Efficient synthesis of ω-mercaptoalkyl 1,2-trans-glycosides from sugar peracetates

Article abstract of DOI:10.1016/j.carres.2007.02.024

Lewis acid-promoted reactions of peracetylated sugars (glucose, galactose, maltose, lactose) with ω-bromo-1-alkanols (C₈, C₁₂) were investigated. ZnCl₂ was found to promote the 1,2-trans-glycosylation of the alcohols in toluene at about 60 °C in a stereocontrolled manner with better yields than commonly employed promoters such as SnCl₄. The ω-bromoalkyl acetylated glycosides were readily converted to ω-mercaptoalkyl glycosides, which are useful for the preparation of glycoclusters.

Full text of DOI:10.1016/j.carres.2007.02.024

Carbohydrate Research 342 (2007) 1009–1020
Efficient synthesis of x-mercaptoalkyl 1,2-trans-glycosides
from sugar peracetates
Teiichi Murakami,* Reiko Hirono, Yukari Sato and Kiyotaka Furusawa
Institute for Biological Resources and Functions, National Institute of Advanced Industrial Science and Technology (AIST),
Tsukuba Central 5, Tsukuba, Ibaraki 305-8565, Japan
Received 5 January 2007; received in revised form 16 February 2007; accepted 20 February 2007
Available online 25 February 2007
Abstract—Lewis acid-promoted reactions of peracetylated sugars (glucose, galactose, maltose, lactose) with x-bromo-1-alkanols
(C8, C12) were investigated. ZnCl2 was found to promote the 1,2-trans-glycosylation of the alcohols in toluene at about 60 ꢀC in
a stereocontrolled manner with better yields than commonly employed promoters such as SnCl4. The x-bromoalkyl acetylated
glycosides were readily converted to x-mercaptoalkyl glycosides, which are useful for the preparation of glycoclusters.
ꢁ 2007 Elsevier Ltd. All rights reserved.
Keywords: Glycosylation; Glycolipids; Sugar peracetates; Lewis acids; Alkanethiols
1. Introduction
at the terminal position of the hydrocarbon chain.
Although such glycolipids have been prepared, the
synthetic methods suffer from some drawbacks. For
Recent studies in molecular biology have revealed that
carbohydrate–protein interactions on cell surfaces are
involved in essential biological processes such as cell
growth, cellular adhesion, immune response, and
inflammation.1 Carbohydrate–protein binding events
usually involve several simultaneous contacts between
carbohydrates that are clustered on cell surfaces and
protein receptors that contain multiple binding sites.2
Such aggregated structures enhance the low binding
affinity of the monomeric interaction, an observation
referred to as the cluster glycoside effect.3 Because of the
complexity of cell surfaces, it would be difficult to eval-
uate carbohydrate–protein binding events in their native
state. Simplified model systems such as self-assembled
glycolipid monolayers4 and gold glyconanoparticles5
have been usually used to study polyvalent interactions.
We planned to study specific carbohydrate–lectin
interactions using multivalent carbohydrate model sys-
tems. To prepare the assembled systems, we required
substantial quantities of glycolipids having a thiol group
´
example, Penades and co-workers have prepared 11-
mercaptoundecyl-b-lactoside and -b-maltoside (each di-
meric form as the disulfide).5c They employed O-benzoyl
protected sugar 1-O-trichloroacetimidates as glycosyl
donors whose preparation can be laborious. Lin et al.
have prepared 5-mercaptopentyl a-D-mannoside (di-
mer),5b whose synthesis is rather straightforward, but
with the drawback that they used toxic Hg(CN)2 as gly-
cosylation promoter. Therefore, a relatively simple and
safe procedure is needed to enable a rapid synthesis in
good yields. Herein we report a general and convenient
route to the lipids.
2. Results and discussion
2.1. Glycosylation studies
Glycosylation of alcohols (O-glycosylation)6 is an essen-
tial process for the synthesis of oligosaccharides and gly-
coconjugates. Simple n-alkyl 1,2-trans-glycosides such as
octyl b-glucoside, a nonionic detergent, have been
traditionally prepared from O-acetyl-protected glycosyl
*
Corresponding author. Tel.: +81 29 861 9394; fax: +81 29 861
4549; e-mail: t-murakami@aist.go.jp
0008-6215/$ - see front matter ꢁ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2007.02.024

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T. Murakami et al. / Carbohydrate Research 342 (2007) 1009–1020
bromides with n-alkanols in the presence of promoter(s).
Typical promoters employed in this type of glycosyl-
ation are silver salts (Ag2CO3,7a Ag2CO3 with a catalytic
amount of I2,7c,d AgOTf,7b AgClO47e) (Koenigs–Knorr
method) and mercury salts (Hg(CN)2–HgBr2,8a,c
Hg(CN)2,5b HgBr28b). To avoid the use of these heavy
metal salts, some Lewis acids (Sn(OTf)2,9a InCl3,9b
FeCl39c) or iodonium reagents10 have occasionally been
employed.
Another effective method is Lewis acid-catalyzed gly-
cosylation using sugar peracetates. Typical acid catalysts
employed are SnCl4,11 BF3ÆOEt2,12 Me3SiOTf,13 and
FeCl3.14 Peracetylated sugars would be preferable glyco-
syl donors in view of their ready accessibility (available
by only one-step acetylation of the parent sugar) and
stability. In addition, peracetylated sugars are versatile
precursors of other donors such as anomeric halides,15
1-thio-sugars,16 and 1-O-trichloroacetimidates.17 It has
been known that, as for glucose and galactose deriva-
tives, the anomeric b-acetate is much more reactive than
the corresponding a-acetate.18 In general, reactions of
O-acetyl-protected sugars with alcohols preferentially
give 1,2-trans-glycosides due to the neighboring C-2
acetoxy group participation.6 However, recent reports
have indicated that thermodynamically more stable
1,2-cis-a-glycosides (glucosides or galactosides at the
reducing end) are preferentially formed via anomeriza-
tion under acidic conditions.11b,e,14,19 Penta-O-acetyl-
mannose should give 1,2-trans-a-mannoside exclusively
as dictated by both the neighboring group participation
and the anomeric effect.
of b-maltose octaacetate 2 and commercially available
x-bromo-1-alkanols 3 under Lewis acid conditions.21
According to a literature precedent,11a b-maltose
octaacetate (2) was treated with 12-bromo-1-dodecanol
(3a, 1.25 equiv) using SnCl4 (1.25 equiv) as a promoter
at 0 to 5 ꢀC for 5 h. The reaction gave the expected bro-
mododecyl b-maltoside 4a in 46% yield along with sev-
eral byproducts: 12-bromododecyl acetate 6a (32%
based on 2), 2-O-deacetylated bromododecyl maltoside
7a (a/b-mixture, 3%), and hepta-O-acetyl-a-maltosyl
chloride 8 (14%) (Scheme 2). Partially anomerized octa-
acetate 2 (12%, b/a = 2) and more polar, hepta-O-acetyl
maltose (15%) were also formed. Prolonged reaction at
rt for 10 h reduced the amounts of 2 and the chloride
8 (3%). However, 6a and 7a increased, and the major
product was an inseparable mixture of 4a and the a-ano-
mer 5a (2:1, 50% yield). The a/b ratio of the mixture was
1
determined by H NMR spectroscopy. SnCl4-promoted
reaction of 2 with 8-bromo-1-octanol 3b was also exam-
ined. The reaction at 0 to 5 ꢀC for 5 h gave the 8-bro-
mooctyl b-maltoside 4b in 40% yield containing a trace
amount of the a-anomer 5b (1%), whereas prolonged
reaction at rt for 16 h gave an inseparable mixture of
4b and 5b (2:3) in 42% yield. These results indicate that
initially formed b-anomer was epimerized to more stable
a-maltoside by SnCl4 at rt. Banoub and Bundle repor-
ted11b the almost complete b to a anomerization of 8-
ethoxycarbonyloctyl maltoside by SnCl4 at rt for 4 h.
