced
the reaction time to several hours under reflux condi-
tions, and the conversion was also higher. However,
the separation of the 9exo and 9endo isomers still re-
mained the bottleneck of this synthetic route because
of their low stability on silica. Nevertheless, all three
compounds were crystalline, and their 1H and 13C
NMR spectra verified the postulated structures.
H3C
O
i)
i)
3a
3b
O
O
4a
SPh
H3C
ii)
O
SPh
H3C
O
OH
O
O
O
O
O
5 (96%)
4b (89%)
iii)
SPh
ONAP
OBn
7 (94%)
SPh
ONAP
H3C
BnO
O
H3C
O
iv)
Hydrogenolysis of the acetals 9exo and 9endo proceeded
smoothly and with complete stereoselectivity. The acetal
ring cleavage required only AlH3 (LiAlH4/AlCl3 = 3:1)
and the reaction time was 15–20 min at room tempera-
ture. Compound 9exo furnished the 3-O-NAP ether 11
(97%) and the 9endo gave the 4-O-NAP ether 12
(98%). The structure of compound 10 was confirmed
also by hydrogenolysis, and it produced compound 12
under cleavage conditions, showing that the cyclic acetal
ring had the endo configuration. This reaction did not
give any information about the absolute configuration
of the mixed acetal at position 2.
OH
HO
6 (91%)
Scheme 2. Preparation of phenyl 3,4-di-O-benzyl-2-O-(2-naphthyl)-
methyl-1-thio-b-L-fucopyranoside. Reagents and conditions: (i) 2,2-
dimethoxypropane, pTSA, 48 h, rt; (ii) NaH, NAPBr, DMF, 2h, rt;
(iii) HCl(aq)–MeOH, 2h, 50 ꢁC; (iv) NaH, BnBr, DMF, 3 h, rt.
were, where available, compared to that of D-
enantiomers.
Our retrosynthetic analysis showed that the other two
glycosyl donors 13 and 14 might be synthesized from
the exo- 9exo and endo-naphthyl 9endo isomers of phe-
nyl 3,4-O-(2-naphthyl)methylene-1-thio-b-L-fucopyran-
oside.
Since the chromatographic separation of compounds 11
and 12 can be easily achieved, hydrogenolysis of the ace-
tal mixture 9exo/endo, 10 and separation of compounds
11 and 12 resulted in higher yields than the step-by-step
isolation of the intermediates of the whole synthesis.
It is well documented that the direction of the hydrogen-
olysis of the dioxolane-type acetals is independent of the
reagent, but rather depends on the configuration of the
acetalic carbon atom: equatorial ethers are obtained
from the exo-(alkyl,aryl)-acetals; the endo-isomers, on
the other hand, react in an opposite way and axial ethers
are produced. Up to now the dioxolane-type (2-naph-
thyl)methylene acetals of fucose derivatives have not
been investigated, but the ring cleavage of the (2-naph-
thyl)methylene acetals of rhamnosides17 followed the
general rules.
Benzylation of compound 11 yielded the fully protected
second glycosyl donor 13, similarly compound 12 gave
the third glycosyl donor 14 under the same conditions.
In both cases the yields were above 90%.
2.2. Preparation of the NAP ethers via stannylene
derivatives
To shorten the synthesis and increase the yields during
the preparation of compounds 13 and 14 our attention
turned to the stannylene acetal method.20–22
Completion of the reaction of 3b with two equivalents of
2-(dimethoxymethyl)naphthalene 8 (Fig. 2) in DMF re-
quired 7 days and three products could be detected. The
compound with the highest chromatographic mobility
proved to be the 3,4-O-(exo-2-naphthyl)methylene ace-
tal 9exo, its isolated yield was 22%. Compound having
the lowest mobility was the 3,4-O-(endo-2-naph-
Selective acylation, alkylation or aralkylation of 1,2-,
1,3-diols or even polyols can be achieved by the so-
called stannylenation. The procedure involves a stannyl-
ene formation step, when the appropriate diol is heated
with Bu2SnO, either under the azeotropic removal of
water (in benzene or toluene), or in dry methanol, with-
out the removal of water. The formed stannylene deriv-
ative is directly reacted with the alkylating agent in
DMF in the presence of Bu4N+Brꢀ or Iꢀ, or caesium
fluoride.22 In the course of the alkylating step the more
reactive oxygen atom of the tin acetal is alkylated, in the
case of cis-diols it is the oxygen atom in equatorial posi-
tion. Firstly, our thio-fucoside compounds were reacted
with dibutyltin oxide in methanolic solution then with 2-
(naphthyl)methyl bromide in DMF, but no aralkylated
product was formed. On the other hand, when the
OCH3
OCH3
8
Figure 2. 2-(Dimethoxymethyl)-naphthalene used for the preparation
of (2-naphthyl)methylene acetals of glycosides.

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Z. B. Szabo et al. / Tetrahedron: Asymmetry 16 (2005) 83–95
86
3b
i)
SPh
SPh
OH
H3C
SPh
O
H
H3C
O
H3C
O
OH
O
OCH3
O
H
*
O
O
O
+
O
H
O
H
+
10 (6%)
9endo (25%)
9exo (22%)
ii)
ii)
ii)
SPh
SPh
H3C
HO
O
H3C
O
OH
OH
ONAP
OH
NAPO
11 (97%)
12 (98%)
iii)
iii)
SPh
OBn
H3C
BnO
O
SPh
OBn
H3C
O
ONAP
OBn
NAPO
13 (93%)
14 (93%)
Scheme 3. Preparation and hydrogenolysis of 2-(naphthyl)methylene acetals of phenyl 1-thio-b-L-fucopyranoside. Reagents and conditions: (i) 2-
naphthaldehyde-dimethylacetal, CSA, DMF, 7 days, rt; (ii) LiAlH4/AlCl3 (3:1), CH2Cl2/Et2O (1:1), 15 min, rt; (iii) NaH, BnBr, DMF, 3 h, rt.
acetalization step was carried out in toluene, the aralky-
lation proceeded satisfactorily, indicating that the acetal
formation was not successful in methanol. 2-(Naph-
thyl)methyl bromide was applied only most recently by
Matta and co-workers23 for the aralkylation of dibutyl-
tin acetals.
in DMF to give the crystalline compound 18 (93%).
Conventional (2-naphthyl)methylation of 18 proceeded
with an excellent yield (92%) and furnished compound
14.
The 2-O-benzyl ether 17 of phenyl b-L-fucopyranoside
was naphthylmethylated under tin-mediated conditions
to obtain 19 (82%), the benzylation of which resulted
in compound 13 (94%, Scheme 5).
Treatment of compound 3b with Bu2SnO and subse-
quent aralkylation with 2-(naphthyl)methyl bromide in
DMF gave two products. The main and faster moving
product proved to be the crystalline 3-O-NAP ether 11
(68%). The slower moving component was also crystal-
line and the NMR data gave the structure: phenyl
3-O-(2-naphthyl)methyl-1-thio-a-L-fucopyranoside 15,
showing that the b-anomer partly anomerized into the
a-anomer, the yield was 13% (Scheme 4).
In summary all three planned glycosyl donors 7, 13 and
14 were prepared, compound 13 and 14 were synthesized
either by the reductive (AlH3) hydrogenolysis of the dia-
stereomeric dioxolane-type (2-naphthyl)methylene ace-
tals or by tin-mediated regioselective alkylation. Both
methods proceeded with excellent selectivity, the latter
with very high yields.
SPh
2.3. Synthesis of partially protected a-L-fucopyranosyl-
(1!2)-b-D-galactopyranosides
SPh
OH
i)
H3C
HO
O
H3C
HO
O
OH
3b
+
ii)
ONAP
ONAP
For the preparation of a 1,2-cis-fucopyranosyl bond a
non-participating protecting group at 2-OH is necessary.
Searching the literature for 2-O-alkyl 1-thio-fucopyr-
anosyl derivatives the following compounds were found:
methyl 1-thio-b-L-fucopyranoside with 2-O-benzyl,19 2-
O-p-methoxy-benzyl,24 ethyl 1-thio-b-L-fucopyranoside
with 2-O-benzyl,25 2-O-p-chlorobenzyl,26 2-O-methyl,27
2-O-[2-(benzoylhydroxy)ethyl]28 and 2-O-[2-(trimethyl-
silyl)ethoxymethoxybenzyl],29 p-tolyl 1-thio-b-L-fuco-
pyranoside with a 2-O-benzyl,30 phenyl 1-thio-b-L-
fucopyranoside with 2-O-benzyl,31 and p-(chloro)phenyl
1-thio-b-L-fucopyranoside with 2-O-benzyl32 protecting
groups.
