Fucosylation of linear alcohols: A study of parameters influencing the stereochemistry of glycosylation

Article abstract of DOI:10.1002/1099-0690(200101)2001:1<193::aid-ejoc193>3.0.co;2-s

L-Fucose is a constituent of many glycoconjugates and often has a key role in the epitope involved in biological functions. The chemical synthesis of such compounds is necessary to generate sufficient material to explore the molecular details of their bioactivity. In this context, the development of practical and stereoselective α-fucosylation reactions is essential. Here are described several procedures for fucosylation of linear alcohols 9-16 with L-fucose (1) and a series of 2-O-benzyl-protected fucopyranosyl donors 3-8, together with parameters influencing the stereochemistry of glycosylation, such as protecting groups, catalysts, and dielectric constants of solvents. Although high α-selectivities have often been reported for fucosylation reactions with glycosyl acceptors, complete α-selectivity was never observed here, using linear spacer alcohols 9-16. Generally, the best α-selectivities were obtained in fucosylations of the alcohols under in situ anomerization conditions using tetrabutylammonium bromide (75-90% α-anomer), whereas promotion by NIS/TfOH(cat.) proceeded with poor stereoselectivity in treatment of the ethyl thiofucosides 3-5. No directing effects from the 4-O protecting groups were noted. For the 2-O-benzyl-protected 1-O-thioethyl fucopyranosyl donors 3-5, electronic effects of the fucosyl donor could not explain the observed stereoselectivity. The difference between the observed selectivities for α-fucosylations of glycosyl acceptors, in comparison with the linear spacer alcohols used here, is probably due to steric effects of the more bulky glycosyl acceptors.

Full text of DOI:10.1002/1099-0690(200101)2001:1<193::aid-ejoc193>3.0.co;2-s

FULL PAPER
Fucosylation of Linear Alcohols: A Study of Parameters
Influencing the Stereochemistry of Glycosylation
Henricus J. Vermeer,[a] Christiaan M. van Dijk,[a] Johannis P. Kamerling,*[a] and
Johannes F. G. Vliegenthart[a]
Keywords: Alcohols / Carbohydrates / Glycoconjugates / Glycosylations / Protecting groups
L-Fucose is a constituent of many glycoconjugates and often
spacer alcohols 9−16. Generally, the best α-selectivities were
has a key role in the epitope involved in biological functions.
obtained in fucosylations of the alcohols under in situ ano-
The chemical synthesis of such compounds is necessary to merization conditions using tetrabutylammonium bromide
generate sufficient material to explore the molecular details
of their bioactivity. In this context, the development of prac-
tical and stereoselective α-fucosylation reactions is essential.
Here are described several procedures for fucosylation of lin-
(75−90% α-anomer), whereas promotion by NIS/TfOH(cat.)
proceeded with poor stereoselectivity in treatment of the
ethyl thiofucosides 3−5. No directing effects from the 4-O
protecting groups were noted. For the 2-O-benzyl-protected
1-O-thioethyl fucopyranosyl donors 3−5, electronic effects of
the fucosyl donor could not explain the observed stereo-
selectivity. The difference between the observed selectivities
for α-fucosylations of glycosyl acceptors, in comparison with
ear alcohols 9−16 with
L-fucose (1) and a series of 2-O-
benzyl-protected fucopyranosyl donors 3−8, together with
parameters influencing the stereochemistry of glycosylation,
such as protecting groups, catalysts, and dielectric constants
of solvents. Although high α-selectivities have often been re- the linear spacer alcohols used here, is probably due to steric
ported for fucosylation reactions with glycosyl acceptors,
effects of the more bulky glycosyl acceptors.
complete α-selectivity was never observed here, using linear
Introduction
were investigated for eight alcohols: ethanol (9), 1-propanol
(10), allyl alcohol (11), 1-butanol (12), 3-bromopropanol
(13), 3-azidopropanol (14), 5-azidopentanol (15), and 1-de-
canol (16).
Most coupling reactions gave moderate or high yields
(Tables 1Ϫ5). The α/β ratio of the products was determined
by integration of typical proton signals (using either anom-
eric or methyl protons) in the corresponding 1H NMR spec-
tra, measured at 300 MHz.
In naturally occurring glycoconjugates, -fucose usually
occupies a non-reducing position.[1] Procedures to synthes-
ize oligosaccharides containing α--fucose residues have
been the subject of many studies, and various fucosyl
donors have been used: among them thiofucosides,[2Ϫ5] fu-
cosyl halides,[6Ϫ9] fucosyl trichloroacetimidates,[10] fucosyl
phosphites,[11] and fucosyl methoxyacetates.[12] Direct fuco-
sylation of a spacer aglycon with -fucose can be accomp-
lished using a Fischer-type glycosylation reaction. The de-
velopment of practical and stereoselective α-fucosylations
is an important area. However, a practical problem is that
glycosylation of (protected) fucose moieties often results in
anomeric mixtures that are difficult to separate.[13Ϫ15] In
this paper, the stereoselectivity of fucosylation reactions
with some linear alcohols has been investigated. Several
parameters important for the stereochemical outcome of
the glycosylation reactions were studied, including the type
of activating group, the type and position of donor pro-
tecting groups, the dielectric constants of solvent systems
used, and the influence of the catalyst/promoter.
Synthesis of Fucopyranosyl Donors
Firstly, direct glycosylation was performed using -fucose
(1). Additionally, the effect on the α/β ratio of various pro-
tecting groups at O-3 and O-4 of some 2-O-benzyl-pro-
tected fucopyranosyl donors was also studied, in order to
investigate participating and activating/deactivating effects
during coupling reactions. For this reason, couplings using
the 2,3,4-tri-O-benzylfucopyranosyl donor, the most often
used donor described in the literature, were not studied
here. Ethyl 3,4-di-O-acetyl-2-O-benzyl-1-thio-β--fucopyr-
anoside (3) [donor 3 was prepared from ethyl 2-O-benzyl-
1-thio-β--fucopyranoside[2] by acetylation (Ǟ 3, 92%)],
Results and Discussion
ethyl
3-O-acetyl-2,4-di-O-benzyl-1-thio-β--fucopyrano-
side[14] (4), ethyl 2-O-benzyl-3,4-O-isopropylidene-1-thio-β-
-fucopyranoside[2] (5), 3,4-di-O-acetyl-2-O-benzyl-α--fuco-
pyranosyl bromide[16] (6), 3-O-acetyl-2,4-di-O-benzyl-α--
fucopyranosyl bromide[17] (7), and 2-O-benzyl-3,4-O-iso-
propylidene-α--fucopyranosyl bromide (8) (glycosyl brom-
ides 6؊8 were obtained by treatment of the corresponding
Stereochemical outcomes (in terms of the anomeric ra-
tios) of the condensation reactions of fucose donors 1؊8
[a]
Bijvoet Center, Department of Bio-Organic Chemistry,
Utrecht University,
P. O. Box 80075, 3508 TB Utrecht, The Netherlands
Eur. J. Org. Chem. 2001, 193Ϫ203
WILEY-VCH Verlag GmbH, 69451 Weinheim, 2001
1434Ϫ193X/01/0101Ϫ0193 $ 17.50ϩ.50/0
193

H. J. Vermeer, C. M. van Dijk, J. P. Kamerling, J. F. G. Vliegenthart
FULL PAPER
thioethyl analogues 3؊5 with bromine) were selected as is thought that the Fischer glycosylation of -fucose occurs
donors for treatment with aglycons 9؊16 (Scheme 1).
via a bicyclic intermediate (17) (Pater et al.,[25] Scheme 2),
followed by an SN1 ring-opening of 17, allowing the alcohol
to attack on both sides at ring 18.
According to the literature,[25,26] preparation of methyl α/
β--fucopyranosides utilizing cation exchange resins (Hϩ)
in boiling methanol gave an anomeric ratio α/β ϭ 67:33
after 12 h. For the alcohols used in this study, Table 1 shows
that comparable stereochemical product distributions were
obtained (entries 1, 3, 6, 8, 11). Repetition of these experi-
ments, but changing the catalyst for HCl (achieved by the
addition of acetyl chloride[27]) showed rapid conversions of
1. In most cases, when using HCl as catalyst, the formation
of α-linked products was slightly favored in comparison
with the ion exchange-catalyzed procedures. So it might be
that the product distribution is influenced either by the na-
ture of the catalyst, or by whether a heterogeneous (ion ex-
change resin) or homogeneous (HCl) reaction mixture is
used. Furthermore, the Lewis acid-catalyzed (FeCl3) reac-
tion of 1 with 11 in a homogeneous reaction mixture also
gave a higher α-selectivity (compare entries 3, 4, 5). Rela-
tively higher levels of the thermodynamically more favored
α-adducts in homogeneous systems might be explained by
equilibrated mixtures being reached earlier.[1] Finally, the
anomeric ratios in Table 1 show that no significant influ-
ence of the length of the aglycon could be observed.
Experiments with 2-O-Benzyl-Protected Fucopyranosyl
Donors
A series of experiments was performed using fucosyl
donors possessing a non-participating benzyl function at O-
2, with varying protecting groups at O-3 and O-4. Donors
3 or 6 (Table 2) have an electron-withdrawing 4-O substitu-
ent, donors 4 or 7 (Table 3) an electron donating one,
whereas donors 5 and 8 (Table 4) have an acetonide func-
Scheme 1
Although α-selectivity has sometimes been reported in
the literature with protected fucosyl donors possessing an
anchimeric assistant 2-O-acetyl protecting group with gly-
cosyl acceptors[18,19] or aliphatic alcohols,[20] we never suc-
ceeded in obtaining α--linked products using these ap-
proaches (results not shown).
1
tion at O-3,4, thus existing as a distorted C4 chair. The
ethyl 1-thio-β--fucopyranoside donors (3؊5) were coupled
with 11 and 13؊16 using the strongly thiophilic promoter
system N-iodosuccinimide and trifluoromethanesulfonic
acid (NIS/TfOH cat.), at different temperatures and in dif-
ferent solvents. Alternatively, they were converted into their
corresponding α-bromides (6؊8) for condensations with 10,
11, 13, 14, and 16 in the presence of tetrabutylammonium
bromide (TBAB), using in situ anomerization conditions to
convert α-bromides into the more reactive β-bromides.[28]
Also, some miscellaneous coupling methods were applied
with a limited number of examples. As shown in Tables 2
and 3, neither α- nor β--fucosides were ever formed exclus-
ively, and all isolated products 25؊33 showing as a single
spot on TLC were isolated as inseparable mixtures of ano-
mers (Scheme 3).