In our cases, however, the equilibrium would not lie
close to the a-anomer.
It proved very difficult to separate the a and b ano-
mers of bromoalkyl acetylated maltosides. Although
concanavalin A would recognize both a- and b-malto-
sides, stereochemically pure compounds are desirable
for proper evaluation. Thus formation of the a anomers
should be minimized. It has been reported that the two
anomers of disaccharides could be separated after
deacetylation.9c However, for our purpose, it would be
preferable to separate the anomers before deacetylation.
Concanavalin A, a readily available lectin,20 can spe-
cifically recognize a 1,2-trans-a-mannoside and a 1,2-cis-
a-glucoside residue at the nonreducing end of the glyco-
sides. In mammalian glycolipids, glucose is a major
component, whereas mannose is a minor one. We
planned to prepare x-mercaptoalkyl b-maltosides 1,
which have an a-glucoside residue as shown in Scheme
1. For the synthesis of 1, we first examined the reaction
OH
O
OAc
HO
HO
OH
O
AcO
AcO
OAc
HO
O
O
AcO
O
O
AcO
-
O (CH2)n-SH
HO
-
O (CH2)n-X
HO
AcO
12-mercaptododecyl β-maltoside
8-mercaptooctyl β-maltoside
1a (n = 12)
1b (n = 8)
Lewis acid
OAc
O
AcO
AcO
OAc
+
HO-(CH2)n-Br
AcO
O
O
AcO
OAc
3a (n = 12)
3b (n = 8)
AcO
2
Scheme 1.

T. Murakami et al. / Carbohydrate Research 342 (2007) 1009–1020
1011
OAc
OAc
SnCl4
(1.25 eq.)
O
Ac-α-Glc-O
Br-(CH2)n-OAc
-
O (CH2)nBr
O
Ac-α-Glc-O
AcO
AcO
AcO
4 (β-maltoside)
2
+
3
6 (acetylated alcohol)
AcO
CH2Cl2
Cl
(1.25 eq.)
OAc
OAc
8
O
O
Ac-α-Glc-O
AcO
Ac-α-Glc-O
AcO
-
O (CH2)nBr
AcO
HO
(a: n =12, b: n = 8)
-
O (CH2)nBr
5 (α-maltoside)
OAc
7 (α/β mixture)
O
AcO
Ac-α-Glc =
AcO
AcO
Yields (based on 2)
conditions
By-products
alcohol
Maltosides
6a (32%), 7a (3%), 8 (14%)
6a (55%), 7a (15%), 8 (3%)
6b (34%), 7b (2%), 8 (18%)
6b (56%), 7b (20%), 8 (3%)
4a (46%) + 5a (<1%)
5 °C, 5 h
3a
3a
3b
3b
5 °C to rt, 10 h
5 °C, 5 h
4a + 5a (50%, 2:1 mixture)
4b (40%) + 5b (1%)
5 °C to rt, 16 h
4b + 5b (42%, 2:3 mixture)
Scheme 2. Maltosylation of bromo-alkanols 3a,b promoted by SnCl4.
OAc
OAc
Lewis acid
OAc
O
O
AcO
AcO
Br-(CH2)12-OH
AcO
AcO
+
O
-
O (CH2)12Br
AcO
AcO
(CH2Cl2)
OAc
AcO
AcO
3a
-
O (CH2)12Br
AcO
10a (β-glucoside)
11a (α-glucoside)
9
OAc
OAc
Br-(CH2)12-OAc
O
O
AcO
AcO
AcO
AcO
6a
RO
-
O (CH2)12Br
HO
Cl
12 (α/β mixture)
13 (R = Ac)
14 (R = H)
Scheme 3. Lewis acid-promoted reaction of b-D-glucose pentaacetate (9) with 12-bromo-1-dodecanol (3a).
Table 1. Lewis acid-promoted reaction of b-D-glucose pentaacetate (9) with 12-bromo-1-dodecanol (3a)a
Entry
Lewis acid
Additive (equiv)
Conditionsb
Yieldc (%)
11a (a)
10a (b)
12
6a
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
SnCl4
SnCl4
SnCl4
SnCl4
SnCl4
SnCl4
BF3ÆOEt2
Me3SiOTf
FeCl3
ZrCl4
InBr3
CeCl3
BiCl3
ZnCl2
ZnCl2
Zn(OTf)2
5 ꢀC, 5 h
43
3
3
54
0
1
4
1
2
0
4
4
6
6
8
4
7
5
5
26
4
33
50
37
31
38
36
34
92
63
61
56
5 ꢀC to rt, 20 h
ꢀ10 to 0 ꢀC, 15 h
5 ꢀC, 3 h
AgClO4 (0.6)d
Ag2CO3 (1.0)
CaCO3 (1.2)
TMUe (0.5)
24
44
47
40
42
25
27
19
27
5 ꢀC, 5 h
5–15 ꢀC, 5 h
5 ꢀC to rt, 3 h
ꢀ20 to 0 ꢀC, 3 h
5 ꢀC, 1 h
MS4A
5 ꢀC, 5 h
0
1
5–15 ꢀC, 4 h
rt to 40 ꢀC, 1 h
rt, 2 h
5 ꢀC to rt, 2 h
rt to 65 ꢀC,f 1 h
rt to 75 ꢀC,f 3 h
25
No reaction
2
No reaction
3
1
12
42
70
58
4
16
13
28
52
a Lewis acid and 3a used were 1.25–1.50 equiv to 9.
b Reaction was carried out in CH2Cl2 unless otherwise noted.
c Isolated yield after chromatography, based on sugar 9, not on alcohol 3a.
d
˚
4 A Molecular sieves were also added.
e Tetramethylurea.
f The reaction was carried out in toluene.

1012
T. Murakami et al. / Carbohydrate Research 342 (2007) 1009–1020
In order to improve the yield of 1,2-trans-glycosides,
tle effect. To suppress the anomerization and by-product
formation, addition of proton scavengers was examined.
However, both CaCO3 and tetramethylurea did not
have much effect on the yield of 10a.
Next, other commonly employed Lewis acids
(BF3ÆOEt2, Me3SiOTf, FeCl3) were examined. Glucosyl-
ation using BF3ÆOEt2 at rt gave 10a in 42% yield with a
small amount of a-anomer 11a. This yield is consistent
with that reported for the reaction of 9 and 2-bromo-
ethanol with 5 equiv of BF3ÆOEt2 (42%).12b Me3SiOTf
and FeCl3 gave lower yields of 10a and higher yields
of bromododecyl acetate 6a.