11 (68%)
15 (13%)
Scheme 4. 2-(Naphthyl)methylation of compound 3b under tin-med-
iated conditions. Reagents and conditions: (i) Bu2SnO, toluene, 3 h,
reflux; (ii) NAPBr, CsF, DMF, 18 h, rt.
Compound 4b was benzylated with 1.2equiv of benzyl
bromide in the presence of NaH and the crystalline 16
was treated with HCl(aq)–MeOH at 50 ꢁC for 2.5 h and
crystalline 17 was isolated with 92% yield for the two
steps. Compound 17 was stannylenated and the crude
reaction product was benzylated with benzyl bromide

´
Z. B. Szabo et al. / Tetrahedron: Asymmetry 16 (2005) 83–95
87
SPh
OR1
For our synthetic plans the 20-OH, 30-OH and 40-OH
derivatives of the a-L-fucopyranosyl-(1!2)-b-D-galacto-
pyranoside might be prepared by using the glycosyl
donors 7, 13 and 14. The 2-O-NAP ether of thio-fuco-
sides for the preparation of the 1,2-cis-fucopyranosyl
bond has not been used yet.
H3C
R3O
O
OR2
4b R1 = H; R2 , R3 = isopropylidene
16 R1 = Bn; R2 , R3 = isopropylidene
i)
The selected aglycone, compound 1,8 was glycosylated
with the donor 7. The coupling reaction was achieved
by NIS/TfOH promotor in dry dichloromethane at
ꢀ30 ꢁC and the major product 20 was obtained in a
ii)
iii)
iv)
SPh
OBn
SPh
OBn
H3C
O
H3C
HO
O
OH
OBn
1
yield of 68%. Its structure was confirmed by H, 13C
HO
(92% for the two steps)
v)
17
18 (93%)
NMR spectra. A small amount of the b-anomer 21
was also detected in the reaction mixture and it was also
isolated and characterized. Under similar conditions as
above, coupling of compounds 1 and 13 resulted in
73% of the disaccharide 22, and in this case the b-ano-
mer 23 could also be isolated in pure form and the spec-
troscopic investigations verified their structures. The
third coupling reaction between compounds 1 and 14
proceeded also smoothly and again both anomers were
detected and isolated. The yield of the a-anomer 24
reached 75%, the b-anomer 25 was present in approx.
iii)
vi)
SPh
OBn
SPh
OBn
H3C
RO
O
H3C
O
ONAP
OBn
14 (92%)
NAPO
19 R = H (82%)
13 R = Bn (94%)
i)
Scheme 5. Synthesis of compounds 13 and 14 using the stannylene
acetal method. Reagents and conditions: (i) NaH, BnBr, DMF, 2h, rt;
(ii) HCl(aq)–MeOH, 2.5 h, 50 ꢁC; (iii) Bu2SnO, toluene, 3 h, reflux; (iv)
BnBr, CsF, DMF, 18 h, rt; (v) NAPBr, CsF, DMF, 18 h, rt; (vi) NaH,
NAPBr, DMF, 3 h, rt.
1
10% (Scheme 6). The H–1H COSY and HMQC exper-
iments for compounds 7 and 20–25 were preformed on a
Bruker 360 MHz spectrometer at 298 K. Comparing the
OBn
BnO
OBn
BnO
O
O
BnO
OCH3
BnO
OCH3
+
O
ONAP
O
O
H3C
BnO
O
ONAP
H3C
OBn
OBn
OBn
20 (68%)
21 (11%)
7
OBn
O
BnO
BnO
OCH3
OH
1
13
14
OBn
BnO
BnO
OBn
O
BnO
BnO
H3C
NAPO
O
O
OCH3
OCH3
O
22 (73%)
H3C
BnO
O
O
24 (75%)
OBn
OBn
ONAP
OBn
+
+
OBn
O
OBn
O
BnO
BnO
BnO
BnO
OCH3
OCH3
25 (7%)
O
OBn
O
23 (9%)
OBn
O
O
H3C
NAPO
H3C
OBn
ONAP
BnO
Scheme 6. Synthesis of L-fucopyranosyl-(1!2)-D-galactopyranoside derivatives. Conditions: 1.5 equiv of donor 7, 13 and 14, 2.25 equiv of NIS,
0.38 equiv of TfOH, CH2Cl2, ꢀ30 ꢁC, 20 min.

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Z. B. Szabo et al. / Tetrahedron: Asymmetry 16 (2005) 83–95
88
Table 1. 1H NMR chemical shifts (d in ppm) and coupling constants (J in Hz) for compounds 7 and 20–25
Monosaccharide unit
H-1, J1,2
H-2, J2,3
H-3, J3,4
H-4, J4,5
H-5, J5,6a
H-6a, Jgem.
1.27d, 6.4
3.64–3.54m
H-6b, J5,6b
OMe
—
7
b-L-Fuc
4.63d, 9.3
3.99t, 9.3
3.61dd, 2.8
3.63d, 2.8
3.53m, 6.4
20
b-D-Gal
a-L-Fuc
4.40d, 7.7
5.68d, 3.8
4.23dd, 9.7
4.09dd, 10.2
3.75dd, 2.7
3.97dd, 2.7
3.96bd, 2.8
3.70bd, 2.8
3.64–3.54m
4.31m, 6.5
3.64–3.54m
3.60–3.52m
3.46s
—
1.12d, 6.5
21
22
23
24
25
b-D-Gal
b-L-Fuc
4.26d, 7.6
4.85d, 7.7
4.21dd, 8.9
3.83dd, 9.0
3.51dd, 2.8
3.56dd, 3.0
3.89d, 2.9
3.60–3.52m
3.60–3.52m
3.34d, 6.4
3.60–3.52m
3.42s
—
1.12d, 6.4
b-D-Gal
a-L-Fuc
4.37d, 7.7
5.66d, 3.7
4.22dd, 9.7
4.08dd, 10.1
3.73dd, 2.7
4.00dd, 2.7
3.94bd, 2.8
3.71bd, 2.7
3.64–3.54m
4.31bd, 6.5
3.64–3.54m
3.64–3.54m
3.44s
—
1.14d, 6.5
b-D-Gal
b-L-Fuc
4.39d, 7.6
4.96d, 7.6
4.33dd, 9.0
3.94dd, 9.7
3.66dd, 3.0
3.70dd, 2.9
4.03d, 3.0
3.75–3.65m
3.75–3.65m
3.44d, 6.5
3.75–3.65m
3.75–3.65m
3.56s
—
1.23d, 6.4
b-D-Gal
a-L-Fuc
4.37d, 7.7
5.66d, 3.8
4.20dd, 9.7
4.08dd, 10.1
3.73dd, 2.8
3.96dd, 2.7
3.94bd, 2.9
3.73bd, 2.8
3.62–3.55m
4.31bd, 6.5
3.62–3.55m
3.62–3.55m
3.44s
—
1.14d, 6.5
b-D-Gal
b-L-Fuc
4.36d, 7.6
4.94d, 7.6
4.30dd, 8.9
3.91d, 8.0
3.63a
3.63a
4.00d, 2.7
3.72–3.65m
3.72–3.56m
3.41d, 6.4
3.72–3.56m
3.72–3.56m
3.53s
—
1.21d, 6.3
a Overlap.
Table 2. 13C NMR data (d in ppm) for compounds 7 and 20–25
Monosaccharide unit
C-1
87.8
C-2C-3
77.4
C-4
C-5
C-6
OMe
17.6
7
b-L-Fuc
84.8
76.9
74.9
—
20
b-D-Gal
a-L-Fuc
102.8
97.3
72.9
75.5
83.9
79.5
71.8
77.7
73.2
66.3
68.8
16.4
56.4
—
a
21
22
23
24
25
b-D-Gal
b-L-Fuc
104.5
102.7
77.281.4
80.2
73.5
73.3
68.9
16.8
57.0
—
82.7
76.9a
70.0
73.1
b-D-Gal
a-L-Fuc
102.8
97.3
72.8
75.6
83.9
79.5
71.9
77.8
68.7
56.4
66.216.4
—
b-D-Gal
b-L-Fuc
104.4
102.7
77.1
80.2
81.5
82.5
73.3
77.0a
73.5a
70.0
68.9
16.8
56.9
—
b-D-Gal
a-L-Fuc
102.9
97.4
72.8
75.7
83.9
79.7
71.9
77.5
73.2
66.3
68.8
16.5
56.4
—
b-D-Gal
b-L-Fuc
104.5
102.9
77.3
80.3
81.7
82.8
73.5
76.9a
73.5a
70.1
69.0
17.0
57.1
—
a Interchangeable assignments.
obtained data with the spectra of methyl 3,4,6-tri-O-
benzyl-2-O-(2,3,4-tri-O-benzyl-a-L-fucopyranosyl)-b-D-
galactopyranoside described by Watt et al8., it turned
out that the (2-naphthyl)methylated carbon atoms reso-
nated at higher fields than the benzylated ones. For the
protons attached to the (2-naphthyl)methylated carbon
a shift to the lower magnetic field was observed. These
differences are not very large but they are characteristic
and could only be observed in the case of the a-L-fuco-
pyranosyl unit-containing disaccharides. The b-anomers
did not show such a behaviour. The chemical shift data
and the coupling constants of compounds 7 and 20–25
are collected in Tables 1 and 2.