Modified Fischer Glycosylation
Fischer fucosylations of 9؊11, 13, 14, and 16 with 1 were
performed using the alcohol both as solvent and as reagent
for the reaction. Either HCl or an ion-exchange resin
[Dowex-50 (Hϩ)] were used as catalyst. Fucosylation of 14
with 2[21,22] was performed using p-toluenesulfonic acid in
N,N-dimethylformamide at 50°C. Most reactions proceeded
smoothly in good yields (Table 1); all products (19؊24)
were obtained as mixtures of anomers (Scheme 2). Isolation
of one anomer was sometimes possible, as is described for
the preparation of allyl α--fucopyranoside by crystalliza-
tion[23] (cf. entry 3). As well as the thermodynamically more
stable pyranosides[24] (19؊24), fucofuranosides were always
observed to be present in the reaction mixtures (NMR ana-
lysis; data not shown). Performing the reactions at lower
Iodonium-assisted Fucosylation With Donors 3 and 4
Treatment of 3 with 11, 13, and 16 was examined in the
temperatures afforded more furanoside products (results presence of NIS/TfOH at 0°C in dichloromethane (Table 2;
not shown). The formation of anomeric products is evident entries 14, 18, and 21). Additionally, treatment of 3 with 11
from the proposed mechanism for this type of reaction. It was also studied, using either a mixture of dichlorome-
194
Eur. J. Org. Chem. 2001, 193Ϫ203

Fucosylation of Linear Alcohols
FULL PAPER
Table 1. Glycosylation of alcohols 9؊11, 13, 14, and 16 with donor 1 or 2
Entry
Donor
Alcohol
Method[a]
Product
Yield[b] [%]
Anomeric ratio (α/β)[c]
1
1
1
1
1
1
1
1
1
1
2
1
1
9
A
B
A
B
C
A
B
A
B
D
A
B
19
20
21
21
21
22
22
23
23
23
24
24
65
67
64
74
73
38
67
31
26
19
48
75
64:36
75:25
70:30
67:33
72:28
64:36
83:17
60:40
68:32
71:29
71:29
74:26
2
10
11
11
11
13
13
14
14
14
16
16
3
4
5
6
7
8
9
10
11
12
[a]
A (GP 1): Dowex-50 (Hϩ), 75 °C, 12 h; B (GP 2): Acetyl chloride, 65 °C, 3 h; C: FeCl3, 55 °C, 3 h; D: pTsOH.H2O, DMF, 50 °C, 5
days. Ϫ [b] The yield is based on the isolation of only pyranosides. Ϫ [c] Anomeric ratios are only calculated for pyranoside products, and
do not reflect the total anomeric composition of all formed products.
Scheme 3
cept for their reaction with 16. No significant changes in
the anomeric ratios were observed for reactions conducted
in diethyl ether/dichloromethane (entries 14 versus 16 and
23 versus 24). However, reactions performed in dichlorome-
thane showed an increased selectivity for the α-anomeric
product at higher temperatures[29Ϫ31] (reaction of 4 with 14;
entries 28Ϫ30). The formation of β-fucosides was favored
when 3 or 4 were coupled with some alcohols in a polar
Scheme 2
mixture of acetonitrile/dichloromethane (entries 17, 25,
and 32).
thane/diethyl ether (entry 16), or dichloromethane/aceto-
According to the literature, high α-selectivities had some-
nitrile (entry 17). Coupling experiments with the more react- times been found in fucosylations of glycosyl acceptors, us-
ive donor 4 were performed in dichloromethane with 11, ing the trichloroacetimidate method.[32] However, coupling
13, 14, and 16, using identical reaction conditions (Table 3; of 3,4-di-O-acetyl-2-O-benzyl-α--fucopyranosyl trichlo-
entries 23, 26, 29, and 31). Treatment of 4 with 14 in dichlo- roacetimidate[33] with 14 did not improve the α-selectivity
romethane was also studied at different temperatures (results not shown).
(Ϫ30°C, 0°C, room temperature; entries 28Ϫ30), while
In order to find a possible explanation for the observed
couplings with 11 and 16 were also conducted in mixtures poor selectivity of iodonium-assisted fucosylations using
of dichloromethane/diethyl ether and dichloromethane/ace- either 3 or 4, it should be noted first that the reported ex-
tonitrile (Table 3; entries 24, 25, and 32).
clusive formation of 1,2-cis linkages with comparable
Most fucosylations with 3 and 4 in dichloromethane pro- donors (i.e., possessing a non-participating protecting
ceeded in moderate or high yields, but with only marginal group at O-2) relate to couplings with glycosyl acceptors.[2]
differences in stereoselectivity. In general, couplings with 3 Generally, the influence of protecting groups on fucosyla-
and 4 in dichloromethane showed a slight α-selectivity, ex- tions has been explained in terms of inductive effects,[9,11,34]
Eur. J. Org. Chem. 2001, 193Ϫ203
195

H. J. Vermeer, C. M. van Dijk, J. P. Kamerling, J. F. G. Vliegenthart
Table 2. Glycosylation of alcohols 10, 11, 13, 14, and 16 with donor 3 or 6
FULL PAPER
Entry
Donor
Alcohol
Method[a]
Product
Yield [%]
Anomeric ratio (α/β)
13
14
15
16
17
18
19
20
21
22
6
3
6
3
3
3
6
6
3
6
10
11
11
11
11
13
13
14
16
16
A
B
A
C
D
B
25
26
26
26
26
27
27
28
29
29
87
90
85
62[b]
96
92
59
54
83
72
77:23
62:38
87:13
69:31
22:78
70:30
88:12
88:12
47:53
83:17
A
A
B
A
[a]
A (GP 5): TBAB, DCM/DMF, room temp., 2 days; B (GP 4 A): NIS/TfOH, DCM, 0 °C, 1 h; C (GP 4 B): NIS/TfOH, Et2O/DCM,
[b]
0 °C, 1 h; D (GP 4 C): NIS/TfOH, CH3CN/DCM, 0 °C, 1 h. Ϫ
and 35% starting donor (3).
Total isolated material consisted of 62% fucosidation products (26)
Table 3. Glycosylation of alcohols 11, 13, 14, and 16 with donor 4 or 7
Entry
Donor
Alcohol
Method[a]
Product
Yield [%]
Anomeric ratio (α/β)
23
24
25
26
27
28
29
30
31
32
33
4
4
4
4
7
4
4
4
4
4
7
11
11
11
13
13
14
14
14
16
16
16
A
B
C
A
D
E
A
F
A
C
D
30
30
30
31
31
32
32
32
33
33
33
93
61:39
56:44
36:64
60:40
77:23
64:36
72:28
83:17
44:56
27:73
73:27
92
80
95
71
27[b]
81[c]
96
93
88
76
[a]
A (GP 4 A): NIS/TfOH, DCM, 0 °C, 1 h; B (GP 4 B): NIS/TfOH, Et2O/DCM, 0 °C, 1 h; C (GP 4 C): NIS/TfOH, CH3CN/DCM,
0 °C, 1 h; D (GP 5): TBAB, DCM/DMF, room temp., 2 days; E (cf. GP 4 A): NIS/TfOH, DCM, Ϫ30°C, 1 h; F (cf. GP 4 A): NIS/TfOH,
[b]
[c]
DCM, room temp., 1 h. Ϫ The total isolated material consisted of 27% fucosidation products (32) and 34% starting donor (4). Ϫ
The total isolated material consisted of 81% fucosidation products (32) and 10% starting donor (4).
4-O-acyl participation,[17,35] or through-bond interactions.[2] can compete effectively with the alcohol, thanks to its high
Although fucosylation of glycosyl acceptors is controlled donicity,[34] thus providing time for anomerization of 34A,
both by steric effects Ϫ i.e., the spatial orientation (axial or whereas in acetonitrile (high dielectric constant: ε ϭ 38) ion
equatorial) of both the hydroxyl group to be glycosylated separation (Ǟ 34B), or anomerization into 34C is fav-
and the blocking groups around this hydroxyl group[36]
Ϫ
ored.[37] Indeed, couplings conducted in dichloromethane/
and by electronic effects, it might be expected that electronic acetonitrile, of 3 with 11 (Table 2; entry 17) and of 4 with
effects exerted by protecting groups on the fucosyl donor 11 and 16 (Table 3; entries 25 and 32, respectively), showed
would predominantly determine the stereochemical out- high selectivity for β-glycosides. However, besides anomer-
come of reactions with the reactive and flexible linear alco- ization of 34A into 34C being favored under these condi-
hols 11, 13, 14, and 16. However, as shown later, fucosyl tions, this high selectivity towards β-glycosides can also be
donor electronic effects could not explain the observed ste- explained by the occurrence of the ‘‘nitrile effect’’.[39,40]
reoselectivity here.
The slight α-selectivity of couplings conducted in dichloro-
The mechanism of reactions promoted by NIS/TfOH
methane might indicate that the coupling reactions pro-
(cat.) is shown in Scheme 4. The β- and α-iodosulfonium-
ceed predominantly via intermediates 34A and 34B. The in-
oxocarbonium intermediates Ϫ 34A and 34C, respectively
creased selectivity at higher temperatures for α-fucosylation
Ϫ will glycosylate by means of an SN2-type bimolecular
in dichloromethane (entries 28Ϫ30) can be explained by the
mechanism, whereas reaction of fucosyloxocarbonium ion
higher reactivity of 34A at higher temperatures.
34B will proceed by an SN1-type mechanism, resulting in
loss of steric control. In principle, it may be expected that
reactions in solvents with a low dielectric constant (such as
dichloromethane: ε ϭ 8.9) should proceed with a high de-
As mentioned earlier, participation of the 4-O-acyl group
is sometimes presumed to explain high α-stereoselectivities
in glycosylation reactions, by means of an intermediate
(1Ϫ4)-cyclic acyloxonium ion, as depicted in Scheme 5.[35]
gree of α-selectivity by means of an SN2 reaction of 34A.
However, it is evident that 4-O-acyl participation is not an
Moreover, the tight β-ion pair 34A will react more rapidly,
appropriate explanation in our study, since comparable ste-
since it is thermodynamically less stable than the corres-
reochemical results were obtained for treatment of 3 and 4
ponding tight α-ion pair (34C), and therefore energetically
closer to its transition state.[28,37,38] Ethyl ether (ε ϭ 4.3)
in dichloromethane.