Less common Lewis acids (ZrCl4, InBr3, CeCl3, BiCl3)
were also examined. These salts except CeCl3 promoted
the reaction at 5 ꢀC to rt, but the yields of 10a were low
(12–27%). With ZrCl4, the anomeric chloride 13 was
formed at the early stage, and then gradually decreased,
and 3,4,6-tri-O-acetyl-a-D-glucopyranosyl chloride (14)
was obtained in 30% yield as a major product. The prod-
uct distribution by InBr3 was similar to that by FeCl3.
BiCl3 gave 2-O-deacetylated glucoside 12 (a/b = 2:3)
as a major product.
we investigated the reaction of b-D-glucopyranose
pentaacetate (9) with 12-bromododecanol (3a, 1.2–
1.5 equiv) under various Lewis acid conditions (Scheme
3). Penta-O-acetyl-b-D-glucose (9) is cheap, and the
products, alkyl a- and b-glucosides (10a and 11a) can
be separated by silica gel chromatography. The results
are summarized in Table 1. Molecular sieves were not
used in principle because they sometimes considerably
retard this type of glycosylation. The reaction was
quenched when most of the b-peracetate 9 was con-
sumed, though the end point was not clear because of
the similarity in its mobility on TLC with the much less
reactive, a-anomerized 9.
With SnCl4, similar to the maltosylation, b-glucoside
10a was selectively formed at 5 to 10 ꢀC. Above 10 ꢀC,
the anomerization was observed, and a-glucoside 11a,
less polar anomer, was predominantly obtained in 54%
yield at rt for 16 h. Below 10 ꢀC, a significant amount
of anomeric chloride 13 (10–20%) was formed by
SnCl4,11a and separation from the glucoside 10a was dif-
ficult in this case. For the reaction of the chloride 13
with 3a, addition of silver salt was attempted: addition
of AgClO4 decreased the yield, whereas Ag2CO3 had lit-
No reaction took place by using ZnCl2 at rt. However,
the glucoside 10a was formed above 50 ꢀC, and the best
1-chloride 13
α-glucoside 11a
MCln
LA
(anomerization)
(M: Sn, Zr)
(or H+)
OAc
OAc
OAc
O
O
AcO
AcO
AcO
AcO
-
O (CH2)12Br
AcO
10a
O
O
LA
β-D-glucose
pentaaceate
(9)
A
ROH (3a)
(rearrangement)
LA
OAc
OAc
OAc
OAc
O
O
AcO
AcO
AcO
AcO
O
AcO
9-α
AcO
AcO
O
O
O
O
OAc
-
O (CH2)12Br
B
orthoester 15
+ ROH (3a)
(degradation)
LA (or H+)
(LA: Lewis acid)
OAc
O
OAc
OAc
AcO
AcO
O
O
AcO
AcO
AcO
AcO
-
O (CH2)12Br
HO
OH
AcO
OAc
HO
12 (α/β mixture)
16
17
+
+ 6a
AcO-(CH2)12Br
6a
Scheme 4. Plausible reaction pathways.

T. Murakami et al. / Carbohydrate Research 342 (2007) 1009–1020
1013
yield (58%) was obtained in toluene at 65 ꢀC for 1 h. In
contrast to ZnCl2, zinc triflate gave 10a in very low
yield.
jor) and 17 (minor) (total 15–30% based on 9), a mixture
of 9 and 9-a (3–10%), and the glucosyl chlorides (13, 14)
(10–20% using SnCl4). The combined yields of the cou-
pled products (10a, 11a, 12) and the byproducts derived
from 9 were 85–95% in all, and the total yield of the
deacetylated products (12, 16, 17) was comparable to
the yield of the acetylated alcohol 6a. These results
would suggest a degradation pathway(s) to both 6a
and 16/17. Further studies will be necessary to elucidate
the mechanism of the formation of these byproducts
under essentially anhydrous conditions.
We next examined the ZnCl2-promoted glycosylation
of 3a,b with b-peracetylated sugars (glucose 9, galactose
18, maltose 2, and lactose 21), and compared to SnCl4-
promoted glycosylation (Scheme 5). The results are
summarized in Table 2. It was observed that initially
dispersed zinc halide, which is almost insoluble in
toluene, began to deposit and finally attached to the
flask with the progress of the reaction. 8-Bromooctyl-
The plausible reaction pathways of the glycosylation
are depicted in Scheme 4.22 The initial step of the reac-
tion is a Lewis acid-promoted dissociation of 9, involv-
ing the participation of the C-2 acetoxy group, to give
an oxocarbenium–acetate ion pair (A) or a more stabi-
lized dioxolenium ion (B). The carbenium ion would
react with the alcohol 3a to give the desired 1,2-trans-
glucoside 10a and 1,2-orthoester 15. Under acidic reac-
tion conditions, the orthoester 15 would rearrange23 to
10a or would react with 3a to give the acetylated alcohol
6a and 2-O-deacetylated glucoside 12. However, in most
entries in Table 1, the yield of 6a was much higher than
that of 12. In the SnCl4- and BF3-promoted glucosyl-
ations, the yields of 10a were modest (40–50%), but it
would be acceptable in view of the precedents.11,12,21
Other byproducts were tetra-O-acetyl-glucoses 16 (ma-
R2
OAc
R2
OAc
R2
OAc
(A), (B), or (C)
+
O
Br-(CH2)n-OH
R1
O
+
R1
O
R1
-
O (CH2)nBr
OAc
AcO
AcO
AcO
AcO
AcO
3a (n = 12)
3b (n = 8)
AcO
-
O (CH2)nBr
9
(R1 = OAc, R2 = H)
18 (R1 = H, R2 = OAc)
(R1 = tetra-Ac-α-Glc-O-, R2 = H)
21 (R1 = tetra-Ac-β-Gal-O-, R2 = H)
10 (Ac-β-Glc)
19 (Ac-β-Gal)
4 (Ac-β-Mal)
22 (Ac-β-Lac)
11 (Ac-α-Glc)
20 (Ac-α-Gal)
5 (Ac-α-Mal)
23 (Ac-α-Lac)
2
Scheme 5. Glycosylation of 3a,b with peracetylated b-D-sugars. Reagents and conditions: (A) SnCl4, CH2Cl2, 5–10 ꢀC, 3–5 h. (B) ZnCl2, toluene, 60–
65 ꢀC, 0.5–1 h. (C) ZnBr2 (CaCO3), toluene, 60–65 ꢀC, 0.5–1 h.
Table 2. Glycosylation of 3a,b with peracetylated b-D-sugarsa promoted by SnCl4, ZnCl2, or ZnBr2
Sugar
Alcohol
Yieldb (b:a ratio)c
By SnCl4
By ZnCl2
By ZnBr2
b
a
b
a
b
a
9 (Glc)
9
3a
3b
3a
3b
43
40
60
53
3
7
2
58
50
64
54
3
3
4
5
57
39
63
39d
6
14
7
17d
16 (Gal)
16
<1
2 (Mal)
3a
3b
3a
3b
46
(100:<1)
57
(100:2)
67
(100:6)e
2
40
(100:1)
57
(100:3)
60
(100:13)d,f
19 (Lac)
19
40
(100:2)
51
(100:2)
55
(100:6)e
42
(100:<1)
45
(100:4)
46
(100:14)g
a Alcohol and Lewis acid used were 1.2–1.5 equiv to sugar peracetate.
b Isolated yield (%) after chromatography.
c The ratio in parenthesis was determined by 1H NMR spectroscopy.
d The reaction was carried out at 50 ꢀC for 0.5 h.
e CaCO3 (1.5 equiv) was added.
f In the absence of CaCO3, a 1:1 mixture was obtained in 60% yield.
g CaCO3 (3 equiv) was added.