(2,3-dichloro-5,6-dicyano-1,4-benzoquinone) under con-
ditions when the other usual protecting groups such as
acetyl, pivaloyl, phthalimido, benzyl and benzylidene
survive.11,12,15
Compounds 20, 22 and 24 were treated, separately, with
1.5 equiv of DDQ in dichloromethane–methanol (4:1) at
room temperature for 3 h. In each case complete conver-
sion of the starting material was observed by TLC and
the monohydroxy derivatives, OH-20 26 (84%), OH-30
27 (87%) and OH-40 28 (85%), were obtained and char-
acterized (Scheme 7).
Having our three target disaccharides 20, 22 and 24, the
last steps were aimed at the removal of the NAP ethers
and the regeneration of the OH-20, OH-30 and OH-40. It
was shown earlier that the NAP ethers could be hydro-
genolyzed in the presence of benzyl ethers and esters28
and they are less sensitive to acids than the p-methoxy-
benzyl ethers. The most important observation, however,
is that the NAP ethers can easily be removed by DDQ
3. Conclusion
In the synthesis of the perbenzylated a-L-Fucp-(1!2)-b-
D-Galp-(1!OMe) disaccharides carrying a single free
OH group either at position C-20, C-30 or C-40, all of
the three possible regioisomers of phenyl di-O-benzyl-
mono-O-(2-naphthyl)methyl-1-thio-b-L-fucopyranoside
were used as glycosyl donors. For the easy preparation

´
Z. B. Szabo et al. / Tetrahedron: Asymmetry 16 (2005) 83–95
89
OBn
O
(k = 256 nm) with a flow rate of 0.5 mL/min. The com-
position of the eluent was hexane/EtOAc = 89:11, 2a
(Rf = 9.76 min), 2b (Rf = 15.15 min).
BnO
BnO
OCH3
i)
20
O
4.2. General method A for performing aralkylation
reactions (for compounds 5, 7, 13, 14, 16)
H3C
BnO
O
OH
26 (84%)
OBn
The starting material (10 mmol) was dissolved in dry
DMF (15 mL) and cooled to 0 ꢁC. NaH (12mmol,
1.2equiv, 60%, previously treated with hexane) was
added carefully to the mixture and stirred for half an
hour. Then the aralkylating agent (12mmol, 1.2equiv)
was added to the mixture. Reactions usually reached
completion within 2–3 h. The excess NaH was decom-
posed by the addition of some drops of MeOH and
the solvent was evaporated in vacuo. The residue was
dissolved in DCM and was extracted three times with
water, then the organic layer was dried and the solvent
was evaporated.
OBn
BnO
BnO
O
OCH3
i)
O
22
H3C
BnO
O
OBn
27 (87%)
OH
OBn
BnO
BnO
H3C
HO
O
OCH3
i)
O
24
4.3. General method B for the hydrogenolysis of (2-
naphthyl)methylene acetals of 1-thio fucosides (for
compounds 11, 12)
O
OBn
28 (85%)
OBn
To
a solution of the starting acetal compound
Scheme 7. Deprotection of the NAP group from disaccharides 20, 22,
24. Reagents and conditions: (i) DDQ, CH2Cl2/MeOH = 4:1, 3 h, rt.
(6.0 mmol) in a mixture of dry DCM and dry Et2O
(20 mL and 10 mL), LiAlH4 (27 mmol, 4.5 equiv) was
added and the resulting mixture was cooled to 0 ꢁC.
of the regioisomeric O-NAP ethers different methods
were presented. In each case the O-NAP group served
successfully as a temporary protecting group and could
be cleaved in the presence of benzyl groups. It also acted
as a non-participating substituent and governed the for-
mation of an 1,2-cis-fucopyranosyl interglycosidic bond
at position C-2. The method presented for the prepara-
tion of the disaccharides can be utilized for the total
synthesis of those pentasaccharides and oligosacchar-
ides, that involve a non-terminal L-fucose unit.
Then
a solution of anhydrous AlCl3 (9.0 mmol,
1.5 equiv) in dry Et2O (10 mL) was added dropwise to
the mixture. Reactions usually reached completion with-
in 15–20 min. The reaction mixture was diluted with
Et2O (200 mL) and the excess of LiAlH4 was decom-
posed by the addition of a small amount of EtOAc
and careful addition of water. The solution was dec-
anted, poured into a separatory funnel and was ex-
tracted three times with water. The solution was then
dried and evaporated, the crude product was purified
either by crystallization or by column chromatography.
4. Experimental
4.4. General method C for performing aralkylation
reactions via a stannylene acetal (for compounds 11, 15,
18, 19)
4.1. General methods
Optical rotations were measured at room temperature
with a Perkin–Elmer 241 automatic polarimeter. Melt-
A mixture of the starting material (3.0 mmol) and Bu2-
SnO (3.9 mmol, 1.3 equiv) was suspended in dry toluene
(25 mL) and was refluxed for three hours under a Dean–
Stark apparatus. Then CsF (6.0 mmol, 2.0 equiv) was
added to the solution and following another 10 min
refluxing the solvent was evaporated to dryness in
vacuo. The residue was redissolved in dry DMF
(20 mL) and the aralkylating agent (6.0 mmol, 2.0 equiv)
was added. Reactions usually took place within 16–18 h.
Then the reaction mixture was diluted with DCM
(250 mL), the precipitating salts were filtered through
a Celite layer, and the filtrate was extracted with water
and saturated NaCl solution, dried and evaporated.
¨
ing points were determined on a BUCHI-B-540 appara-
tus and are uncorrected. TLC was performed on
Kieselgel 60 F254 (Merck) with detection by charring
with 50% aqueous sulfuric acid. Column chromatogra-
phy was performed on Silica Gel 60 (E. Merck 0.062–
0.200 mm). The organic solutions were dried over
1
MgSO4 and concentrated in vacuo. The H (200 and
500 MHz) and 13C (50.30, 125.76 MHz) spectra were re-
corded with Bruker WP-200SY, Bruker AC-200 and
Bruker DRX-500 spectrometers for solutions in CDCl3,
1
or CD3OD. The H–1H COSY and HMQC measure-
ments for compounds 7 and 20–25 were performed on
Bruker 360 MHz spectrometer at 298 K in CDCl3. Inter-
nal references: TMS (0.00 ppm for 1H), CDCl3
(77.00 ppm for 13C), CD3OD (49.05 ppm for 13C). The
ratio of compounds 2a and 2b in the reaction mixture
was determined by HPLC (Merck Hitachi) using a
Purospher Si 3 lm column, a diode array detector
4.5. General method D for fucosylation reactions (for
compounds 20–25)
To a solution of the galactoside acceptor 18 (0.50 mmol)
and the appropriate fucoside donor (0.75 mmol,

´
Z. B. Szabo et al. / Tetrahedron: Asymmetry 16 (2005) 83–95
90
1.5 equiv) in dry DCM (5 mL), 4 A molecular sieves
(0.5 g) were added and the mixture was stirred for 1 h
at room temperature. Then the solution was cooled to
ꢀ30 ꢁC and a mixture of N-iodosuccinimide (0.253 g,
1.12 mmol, 2.25 equiv) and trifluoromethanesulfonic
acid (16.5 lL, 0.19 mmol, 0.38 equiv) dissolved in 1:1
mixture of dry THF and dry DCM (1 mL) was added
to promote the reaction. The colour of the solution
turned into deep brown immediately after the addition
of the promoter. The mixture was kept at ꢀ30 ꢁC for
20 min when t.l.c. (DCM/acetone = 97:3) showed the
disappearance of the acceptor. It was then neutralized
with Et3N and allowed to warm up. The mixture was fil-
tered and the filtrate was diluted with DCM, washed
twice with 5% Na2S2O3 and once with satd. NaHCO3
solutions. The organic layer was dried, evaporated and
the syrupy residue was purified by column chromatogra-
phy (DCM/acetone = 99:1 ! 98:2) and the a and b iso-
mers were separated.