196
Eur. J. Org. Chem. 2001, 193Ϫ203

Fucosylation of Linear Alcohols
FULL PAPER
Scheme 4
Scheme 5
Furthermore, polar or resonance effects do not provide observed product composition. For example, the high de-
a suitable explanation for the fucosylations described here. gree of formation of 1,2-cis linked products involving 35B
In principle, inductive effects from the electron-withdrawing can be explained by the fact that an attack of bulky glycosyl
4-O-acetyl group on 3 would destabilize the positive charge acceptors on the β-side of 35B is sterically hindered by the
on 34B, whereas 34B would be stabilized by the presence of O-3, O-4, and the methyl substituent on the donor. In con-
the electron-donating 4-O-benzyl group on the ring system trast, the reactive and flexible linear alcohol acceptors have
of 4. However, as shown, the α-selectivity is not lower in more conformational freedom, and thus might exert less
fucosidation reactions with 4 (cf. Table 2 and Table 3).
steric hindrance by 35B. This might explain the poor stereo-
Alternatively, the occurrence of through-bond orbital in- selectivities resulting from treatment of 3 and 4 with the
teractions is sometimes used to explain why 4-O equatorial spacer alcohols 11, 13, 14, and 16.
electron-withdrawing groups on glycopyranosyl donors
suppress the formation of the intermediate oxocarbonium
ion (cf. 34B), and thus favor an SN2 type of glycosylation
reaction.[2,41] In through-bond models,[42Ϫ44] the lone pair
of a particular atom lies all-trans to the σ-bond, or else a
succession of such trans bridges is available to carry the
interaction from one orbital to the other. According to the
literature, the sometimes high, or exclusive, formation of
1,2-cis linked products in fucosylations of glycosyl ac-
ceptors with thioalkyl donors (cf. refs.[2,4]) can be explained
by through-bond interactions, as the fucopyranosyl ring
(35A, Scheme 6) comprises a system that is capable of re-
laying through-bond electronic interactions between the
lone pairs (O-4 and the ring oxygen) and the σ-component
(C-4ϪC-5) of 35A. However, the results for the iodonium-
assisted fucosylations of acceptors 11, 13, 14, and 16
(Table 2 and 3) indicate that through-bond orbital interac-
tions probably play only a minor role in favoring fucosyla-
tions via 34A. Thus, steric influences both of the donor and
of the acceptor might be predominantly responsible for the Scheme 6
Eur. J. Org. Chem. 2001, 193Ϫ203
197

H. J. Vermeer, C. M. van Dijk, J. P. Kamerling, J. F. G. Vliegenthart
FULL PAPER
A (dichloromethane/acetone, 9:1), System B (dichloromethane/
acetone, 95:5), System C (dichloromethane/acetone, 97:3), System
D (dichloromethane Ǟ dichloromethane/acetone, 95:5), System E
(dichloromethane Ǟ dichloromethane/acetone, 97:3), System F
(dichloromethane Ǟ dichloromethane/ethyl acetate, 95:5), System
G (dichloromethane/methanol, 9:1), System H (dichloromethane/
methanol, 95:5), System I (dichloromethane Ǟ dichloromethane/
methanol, 9:1), System J (dichloromethane Ǟ dichloromethane/
methanol, 95:5). Ϫ Optical rotations: PerkinϪElmer 241 polari-
meter; 10 cm 1 mL cell at 20°C. Ϫ 1H NMR: Bruker AC 300
(300 MHz) instrument; internal standard tetramethylsilane (δ 0) for
solutions in CDCl3. The α/β ratio of the glycosylation products was
determined by integration of typical proton signals. Ϫ FABMS:
JEOL JMS SX/SX 102A four-sector mass spectrometer; 10 kV ac-
celerating voltage; JEOL MS-FAB 10 D FAB gun; 10 mA emission
current; beam: 6 keV Xe atoms.
Usage of Donors 6 and 7 in TBAB-Catalyzed
Fucosidations
From Table 2 and Table 3 it is clear that best α-selectivit-
ies were obtained with donors 6 and 7 under in situ ano-
merization conditions, using TBAB. No significant influ-
ence of the spacer length could be discerned. Reactions with
6 showed a slightly higher α-selectivity than coupling with
7. It is tempting to suggest here a slight resonance effect
of the 4-O-benzyl group on 7, causing stabilization of the
fucosyloxocarbonium ion (cf. 34B or 35B). Couplings via
34B can thus compete with the SN2 reaction between the
in situ generated β-bromide analog of 7 (cf. β-bromide ana-
log of 34C) and the acceptor alcohol.
Fucosylations of Alcohols 11 and 13؊16 with 5 and 8
Ethyl 3,4-Di-O-acetyl-2-O-benzyl-1-thio-β-
L-fucopyranoside (3): To
solution of ethyl 2-O-benzyl-1-thio-β--fucopyranoside[2]
Because of constraints imposed by the 3,4-acetonide
a
function in 5 and 8, the carbohydrate rings exist as distorted (170 mg, 0.57 mmol) in pyridine (2.6 mL) was added acetic anhyd-
1C4 chairs.[45] In Table 4, it is indicated that for the NIS/
TfOH-catalyzed reaction of 5 with the alcohols, giving
ride (2.6 mL). After stirring for 16 h at room temperature, toluene
(40 mL) was added and the solution was concentrated. The re-
maining oil was co-concentrated with toluene (2 ϫ 25 mL), ethanol
products 36؊40 (Scheme 7), almost equal amounts of α-
(2 ϫ 25 mL), and dichloromethane (2 ϫ 25 mL). Column chroma-
and β-anomers were produced (entries 34, 35, 37, 39, 40),
tography (System E) of the residue yielded 3, isolated as a colorless
except for the coupling with 16. It is reasonable to suggest
syrup (200 mg, 92%). Ϫ TLC (System A): Rf ϭ 0.77. Ϫ [α]D
ϭ
that the conformational differences in the chair result in a
better stabilization of the fucosyloxycarbonium ion (34B or
35B). For TBAB-catalyzed couplings with 8, α/β-ratios ob-
tained were in the same range as those found for corres-
ponding couplings using 6 and 7 (entries 36, 38, 41).
1
Ϫ21° (c ϭ 1, CHCl3). Ϫ H NMR: δ ϭ 1.19 (d, J5,6 ϭ 6.4 Hz, 3
H, 6,6,6-H), 1.33 (t, 3 H, SCH2CH3), 1.93 and 2.15 (2 s, each 3 H,
COCH3), 2.74Ϫ2.82 (m, 2 H, SCH2CH3), 3.63 (t, J1,2/2,3 ϭ 9.7 Hz,
1 H, 2-H), 3.77 (m, J4,5 Ͻ 1.0 Hz, 1 H, 5-H), 4.52 (d, 1 H, 1-H),
4.60 and 4.87 (2 d, each 1 H, C6H5CH2), 5.01 (dd, J3,4 ϭ 3.4 Hz,
Table 4. Glycosylation of alcohols 11, 13؊16 with donor 5 or 8
Entry
Donor
Alcohol
Method[a]
Product
Yield[b] [%]
Anomeric ratio (α/β)
34
35
36
37
38
39
40
41
5
5
8
5
8
5
5
8
11
13
13
14
14
15
16
16
A
A
B
A
B
A
A
B
36
37
37
38
38
39
40
40
77
63
57
68
48
74
56
74
51:49
51:49
87:13
46:54
89:11
48:52
31:69
88:12
[a]
A (GP 4 A): NIS/TfOH, DCM, 0 °C, 1 h; B (GP 5): TBAB, DCM/DMF, room temp., 2 days.
1 H, 3-H), 5.25 (dd, 1 H, 4-H), 7.25Ϫ7.34 (m, 10 H, 2 C6H5CH2).
Ϫ C19H26O6S (382.4): MS (FABϩ) m/z ϭ 405.1 [M ϩ Na]ϩ.
Fischer Glycosylation with L
-Fucose and Dowex-50 (H؉) Resin as
Catalyst (GP 1): To -fucose (1) was added the alcohol (9, 11, 13,
14, and 16; 10 equiv.) and Dowex-50 (Hϩ) resin. After stirring for
12 h at 75 °C, the mixture was filtered, and immediately purified
by column chromatography to give the corresponding alkyl fucopy-
ranoside. All products were obtained as a white glass unless other-
wise stated.
Scheme 7
Fischer Glycosylation of L-Fucose with Acetyl Chloride as Catalyst
Experimental Section
(GP 2): To -fucose (1) was added the alcohol (10, 11, 13, 14, and
16; 10 equiv.), and, after cooling to 0 °C, acetyl chloride (2 equiv.)
was added dropwise. The mixture was stirred for 3 h at 65 °C, then
neutralized with solid NaHCO3, and concentrated. Column chro-
matography of the residue yielded the corresponding alkyl fucopyr-
anoside. All products were obtained as a white glass, unless other-
wise stated.
General: Solvents were purified by standard procedures; alcohols
9؊13 and 16 were commercially available. Ϫ Thin layer chromato-
graphy (TLC): Kieselgel 60 F254 (Merck); compounds were de-
veloped by charring with ethanolic 10% H2SO4. Ϫ Column chro-
matography: Kieselgel 60 F254 (Merck). Ϫ Eluent systems: System
198
Eur. J. Org. Chem. 2001, 193Ϫ203

Fucosylation of Linear Alcohols
FULL PAPER
Thioglycoside Activation with NIS/TfOH (cat.) (GP 4, A, B, C):
reaction was complete. The solution was neutralized with triethyl-
amine, then purified by column chromatography (System J) to fur-
The donors 3, ethyl 3-O-acetyl-2,4-di-O-benzyl-1-thio-β--fucopyr-
anoside[14] (4) and ethyl 2-O-benzyl-3,4-O-isopropylidene-1-thio-β- nish 21 (100 mg, 73%); 21α 72%, 21β 28%. Ϫ TLC (dichlorome-
-fucopyranoside[2] (5) were dried for 12 h in the presence of 4 A
molecular sieves. After addition of the alcohol (11, 13؊16; 6 equiv.)
to the donor, the mixture was stirred for 1 h under Ar in (A) dry
dichloromethane; (B) dry dichloromethane/diethyl ether, 5:1; or (C)
dry dichloromethane/acetonitrile, 5:1. Then, either at 0 °C or at
room temperature, N-iodosuccinimide (NIS, 2.5 equiv.) and trifluo-
thane/methanol, 3:1): Rf ϭ 0.80. Ϫ 1H NMR (CDCl3/CD3OD,
˚
1:1): 21α δ ϭ 1.26 (d, J5,6 ϭ 6.7 Hz, 3 H, 6,6,6-H), 4.87 (d, J1,2
3.1 Hz, 1 H, 1-H), 5.20 and 5.32 (2 m, 2 H, OCH2CHϭCH2),
5.87Ϫ6.00 (m, 1 H, OCH2CHϭCH2); 21β δ ϭ 1.31 (d, J5,6
ϭ
ϭ
6.5 Hz, 3 H, 6,6,6-H), 4.28 (d, J1,2 ϭ 6.9 Hz, 1 H, 1-H), 5.25 and
5.37 (2 m, 2 H, OCH2CHϭCH2), 5.90Ϫ6.05 (m, 1 H, OCH2CHϭ
romethanesulfonic acid (TfOH) (0.3 equiv.) were added, and the CH2). Ϫ C9H16O5 (204.2): MS (FABϩ) m/z ϭ 205.1 [M ϩ H]ϩ.
mixture was stirred for 1 h at room temperature. Afterwards, the
3-Bromopropyl α/β-L-Fucopyranoside (22): (i): GP 1, 1 (50 mg,
solution was neutralized with pyridine, filtered, diluted with ethyl
acetate (80 mL), washed with aq. 5% NaHSO3 (same vol., 3ϫ), aq.