1014
T. Murakami et al. / Carbohydrate Research 342 (2007) 1009–1020
and 12-bromododecyl glycosides were obtained in
45–68% yields by ZnCl2 in toluene at 60–65 ꢀC (bath
temperature) within 1 h. Bromoalkyl acetate 6a,b and
2-O-deacetylated glycosides such as 7 were obtained in
18–36% and 13–25% yields, respectively (individual data
not shown), but glycosyl chlorides were not obtained.
The glucosylation of 3a with ZnCl2 proceeded in dichlo-
roethane at 60 ꢀC with lower stereoselectivity (b: 47%, a:
7%). No reaction took place in acetonitrile even at
80 ꢀC, presumably due to the Lewis base character of
the solvent.
ation should involve various factors that would affect
the product distribution as shown in Scheme 4. When
a reactive primary alcohol and/or an active catalyst
are employed, side reactions such as orthoester forma-
tion and the degradation, anomerization, and anomeric
halogenation would also proceed rapidly, resulting in
the decrease of b-glycoside.
2.2. Synthesis of x-mercaptoalkyl glycosides
Synthesis of x-mercaptoalkyl glycosides from protected
x-bromoalkyl glycosides is straightforward as shown in
Scheme 6. Besides b-maltosides 4a,b, b-glucosides 10a,b,
and a-glucoside 11a were used for comparison. These
x-bromoalkyl glycosides were treated with potassium
thioacetate in DMF to give the thioacetates (24a,b,
25a,b, 26) in high yields. Deacetylation with NaOMe
(ca. 1 equiv) in MeOH and CH2Cl2 afforded x-mercapto-
alkyl glycosides (1a,b, 27a,b, 28) as major products
(82–85% yields) and the disulfides as minor ones (10–
15% yields). The disulfides were much more polar than
the corresponding thiols on TLC, for example, Rf 0.36
for 27a and 0.05 for the disulfide (8:1, CH2Cl2–MeOH).
In the 13C NMR spectra of the thiols in CDCl3 with
CD3OD (10:1), the terminal carbon signal appeared to
split (Dd 0.1–0.2 ppm) as shown in Table 8. The signal
of the carbon next to the terminal was slightly split as
The following trends on the yield and stereoselectivity
were observed.
(1) In most cases, the yield of b-glycoside by using
ZnCl2 is ca. 5–15% higher than that by using SnCl4.
However, the b selectivity is slightly lower, proba-
bly due to the higher reaction temperature.
(2) ZnBr2 gave the glycosides in slightly better yields,
but with lower b selectivity than ZnCl2. The ano-
merization was suppressed to some extent by add-
ing CaCO3.
(3) The yields and b selectivities of bromooctyl glyco-
sides are lower than those of bromododecyl glyco-
sides, though bromooctanol 3b appears to be
more reactive than bromododecanol 3a.
(4) Among four sugars, the yields of galactosides are
generally higher, whereas those of lactosides are
lower.
1
well (Dd ca. 0.03 ppm). In their H NMR spectra, small
but sharp triplets (J = 7.8 Hz) were observed at d ca.
1.35 ppm as shoulders of huge methylene signals (d
1.25–1.40 ppm). These observations indicate that both
the thiol (RSH) and the deuterated thiol (RSD) would
exist as an equilibrium mixture with excess CD3OD, in
which all sugar hydroxy groups have been deuterated.
Dodecanethiol derivatives (1a, 27a, 28) solidified,
whereas octanethiol derivatives (1b, 27b) were syrupy.
The thiol group was gradually oxidized in the air to
the disulfide, which can also be used for the preparation
of gold glyconanoparticles.5 Similarly, mercaptoalkyl b-
galactosides and b-lactosides should be prepared from
19 and 22.
Zinc chloride has been employed as a glycosylation
promoter in the following cases: (1) phenols with glycos-
yl peracetates at high temperatures (>100 ꢀC) without
solvent;24 (2) alcohols with 1,2-anhydro sugars;25 (3)
alcohols with ‘armed’ glycosyl phosphites.26 However,
it has rarely been used for the reaction of alcohols with
per-O-acetyl sugars, presumably due to the lower activ-
ity compared to SnCl4 or BF3ÆOEt2. Indeed as shown in
Table 1, ZnCl2 showed little or no activity at rt, but it
gave the b-glucoside 10a on heating with the best yield
among the Lewis acids examined. This type of glycosyl-
OAc
OH
a
b
O
O
RO
AcO
4 or 10
R'O
HO
-
O (CH2)n-SAc
-
O (CH2)n-SH
AcO
HO
24 (R = tetra-Ac-α-Glc-)
25 (R = Ac)
1 (R' = α-D-glucopyranosyl)
27 (R' = H)
OH
O
OAc
O
a
b
11
HO
HO
AcO
AcO
HO
AcO
-
-
O (CH2)12-SH
O (CH2)12-SAc
26
Scheme 6. Reagents and conditions: (a) KSAc, DMF, rt, 2 h; (b) NaOMe, MeOH–CH2Cl2, 5 ꢀC, 2 h.
28

T. Murakami et al. / Carbohydrate Research 342 (2007) 1009–1020
1015
3. Conclusions
spectra were obtained on Hitachi M80B and a JEOL
MS600H mass spectrometers, respectively. Routine
monitoring of reactions was carried out using E. Merck
Silica Gel 60F254 TLC plates, and compounds were
detected by dipping the plates in 10% aq H2SO4, followed
by heating. Column chromatography was performed
with indicated solvents on silica gel (Kanto Chemicals,
neutral, 100–210 lm, or Wakogel C-300, 45–75 lm).
Commercially available sugar peracetates (2, 9, 18, 21)
were used without further purification. SnCl4 (1.0 M
solution in heptane) was purchased from Aldrich and
used as received. Sugar peracetates and solid Lewis acids
were dried in vacuo for over 1 h before use.
To prepare glycolipid clusters, the synthesis of x-merca-
ptoalkyl glycosides was investigated. It was found that
ZnCl2 promotes the 1,2-trans-glycosylation of x-bromo-
1-alkanols (C8, C12) with per-O-acetylated sugars in
toluene at about 60 ꢀC in a stereocontrolled manner
with better yields than commonly employed promoters
such as SnCl4. These results would be advantageous
from an ecological and economical point of view
because of the low toxicity and cost of ZnCl2. We have
developed an efficient synthetic route to x-merca-
ptoalkyl glycosides, which can be used to prepare assem-
bled carbohydrate model systems.