[a]D = ꢀ246.3 (c 0.13, CHCl3), [lit:33 [a]D = ꢀ225.0 (c
˚
1
0.47, CHCl3)]; H NMR (CDCl3) d (ppm): 7.45–7.28
(5H, m, arom.), 5.94 (1H, d, J1,2 = 5 Hz, H-1), 5.43
(3H, m, H-2,3,4), 4.62 (1H, dd, H-5), 2.18–2.04 (9H,
3s, 3 · CH3CO), 1.15 (3H, d, J5,6 = 7 Hz, CH3); 13C
NMR d (ppm): 170.44, 170.12, 169.82 (3 · CH3CO),
133.18, 131.69, 129.00, 127.41 (6C, arom.), 85.52 (C-1),
70.85, 68.56, 68.07, 65.46 (C-2to C-5), 20.76, 20.59,
20.52 (3 · CH3CO), 15.77 (C-6). Anal. Calcd for
C18H22O7S: C, 56.53; H, 5.80; S, 8.38. Found: C,
56.62; H, 5.83; S, 8.29.
2b: [a]D = ꢀ12.8 (c 0.24, CHCl3), [lit:18 [a]D = ꢀ3.0 (c
1
0.90, CH3OH)]ꢀ; H NMR (CDCl3) d (ppm): 7.55–7.32
(5H, m, arom.), 5.23 (2H, m), 5.06 (2H, dd), 4.73 (1H,
d, J1,2 = 10 Hz, H-1), 2.18–1.97 (9H, 3s, 3 · CH3CO),
1.24 (3H, d, J5,6 = 6 Hz, CH3); 13C NMR d (ppm):
170.50, 170.00, 169.36 (3 · CH3CO), 132.80, 132.23,
128.76, 127.84 (6C, arom.), 86.33 (C-1), 73.06, 72.33,
70.26, 67.29 (C-2to C-5), 20.75, 20.50 (3C, 3 · CH3CO),
16.36 (C-6). Anal. Calcd for C18H22O7S: C, 56.53; H,
5.80; S, 8.38. Found: C, 56.59; H, 5.78; S, 8.31.
4.6. General method E for the deprotection of (2-
naphthyl)methyl ethers of glycosides by DDQ (for
compounds 26–28)
4.6.2. Phenyl 1-thio-a/b-L-fucopyranoside 3a and 3b. To
a solution of phenyl 1-thio-2,3,4-tri-O-acetyl-L-fucopyr-
anoside a and b mixture (93.77 g, 2a and 2b) in dry
MeOH (900 mL) a catalytic amount of NaOMe was
added and the mixture was stirred for overnight. After
completion the solution was neutralized by AMBER-
LITE IR-120 H+ ion exchange resin, filtered and the sol-
vent was evaporated. The syrupy crude product
(64.05 g) was dissolved in hot ethanol (645 mL) and
allowed to cool down. Then hexane (ꢁ1200 mL) was
added to the solution, which allowed to crystallize the
b-isomer 3b as white needles. More product could be ob-
tained from the mother liquor by crystallization and by
column chromatography (DCM/EtOAc/MeOH = 5:4:1;
Rf,a = 0.47, Rf,b = 0.36), the latter afforded also the a-
anomer in pure form.
The starting material (0.2mmol) was dissolved in a mix-
ture of DCM and MeOH (4:1, 2mL) and freshly crystal-
lized DDQ (0.3 mmol, 1.5 equiv) was added. Reactions
reached completion within three hours (DCM/ace-
tone = 97:3). The reaction mixture was neutralized by
the addition of Et3N and the solvents were evaporated.
The residue was purified by column chromatography.
4.6.1. Phenyl 2,3,4-tri-O-acetyl-1-thio-a/b-L-fucopyrano-
side 2a and b. To a cooled (0 ꢁC) solution of L-fucose
(42.30 g, 0.258 mol) in dry pyridine (200 mL) acetic
anhydride (200 mL) was added in four portions. The
reaction reached completion within six hours (hexane/
acetone = 1:1, Rf = 0.85). The solution was poured onto
ice water, the aqueous phase was decanted and the syr-
upy residue was dissolved in dichloromethane. It was ex-
tracted with 0.5 M H2SO4 solution, then neutralized
with aqueous NaHCO3. The decanted aqueous phase
was also extracted with DCM and washed as indicated
previously. The organic phases were dried, evaporated
and the residue was directly used for the next step.
The syrupy residue (85.60 g) was dissolved in dry
DCM (440 mL), thiophenol (32mL, 0.314 mol,
1.2equiv) was added and the mixture was cooled to
0 ꢁC. Then BF3ÆEt2O (94.6 mL, 0.769 mol, 3.0 equiv)
was poured to the solution in several portions and the
resulting mixture was refrigerated. The reaction reached
completion overnight (DCM/acetone = 96:4, Rf,a = 0.77,
Rf,b = 0.68). The solution was diluted with DCM
(500 mL), and the excess Lewis acid was decomposed
by the addition of solid NaHCO3 and aqueous NaH-
CO3. When the evolution of CO2 ceased the phases were
separated in a separatory funnel. The organic layer was
washed with 1 M NaOH (2 · 600 mL) solution, then
with water, dried and evaporated. A small fraction of
the syrupy mixture was purified by column chromato-
graphy and the separated 2a and 2b compounds (both
syrups) were characterized by NMR. The mixture of
2a and 2b was directly used for the next step. 2a:
Overall yield for 3b including all purification steps:
53.24 g (80%); mp: 91–93 ꢁC; [a]D = ꢀ8.3 (c 0.13,
MeOH), [lit:18 91–92 ꢁC; [a]D = +68.0 (c 0.6, MeOH)];
1H NMR (CD3OD) d (ppm): 7.55–7.28 (5H, m, arom.),
4.55 (1H, d, J1,2 = 9 Hz, H-1), 3.70–3.45 (4H, m, H-
2,3,4,5), 1.27 (3H, d, J5,6 = 7 Hz, CH3); 13C NMR d
(ppm): 135.99, 132.21, 129.87, 128.08 (6C, arom.),
89.97 (C-1, JC-1,H-1 = 155.13 Hz), 76.48, 75.97, 73.08,
70.84 (C-2to C-5), 17.06 (CH3). Anal. Calcd for
C12H16O4S: C, 56.23; H, 6.29; S, 12.51. Found: C,
56.17; H, 6.28; S, 12.58.
Overall yield for the a-isomer: 8.65 g (13%), syrup,
1
[a]D = +258.1 (c 0.32, MeOH); H NMR (CD3OD) d
(ppm): 7.53–7.27 (5H, m, arom.), 5.26 (1H, d,
J1,2 = 5 Hz, H-1), 4.03–3.70 (4H, m, H-2,3,4,5), 1.25
(1H, d, J5,6 = 6 Hz, CH3); 13C NMR d (ppm): 136.18,
132.82, 129.85, 128.24 (6C, arom.), 92.89 (C-1, JC-1,H-1
=
ꢀ The [a]D value for phenyl 2,3,4-tri-O-acetyl-1-thio-b-D-fucopyrano-
side is +11.9 (c 1.0, CHCl3).34

´
Z. B. Szabo et al. / Tetrahedron: Asymmetry 16 (2005) 83–95
91
166.74 Hz), 87.03, 83.54, 78.35, 67.80 (C-2to C-5), 19.79
(CH3). Anal. Calcd for C12H16O4S: C, 56.23; H, 6.29; S,
12.51. Found: C, 56.26; H, 6.31; S, 12.57.
3.84 (1H, m), 3.59 (1H, m), 1.43 (3H, d, J5,6 = 7 Hz,
3 · H-6), 1.41, 1.40 (6H, 2 · s, 2 · CH3); 13C NMR d
(ppm): 135.40, 133.76, 133.20, 133.03, 132.05, 128.68,
127.94, 127.60, 127.28, 126.97, 126.28, 125.89, 125.76
(16C, arom.), 109.63 (Cacetalic), 86.07 (C-1), 79.81,
78.00, 76.37, 72.36 (C-2to C-5), 73.40 (CH2), 27.79,
26.32 (2 · CH3, Isp), 16.82( C-6). Anal. Calcd for
C26H28O4S: C, 71.53; H, 6.46; S, 7.34. Found: C,
71.42; H, 6.43; S, 7.38.
4.6.3. Phenyl 3,4-O-isopropylidene-1-thio-a-L-fucopyr-
anoside 4a. The title compound was prepared from
3a similarly to 4b (4.6.4.). Mp: 73–75 ꢁC;
[a]D = ꢀ295.0 (c 0.14, CHCl3), [lit:35 mp: 72–74 ꢁC;
[a]D = ꢀ278.0 (c 1.1, MeOH)]; 1H NMR (CDCl3) d
(ppm): 7.50 (2H, d, arom.), 7.33–7.23 (3H, m, arom.),
5.54 (1H, d, J1,2 = 3.4 Hz, H-1), 4.56 (1H, dd), 4.18–
4.05 (3H, m), 2.44 (1H, s, OH), 1.43, 1.36 (6H, 2s,
2 · CH3), 1.35 (3H, d, J5,6 = 6.8 Hz, 3 · H-6); 13C
NMR d (ppm): 134.16, 131.38, 129.04, 127.30, 109.44
(Cacetalic), 88.31 (C-1, JC-1,H-1 = 169.79 Hz), 76.26,
75.75, 70.02, 65.41 (C-2to C-5), 27.89, 25.92 (2 · CH3,
Isp), 16.09 (C-6). Anal. Calcd for C15H20O4S: C,
60.79; H, 6.80; S, 10.82. Found: C, 60.87; H, 6.81; S,
10.76.