10% NaHCO3 (same vol., 2ϫ), and aq. 5% NaCl (half vol., 1ϫ),
dried (MgSO4), filtered, and concentrated. Column chromato-
graphy of the residue gave the corresponding alkyl fucopyranoside.
All products were isolated as colorless syrups, unless otherwise
stated.
0.3 mmol), 13 (0.27 mL), Dowex-50 (Hϩ) resin (70 mg). Purifica-
tion (System I) yielded 22 (33 mg, 38%); 22α 64%, 22β 36%. Ϫ
(ii): GP 2, 1 (100 mg, 0.61 mmol), 13 (0.54 mL), acetyl chloride
(0.11 mL). Purification (System I) gave 22 (117 mg, 67%); 22α 83%,
22β 17%. Ϫ TLC (System C): Rf ϭ 0.57. Ϫ 1H NMR (CDCl3/
CD3OD, 1:1): 22α δ ϭ 1.27 (d, J5,6 ϭ 6.5 Hz, 3 H, 6,6,6-H),
2.04Ϫ2.24 (m, 2 H, OCH2CH2CH2Br), 4.86 (d, J1,2 ϭ 3.2 Hz, 1 H,
1-H); 22β δ ϭ 1.31 (d, J5,6 ϭ 6.5 Hz, 3 H, 6,6,6-H), 2.04Ϫ2.24
(m, 2 H, OCH2CH2CH2Br), 4.22 (d, J1,2 ϭ 7.1 Hz, 1 H, 1-H). Ϫ
C9H17O5Br (284.2): MS (FABϩ) m/z ϭ 285.1 [M ϩ H]ϩ.
Fucopyranosyl Bromide Activation by Tetrabutylammonium Bromide
(GP 5): A solution of donor 3, 4, or 5 in dry dichloromethane
(0.4 mL) was cooled to 0 °C and treated for 20 min with bromine
(2 equiv.). Then, cyclohexene was added dropwise until the orange
color disappeared. A freshly prepared solution of the alcohol (10,
11, 13, 14, and 16; 6 equiv.), tetrabutylammonium bromide
3-Azidopropyl α/β-L-Fucopyranoside (23): (i): GP 1, 1 (100 mg,
0.61 mmol), 14 (620 mg), Dowex-50 (Hϩ) resin (70 mg). Purifica-
tion (System J) gave 23, isolated as a colorless oil (47 mg, 31%);
23α 60%, 23β 40%. Ϫ (ii): GP 2, 1 (100 mg, 0.61 mmol), 14
(620 mg), acetyl chloride (0.11 mL). Purification (System J) gave
23, isolated as a colorless syrup (39 mg, 26%); 23α 68%, 23β 32%.
Ϫ (iii): To a solution of methyl α/β--fucopyranoside[21,22] (2)
(140 mg, 0.79 mmol) in dry dimethylformamide (4 mL) were added
14 (800 mg) and p-toluenesulfonic acid (pH 3). The mixture was
stirred for 5 days at 50 °C, filtered, and purified by column chroma-
tography (System J), yielding 23, isolated as a colorless oil (36 mg,
19%); 23α 71%, 23β 29%. Ϫ TLC (System C): Rf ϭ0.29. Ϫ 1H
NMR (CDCl3/CD3OD, 1:1): 23α δ ϭ 1.27 (d, J5,6 ϭ 6.6 Hz, 3
H, 6,6,6-H), 1.87Ϫ1.95 (m, 2 H, OCH2CH2CH2N3), 3.39 (t, 2 H,
OCH2CH2CH2N3), 4.85 (d, J1,2 ϭ 3.5 Hz, 1 H, 1-H); 23β δ ϭ 1.31
˚
(Bu4NBr, 1 equiv.) and 4 A molecular sieves in dichloromethane/
dimethylformamide (5:3), stirred for 1 h under Ar, was added to
the freshly prepared fucopyranosyl bromide 6, 7, or 8, and the mix-
ture was stirred for 2 days at room temperature. Subsequently, the
mixture was neutralized with pyridine, filtered over Celite, diluted
with ethyl acetate (80 mL), washed with aq. 5% NaHSO3 (same
vol., 3 ϫ), aq. 10% NaHCO3 (same vol., 2 ϫ), and aq. 5% NaCl
(same vol., 1 ϫ), dried (MgSO4), filtered, and concentrated. Col-
umn chromatography of the residue gave the corresponding alkyl
fucopyranoside. All products were obtained as colorless syrups, un-
less otherwise stated.
Ethyl α/β-L-Fucopyranoside (19): GP 2, 1 (100 mg, 0.61 mmol), 9
(0.24 mL), acetyl chloride (0.11 mL). Purification (System I) gave
(d, J5,6
ϭ 6.5 Hz, 3 H, 6,6,6-H), 1.87Ϫ1.95 (m, 2 H,
19 (76 mg, 65%); 19α 64%, 19β 36%. Ϫ TLC (System C): Rf ϭ OCH2CH2CH2N3), 3.42 (t, 2 H, OCH2CH2CH2N3), 4.20 (d, J1,2 ϭ
1
0.24. Ϫ H NMR (CDCl3/CD3OD, 1:1): 19α δ ϭ 1.19Ϫ1.32 (m, 6 7.4 Hz, 1 H, 1-H). Ϫ C9H17O5N3 (247.3): MS (FABϩ) m/z ϭ 248.1
H, 6,6,6-H and OCH2CH3), 3.53 and 3.76 (2 m, 2 H, OCH2CH3), [M ϩ H]ϩ.
4.85 (d, J1,2 Ͻ 1.0 Hz, 1 H, 1-H); 19β δ ϭ 1.19Ϫ1.32 (m, 6 H,
Decyl α/β-L-Fucopyranoside (24): (i): GP 1, 1 (100 mg, 0.61 mmol),
6,6,6-H and OCH2CH3), 4.21 (d, J1,2 ϭ 7.0 Hz, 1 H, 1-H). Ϫ
16 (1.16 mL), Dowex-50 (Hϩ) resin (70 mg). Purification (System
J) yielded 24, isolated as a colorless oil (89 mg, 48%); 24α 71%, 24β
C8H16O5 (192.2): MS (FABϩ) m/z ϭ 193.1 [M ϩ H]ϩ.
Propyl α/β-
L
-Fucopyranoside (20): GP 2, 1 (100 mg, 0.61 mmol), 10 29%. Ϫ (ii): GP 2, 1 (50 mg, 0.3 mmol), 16 (0.59 mL), acetyl chlor-
ide (56 µL). Purification (System J) yielded 24, isolated as a color-
(0.46 mL), acetyl chloride (0.11 mL). Purification (System I) gave
20 (84 mg, 67%); 20α 75%, 20β 25%. Ϫ TLC (System C): Rf ϭ less oil (68 mg, 75%); 24α 74%, 24β 26%. Ϫ TLC (System C): Rf ϭ
1
0.30. Ϫ 1H NMR (CDCl3/CD3OD, 1:1): 20α δ ϭ 0.93 (t, 3 H,
OCH2CH2CH3), 1.24 (d, J5,6 ϭ 6.6 Hz, 3 H, 6,6,6-H), 1.62 (m, 2
0.41. Ϫ H NMR: 24α δ ϭ 0.88 [t, 3 H, OCH2(CH2)8CH3], 1.27
(d, J5,6 ϭ 6.5 Hz, 3 H, 6,6,6-H), 1.26Ϫ1.37 and 1.57Ϫ1.64 [2 m, 16
H, OCH2CH2CH3), 3.41 and 3.63 (2 m, 2 H, OCH2CH2CH3), 4.82 H, OCH2(CH2)8CH3], 3.44 and 3.67 [2 m, each
1 H,
(d, J1,2 ϭ 1.4 Hz, 1 H, 1-H); 20β δ ϭ 0.93 (t, 3 H, OCH2CH2CH3), OCH2(CH2)8CH3], 4.84 (d, J1,2 ϭ 3.3 Hz, 1 H, 1-H); 24β δ ϭ 0.88
1.31 (d, J5,6 ϭ 6.4 Hz, 3 H, 6,6,6-H), 1.64 (m, 2 H, OCH2CH2CH3), [t, 3 H, OCH2(CH2)8CH3], 1.31 (d, J5,6 ϭ 6.4 Hz, 3 H, 6,6,6-H),
4.19 (d, J1,2 ϭ 7.3 Hz, 1 H, 1-H). Ϫ C9H18O5 (206.2): MS (FABϩ)
m/z ϭ 207.1 [M ϩ H]ϩ.
1.26Ϫ1.37 and 1.57Ϫ1.64 [2 m, 16 H, OCH2(CH2)8CH3], 4.19 (d,
J1,2 ϭ 7.4 Hz, 1 H, 1-H). Ϫ C16H32O5 (304.4): MS (FABϩ) m/z ϭ
305.2 [M ϩ H]ϩ.
Allyl α/β-L-Fucopyranoside (21): (i): GP 1, 1 (50 mg, 0.3 mmol), 11
(0.21 mL), Dowex-50 (Hϩ) resin (70 mg). Purification (System I)
gave 21 (39 mg, 64%); 21α 70%, 21β 30%. Ϫ (ii): GP 2, 1 (50 mg,
0.3 mmol), 11 (0.21 mL), acetyl chloride (56 µL). Purification (Sys-
Propyl 3,4-Di-O-acetyl-2-O-benzyl-α/β-L-fucopyranoside (25): GP 5,
3 (22 mg, 58 µmol), bromine (5.9 µL). Then, residue (6), 10 (26
µL), Bu4NBr (19 mg), molecular sieves (50 mg), solvent (0.4 mL).
tem I) gave 21 (45 mg, 74%); 21α 67%, 21β 33%. Ϫ (iii): To 1 Purification (System B) gave 25 (19 mg, 87% overall); 25α 77%, 25β
1
(110 mg, 0.67 mmol) was added 11 (0.46 mL). The solution was 23%. Ϫ TLC (System B): Rf ϭ 0.76. Ϫ H NMR: 25α δ ϭ 0.95 (t,
cooled to 0 °C, and FeCl3 (160 mg, 0.95 mmol) was added slowly.