4.1.1. General glycosylation procedure (A) using SnCl4 as
promoter. To a cooled solution of sugar peracetate
(0.30 mmol) and bromo-1-alkanol (3, 0.40 mmol) with
or without additive in CH2Cl2 (3 mL) was added drop-
wise a 1.0 M solution of SnCl4 in heptane (0.4 mL,
0.4 mmol), and the mixture was stirred at 0–5 ꢀC until
most of the peracetate was consumed. (For the synthesis
of the a-glucoside, the mixture was stirred at rt for more
than 5 h.) The resulting mixture was diluted with EtOAc
(20 mL) and aq NaHCO3 (20 mL), and the mixture was
stirred for 10 min, filtered through Celite, and washed
thoroughly with EtOAc (10 mL). The combined filtrate
and washings were successively washed with H2O and
brine. The aqueous phase was extracted with EtOAc
(2 · 20 mL), and the combined organic layers were dried
over Na2SO4. Removal of the solvent gave a residue
that was purified by silica gel column chromatography.
For maltose derivatives, the column was eluted with
2:1!1.5:1 hexane–EtOAc to give acetylated alcohol 6,
4. Experimental
4.1. General methods
Melting points were determined with a Yanaco melting
point apparatus MP-500D. Optical rotations were mea-
sured with a JASCO DIP-1000 polarimeter, and [a]D
values are given in 10ꢀ1 deg cm2 gꢀ1. H NMR spectra
1
were recorded at 270 MHz on a JEOL JNM-GSX-270
spectrometer, and chemical shifts (d) are reported in
ppm relative to internal tetramethylsilane (d 0.00). 13C
NMR spectra were recorded at 67.8 MHz and chemical
shifts (d) are reported in ppm relative to CDCl3 (d 77.0).
Most of the NMR data are summarized in Tables 3–8.
Elemental analyses were performed in the analytical sec-
tion in this Institute (AIST). High-resolution mass
(HRMS) and fast-atom bombardment mass (FABMS)
Table 3. 1H NMR chemical shifts (d in ppm) of acetylated monosaccharides in CDCl3
Glucoside
Galactoside
10a
10b
11a
25a
25b
26
19a
19b
H-10
H-20
H-30
H-40
H-50
H-60a
H-60b
4.49
4.99
5.21
5.09
3.69
4.14
4.27
4.49
4.98
5.21
5.09
3.69
4.14
4.27
5.07
4.85
5.49
5.05
4.01
4.09
4.26
4.49
4.98
5.21
5.08
3.69
4.13
4.27
4.49
4.98
5.20
5.08
3.69
4.13
4.27
5.06
4.85
5.48
5.05
4.02
4.09
4.26
4.46
5.20
5.02
5.39
3.90
4.13
4.19
4.46
5.20
5.02
5.38
3.90
4.13
4.19
H-1a
H-1b
2-H2
3-H2
CH2–C–Xa
CH2–Xa
Other CH2
3.47
3.87
1.85
1.42
1.56
3.41
1.26
3.47
3.87
1.85
1.42
1.56
3.41
1.30
3.42
3.68
1.86
1.43
1.59
3.41
1.28
3.47
3.86
1.56
1.33
1.56
2.86
1.25
3.47
3.86
1.56
1.42
1.56
2.85
1.29
3.42
3.68
1.57
1.35
1.55
2.86
1.27
3.47
3.88
1.85
1.42
1.57
3.41
1.27
3.48
3.88
1.85
1.43
1.57
3.40
1.30
AcO
2.01
2.03
2.04
2.09
2.01
2.03
2.04
2.09
2.02
2.03
2.06
2.09
2.00
2.02
2.04
2.06
2.32
2.00
2.02
2.04
2.08
2.32
2.01
2.03
2.06
2.09
2.32
1.98
2.05
2.05
2.15
1.98
2.04
2.05
2.15
Ac–S
a X = Br or S.

1016
T. Murakami et al. / Carbohydrate Research 342 (2007) 1009–1020
Table 4. 13C NMR chemical shifts (d in ppm) of acetylated monosaccharides in CDCl3
Glucoside
Galactoside
19b
10a
10b
11a
95.5
70.2
70.9
67.1
68.6
61.9
25a
25b
26
95.5
70.2
70.9
67.0
68.6
61.9
19a
C-10
C-20
C-30
C-40
C-50
C-60
100.8
71.4
72.9
70.2
71.7
62.0
100.8
71.3
72.8
70.1
71.7
62.0
100.8
71.3
72.8
70.1
71.7
61.9
100.8
71.3
72.8
70.1
71.7
62.0
101.3
70.3
70.5
67.0
70.9
61.2
101.3
70.0
70.5
67.0
70.9
61.2
C-1
68.5
34.0
32.8
25.8
28.1
28.7
29.27
29.36
29.37
29.47
29.49
29.52
68.5
33.9
32.7
25.7
28.0
28.6
29.0
29.3
68.7
34.0
32.7
25.9
28.1
28.7
29.17
29.25
29.34
29.43
29.48
29.49
68.5
30.5
68.5
30.5
68.7
30.6
68.9
34.0
32.8
25.8
28.1
28.7
29.27
29.36
29.37
29.46
29.48
29.51
68.9
33.8
32.6
25.6
27.9
28.5
29.0
29.3
CH2–Xa
CH2–C–Br
C-3
25.7
28.7
29.0
29.1
25.7
28.6
28.9
29.01
29.02
29.3
29.4
25.9
28.7
Other CH2
29.03
29.07
29.17
29.25
29.37
29.42
29.46
29.48
29.2
29.31
29.36
29.41
29.45b
29.48
CH3CO
O–C@O
20.56
20.59
20.61
20.70
169.2
169.4
170.3
170.7
20.55
20.58
20.61
20.69
169.2
169.4
170.3
170.6
20.56
20.61
20.65b
20.50
20.53
20.55
20.63
169.2
169.3
170.2
170.6
195.9
20.50
20.53
20.56
20.64
169.2
169.3
170.2
170.6
195.9
20.55
20.60
20.64b
20.57
20.64b
20.71
20.45
20.53b
20.62
169.6
169.6
170.06
170.10
170.6
195.9
169.3
170.1
170.2
170.3
169.2
170.0
170.1
170.2
170.07
170.11
170.6
S–C@O
a X = Br or S.
b Two carbons would overlap.
unreacted 3, maltoside 4/5 (a/b mixture), maltosyl chlo-
ride 8 (if formed), and a mixture of 2 and 7 in that order.
For glucose derivatives, elution with 3:1!2:1 hexane–
EtOAc gave acetylated alcohol 6, unreacted 3, a-gluco-
side 11, b-glucoside 10, glucosyl chloride 13 (if formed),
12, and 9 (a/b mixture) in that order. When the separa-
tion was incomplete, the product ratio in fractions of
4.1.3. 12-Bromododecyl 2,3,4,6-tetra-O-acetyl-a-D-gluco-
pyranosyl-(1!4)-2,3,6-tri-O-acetyl-b-D-glucopyranoside
(4a). Compound 4a was prepared from 2 and 3a either
using general procedure (A) in 46% yield or (B) in 57%
24
yield as a colorless solid: mp 82–85 ꢀC; ½aꢁD +37.5 (c 1.6,
CHCl3); Rf 0.44 (3:2 hexane–EtOAc). Anal. Calcd for
C38H59BrO18: C, 51.64; H, 6.73. Found: C, 51.80; H,
6.93.
1
the mixture was determined by H NMR spectroscopy.