4.6.6. Phenyl 2-O-(2-naphthyl)methyl-1-thio-b-L-fucopyr-
anoside 6. To a solution of 5 (4.56 g, 10 mmol) in
methanol (20 mL) cc. HCl(aq)/water = 1:3 mixture
(0.7 mL cc. HCl + 2.1 mL H2O) was added and the solu-
tion was kept at 50 ꢁC for two hours. According to t.l.c.
(DCM/EtOAc = 9:1, Rf = 0.24) the conversion was
above 95%. The mixture was neutralized with Et3N,
evaporated in vacuo, and was co-evaporated once with
toluene. The crude product was recrystallized from
EtOAc–hexane solvent system, the mother liquor was
purified by chromatography. Yield: 3.79 g (91%), mp:
133–134 ꢁC, [a]D = ꢀ27.0 (c 0.21, CHCl3); 1H NMR
(CDCl3) d (ppm): 7.90–7.75 (4H, m, arom.), 7.60–7.40
(5H, m, arom.), 7.37–7.25 (3H, m, arom.), 5.62–4.87
(2H, 2 · d, Jgem. ꢁ 11 Hz, CH2), 4.65 (1H, d,
J1,2 = 9 Hz, H-1), 3.75–3.50 (4H, m, H-2,3,4,5), 2.50
(2H, s, 2 · OH), 1.34 (3H, d, J5,6 = 7 Hz, CH3); 13C
NMR d (ppm): 135.44, 134.03, 133.07, 131.64, 128.92,
128.41, 127.94, 127.67, 127.40, 127.13, 126.15, 126.05
(16C, arom.), 87.37 (C-1), 77.89, 75.28, 74.42, 71.67
(C-2to C-5), 75.22 (CH2), 16.57 (C-6). Anal. Calcd for
C23H24O4S: C, 69.67; H, 6.10; S, 8.09. Found: C,
69.80; H, 6.07; S, 8.13.
4.6.4. Phenyl 3,4-O-isopropylidene-1-thio-b-L-fucopyr-
anoside 4b. Compound 3b (10.00 g, 39 mmol) was sus-
pended in dimethoxypropane (35 mL) and a catalytic
amount of p-toluenesulfonic acid were added, which
was followed by the immediate clarification of the mix-
ture. After two days t.l.c. showed a conversion above
95% (hexane/EtOAc = 6:4, Rf = 0.60). The solution
was neutralized with some drops of Et3N, and was evap-
orated. The crude product (11.44 g) was a colourless syr-
up, which was dissolved in diethyl ether and by the
addition of hexane the crystalline product appeared as
white needles. The mother liquor could be purified by
column chromatography with hexane/EtOAc = 7:3 as
eluent. After crystallization and chromatographic purifi-
cation the yield is 10.34 g (89%), mp: 86–87 ꢁC;
[a]D = ꢀ7.0 (c 0.63, CHCl3), [lit:35 mp: 82–83 ꢁC;
[a]D = +35.1 (c 1.0, MeOH)]ꢁ; 1H NMR (CDCl3)
d (ppm): 7.60–7.30 (5H, m, arom.), 4.43 (1H, d,
J1,2 = 10 Hz, H-1), 4.05 (2H, m), 3.89 (1H, dd), 3.57
(1H, m), 2.88 (1H, s, OH), 1.43 (3H, d, J5,6 = 7 Hz,
3 · H-6), 1.43, 1.36 (6H, 2s, 2 · CH3); 13C NMR d
(ppm): 132.48, 132.12, 128.84, 127.84 (6C, arom.),
109.78 (Cacetalic), 87.65 (C-1, JC-1,H-1 = 153.33 Hz),
79.04, 76.18, 72.63, 71.17 (C-2to C-5), 25.48, 23.72
(2 · CH3, Isp), 14.31 (C-6). Anal. Calcd for
C15H20O4S: C, 60.79; H, 6.80; S, 10.82. Found: C,
60.85; H, 6.82; S, 10.78.
4.6.7. Phenyl 3,4-di-O-benzyl-2-O-(2-naphthyl)methyl-1-
6
thio-b-L-fucopyranoside 7. Compound
(3.10 g,
7.8 mmol) was reacted with double amounts of BnBr
according to General method A. The reaction reached
completion in three hours (hexane/EtOAc = 8:2,
Rf = 0.48). The crude product (a pale yellowish syrup)
was purified by column chromatography (hexane/
EtOAc = 8:2 ! 7:3). Yield: 4.16 g (94%). The product
can be crystallized from EtOAc–hexane system, mp:
1
81.5–82.5 ꢁC, [a]D = ꢀ19.9 (c 0.45, CHCl3); H NMR
(CDCl3) d (ppm): 7.90–7.23 (22H, m, arom.), 5.13–
4.68 (7H, m, 3 · CH2, H-1); 13C NMR d (ppm):
138.97, 138.61, 136.18, 134.63, 133.54, 133.26, 131.72,
128.98, 128.63, 128.40, 128.19, 127.88, 127.76, 127.69,
127.18, 126.68 (28C, arom.), 75.79, 74.85, 73.05
(3 · CH2). Anal. Calcd for C36H36O4S: C, 76.57; H,
6.43; S, 5.68. Found: C, 76.44; H, 6.48; S, 5.74.
4.6.5. Phenyl 3,4-O-isopropylidene-2-O-(2-naphthyl)-
4
methyl-1-thio-b-L-fucopyranoside 5. Compound
(4.00 g, 13.5 mmol) was reacted with NAPBr according
to General method A, to give 5 in two hours (t.l.c, hex-
ane/EtOAc = 8:2, Rf = 0.38). Yield: 5.63 g (96%), mp:
132–134 ꢁC (from EtOH), [a]D = ꢀ11.5 (c 0.27, CHCl3);
1H NMR (CDCl3) (ppm): 7.90–7.75 (4H, m, arom.),
7.65–7.40 (5H, m, arom.), 7.38–7.23 (3H, m, arom.),
5.05–4.80 (2H, 2 · d, Jgem. ꢁ 11 Hz, CH2), 4.63 (1H, d,
J1,2 = 9 Hz, H-1), 4.28 (1H, t, J = 6 Hz), 4.06 (1H, dd),
4.6.8. Preparation of 2-(dimethoxymethyl)naphthalene
8. To
a
solution of 2-naphthaldehyde (15.6 g,
0.10 mol) in dry methanol (30 mL) trimethyl-orthofor-
mate (15.6 mL, 0.15 mol, 1.5 equiv) and a catalytic
amount (ꢁ45 mg) of p-toluene-sulfonic acid were added.
The overnight reaction reached a conversion greater
than 95% and a product of higher mobility formed
(t.l.c: hexane/EtOAc = 8:2, Rf = 0.67). The mixture was
diluted with DCM (500 mL) and was washed with satd.
NaHCO3 solution and water. The organic layer was
dried and evaporated. Yield: 19.6 g, orange-coloured
ꢁ The [a]D value for phenyl 3,4-O-isopropylidene-1-thio-b-D-fucopyr-
anoside is +7.6.36

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Z. B. Szabo et al. / Tetrahedron: Asymmetry 16 (2005) 83–95
92
liquid, which was pure enough for transacetalization
reactions. Vacuum distillation (bp 141–143 ꢁC/2mmHg;
d 1.10 g cmꢀ3) of the crude product afforded a colourless
liquid. 1H NMR (CDCl3) d (ppm): 7.93–7.77 (4H,
arom.), 7.54 (1H, dd, arom.), 7.50–7.42(H2 , arom.),
5.53 (1H, s, Hacetalic), 3.34 (6H, s, 2 · OCH3); 13C
NMR d (ppm) 135.39, 133.31, 132.90, 128.20, 127.97,
127.57, 126.12, 126.00, 124.28 (10C, arom.), 103.05
(Cacetalic), 52.60 (OCH3).
(CDCl3) d (ppm): 6.40 (1H, s, Hacetalic), 6.05 (1H, s,
Hacetalic), 2.80 (3H, s, OCH3). Anal. Calcd for
C35H32O5S: C, 74.44; H, 5.71; S, 5.68. Found: C,
74.61; H, 5.75; S, 5.60.