The mixture was stirred for 3 h at 55 °C, when TLC indicated the
3 H, OCH2CH2CH3), 1.11 (d, J5,6 ϭ 6.6 Hz, 3 H, 6,6,6-H),
1.59Ϫ1.68 (m, 2 H, OCH2CH2CH3), 1.98 and 2.13 (2 s, each 3 H,
Eur. J. Org. Chem. 2001, 193Ϫ203
199

H. J. Vermeer, C. M. van Dijk, J. P. Kamerling, J. F. G. Vliegenthart
FULL PAPER
2 COCH3), 3.37 and 3.59 (2 m, each 1 H, OCH2CH2CH3), 3.83 (6), 14 (44 mg), Bu4NBr (28 mg), molecular sieves (50 mg), solvent
(dd, J1,2 ϭ 3.6, J2,3 ϭ 10.1 Hz, 1 H, 2-H), 4.14 (m, J4,5 ϭ 1.3 Hz, (0.4 mL). Purification (System B) yielded 28 (17 mg, 54% overall);
1 H, 5-H), 4.59 and 4.70 (2 d, each 1 H, C6H5CH2), 4.81 (d, 1 H, 28α 88%, 28β 12%. Ϫ TLC (System B): Rf ϭ 0.67. Ϫ 1H NMR:
1-H), 5.28 (dd, J3,4 ϭ 3.4 Hz, 1 H, 4-H), 5.33 (dd, 1 H, 3-H),
7.26Ϫ7.34 (m, H, C6H5CH2); 25β 0.97 (t, H,
28α δ ϭ 1.11 (d, J5,6 ϭ 6.6 Hz, 3 H, 6,6,6-H), 1.03Ϫ1.43 (m, 2 H,
OCH2CH2CH2N3), 1.98 and 2.13 (2 s, each 3 H, 2 COCH3), 3.83
5
δ
ϭ
3
OCH2CH2CH3), 1.20 (d, J5,6 ϭ 6.5 Hz, 3 H, 6,6,6-H), 1.59Ϫ1.68 (dd, J2,3 ϭ 10.1 Hz, 1 H, 2-H), 4.10 (m, 1 H, 5-H), 4.59 and 4.69
(m, 2 H, OCH2CH2CH3), 1.95 and 2.13 (2 s, each 3 H, 2 COCH3), (2 d, each 1 H, C6H5CH2), 4.80 (d, J1,2 ϭ 3.6 Hz, 1 H, 1-H), 5.28
3.49 and 3.95 (2 m, each 1 H, OCH2CH2CH3), 3.60 (dd, J1,2 ϭ 7.8,
(dd, J4,5 ϭ 1.2 Hz, 1 H, 4-H), 5.30 (dd, J3,4 ϭ 3.6 Hz, 1 H, 3-H),
J2,3 ϭ 10.2 Hz, 1 H, 2-H), 3.76 (m, J4,5 ϭ 1.1 Hz, 1 H, 5-H), 4.43 7.25Ϫ7.34 (m, 5 H, C6H5CH2); 28β δ ϭ 1.20 (d, J5,6 ϭ 6.4 Hz, 3
(d, 1 H, 1-H), 4.63 and 4.89 (2 d, each 1 H, C6H5CH2), 4.97 (dd, H, 6,6,6-H), 1.03Ϫ1.43 (m, 2 H, OCH2CH2CH2N3), 1.94 and 2.14
J3,4 ϭ 3.5 Hz, 1 H, 3-H), 5.20 (dd, 1 H, 4-H), 7.26Ϫ7.34 (m, 5 H, (2 s, each 3 H, 2 COCH3), 3.60 (dd, J2,3 ϭ 10.3 Hz, 1 H, 2-H), 3.65
C6H5CH2). Ϫ C20H28O7 (380.2): MS (FABϩ) m/z ϭ 381.2 [M ϩ and 4.02 (2 m, each 1 H, OCH2CH2CH2N3), 4.42 (d, J1,2 ϭ 7.7 Hz,
H]ϩ, 403.2 [M ϩ Na]ϩ.
1 H, 1-H), 4.63 and 4.83 (2 d, each 1 H, C6H5CH2), 4.97 (dd, J3,4 ϭ
3.5 Hz, 1 H, 3-H), 5.20 (dd, J4,5 ϭ 1.0 Hz, 1 H, 4-H), 7.25Ϫ7.34
(m, 5 H, C6H5CH2). Ϫ C20H27N3O7 (421.4): MS (FABϩ) m/z ϭ
422.2 [M ϩ H]ϩ, 444.2 [M ϩ Na]ϩ.
Allyl 3,4-Di-O-acetyl-2-O-benzyl-α/β-L-fucopyranoside (26): (i): GP
4 A, 3 (25 mg, 76 µmol), 11 (31 µL), molecular sieves (50 mg), solv-
ent (1.2 mL), NIS (43 mg), TfOH (2 µL), T ϭ 0 °C. Purification
(System D) yielded 26 (26 mg, 90%); 26α 62%, 26β 38%. Ϫ (ii): Decyl 3,4-Di-O-acetyl-2-O-benzyl-α/β-
L-fucopyranoside (29): (i):
GP 4 B, 3 (28 mg, 85 µmol), 11 (35 µL), molecular sieves (50 mg), GP 4 A, 3 (70 mg, 0.2 mmol), 16 (0.23 mL), molecular sieves
solvent (1.3 mL), NIS (48 mg), TfOH (2.2 µL), T ϭ 0 °C. Purifica-
tion (System D) furnished a mixture of starting donor and products
(150 mg), solvent (3.5 mL), NIS (121 mg), TfOH (5.5 µL), T ϭ 0
°C. Purification (System D) yielded 29 (79 mg, 83%); 29α 47%, 29β
(29 mg); 3 35%, 26 62% (26α 69%, 26β 31%). Ϫ (iii): GP 4 C, 3 53%. Ϫ (ii): GP 5, 3 (22 mg, 67 µmol), bromine (6.8 µL). Then,
(19 mg, 58 µmol), 11 (24 µL), molecular sieves (50 mg), solvent
(0.9 mL), NIS (33 mg), TfOH (1.5 µL), T ϭ 0 °C. Purification (Sys-
tem D) furnished 26 (21 mg, 96%); 26α 22%, 26β 78%.Ϫ (iv): GP
residue (6), 16 (75 µL), Bu4NBr (22 mg), molecular sieves (50 mg),
solvent (0.4 mL). Purification (System D) gave 29 (23 mg, 72%
overall); 29α 83%, 29β 17%. Ϫ TLC (System A): Rf ϭ 0.76. Ϫ H
1
5, 3 (24 mg, 73 µmol), bromine (7.4 µL). Then, residue (6), 11 (30 NMR: 29α δ ϭ 0.88 [t, 3 H, OCH2(CH2)8CH3], 1.10 (d, J5,6
ϭ
µL), Bu4NBr (24 mg), molecular sieves (50 mg), solvent (0.5 mL).
Purification (System D) gave 26 (23 mg, 85% overall); 26α 87%,
6.6 Hz, 3 H, 6,6,6-H), 1.23Ϫ1.64 [m, 16 H, OCH2(CH2)8CH3], 1.97
and 2.12 (2 s, each 3 H, 2 COCH3), 3.40 and 3.63 [2 m, each 1 H,
26β 13%. Ϫ TLC (System A): Rf ϭ 0.81. Ϫ 1H NMR: 26α δ ϭ OCH2(CH2)8CH3], 3.82 (dd, J1,2 ϭ 3.7, J2,3 ϭ 10.2 Hz, 1 H, 2-H),
1.10 (d, J5,6 ϭ 6.6 Hz, 3 H, 6,6,6-H), 1.98 and 2.12 (2 s, each 3 H,
2 COCH3), 3.84 (dd, J2,3 ϭ 10.5 Hz, 1 H, 2-H), 4.60 and 4.67 (2 C6H5CH2), 4.81 (d, 1 H, 1-H), 5.28 (dd, J3,4 ϭ 3.4 Hz, 1 H, 4-H),
d, each 1 H, C6H5CH2), 4.88 (d, J1,2 ϭ 3.6 Hz, 1 H, 1-H), 5.21 and 5.32 (dd, 1 H, 3-H), 7.26Ϫ7.33 (m, 5 H, C6H5CH2); 29β δ ϭ 0.87
5.33 (2 m, each 1 H, OCH2CHϭCH2), 5.28 (dd, J4,5 ϭ 1.4 Hz, 1 [t, 3 H, OCH2(CH2)8CH3], 1.20 (d, J5,6 ϭ 6.4 Hz, 3 H, 6,6,6-H),
H, 4-H), 5.35 (dd, J3,4 ϭ 3.4 Hz, 1 H, 3-H), 5.92 (m, 1 H, 1.23Ϫ1.64 [m, 16 H, OCH2(CH2)8CH3], 1.94 and 2.12 (2 s, each 3
OCH2CHϭCH2), 7.26Ϫ7.41 (m, 5 H, C6H5CH2); 26β δ ϭ 1.20 (d, H, 2 COCH3), 3.53 and 3.84 [2 m, each 1 H, OCH2(CH2)8CH3],
4.12 (m, J4,5 ϭ 1.3 Hz, 1 H, 5-H), 4.59 and 4.69 (2 d, each 1 H,
J5,6 ϭ 6.4 Hz, 3 H, 6,6,6-H), 1.94 and 2.12 (2 s, each 3 H, 2
COCH3), 3.63 (dd, J2,3 ϭ 10.2 Hz, 1 H, 2-H), 4.49 (d, J1,2 ϭ 7.8 Hz,
1 H, 1-H), 4.64 and 4.89 (2 d, each 1 H, C6H5CH2), 4.97 (dd, J3,4 ϭ
4.43 (d, J1,2 ϭ 7.7 Hz, 1 H, 1-H), 4.63 and 4.88 (2 d, each 1 H,
C6H5CH2), 4.96 (dd, J2,.3 ϭ 10.1, J3,4 ϭ 3.5 Hz, 1 H, 3-H),
7.26Ϫ7.33 (m, 5 H, C6H5CH2). Ϫ C27H42O7 (478.3): MS (FABϩ)
3.5 Hz, 1 H, 3-H), 5.18 and 5.27 (2 m, each 1 H, OCH2CHϭCH2), m/z ϭ 501.3 [M ϩ Na]ϩ.
5.32 (dd, J4,5 ϭ Ͻ 1 Hz, 1 H, 4-H), 5.93 (m, 1 H, OCH2CHϭCH2),
Allyl 3-O-Acetyl-2,4-di-O-benzyl-α/β-L-fucopyranoside (30): (i): GP
7.26Ϫ7.41 (m, 5 H, C6H5CH2). Ϫ C20H26O7 (378.2): MS (FABϩ)
m/z ϭ 401.2 [M ϩ Na]ϩ.