This procedure was also applied to the glycosylation
with liquid Lewis acids (BF3ÆOEt2, Me3SiOTf). When
solid acids were used (except zinc salts), bromo-alkanol
in CH2Cl2 was added to a cooled mixture of sugar
acetate and a Lewis acid in CH2Cl2.
4.1.4. 8-Bromooctyl 2,3,4,6-tetra-O-acetyl-a-D-glucopyr-
anosyl-(1!4)-2,3,6-tri-O-acetyl-b-D-glucopyranoside (4b).
Compound 4b was prepared from 2 and 3b either using
(A) in 40% yield or (B) in 57% yield as a colorless oil:
23
½aꢁD +51.7 (c 1.2, CHCl3); Rf 0.38 (3:2 hexane–EtOAc);
4.1.2. General glycosylation procedure (B) using ZnCl2 as
promoter. To
FABMS (positive-ion, NBA) m/z (%) 851.2 ([M+Na]+,
a
mixture of sugar peracetate
6), 619.3 (14), 559.1 (7), 331.2 (20).
(0.30 mmol), bromo-1-alkanol (3, 0.4 mmol), and ZnCl2
(56 mg, 0.4 mmol, dried in vacuo at 110 ꢀC for 1 h
prior to use) with or without additive was added
toluene (4 mL), and the suspension was stirred at
60–65 ꢀC for 0.5–1 h. The reaction was quenched by
dilution with EtOAc (20 mL) and aq NaHCO3
(20 mL), and the mixture was worked up as described
in procedure (A).
4.1.5. 12-Bromododecyl 2,3,4,6-tetra-O-acetyl-b-D-gluco-
pyranoside (10a). Compound 10a was prepared from 9
and 3a either using (A) in 43% yield or (B) in 58% yield as
24
a colorless solid: mp 50–52 ꢀC; ½aꢁD ꢀ12.7 (c 2.2, CHCl3);
Rf 0.31 (3:1 hexane–EtOAc). Anal. Calcd for
C26H43BrO10: C, 52.44; H, 7.28. Found: C, 52.48; H,
7.17.

T. Murakami et al. / Carbohydrate Research 342 (2007) 1009–1020
1017
Table 5. 1H NMR chemical shifts (d in ppm) of acetylated disaccha-
Table 6. 13C NMR chemical shifts (d in ppm) of acetylated
ridesa in CDCl3
disaccharidesa in CDCl3
Maltoside
Lactoside
Maltoside
Lactoside
4a
4b
24a
24b
22a
22b
4a
4b
24a
24b
22a
22b
H-10
H-20
H-30
H-40
H-50
H-60a
H-60b
4.51
4.81
5.25
4.00
3.67
4.23
4.47
4.51
4.81
5.25
4.00
3.67
4.23
4.47
4.51
4.81
5.25
4.00
3.67
4.23
4.47
4.51
4.81
5.25
4.00
3.68
4.24
4.47
4.49
4.88
5.19
3.79
3.59
4.11
4.47
4.49
4.87
5.19
3.79
3.59
4.11
4.47
C-10
C-20
C-30
C-40
C-50
C-60
100.2
72.2
75.4
72.7
72.0
62.8
100.2 100.2
100.2
72.2
75.4
72.7
72.0
62.8
100.5
71.7
72.8
76.3
72.5
62.0
100.5
71.7
72.8
76.3
72.6
62.0
72.2
75.4
72.7
72.0
62.8
72.2
75.4
72.7
72.0
62.8
C-100
C-200
C-300
C-400
C-500
C-600
95.4
70.1
69.9
68.0
69.3
61.5
95.5
70.1
69.9
68.0
69.3
61.5
95.4
70.2
69.9
68.0
69.3
61.4
95.5
70.1
69.9
68.0
69.3
61.5
101.0
70.2
70.9
66.6
70.6
60.7
101.0
70.0
71.0
66.6
70.7
60.8
H-100
H-200
H-300
H-400
H-500
H-600a
H-600b
5.42
4.86
5.36
5.05
3.98
4.03
4.26
5.41
4.86
5.36
5.05
3.98
4.04
4.26
5.42
4.86
5.36
5.05
3.98
4.03
4.23
5.41
4.86
5.36
5.05
3.98
4.04
4.24
4.45
5.11
4.95
5.34
3.87
4.08
4.14
4.45
5.10
4.96
5.34
3.87
4.08
4.14
C-1
68.4
34.0
32.8
25.7
28.1
28.7
29.2
29.30
29.34
29.42
29.45
29.48
68.4
33.9
32.7
25.6
28.0
28.6
29.0
29.3
68.4
30.6
68.4
30.6
69.1
34.0
32.8
25.7
28.1
28.7
29.23
29.35c
29.44c
29.49
69.1
33.8
32.7
25.6
28.0
28.6
29.0
29.3
CH2–Xb
CH2–C–Br
C-3
H-1a
H-1b
2-H2
3-H2
CH2–C–Xb
CH2–Xb
Other CH2
Ac–S
3.47
3.84
1.85
1.41
1.55
3.41
1.26
3.47
3.84
1.84
1.42
1.55
3.40
1.30
3.47
3.85
1.55
1.33
1.55
2.86
1.25
2.32
3.46
3.84
1.55
1.33
1.55
2.85
1.28
2.32
3.45
3.82
1.85
1.42
1.54
3.41
1.26
3.45
3.82
1.85
1.42
1.55
3.40
1.30
25.7
28.7
29.0
29.1
29.2
29.3
29.38
29.43
29.48
25.7
28.6
28.96
29.04c
29.3
Other CH2
29.4
a Acetoxy proton signals (1.95–2.15 ppm) are not shown.
b X = Br or S.
O–C@O
S–C@O
169.3
169.5
169.9
170.2
170.4
169.4 169.4
169.5 169.5
169.9 169.9
170.2 170.2
170.4 170.4
169.4
169.5
169.9
170.2
170.4
169.0
169.5
169.8
170.0
170.1
169.0
169.5
169.7
169.9
170.0
4.1.6. 8-Bromooctyl 2,3,4,6-tetra-O-acetyl-b-D-glucopyr-
anoside (10b). Compound 10b was prepared from 9
and 3b either using (A) in 40% yield or (B) in 50% yield
170.5c 170.5c 170.5c 170.5c
170.28 170.22
170.32 170.25
24
as a colorless oil: ½aꢁD ꢀ14.2 (c 1.1, CHCl3); Rf 0.23 (3:1
hexane–EtOAc); FABMS (positive-ion, NBA) m/z 563
([M (for 81Br)+Na]+, 3), 561 ([M (for 79Br)+Na]+, 3),
331 (100).
196.0 196.0
a The methyl signal of acetyl group (20.4–21.0 ppm) is not shown.
b X = Br or S.
c Two carbons would overlap.
4.1.7. 12-Bromododecyl 2,3,4,6-tetra-O-acetyl-b-D-galacto-
pyranoside (19a). Compound 19a was prepared from
18 and 3a either using (A) in 53% yield or (B) in 54%
3a either using (A) in 40% yield or (B) in 51% yield as
24
a colorless oil: ½aꢁD ꢀ10.3 (c 2.7, CHCl3); Rf 0.35 (3:2
24
yield as a colorless oil: ½aꢁD ꢀ9.1 (c 2.75, CHCl3); Rf
hexane–EtOAc); FABMS (positive-ion, NBA) m/z (%)
0.31 (3:1 hexane–EtOAc); FABMS (positive-ion,
NBA) m/z (%) 619 ([M (for 81Br)+Na]+, 16), 617 ([M
(for 79Br)+Na]+, 16), 331 (100).