4.6.11. Phenyl 3-O-(2-naphthyl)methyl-1-thio-b-L-fuco-
pyranoside 11. Compound 9exo (2.36 g, 6 mmol) was
reacted according to General method B. The yield after
chromatographic purification (DCM/EtOAc = 85:15,
Rf = 0.44): 2.30 g (97%), mp: 113–115 ꢁC (EtOAc–hex-
1
4.6.9. Phenyl 3,4-O-exo/endo-(2-naphthyl)methylene-1-
thio-b-L-fucopyranoside 9exo and 9endo. To a solution
of 3b (10.00 g, 39 mmol) in dry DMF (15 mL) 8
(15.8 mL, 78 mmol, 2.0 equiv) and a catalytic amount
of 10-camphorsulfonic acid (CSA) were added. After
seven days t.l.c. (DCM/acetone = 97:3, Rf,exo = 0.58,
ane), [a]D = +26.3 (c 0.32, CHCl3); H NMR (CDCl3)
d (ppm): 7.85–7.80 (4H, m, arom.), 7.58–7.56 (2H, dd,
arom.), 7.51–7.47 (3H, m, arom.), 7.33–7.26 (3H, m,
arom.), 4.90 (2H, dd, CH2), 4.48 (1H, d, J1,2 = 10 Hz,
H-1), 3.81 (1H, m), 3.58 (1H, dd), 3.5 (1H, dd), 2.40
(2H, s, 2 · OH), 1.38 (3H, d, J5,6 = 6 Hz, CH3); 13C
NMR d (ppm): 135.09, 133.18, 132.52, 128.91, 128.47,
127.87, 127.71 126.82, 126.25, 126.10, 125.71 (16C,
arom.), 88.45 (C-1), 81.54, 74.60, 69.39, 68.76 (C-2to
C-5), 72.15 (CH2), 16.70 (C-6). Anal. Calcd for
C23H24O4S: C, 69.67; H, 6.10; S, 8.09. Found: C,
69.81; H, 6.07; S, 8.06.
R
f,10 = 0.47, Rf,endo = 0.40) showed an acceptable con-
version of the starting material (ꢁ80%), the exo and
endo isomers were formed approx. in a 1:1 ratio, com-
pound 10 (see 4.6.10.) was formed in a small quantity.
The mixture was neutralized with Et3N, diluted with
DCM (700 mL) and washed with satd. NaHCO3 and
water. The organic layer was dried, evaporated and
the resulting crude product was purified by column
chromatography (DCM/acetone = 98:2 ! 97:3). Com-
plete separation of the exo and endo isomers could not
be achieved due to 10, thus the non-homogeneous frac-
tions were collected and purified further. The material in
the unique fractions could be recrystallized from
EtOAc–hexane solvent mixture, the mother liquors were
purified further. Yield for 9exo: 3.30 g (22%), mp:
143–144 ꢁC, [a]D = ꢀ16.7 (c 0.32, CHCl3); 1H NMR
4.6.12. Phenyl 4-O-(2-naphthyl)methyl-1-thio-b-L-fuco-
pyranoside 12. Compound 9endo (2.36 g, 6 mmol)
was reacted according to General method B. The yield
after chromatographic purification (DCM/EtOAc =
85:15, Rf = 0.24): 2.33 g (98%), amorphous solid,
could not be recrystallized from solvents generally used,
1
mp: 134–137 ꢁC, [a]D = +3.4 (c 0.89, CHCl3); H NMR
(CDCl3) d (ppm): 7.85 (4-H, m, arom.), 7.65–7.45
(5H, m, arom.), 7.28 (3H, dd, arom.), 4.93 (2H, s,
CH2), 4.50 (1H, d, J1,2 = 9 Hz, H-1), 3.80–3.55 (4H,
m, H-2,3,4,5), 2.67 (2H, s, 2 · OH), 1.37 (3H, d,
J5,6 = 7 Hz, CH3); 13C NMR d (ppm): 135.72, 133.17,
132.91, 132.77, 132.02, 128.81, 128.11, 127.84, 127.66,
127.56, 126.29, 126.10, 125.88, 125.72 (16C, arom.),
88.27 (C-1), 79.14, 75.68, 74.98, 69.93 (C-2to C-5),
75.56 (CH2), 17.26 (C-6). Anal. Calcd for C23H24O4S:
C, 69.67; H, 6.10; S, 8.09. Found: C, 69.76; H, 6.13; S,
8.14.
(CDCl3)
d (ppm): 7.95–7.80 (4H, arom.), 7.65–
7.44 (5H, arom.), 7.40–7.32(3H, arom.), 6.30 (1H, s,
Hacetalic), 4.53 (2H, m), 4.09 (1H, dd), 3.82 (2H, m),
2.81 (1H, s, OH), 1.50 (3H, d, J5,6 = 7 Hz, 3 · H-6);
13C NMR d (ppm): 136.14, 133.64, 132.83, 132.62,
132.10, 129.03, 128.28, 128.06, 127.65, 126.39, 126.22,
125.53, 123.85 (16C, arom.), 103.31 (Cacetalic), 87.92
(C-1), 80.07, 76.21, 72.95, 69.07 (C-2to C-5), 17.07
(C-6). Anal. Calcd for C23H22O4S: C, 70.03; H, 5.62;
S, 8.13. Found: C, 69.92; H, 5.66; S, 8.09.
4.6.13. Phenyl 2,4-di-O-benzyl-3-O-(2-naphthyl)methyl-
1-thio-b-L-fucopyranoside 13. Compound 11 (1.77 g,
4.5 mmol) was reacted with double amounts of BnBr
according to General method A. The reaction reached
completion in three hours (hexane/EtOAc = 8:2,
Rf = 0.46). Yield after chromatography (hexane/
EtOAc = 8:2 ! 7:3): 2.36 g (93%), mp: 84–86 ꢁC, de-
comp. (Et2O–hexane), [a]D = ꢀ20.4 (c 0.72, CHCl3);
1H NMR (CDCl3) d (ppm): 7.88–7.12 (22H, m, arom.),
5.13–4.69 (6H, m, 3 · CH2), 4.64 (1H, d, J1,2 = 10 Hz,
H-1), 3.99 (1H), 3.67 (2H, m), 3.54 (1H, m), 1.30 (3H,
d, J5,6 = 6 Hz, CH3); 13C NMR d (ppm) 138.71,
138.40, 135.79, 134.34, 133.22, 132.94, 131.48, 128.71,
128.30, 128.15, 127.89, 127.67, 127.45, 126.91, 126.26,
126.11, 125.90, 125.63 (28C, arom.), 87.52 (C-1), 84.28,
77.12, 76.68, 74.59 (C-2to C-5), 75.51, 74.59, 72.85
(3 · CH2), 17.27 (C-6). Anal. Calcd for C36H36O4S: C,
76.57; H, 6.43; S, 5.68. Found: C, 76.48; H, 6.47; S, 5.74.
Yield for 9endo: 3.86 g (25%), mp: 147–148 ꢁC,
[a]D = +18.1 (c 0.27, CHCl3); 1H NMR (CDCl3) d
(ppm): 7.96–7.72(4H, m, arom.), 7.61–7.40 (5H, m,
arom.), 7.36–7.26 (3H, m, arom.), 6.08 (1H, s, Hacetalic),
4.50 (1H, d, J1,2 = 10 Hz, H-1), 4.22 (1H, t, J = 6 Hz),
4.11 (1H, dd), 3.92(1H, m), 3.63 (1H, dd), 3.30 (1H, s,
OH), 1.52(3H, d, J5,6 = 7 Hz, 3 · H-6); 13C NMR d
(ppm): 134.72, 133.77, 132.83, 131.75, 128.81, 128.25,
127.88, 127.60, 126.42, 126.32, 126.08, 123.80 (16C,
arom.), 104.50 (Cacetalic), 87.43 (C-1), 78.80 (2C),
72.45, 71.44 (C-2to C-5), 16.82( C-6). Anal. Calcd for
C23H22O4S: C, 70.03; H, 5.62; S, 8.13. Found: C,
69.90; H, 5.68; S, 8.17.