4 A, 4 (38 mg, 88 µmol), 11 (37 µL), molecular sieves (75 mg), solv-
ent (1.5 mL), NIS (50 mg), TfOH (2.3 µL), T ϭ 0 °C. Purification
(System D) yielded 30 (35 mg, 93%); 30α 61%, 30β 39%. Ϫ (ii):
GP 4 B, 4 (24 mg, 56 µmol), 11 (24 µL), molecular sieves (50 mg),
3-Bromopropyl
3,4-Di-O-acetyl-2-O-benzyl-α/β-L-fucopyranoside
(27): (i): GP 4 A, 3 (48 mg, 0.14 mmol), 13 (76 µL), molecular
sieves (150 mg), solvent (2.5 mL), NIS (83 mg), TfOH (3.8 µL), solvent (1 mL), NIS (32 mg), TfOH (1.5 µL), T ϭ 0 °C. Purification
T ϭ 0 °C. Purification (System D) furnished 27 (59 mg, 92%); 27α (System D) yielded 30 (22 mg, 92%); 30α 56%, 30β 44%. Ϫ (ii):
70%, 27β 30%. Ϫ (ii): GP 5, 3 (25 mg, 76 µmol), bromine (7.7 µL). GP 4 C, 4 (25 mg, 58 µmol), 11 (25 µL), molecular sieves (50 mg),
Then, residue (6), 13 (40 µL), Bu4NBr (25 mg), molecular sieves
(50 mg), solvent (0.4 mL). Purification (System C) yielded 27
solvent (1 mL), NIS (33 mg), TfOH (1.6 µL), T ϭ 0 °C. Purification
(System D) yielded 30 (19 mg, 80%); 30α 36%, 30β 64%.Ϫ TLC
(21 mg, 59% overall); 27α 88%, 27β 12%. Ϫ TLC (System B): Rf ϭ (System B): Rf ϭ 0.82. Ϫ 1H NMR: 30α δ ϭ 1.15 (d, J5,6 ϭ 6.6 Hz,
1
0.71. Ϫ H NMR: 27α δ ϭ 1.12 (d, J5,6 ϭ 6.6 Hz, 3 H, 6,6,6-H), 3 H, 6,6,6-H), 1.98 (s, 3 H, COCH3), 3.79 (dd, J3,4 ϭ 3.1, J4,5
ϭ
1.95Ϫ2.16 (m, 2 H, OCH2CH2CH2Br), 1.99 and 2.13 (2 s, each 3 1.2 Hz, 1 H, 4-H), 4.02 (dd, J1,2 ϭ 3.7, J2,3 ϭ 10.5 Hz, 1 H, 2-H),
H, 2 COCH3), 3.47Ϫ3.88 (m, 4 H, OCH2CH2CH2Br), 3.82 (dd, 1 4.59 and 4.65, 4.62 and 4.68 (4 d, each 1 H, 2 C6H5CH2), 4.87 (d,
H, 2-H), 4.14 (m, 1 H, 5-H), 4.60 and 4.69 (2 d, each 1 H, 1 H, 1-H), 5.27 (dd, 1 H, 3-H), 5.85Ϫ5.98 (m, 1 H, OCH2CHϭ
C6H5CH2), 4.83 (d, J1,2 ϭ 3.7 Hz, 1 H, 1-H), 5.27 (dd, J4,5
ϭ
CH2), 7.25Ϫ7.34 (m, 10 H, 2 C6H5CH2); 30β δ ϭ 1.23 (d, J5,6
ϭ
1.5 Hz, 1 H, 4-H), 5.29 (dd, J2,3 ϭ 10.5, J3,4 ϭ 3.4 Hz, 1 H, 3-H),
6.4 Hz, 3 H, 6,6,6-H), 1.92 (s, 3 H, COCH3), 3.60 (m, 1 H, 5-H),
7.26Ϫ7.33 (m, 5 H, C6H5CH2); 27β δ ϭ 1.20 (d, J5,6 ϭ 6.4 Hz, 3 3.64 (dd, J3,4 ϭ 3.2, J4,5 ϭ 1.0 Hz, 1 H, 4-H), 3.78 (dd, J1,2 ϭ 7.7,
H, 6,6,6-H), 1.94 and 2.13 (2 s, each 3 H, 2 COCH3), 4.44 (d, J1,2 ϭ J2,3 ϭ 10.2 Hz, 1 H, 2-H), 4.44 (d, 1 H, 1-H), 4.55 and 4.90, 4.62
7.8 Hz, 1 H, 1-H), 4.62 and 4.84 (2 d, each 1 H, C6H5CH2), 5.20
(dd, 1 H, 4-H), 7.26Ϫ7.33 (m, 5 H, C6H5CH2). Ϫ C20H27O7Br (m, 1 H, OCH2CHϭCH2), 7.25Ϫ7.34 (m, 10 H, 2 C6H5CH2). Ϫ
(458.2): MS (FABϩ) m/z ϭ 459.1 [M ϩ H]ϩ, 481.2 [M ϩ Na]ϩ. C25H30O6 (426.3): MS (FABϩ) m/z ϭ 449.1 [M ϩ Na]ϩ.
and 4.68 (4 d, each 1 H, 2 C6H5CH2), 4.87 (d, 1 H, 3-H), 5.85Ϫ5.98
3-Azidopropyl 3,4-Di-O-acetyl-2-O-benzyl-α/β- -fucopyranoside 3-Bromopropyl 3-O-Acetyl-2,4-di-O-benzyl-α/β- -fucopyranoside
L
L
(28): GP 5, 3 (28 mg, 73 µmol), bromine (7.5 µL). Then, residue
(31): (i): GP 4 A, 4 (32 mg, 74 µmol), 13 (40 µL), molecular sieves
200
Eur. J. Org. Chem. 2001, 193Ϫ203

Fucosylation of Linear Alcohols
FULL PAPER
(75 mg), solvent (1.3 mL), NIS (42 mg), TfOH (1.9 µL), T ϭ 0 °C.
[2 m, 16 H, OCH2(CH2)8CH3], 1.91 (s, 3 H, COCH3), 3.48 and
Purification (System E) yielded 31 (36 mg, 95%); 31α 60%, 31β 3.94 [2 m, each 1 H, OCH2(CH2)8CH3], 3.59 (m, 1 H, 5-H), 3.65
40%. Ϫ (ii): GP 5, 4 (30 mg, 69 µmol), bromine (7 µL). Then,
residue (7), 13 (37 µL), Bu4NBr (23 mg), molecular sieves (50 mg),
(d, 1 H, 4-H), 3.74 (dd, J1,2 ϭ 7.7, J2,3 ϭ 10.3 Hz, 1 H, 2-H), 4.37
(d, 1 H, 1-H), 4.56 and 4.89, 4.58 and 4.65 (4 d, each 1 H, 2
C6H5CH2), 4.86 (dd, J3,4 ϭ 3.2 Hz, 1 H, 3-H), 7.25Ϫ7.35 (m, 10
solvent (0.3 mL). Purification (System E) furnished 31 (25 mg, 71%
1
overall); 31α 77%, 31β 23%. Ϫ TLC (System B): Rf ϭ 0.79. Ϫ H H, 2 C6H5CH2). Ϫ C32H46O6 (526.3): MS (FABϩ) m/z ϭ 549.2 [M
NMR: 31α δ ϭ 1.16 (d, J5,6 ϭ 6.6 Hz, 3 H, 6,6,6-H), 1.98 (s, 3 H,
COCH3), 2.06Ϫ2.26 (m, 2 H, OCH2CH2CH2Br), 3.78 (dd, J3,4
ϩ Na]ϩ.
ϭ
Allyl 2-O-Benzyl-3,4-O-isopropylidene-α/β-L-fucopyranoside (36):
3.5, J4,5 ϭ 1.1 Hz, 1 H, 4-H), 4.01 (dd, J1,2 ϭ 3.7, J2,3 ϭ 10.6 Hz,
1 H, 2-H), 4.59 and 4.65, 4.61 and 4.68 (4 d, each 1 H, 2 C6H5CH2),
4.82 (d, 1 H, 1-H), 5.21 (dd, 1 H, 3-H), 7.25Ϫ7.35 (m, 10 H, 2
C6H5CH2); 31β δ ϭ 1.22 (d, J5,6 ϭ 6.5 Hz, 3 H, 6,6,6-H), 1.91 (s,
3 H, COCH3), 2.06Ϫ2.26 (m, 2 H, OCH2CH2CH2Br), 3.50 (dd,
J1,2 ϭ 7.7, J2,3 ϭ 10.6 Hz, 1 H, 2-H), 3.60 (m, 1 H, 5-H), 3.66 (dd,
GP 4 A, 5 (38 mg, 0.11 mmol), 11 (46 µL), molecular sieves
(100 mg), solvent (2 mL), NIS (62 mg), TfOH (2.9 µL), T ϭ 0 °C.
Purification (System C; 0.1% TEA) gave 36 (28 mg, 77%); 36α 51%,
36β 49%. Ϫ TLC (System A): Rf ϭ 0.82 (36α) and 0.87 (36β). Ϫ
1H NMR: 36α δ ϭ 1.31 (d, J5,6 ϭ 6.7 Hz, 3 H, 6,6,6-H), 1.33 and
1.40 [2 s, 6 H, C(CH3)2], 3.52 (dd, J2,3 ϭ 7.9 Hz, 1 H, 2-H), 3.86
J3,4 ϭ 3.2, J4,5 ϭ Ͻ 1.0 Hz, 1 H, 4-H), 4.39 (d, 1 H, 1-H), 4.56 and
(m, 1 H, 5-H), 4.04 (dd, J4,5 ϭ 2.7 Hz, 1 H, 4-H), 4.34 (dd, J3,4
ϭ
4.66, 4.64 and 4.85 (4 d, each 1 H, 2 C6H5CH2), 5.21 (dd, 1 H, 3-
H), 7.25Ϫ7.35 (m, 10 H, 2 C6H5CH2). Ϫ C25H31O6Br (506.3): MS
(FABϩ) m/z ϭ 507.0 [M ϩ H]ϩ, 529.3 [M ϩ Na]ϩ.