907.5 ([M+Na]+, 36), 619.3 (53), 559.2 (28), 331.0 (100).
4.1.10. 8-Bromooctyl 2,3,4,6-tetra-O-acetyl-b-D-galacto-
pyranosyl-(1!4)-2,3,6-tri-O-acetyl-b-D-glucopyranoside
(22b). Compound 22b was prepared from 21 and 3b
either using (A) in 42% yield or (B) in 45% yield as a col-
4.1.8. 8-Bromooctyl 2,3,4,6-tetra-O-acetyl-b-D-galacto-
pyranoside (19b). Compound 19b was prepared from
18 and 3b either using (A) in 60% yield or (B) in 64%
24
24
orless oil: ½aꢁD ꢀ10.8 (c 1.2, CHCl3); Rf 0.30 (3:2 hex-
yield as a colorless oil: ½aꢁD ꢀ9.0 (c 2.1, CHCl3); Rf
ane–EtOAc); FABMS (positive-ion, NBA) m/z (%)
851.4 ([M+Na]+, 18), 619.1 (33), 559.2 (34), 475.3 (35),
331.0 (100).
0.27 (3:1 hexane–EtOAc); CIHRMS m/z calcd for
C20H31BrO8 [MꢀAcOH]+: 478.1202 for 79Br and
480.1182 for 81Br. Found: 478.1076 and 480.1069. (M+
was not observed.)
4.1.11. 12-Bromododecyl 2,3,4,6-tetra-O-acetyl-a-D-
glucopyranoside (11a). Compound 11a was prepared
from 9 and 3a by using (A) (at rt for 20 h) in 54% yield
as a colorless oil: ½aꢁD +81.2 (c 2.4, CHCl3); Rf 0.37 (3:1
4.1.9. 12-Bromododecyl 2,3,4,6-tetra-O-acetyl-b-D-galac-
topyranosyl-(1!4)-2,3,6-tri-O-acetyl-b-D-glucopyrano-
side (22a). Compound 22a was prepared from 21 and
24

1018
T. Murakami et al. / Carbohydrate Research 342 (2007) 1009–1020
Table 7. 1H–1H coupling constant (J)a data for 12-bromododecyl per-
O-acetylglycosidesb
4.2. General procedure for the synthesis of x-acetyl-
thioalkyl per-O-acetylglycosides
10a
(b-Glc)
11a
(a-Glc)
19a
(b-Gal)
4a
(b-Mal)
22a
(b-Lac)
A
solution of x-bromoalkyl per-O-acetylglycoside
0
0
0
0
0
0
J1 ;2
8.1
9.5
9.5
9.8
2.4
3.9
10.3
9.5
10.3
2.2
7.8
10.5
3.4
<1
6.8
8.1
9.5
9.2
9.2
5.6
8.1
9.5
9.1
9.9
2.1
(0.20 mmol) and potassium thioacetate (0.60 mmol) in
N,N-dimethylformamide (1.5 mL) was stirred at rt for
2 h. The reaction mixture was diluted with 1:1 hexane–
EtOAc (10 mL) and H2O (10 mL), and the layers were
separated. The aqueous phase was extracted with 1:1
hexane–EtOAc (2 · 20 mL), and the combined organic
layers were dried over Na2SO4. Removal of the solvent
gave a residue that was purified by chromatography
eluting with 2:1!1.5:1 hexane–EtOAc to give the
x-acetylthioalkyl glycoside in high yield.
0
J2 ;3
0
J3 ;4
0
J4 ;5
0
J5 ;6 a
0
0
J5 ;6 b
4.6
12.2
4.4
12.3
6.6
11.2
2.7
12.2
5.0
12.2
0
J6 a;b
00 00
J1 ;2
00 00
J2 ;3
00 00
J3 ;4
00 00
J4 ;5
3.9
10.5
9.8
10.0
2.0
8.1
10.5
3.4
<1
6.8
00 00
J5 ;6 a
00 00
J5 ;6 b
5.4
6.6
4.2.1. 12-Acetylthiododecyl 2,3,4,6-tetra-O-acetyl-a-
D-glucopyranosyl-(1!4)-2,3,6-tri-O-acetyl-b-D-glucopyr-
anoside (24a). Compound 24a was prepared from 4a in
00
J6 a;b
12.2
11.2
J1a,1b
J1a,2
J1b,2
J11,12
9.8
6.7
6.3
7.0
9.8
6.7
6.6
6.8
9.8
6.7
6.3
7.0
9.8
6.6
6.3
6.8
9.8
6.8
6.1
6.8
25
95% yield as a colorless solid: mp 84–85 ꢀC; ½aꢁD +38.5
(c 1.4, CHCl3); Rf 0.41 (3:2 hexane–EtOAc). Anal. Calcd
for C40H62O19S: C, 54.73; H, 7.00; S, 3.56. Found: C,
54.66; H, 7.11; S, 3.65.
a J Values are given in hertz in CDCl3.
b Coupling constants for the sugar protons of 8-bromooctyl, 12-acet-
ylthiododecyl, and 8-acetylthiooctyl per-O-acetylglycosides are
almost the same as these values.
4.2.2. 8-Acetylthiooctyl 2,3,4,6-tetra-O-acetyl-a-D-gluco-
pyranosyl-(1!4)-2,3,6-tri-O-acetyl-b-D-glucopyranoside
(24b). Compound 24b was prepared from 4b in 96%
Table 8. 13C NMR chemical shift (d)a data for x-mercaptoalkyl
glycosides
25
yield as a colorless solid: mp 56–58 ꢀC; ½aꢁD +51.4 (c
1a
1b
27a
27b
28
2.0, CHCl3); Rf 0.35 (3:2 hexane–EtOAc); FABMS
(positive-ion, NBA) m/z (%) 845.3 ([M+Na]+, 70),
619.2 (44), 559.1 (29), 331.2 (100).
C-10
C-20
C-30
C-40
C-50
C-60
102.6
72.9
76.0
79.4
74.8
61.1
102.6
72.9
76.0
79.3
74.7
61.0
102.7
73.4
76.2
70.2
75.6
61.7
102.8
73.4
76.3
70.4
75.6
61.5
98.5
71.4
74.0
69.3
71.8
61.1
4.2.3. 12-Acetylthiododecyl 2,3,4,6-tetra-O-acetyl-b-D-
glucopyranoside (25a). Compound 25a was prepared
from 10a in 97% yield as a colorless solid: mp 56–
C-100
C-200
C-300
C-400
C-500
C-600
101.3
72.3
73.5
70.3
73.1
60.8
101.3
72.2
73.4
70.2
73.0
60.8
25
58 ꢀC; ½aꢁD ꢀ12.7 (c 2.2, CHCl3); Rf 0.27 (3:1 hexane–
EtOAc). Anal. Calcd for C28H46O11S: C, 56.93; H,
7.85; S, 5.43. Found: C, 57.28; H, 7.77; S, 5.39.