4.6.10. Phenyl 2-O-R/S(methoxy-20-naphthyl)methyl-3,4-
O-(endo-2-naphthyl)methylene 1-thio-b-L-fucopyranoside
10. The title compound was isolated in the course of
the preparation of compounds 9exo and 9endo (DCM/
acetone = 97:3, Rf = 0.47). Yield: 1.37 g (6%), mp:
147–152 ꢁC, [a]D = ꢀ63.9 (c 0.37, CHCl3); 1H NMR
4.6.14. Phenyl 2,3-di-O-benzyl-4-O-(2-naphthyl)methyl-
1-thio-b-L-fucopyranoside 14. Compound 12 (3.32g,

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Z. B. Szabo et al. / Tetrahedron: Asymmetry 16 (2005) 83–95
93
8.4 mmol) was reacted with double amounts of BnBr
according to General method A. The reaction took place
in three hours (hexane/EtOAc = 8:2, Rf = 0.46). Yield
after chromatography (hexane/EtOAc = 8:2 ! 7:3):
3.45 g (93%), mp: 83–85 ꢁC, decomp. (Et2O–hexane),
[a]D = ꢀ21.5 (c 0.53, CHCl3); 1H NMR (CDCl3) d
(ppm): 7.92–7.80 (4H, m, arom.) 7.72–7.20 (18H,
arom.), 5.22 (1H, d, CHH), 4.96–4.75 (5H,
m, 2.5 · CH2), 4.68 (1H, d, J1,2 = 9 Hz, H-1), 4.04
(1H, t, J = 9 Hz), 3.75–3.53 (3H, m), 1.34 (3H, d,
J5,6 = 6 Hz, CH3); 13C NMR d (ppm): 138.30, 136.12,
134.36, 133.12, 132.88, 131.40, 128.68, 128.39, 128.27,
127.80, 127.64, 127.51, 126.89, 126.50, 126.21, 125.94,
125.72 (28C, arom.), 87.59 (C-1), 84.53, 77.16, 76.45,
74.56 (C-2to C-5), 75.50, 74.56, 72.89 (3 · CH2), 17.33
(C-6). Anal. Calcd for C36H36O4S: C, 76.57; H, 6.43;
S, 5.68. Found: C, 76.65; H, 6.45; S, 5.65.
and the mixture was kept at 50 ꢁC for 2.5 h. The solvent
was evaporated in vacuo and co-evaporated once with
toluene. The product was recrystallized from MeOH,
the mother liquor was purified by column chromatogra-
phy (DCM/acetone = 85:15; Rf = 0.51). Yield from 4b:
4.73 g (92%), mp: 110.5–111.0 ꢁC, [a]D = ꢀ10.9 (c 0.27,
CHCl3); 1H NMR (CDCl3) d (ppm): 7.60–7.55 (2H,
dd, arom.), 7.45–7.27 (8H, m, arom.), 4.97 (1H, d,
Jgem. = 11 Hz, CHH), 4.73 (1H, d, Jgem. = 11 Hz,
CHH), 4.62(1H, d, J1,2 = 9 Hz, H-1), 3.77–3.48 (4H,
m, H-2,3,4,5), 2.51 (2H, s, 2 · OH), 1.36 (3H, d,
J5,6 = 6 Hz, CH3); 13C NMR d (ppm): 138.06, 134.00,
131.63, 128.89, 128.56, 128.24, 128.04, 127.39 (12C,
arom.), 87.38 (C-1), 78.04, 75.28, 74.41, 71.68 (C-2to
C-5), 75.22 (CH2), 16.59 (C-6). Anal. Calcd for
C19H22O4S: C, 65.87; H, 6.40; S, 9.25. Found: C,
65.98; H, 6.42; S, 9.17.
4.6.15. Phenyl 3-O-(2-naphthyl)methyl-a/b-L-fucopyrano-
side 11 and 15. Compound 3b (0.85 g, 3.3 mmol) was
reacted with NAPBr according to General method C.
The crude product was purified and the isomers were
separated by chromatography (DCM/EtOAc = 85:15;
Rf,15 = 0.25). Yield for 11(b): 0.89 g (68%), mp: 114–
116 ꢁC. The [a]D value and NMR data were the same
to that of compound 11 obtained according to General
method B. Yield for 15(a): 0.165 g (13%), mp: 122.5–
124.0 ꢁC, [a]D = ꢀ105.5 (c 0.80, CHCl3); 1H NMR
(CDCl3) d (ppm): 7.90–7.80 (4H, m, arom.), 7.56–7.44
(5H, m, arom.), 7.37–7.24 (3H, m, arom.), 5.66 (1H, d,
J1,2 = 6 Hz, H-1), 4.91 (2H, s, 2 · CH2), 4.46–4.30 (2H,
m), 3.93 (1H, dd), 3.62 (1H, dd), 2.45 (2H, s, 2 · OH),
1.32(3H, d, J5,6 = 7 Hz, CH3); 13C NMR d (ppm):
134.92, 134.21, 133.18, 131.52, 128.96, 128.55, 127.88,
127.72, 127.24, 126.77, 126.31, 126.17, 125.59 (16C,
arom.), 90.10 (C-1), 79.42, 69.29, 67.98, 67.18 (C-2to
C-5), 72.16 (CH2), 16.10 (C-6). Anal. Calcd for
C23H24O4S: C, 69.67; H, 6.10; S, 8.09. Found: C,
69.56; H, 6.12; S, 8.06.
4.6.18. Phenyl 2,3-di-O-benzyl-1-thio-b-L-fucopyranoside
18. Compound 17 (0.72g, 2.0 mmol) was benzylated
according to General method C. The reaction took
place within 16 h (hexane/EtOAc = 7:3, Rf = 0.42). The
crude product was chromatographed in hexane/
EtOAc = 65:35 eluent. Yield: 0.78 g (89%), mp: 95–
1
96 ꢁC (EtOAc–hexane), [a]D = 0.0 (c 0.41, CHCl3); H
NMR (CDCl3) d (ppm): 7.60 (2H, m, arom.), 7.46–
7.25 (13H, m, arom.), 4.89–4.68 (4H, m, 2 · CH2),
4.63 (1H, d, J1,2 = 10 Hz, H-1), 3.85–3.53 (4H, m, H-
2,3,4,5), 2.32 (1H, s, OH), 1.39 (3H, d, J5,6 = 6 Hz,
CH3); 13C NMR d (ppm): 138.17, 137.63, 133.93,
131.85, 128.79, 128.48, 128.30, 128.20, 127.94, 127.83,
127.74, 127.29, 126.90 (18C, arom.), 87.47 (C-1), 82.81,
76.78, 74.14, 69.30 (C-2to
C-5), 75.62, 72.06
(2 · CH2), 16.70 (C-6). Anal. Calcd for C26H28O4S: C,
71.53; H, 6.46; S, 7.34. Found: C, 71.69; H, 6.42; S, 7.31.
4.6.19. Phenyl 2-O-benzyl-3-O-(2-naphthyl)methyl-1-
thio-b-L-fucopyranoside 19. Compound 17 (0.42g,
1.2mmol) was 2-(naphthyl)methylated according to
General method C. The reaction took place within
18 h (t.l.c: hexane/EtOAc = 7:3, Rf = 0.36). The crude
product was purified by column chromatography (hex-
ane/EtOAc = 65:35). Yield: 0.47 g (82%), syrup,
[a]D = ꢀ7.8 (c 0.56, CHCl3); 1H NMR (CDCl3) d
(ppm): 7.90–7.26 (17H, m, arom.), 4.91–4.80 (4H, m,
2 · CH2), 4.65 (1H, d, J1,2 = 10 Hz, H-1), 3.90–3.50
(4H, m, H-2,3,4,5), 2.38 (1H, s, OH), 1.40 (3H, d,
J5,6 = 7 Hz, CH3); 13C NMR d (ppm): 138.18, 135.05,
133.93, 133.09, 132.96, 131.75, 128.74, 128.26, 128.13,
127.79, 127.67, 127.60, 127.22, 126.61, 126.12, 125.98,
125.66 (22C, arom.), 87.45 (C-1), 82.60, 76.80, 74.11,
69.32( C-2to C-5), 75.58, 72.04 (2 · CH2), 16.65 (C-6).
Anal. Calcd for C30H27O4S: C, 74.51; H, 5.63; S, 6.63.
Found: C, 74.40; H, 5.60; S, 6.67.
4.6.16. Phenyl 2-O-benzyl-3,4-O-isopropylidene-1-thio-b-
L-fucopyranoside
16. Compound
4b
(4.32g,
14.6 mmol) was benzylated with BnBr according to
General method A. A small amount of the crude prod-
uct was purified and characterized and the rest (ꢁ5.5 g)
was used directly for the next step, (t.l.c: hexane/
EtOAc = 8:2, Rf = 0.41). mp: 95–98 ꢁC, [a]D = ꢀ8.5 (c
0.78, CHCl3); 1H NMR (CDCl3) d (ppm): 7.60–7.52
(2H, m, arom.), 7.47–7.25 (8H, m, arom.), 4.83 (1H, d,
Jgem. = 11 Hz CHH), 4.67 (1H, d, Jgem. = 11 Hz,
CHH), 4.60 (1H, d, J1,2 = 10 Hz, H-1), 4.24 (1H, t,
J = 6 Hz), 4.05 (1H, dd), 3.83 (1H, m), 3.51 (1H, dd),
1.42, 1.37 (6H, 2 · CH3), 1.40 (3H, d, J5,6 = 6 Hz,
CH3); 13C NMR d (ppm): 137.92, 133.74, 132.06,
128.70, 128.22, 128.17, 127.65, 127.31 (12C, arom.),
109.64 (Cacetalic), 86.05 (C-1), 79.78, 78.06, 76.38, 72.34
(C-2to C-5), 73.40 (CH2), 27.84, 26.35 (2 · CH3),
16.85 (C-6). Anal. Calcd for C22H26O4S: C, 68.37; H,
6.78; S, 8.29. Found: C, 68.50; H, 6.74; S, 8.36.