5.4 Hz, 1 H, 3-H), 4.79 and 4.86 (2 d, each 1 H, C6H5CH2), 4.79
(d, J1,2 ϭ 3.6 Hz, 1 H, 1-H), 5.19 and 5.32 (2 m, each 1 H,
OCH2CHϭCH2), 5.86Ϫ6.02 (m, 1 H, OCH2CHϭCH2), 7.34 (m,
5 H, C6H5CH2); 36β δ ϭ 1.34 and 1.40 [2 s, 6 H, C(CH3)2], 1.39
(d, J5,6 ϭ 6.7 Hz, 3 H, 6,6,6-H), 3.40 (dd, J2,3 ϭ 7.1 Hz, 1 H, 2-
H), 3.80 (m, 1 H, 5-H), 3.97 (dd, J4,5 ϭ 2.1 Hz, 1 H, 4-H), 4.12
(dd, J3,4 ϭ 5.5 Hz, 1 H, 3-H), 4.32 (d, J1,2 ϭ 8.1 Hz, 1 H, 1-H),
4.70 and 4.79 (2 d, each 1 H, C6H5CH2), 5.21 and 5.34 (2 m, each
1 H, OCH2CHϭCH2), 5.86Ϫ6.02 (m, 1 H, OCH2CHϭCH2), 7.34
(m, 5 H, C6H5CH2). Ϫ C19H26O5 (334.2): MS (FABϩ) m/z ϭ 357.1
[M ϩ Na]ϩ.
3-Azidopropyl
3-O-Acetyl-2,4-di-O-benzyl-α/β-L-fucopyranoside
(32): (i): GP 4 A, 4 (23 mg, 53 µmol), 14 (32 mg), molecular sieves
(50 mg), solvent (1 mL), NIS (30 mg), TfOH (1.4 µL), T ϭ Ϫ30
°C. Purification (System D) yielded a mixture of starting donor
and products (15 mg); 4 34%, 32 27% (32α 64%, 32β 36%). Ϫ (ii):
GP 4 A, 4 (21 mg, 48 µmol), 14 (30 mg), molecular sieves (50 mg),
solvent (0.9 mL), NIS (28 mg), TfOH (1.2 µL), T ϭ 0 °C. Purifica-
tion (System D) yielded a mixture of starting donor and products
(20 mg); 4 10%, 32 81% (32α 72%, 32β 28%). Ϫ (iii): GP 4 A,
4 (27 mg, 62 µmol), 14 (38 mg), molecular sieves (50 mg), solvent
(1.2 mL), NIS (35 mg), TfOH (1.6 µL), T ϭ room temperature.
Purification (System D) yielded 32 (28 mg, 96%); 32α 83%, 32β
17%. Ϫ TLC (System B): Rf ϭ 0.62. Ϫ 1H NMR: 32α δ ϭ 1.16 (d,
J5,6 ϭ 6.6 Hz, 3 H, 6,6,6-H), 1.98 (s, 3 H, COCH3), 1.84Ϫ1.92 (m,
2 H, OCH2CH2CH2N3), 3.42 (t, 2 H, OCH2CH2CH2N3), 3.79 (dd,
3-Bromopropyl 2-O-Benzyl-3,4-O-isopropylidene-α/β-L-fucopyrano-
side (37): (i): GP 4 A, 5 (43 mg, 0.12 mmol), 13 (65 µL), molecular
sieves (150 mg), solvent (2.2 mL), NIS (70 mg), TfOH (3.3 µL),
T ϭ 0 °C. Purification (System C; 0.1% TEA) gave 37 (30 mg,
63%); 37α 51%, 37β 49%. Ϫ (ii): GP 5, 5 (56 mg, 0.16 mmol),
bromine (16.2 µL). Then, residue (8), 13 (85 µL), Bu4NBr (53 mg),
molecular sieves (100 mg), solvent (0.7 mL). Purification (System
C, 0.1% TEA) yielded 37 (36 mg, 57% overall); 37α 87%, 37β 13%.
Ϫ TLC (System B): Rf ϭ 0.75. Ϫ 1H NMR: 37α δ ϭ 1.32 (d,
J3,4 ϭ 3.1, J4,5 ϭ 1.2 Hz, 1 H, 4-H), 4.01 (dd, J1,2 ϭ 3.7, J2,3
ϭ
10.6 Hz, 1 H, 2-H), 4.56 and 4.65, 4.61 and 4.68 (4 d, each 1 H, 2
C6H5CH2), 4.79 (d, 1 H, 1-H), 5.21 (dd, 1 H, 3-H), 7.25Ϫ7.35 (m,
10 H, 2 C6H5CH2); 32β δ ϭ 1.22 (d, J5,6 ϭ 6.4 Hz, 3 H, 6,6,6-H),
1.91 (s, 3 H, COCH3), 1.84Ϫ1.92 (m, 2 H, OCH2CH2CH2N3), 3.40
(t, 2 H, OCH2CH2CH2N3), 3.42 (dd, J1,2 ϭ 7.7, J2,3 ϭ 10.2 Hz, 1
H, 2-H), 3.66 (dd, J3,4 ϭ 3.2, J4,5 ϭ Ͻ 1.0 Hz, 1 H, 4-H), 4.37 (d,
1 H, 1-H), 4.56 and 4.65, 4.59 and 4.84 (4 d, each 1 H, 2 C6H5CH2),
4.86 (dd, 1 H, 3-H), 7.25Ϫ7.35 (m, 10 H, 2 C6H5CH2). Ϫ
C25H31O6N3 (469.4): MS (FABϩ) m/z ϭ 492.1 [M ϩ Na]ϩ.
J
5,6 ϭ 6.7 Hz, 3 H, 6,6,6-H), 1.35 and 1.39 [2 s, each 3 H, C(CH3)2],
2.01Ϫ2.25 (m, 2 H, OCH2CH2CH2Br), 3.51 (dd, J1,2 ϭ 3.6, J2,3
7.9 Hz, 1 H, 2-H), 3.52 (t, 2 H, OCH2CH2CH2Br), 3.48 and 3.85
(2 m, each 1 H, OCH2CH2CH2Br), 4.04 (dd, J3,4 ϭ 5.4, J4,5
ϭ
ϭ
2.6 Hz, 1 H, 4-H), 4.13 (m, 1 H, 5-H), 4.29 (dd, 1 H, 3-H), 4.68
and 4.79 (2 d, each 1 H, C6H5CH2), 4.74 (d, 1 H, 1-H), 7.24Ϫ7.38
(m, 5 H, C6H5CH2); 37β δ ϭ 1.35 and 1.43 [2 s, each 3 H, C(CH3)2],
1.39 (d, J5,6 ϭ 6.7 Hz, 3 H, 6,6,6-H), 2.01Ϫ2.25 (m, 2 H,
OCH2CH2CH2Br), 3.37 (dd, J1,2 ϭ 8.1, J2,3 ϭ 7.0 Hz, 1 H, H-2),
3.54 (t, 2 H, OCH2CH2CH2Br), 3.68 and 4.00 (2 m, each 1 H,
OCH2CH2CH2Br), 3.83 (m, J4,5 ϭ 2.2 Hz, 1 H, 5-H), 3.98 (dd,
J3,4 ϭ 5.5 Hz, 1 H, 4-H), 4.13 (dd, 1 H, 3-H), 4.28 (d, 1 H, 1-
H), 4.78 and 4.82 (2 d, each 1 H, C6H5CH2), 7.24Ϫ7.38 (m, 5 H,
C6H5CH2). Ϫ C19H27O5Br (414.2): MS (FABϩ) m/z ϭ 415.0 [M
ϩ H]ϩ.
Decyl 3-O-Acetyl-2,4-di-O-benzyl-α/β-L-fucopyranoside (33): (i):
GP 4 A, 4 (25 mg, 58 µmol), 16 (66 µL), molecular sieves (50 mg),
solvent (1 mL), NIS (33 mg), TfOH (1.5 µL), T ϭ 0 °C. Purification
(System C) furnished 33 (28 mg, 93%); 33α 44%, 33β 56%. Ϫ (ii):
GP 4 C, 4 (25 mg, 58 µmol), 16 (66 µL), molecular sieves (50 mg),
solvent (1 mL), NIS (33 mg), TfOH (1.5 µL), T ϭ 0 °C. Purification
(System C) gave 33 (27 mg, 88%); 33α 27%, 33β 73%.Ϫ (iii): GP
5, 4 (30 mg, 70 µmol), bromine (7.1 µL). Then, residue (7), 16 (80
µL), Bu4NBr (23 mg), molecular sieves (50 mg), solvent (0.3 mL).