4.2.4. 8-Acetylthiooctyl 2,3,4,6-tetra-O-acetyl-b-D-gluco-
pyranoside (25b). Compound 25b was prepared from
C-1
C-3
69.5
25.8
24.5
24.3
33.89
33.86
28.2
69.4
25.7
24.4
24.3
33.80
33.77
28.1
28.9
29.2
29.4
70.0
25.7
24.4
24.3
33.85
33.82
28.2
69.4
25.8
24.6
24.5
33.99
33.96
28.3
29.1
29.4
29.6
68.4
26.0
24.6
24.4
33.95
33.92
28.3
25
10b in 95% yield as a colorless oil: ½aꢁD ꢀ13.0 (c 1.8,
CH2–SH
CH2–SD
CH2–C–SH
CH2–C–SD
Other CH2
CHCl3); Rf 0.20 (3:1 hexane–EtOAc); CIHRMS m/z
calcd for C28H46O11S (M+): 534.2135. Found: 534.2122.
4.2.5. 12-Acetylthiododecyl 2,3,4,6-tetra-O-acetyl-a-D-
glucopyranoside (26). Compound 26 was prepared from
28.9
28.9
29.0
29.40b
29.46
29.50c
29.28
29.32
29.39c
29.47
29.36
29.40
29.44
29.50
29.52
29.54
25
11a in 94% yield as a colorless oil: ½aꢁD +91.4 (c 3.5,
CHCl3); Rf 0.34 (3:1 hexane–EtOAc); CIHRMS m/z
calcd for C28H46O11S (M+): 590.2761. Found: 590.2848.
4.3. General procedure for the synthesis of x-mercapto-
alkyl glycosides
a d Values are reported in ppm for solution in 10:1 CDCl3–CD3OD.
b Two carbons would overlap.
c Three carbons would overlap.
To a stirred solution of the thioacetate (0.20 mmol) in
MeOH (1 mL) and CH2Cl2 (2 mL) was added 3.0%
solution of NaOMe in MeOH (0.5 mL, 0.25 mmol),
hexane–EtOAc); FABMS (positive-ion, NBA) calcd for
C26H43BrO10: 595.52. Found 618.5 [M+Na]+.

T. Murakami et al. / Carbohydrate Research 342 (2007) 1009–1020
1019
24
and the mixture was stirred for 2 h at 5–10 ꢀC. HOAc
(50 mg) was added and the solvent was removed. The
residue was purified by silica gel column chromatogra-
phy, eluting with 5:1!4:1 CH2Cl2–MeOH for maltoside
derivatives, or with 9:1!8:1 CH2Cl2–MeOH for gluco-
side derivatives, to afford the glycolipid.
79 ꢀC; ½aꢁD +77.4 (c 0.64, CHCl3); Rf 0.36 (8:1
CH2Cl2–MeOH); 1H NMR (CDCl3–CD3OD): d 1.27
(s-like, 14H), 1.36 (m, 2H), 1.61 (m, 4H), 2.51 (t, 2H,
J 7.2 Hz, CH2S), 3.44 (dt, 1H, J1a,1b 9.8, J1a,2 6.8 Hz,
H-1a), 3.52 (m, 3H, H-20,30,40), 3.66 (dt, 1H, J1a,1b 9.8,
J1b,2 7.0 Hz, H-1b), 3.72 (m, 1H, H-50), 3.75 (dd, 1H,
J5 ;6 a 2:0, J6 a;6 b 12:0 Hz, H-60a), 3.87 (dd, 1H,
0
0
0
0
J5 ;6 b 2:8, J6 a;6 b 12:1 Hz, H-60b), 4.84 (d, 1H,
0
0
0
0
4.3.1. 12-Mercaptododecyl a-D-glucopyranosyl-(1!4)-b-
D-glucopyranoside (1a). From 24a (142 mg, 0.16 mmol)
the title compound was obtained (73 mg, 84%) as a col-
J1 ;2 3:7 Hz, H-10). Anal. Calcd for C18H36O6S: C,
0
0
56.81; H, 9.54; S, 8.43. Found: C, 56.95; H, 9.48; S, 8.35.
23
orless solid: mp ca. 100 ꢀC; ½aꢁD +44.5 (c 1.30, CHCl3–
MeOH); Rf 0.32 (4:1 CH2Cl2–MeOH); 1H NMR
(CDCl3–CD3OD): d 1.27 (s, 14H), 1.37 (m, 2H), 1.61
(m, 4H), 2.51 (t, 2H, J 7.2 Hz, CH2S), 3.36 (m, 4H),
3.48–3.75 (m, 6H), 3.85 (m, 4H), 4.29 (d, 1H,
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J1 ;2 7:6 Hz, H-10), 5.20 (d, 1H, J1 ;2 3:2 Hz, H-100);
CIHRMS m/z calcd for C24H46O11S (M+): 542.2761.
Found: 542.2774.
0
0
00 00
4.3.2. 8-Mercaptooctyl a-D-glucopyranosyl-(1!4)-b-D-
glucopyranoside (1b). From 24b (74 mg, 0.09 mmol)
the title compound was obtained (36 mg, 82%) as a col-
24
orless syrup: ½aꢁD +60.8 (c 0.72, CHCl3–MeOH); Rf 0.28
(4:1 CH2Cl2–MeOH); 1H NMR (CDCl3–CD3OD): d
1.32 (m, 8H), 1.60 (m, 4H), 2.51 (t, 2H, J 7.1 Hz,
´
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CH2S), 3.25–3.95 (m, 14H), 4.29 (d, 1H, J1 ;2 7:3 Hz,
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´
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4.3.3. 12-Mercaptododecyl b-D-glucopyranoside (27a).
From 25a (178 mg, 0.30 mmol) the title compound was
obtained (96 mg, 84%) as a colorless solid: mp 82–
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24
85 ꢀC; ½aꢁD ꢀ25.0 (c 1.45, CHCl3); Rf 0.36 (8:1
CH2Cl2–MeOH); 1H NMR (CDCl3–CD3OD): d 1.27
(14H, s), 1.33 (t, 0.3H, J 7.7 Hz), 1.37 (m, 2H), 1.61
(m, 4H), 2.51 (t, 2H, J 7.1 Hz, CH2S), 3.28 (m, 2H),
3.46 (m, 2H), 3.54 (dt, 1H, J1a,1b 9.3, J1a,2 7.1 Hz, H-
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0
0
4.3.4. 8-Mercaptooctyl b-D-glucopyranoside (27b). From
25b (70 mg, 0.13 mmol), the title compound was ob-
24
tained (35 mg, 83%) as a colorless syrup: ½aꢁD ꢀ31.5 (c
1
1.3, CHCl3); Rf 0.32 (8:1 CH2Cl2–MeOH); H NMR
(CDCl3–CD3OD): d 1.32 (m, 8H), 1.61 (m, 4H), 2.51
(t, 2H, J 7.1 Hz, CH2S), 3.31 (m, 2H), 3.52 (m, 3H),
3.84 (m, 3H), 4.29 (d, 1H, J1 ;2 7:6 Hz, H-1 ); CIHRMS
m/z calcd for C14H28O6S (M+): 324.1607. Found:
324.1634.
0
0
0
4.3.5. 12-Mercaptododecyl a-D-glucopyranoside (28).
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