4.6.20. Methyl 3,4-di-O-benzyl-2-O-(2-naphthyl)methyl-
a- and -b-L-fucopyranosyl-(1fi2)-3,4,6-tri-O-benzyl-b-D-
galactopyranoside 20 and 21. The title compound was
prepared according to General method D using 7 as
the donor. T.l.c: DCM/acetone = 97:3; Rf,a,20 = 0.65;
Rf,b,21 = 0.57. Yield for 20: 0.316 g (68%), syrup,
[a]D = ꢀ45.6 (c 0.37, CHCl3). Anal. Calcd for
C59H62O10: C, 76.11; H, 6.71. Found: C, 76.18; H,
4.6.17. Phenyl 2-O-benzyl-1-thio-b-L-fucopyranoside 17.
Crude compound 16 (5.5 g) was dissolved in MeOH
(30 mL), HCl(aq)/water = 1:3 (4 mL) solution was added

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Z. B. Szabo et al. / Tetrahedron: Asymmetry 16 (2005) 83–95
94
6.68. Yield for 21: 0.051 g (11%), mp: 148–150 ꢁC,
[a]D = ꢀ29.41 (c 0.15, CHCl3). Anal. Calcd for
C59H62O10: C, 76.11; H, 6.71. Found: C, 76.09; H, 6.73.
127.82, 127.64, 127.54, 127.49, 127.30, 126.14, (25C,
arom.) 102.93, 96.67, 84.07, 79.65, 76.04, 75.22, 74.34,
73.58, 73.07, 71.67, 71.45, 70.97, 70.43, 68.68, 66.22,
56.53 (OCH3), 16.39 (C-60). Anal. Calcd for
C48H54O10: C, 72.89; H, 6.88. Found: C, 72.77; H, 6.90.
4.6.21. Methyl 2,4-di-O-benzyl-3-O-(2-naphthyl)methyl-
a- and -b-fucopyranosyl-(1fi2)-3,4,6-tri-O-benzyl-b-D-
galactopyranoside 22 and 23. The title compound was
prepared according to General method D using 13 as
the donor. Rf,a,22 = 0.61; Rf,b,23 = 0.54. Yield for 22:
0.340 g (73%), syrup, [a]D = ꢀ57.9 (c 0.17, CHCl3).
Anal. Calcd for C59H62O10: C, 76.11; H, 6.71. Found:
C, 76.18; H, 6.70. Yield for 23: 0.042g (9%), mp: 151–
153 ꢁC, [a]D = ꢀ27.7 (c 0.10, CHCl3). Anal. Calcd for
C59H62O10: C, 76.11; H, 6.71. Found: C, 76.15; H, 6.70.
4.6.25.
Methyl
2,3-di-O-benzyl-a-L-fucopyranosyl-
28.
(1fi2)-3,4,6-tri-O-benzyl-b-D-galactopyranoside
Disaccharide 24 was treated with DDQ according to
General method E. Rf = 0.32. Yield: 0.134 g (85%),
1
syrup, [a]D = ꢀ57.4 (c 0.39, CHCl3); H NMR d (ppm):
7.36–7.20 (20H, m, arom.), 7.16–7.07 (3H, m, arom.),
0
0
7.03–6.98 (2H, m, arom.), 5.61 (1H, d, J1 ,2 = 3.4 Hz,
H-10), 4.82(1H, d, Jgem. = 12Hz, CH H), 4.76 (2H, d,
Jgem. = 12Hz, C H2), 4.68 (1H, d, Jgem. = 12Hz, C HH),
4.59 (1H, d, Jgem. = 12.8 Hz, CHH), 4.53 (2H, d,
Jgem. = 11.1 Hz, CHH), 4.48–4.40 (3H, m), 4.36 (2H, d,
J = 7.7 Hz), 4.20 (1H, t, J = 8.4 Hz), 3.95 (1H, s), 3.86
(2H, m), 3.78 (1H, dd), 3.71 (1H, dd), 3.64–3.55 (3H,
m), 3.48 (3H, s, OCH3), 2.06 (1H, s, OH), 1.25 (3H, d,
4.6.22. Methyl 2,3-di-O-benzyl-4-O-(2-naphthyl)methyl-
a- and -b-L-fucopyranosyl-(1!2)-3,4,6-tri-O-benzyl-b-D-
galactopyranoside 24 and 25. The title compound was
prepared according to General method D using 14 as
the donor. Rf,a,24 = 0.68; Rf,b,25 = 0.59. Yield for 24:
0.354 g (75%), syrup, [a]D = ꢀ46.8 (c 0.68, CHCl3).
Anal. Calcd for C59H62O10: C, 76.11; H, 6.71. Found:
C, 76.04; H, 6.74. Yield for 25: 0.033 g (7%), mp: 171–
173 ꢁC, [a]D = ꢀ14.28 (c 0.11, CHCl3). Anal. Calcd for
C59H62O10: C, 76.11; H, 6.71. Found: C, 76.05; H, 6.68.
J5 ,6 = 6.8 Hz, H-60); 13C NMR d (ppm): 138.40,
138.26, 138.04, 137.81, 128.43, 128.40, 128.14, 128.04,
127.93, 127.83, 127.74, 127.70, 127.60, 127.50, 127.32,
126.30 (25C, arom.), 102.86, 97.21, 83.97, 78.20, 74.85,
74.34, 73.62, 73.21, 72.40, 71.92, 71.22, 70.33, 68.79,
65.12, 56.45 (OCH3), 15.90 (C-60). Anal. Calcd
for C48H54O10: C, 72.89; H, 6.88. Found: C, 72.81; H,
6.85.
0
0
4.6.23.
Methyl
3,4-di-O-benzyl-a-L-fucopyranosyl-
26.
(1fi2)-3,4,6-tri-O-benzyl-b-D-galactopyranoside
Disaccharide 20 was treated with DDQ according to
General method E. T.l.c: DCM/acetone = 97:3;
Rf = 0.33. Yield: 0.133 g (84%), syrup, [a]D = ꢀ59.7 (c
0.23, CHCl3); 1H NMR (CDCl3) d (ppm): 7.35–7.22
Acknowledgements
(25H, m, arom.), 5.41 (1H, d, J1 ,2 = 4.3 Hz, H-10),
0
0
This work was supported by the Hungarian Research
Fund (OTKA T038066 A.B. and T035128 I.B.).
4.92(1H, d,
Jgem. = 12Hz, CH H), 4.84 (1H, d,
Jgem. = 12Hz, CH H), 4.70–4.60 (5H, m, 2.5 · CH2),
4.54 (1H, d, Jgem. = 12Hz, CH H), 4.44 (2H, dd, CH2),
4.25 (1H, d, J1,2 = 7.7 Hz, H-1), 4.15 (2H, m), 4.04
(1H, t, J = 8.7 Hz), 3.94 (1H, s), 3.68 (2H, m), 3.62–
References
3.52(4H, m), 3.45 (3H, s, OC H3), 2.28 (1H, s, OH),
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1.14 (3H, d, J5 ,6 = 6 Hz, H-6 ); 13C NMR d (ppm):
138.63, 138.53, 138.36, 137.76, 137.41, 128.40, 128.38,
128.31, 128.09, 127.86, 127.81, 127.77, 127.49, 127.44
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1
syrup, [a]D = ꢀ85.8 (c 0.25, CHCl3); H NMR (CDCl3)
d (ppm): 7.35–7.18 (23H, m, arom.), 7.05 (2H, m,
arom.), 5.63 (1H, d, J1 ,2 = 3.4 Hz, H-10), 4.81 (2H, t,
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(6H, m, 3 · CH2), 4.34 (2H, m), 4.16 (2H, m), 4.04
(1H, dd), 3.98 (1H, d, J = 2.6 Hz), 3.72 (1H, dd),
3.68 (1H, dd), 3.65–3.55 (4H, m), 3.46 (3H, s, OCH3),
0
0
2.00 (1H, s, OH), 1.16 (3H, d, J5 ,6 = 6.8 Hz, H-60);
13C NMR d (ppm): 138.58, 138.35, 137.93, 137.85,
137.76, 128.41, 128.35, 128.22, 128.11, 128.08, 127.92,
0
0

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