3-Azidopropyl 2-O-Benzyl-3,4-O-isopropylidene-α/β-
L-fucopyrano-
side (38): (i): GP 4 A, 5 (47 mg, 0.13 mmol), 14 (79 mg), molecular
Purification (System C) furnished 33 (28 mg, 76% overall); 33α sieves (150 mg), solvent (2.5 mL), NIS (76 mg), TfOH (3.6 µL),
73%, 33β 27%. Ϫ TLC (System B): Rf ϭ 0.91. Ϫ 1H NMR: 33α T ϭ 0 °C. Purification (System E, 0.1% TEA) yielded 38 (32 mg,
δ ϭ 0.88 [t, 3 H, OCH2(CH2)8CH3], 1.14 (d, J5,6 ϭ 6.6 Hz, 3 H,
68%); 38α 46%, 38β 54%. Ϫ (ii): GP 5, 5 (25 mg, 69 µmol), brom-
6,6,6-H), 1.23Ϫ1.66 [m, 16 H, OCH2(CH2)8CH3], 1.97 (s, 3 H, ine (8.6 µL). Then, residue (8), 14 (42 mg), Bu4NBr (28 mg), mo-
COCH3), 3.39 and 3.59 [2 m, each 1 H, OCH2(CH2)8CH3], 3.80 lecular sieves (75 mg), solvent (0.4 mL). Purification (System E,
(dd, J3,4 ϭ 3.1, J4,5 ϭ Ͻ 1.0 Hz, 1 H, 4-H), 4.00 (dd, J1,2 ϭ 3.7,
J2,3 ϭ 10.6 Hz, 1 H, 2-H), 4.58 and 4.65, 4.61 and 4.69 (4 d, each
1 H, 2 C6H5CH2), 4.80 (d, 1 H, 1-H), 5.23 (dd, 1 H, 3-H),
0.1% TEA) gave 38 (12 mg, 48% overall); 38α 89%, 38β 11%. Ϫ
TLC (System A): Rf ϭ 0.67 (38α) and 0.68 (38β). Ϫ 1H NMR: 38α
δ ϭ 1.32 (d, J5,6 ϭ 6.7 Hz, 3 H, 6,6,6-H), 1.34 and 1.39 [2 s, each
7.25Ϫ7.35 (m, 10 H, 2 C6H5CH2); 33β δ ϭ 0.87 [t, 3 H, 3 H, C(CH3)2], 1.80Ϫ1.95 (m, 2 H, OCH2CH2CH2N3), 3.40 (t, 2
OCH2(CH2)8CH3], 1.22 (d, J5,6 ϭ 6.4 Hz, 3 H, 6,6,6-H), 1.23Ϫ1.66
Eur. J. Org. Chem. 2001, 193Ϫ203
H, OCH2CH2CH2N3), 3.52 (dd, J1,2 ϭ 3.6, J2,3 ϭ 7.8 Hz, 1 H, 2-
201

H. J. Vermeer, C. M. van Dijk, J. P. Kamerling, J. F. G. Vliegenthart
FULL PAPER
[2]
P. Smid, G. A. de Ruiter, G. A. van der Marel, F. M. Rombouts,
H), 4.04 (dd, J3,4 ϭ 5.5, J4,5 ϭ 2.4 Hz, 1 H, 4-H), 4.09 (m, 1 H, 5-
H), 4.30 (dd, 1 H, 3-H), 4.68 and 4.79 (2 d, each 1 H, C6H5CH2),
4.72 (d, 1 H, 1-H), 7.26Ϫ7.35 (m, 5 H, C6H5CH2); 38β δ ϭ 1.34
and 1.41 [2 s, each 3 H, C(CH3)2], 1.39 (d, J5,6 ϭ 6.6 Hz, 3 H,
J. H. van Boom, J. Carbohydr. Chem. 1991, 10, 833Ϫ849.
[3]
K. Zegelaar-Jaarsveld, G. A. van der Marel, J. H. van Boom,
Tetrahedron 1992, 48, 10133Ϫ10148.
[4]
H. M. Zuurmond, S. C. van der Laan, G. A. van der Marel, J.
6,6,6-H), 1.80Ϫ1.95 (m, 2 H, OCH2CH2CH2N3), 3.37 (dd, J1,2
ϭ
H. van Boom, Carbohydr. Res. 1991, 215, C1ϪC3.
[5]
A. Toepfer, G. Kretzschmar, Bioorg. Med. Chem. Lett. 1997,
8.1, J2,3 ϭ 7.2 Hz, 1 H, 2-H), 3.98 (dd, J3,4 ϭ 5.5, J4,5 ϭ 2.2 Hz, 1
H, 4-H), 4.09 (dd, 1 H, 3-H), 4.26 (d, 1 H, 1-H), 4.80 (s, 2 H,
C6H5CH2), 7.26Ϫ7.35 (m, 5 H, C6H5CH2). Ϫ C19H27N3O5 (377.4):
MS (FABϩ) m/z ϭ 378.2 [M ϩ H]ϩ, 400.2 [M ϩ Na]ϩ.
7, 1311Ϫ1316.
[6]
H. Lönn, Carbohydr. Res. 1985, 139, 105Ϫ113.
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H. M. Flowers, Carbohydr. Res. 1979, 74, 177Ϫ185.
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5-Azidopentyl 2-O-Benzyl-3,4-O-isopropylidene-α/β-L-fucopyrano-
[9]
H. Paulsen, A. Richter, V. Sinnwell, W. Stenzel, Carbohydr. Res.
side (39): GP 4 A, 5 (78 mg, 0.22 mmol), 15 (171 mg), molecular
sieves (250 mg), solvent (4 mL), NIS (126 mg), TfOH (6 µL), T ϭ
0 °C. Purification (toluene/ethyl acetate, 4:1; 0.1% TEA) yielded 39
(63 mg, 74%); 39α 48%, 39β 52%. Ϫ TLC (System B): Rf ϭ 0.65.
1978, 64, 339Ϫ364.
[10]
A. Toepfer, R. R. Schmidt, Tetrahedron Lett. 1988, 33,
5161Ϫ5164.
[11]
C.-C. Lin, M. Shimazaki, M.-P. Heck, S. Aoki, R. Wang, T.
`
Kimura, H. Ritzen, S. Takayama, S.-H. Wu, G. Weitz-Schmidt,
Ϫ
1H NMR: 39α δ ϭ 1.10Ϫ1.73 [m, 6 H, OCH2(CH2)3CH2N3],
C.-H. Wong, J. Am. Chem. Soc. 1996, 118, 6826Ϫ6840.
T. Mukaiyama, K. Takeuchi, S. Higuchi, H. Uchiro, Chem.
Lett. 1996, 1123Ϫ1124.
1.31 (d, J5,6 ϭ 6.4 Hz, 3 H, 6,6,6-H), 1.35 and 1.41 [2 s, each 3 H,
C(CH3)2], 3.25 [t, 2 H, OCH2(CH2)3CH2N3], 3.39 and 3.65 [2 m,
each 1 H, OCH2(CH2)3CH2N3], 3.51 (dd, J2,3 ϭ 7.8 Hz, 1 H, 2-H),
4.04 (dd, J4,5 ϭ 2.5 Hz, 1 H, 4-H), 4.31 (dd, J3,4 ϭ 5.4 Hz, 1 H, 3-
H), 4.69 and 4.80 (2 d, each 1 H, C6H5CH2), 4.73 (d, J1,2 ϭ 3.5 Hz,
1 H, 1-H), 7.26Ϫ7.35 (m, 5 H, C6H5CH2); 39β δ ϭ 1.24Ϫ1.70 [m,
6 H, OCH2(CH2)3CH2N3], 1.34 and 1.38 [2 s, each 3 H, C(CH3)2],
[12]
[13]
T. K. Lindhorst, M. Ludewig, J. Thiem, J. Carbohydr. Chem.
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T. Ziegler, Carbohydr. Res. 1994, 262, 195Ϫ212.
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[18]
[19]
S. E. Zurabyan, G. G. Kolomeer, A. Ya. Khorlin, Bioorg. Khim.
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3925Ϫ3928.
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1.39 (d, J5,6
ϭ
6.7 Hz,
3
H, 6,6,6-H), 3.24 [m,
2
1
H,
H,
OCH2(CH2)3CH2N3], 3.48 and 3.93 [2 m, each
OCH2(CH2)3CH2N3], 3.37 (dd, J2,3 ϭ 7.1 Hz, 1 H, 2-H), 3.98 (dd,
4,5 ϭ 2.1 Hz, 1 H, 4-H), 4.12 (dd, J3,4 ϭ 5.5 Hz, 1 H, 3-H), 4.25 (d,
J
J1,2 ϭ 8.1 Hz, 1 H, 1-H), 4.79 and 4.84 (2 d, each 1 H, C6H5CH2),
7.26Ϫ7.35 (m, 5 H, C6H5CH2). Ϫ C21H31N3O5 (405.4): MS
(FABϩ) m/z ϭ 406.1 [M ϩ H]ϩ, 428.1 [M ϩ Na]ϩ.
[20]
[21]
Decyl 2-O-Benzyl-3,4-O-isopropylidene-α/β-L-fucopyranoside (40):
[22]
[23]
[24]
[25]
(i): GP 4 A, 5 (43 mg, 0.12 mmol), 16 (0.14 mL), molecular sieves
(150 mg), solvent (2.5 mL), NIS (70 mg), TfOH (3.3 µL), T ϭ 0
°C. Purification (System C; 0.1% TEA) yielded 40 (28 mg, 56%);
40α 31%, 40β 69%. Ϫ (ii): GP 5, 5 (27 mg, 75 µmol), bromine (9.3
µL). Then, residue (8), 16 (86 µL), Bu4NBr (30 mg), molecular
sieves (75 mg), solvent (0.3 mL). Purification (System C, 0.1%
TEA) yielded 40 (23 mg, 74% overall); 40α 88%, 40β 12%. Ϫ TLC
(System A): Rf ϭ 0.84. Ϫ 1H NMR: 40α δ ϭ 0.90 [t, 3 H,
OCH2(CH2)8CH3], 1.31 (d, J5,6 ϭ 6.7 Hz, 3 H, 6,6,6-H), 1.33 and
´
V. Horejsı, J. Kocourek, Biochim. Biophys. Acta 1973, 297,
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1.36 [2 s, each
OCH2(CH2)8CH3], 3.50 (dd, J1,2 ϭ 3.6, J2,3 ϭ 7.9 Hz, 1 H, 2-H),
3.37 and 3.62 [2 m, each 1 H, OCH2(CH2)8CH3], 4.03 (dd, J3,4
3 H, C(CH3)2], 1.27Ϫ1.59 [2 m, 16 H,
[28]
[29]
ϭ
5.5, J4,5 ϭ 2.6 Hz, 1 H, 4-H), 4.31 (dd, 1 H, 3-H), 4.69 and 4.79 (2
d, each 1 H, C6H5CH2), 4.73 (d, 1 H, 1-H), 7.25Ϫ7.39 (m, 5 H,
C6H5CH2); 40β δ ϭ 0.90 [t, 3 H, OCH2(CH2)8CH3], 1.34 and 1.41
[2 s, each 3 H, C(CH3)2], 1.39 (d, J5,6 ϭ 6.6 Hz, 3 H, 6,6,6-H),
1.27Ϫ1.59 [2 m, 16 H, OCH2(CH2)8CH3], 3.36 (dd, J1,2 ϭ 8.1,
J2,3 ϭ 7.1 Hz, 1 H, 2-H), 3.97 (dd, J3,4 ϭ 5.5, J4,5 ϭ 2.1 Hz, 1 H,
4-H), 3.80 (m, 1 H, 5-H), 4.10 (dd, 1 H, 3-H), 4.25 (d, 1 H, 1-
H), 4.79 and 4.89 (2 d, each 1 H, C6H5CH2), 7.25Ϫ7.39 (m, 5
H, C6H5CH2). Ϫ C26H42O5 (434.3): MS (FABϩ) m/z ϭ 435.2 [M
ϩ H]ϩ.
[30]
[31]
[32]
[33]
[34]
[35]
[36]
[37]
Acknowledgments
The authors are indebted to Mr. C.H. Grün for recording FAB
mass-spectra. Dr. J. W. Zwikker is gratefully acknowledged for
helpful discussions.
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Fucosylation of Linear Alcohols
FULL PAPER
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203