Introduction of monosaccharides having functional groups onto a carbosilane dendrimer: A broadly applicable one-pot reaction in liquid ammonia involving Birch reduction and subsequent Sn2 reaction

Article abstract of DOI:10.1016/S0008-6215(00)00247-0

Benzylthioalkyl glycosides of D-glucuronic acid, N-acetyl-D-glucosamine, and N-acetylneuraminic acid (common monosaccharide constituents of natural oligosaccharide chains) have been prepared as sulfide precursors for the carbohydrate coating of dendric carbosilane cores and used in a generally applicable one-pot reaction (Birch reduction in liquid ammonia and subsequent Sn2 reaction) to generate a thioether linkage between the monosaccharide moieties and a carbosilane dendrimer. The dendrimers were uniformly functionalized with the monosaccharides in good yields.

Full text of DOI:10.1016/S0008-6215(00)00247-0

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Carbohydrate Research 329 (2000) 765–772
Introduction of monosaccharides having functional
groups onto a carbosilane dendrimer: A broadly
applicable one-pot reaction in liquid ammonia involving
Birch reduction and subsequent S
2 reactionꢀ
N
Koji Matsuoka a,*, Hidehiro Kurosawa a, Yasuaki Esumi b, Daiyo Terunuma a,
Hiroyoshi Kuzuhara a
aDepartment of Functional Materials Science, Faculty of Engineering, Saitama Uni6ersity, Urawa,
Saitama 338-8570, Japan
bThe Institute of Physical and Chemical Research (RIKEN), Wako, Saitama 351-0198, Japan
Received 14 June 2000; accepted 6 August 2000
Abstract
Benzylthioalkyl glycosides of
D
-glucuronic acid, N-acetyl-D-glucosamine, and N-acetylneuraminic acid (common
monosaccharide constituents of natural oligosaccharide chains) have been prepared as sulfide precursors for the
carbohydrate coating of dendric carbosilane cores and used in a generally applicable one-pot reaction (Birch
reduction in liquid ammonia and subsequent SN2 reaction) to generate a thioether linkage between the monosaccha-
ride moieties and a carbosilane dendrimer. The dendrimers were uniformly functionalized with the monosaccharides
in good yields. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: Carbosilane dendrimers; Glycodendrimers; Birch reduction; Sulfides; SN2 reaction
sized and investigated [3]. We have also
reported a novel class of glycodendrimers us-
ing carbosilane dendrimers as the core struc-
tures [4,5]. For the construction of carbosilane
dendrimers uniformly functionalized with car-
bohydrate moieties, as shown in Fig. 1, a
successful one-pot coupling procedure be-
tween the carbohydrate moieties and carbosi-
lane dendrimers was developed. The method
utilizes Birch reduction [Na in liquid ammonia
(liquid NH3)] of benzyl-thioether-functional-
ized carbohydrate precursors and the subse-
1. Introduction
The sugar clustering effect is well-known as
a phenomenon, originally reported by Lee [1],
that can enhance the weak individual interac-
tions between carbohydrates and proteins. For
example, Lee synthesized cluster glycosides
from aminotris(hydroxymethyl)methane as the
core for investigation of such interactions [2].
Recently a number of glycodendrimers in-
tended for similar purposes have been synthe-
ꢀ Part 4. Glyco-silicon functional materials. For Part 3, see
Ref. [4b].
* Corresponding author. Fax: +81-48-8583099.
E-mail address: koji@fms.saitama-u.ac.jp (K. Matsuoka).
quent S 2 replacement of v-bromo groups in
N
dendric carbosilane scaffolds [4,5]. In our pre-
vious study, this procedure was used exclu-
0008-6215/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(00)00247-0

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K. Matsuoka et al. / Carbohydrate Research 329 (2000) 765–772
sively to attach bioactive oligosaccharides
having only hydroxyl groups (neutral sugars)
such as b-cyclodextrin and a globotriaosyl
moiety. We have since directed our attention
toward the feasibility of a one-pot reaction for
other saccharides having such functional
groups as carboxyl or acetamido groups.
In this study, we demonstrate the broad
applicability of a one-pot reaction for con-
structing carbosilane dendrimers uniformly
smoothly in the presence of NaOH, giving the
corresponding carboxylate anion, which was
converted in 95% yield into 5 by the removal
of Na cations by using ion exchange resin
(H+).
Since the preparation of the GlcA derivative
5 had been accomplished, we turned our at-
tention to preparation of the 3-(benzyl-
thio)propyl glycoside 8 of GlcNAc. For this
purpose, the allyl glycoside 6 [7a] was allowed
to react with a-toluenethiol in the presence of
a radical initiator to provide the crystalline
sulfide 7 in 98% yield. The transesterification
of the acetate 7 was carried out in methanolic
sodium methanoate at room temperature to
give 8 in 99% yield.
coated with
D
-glucuronic acid, N-acetyl- -glu-
D
cosamine, or N-acetylneuraminic acid (Fig. 1).
2. Results and discussion
Finally, we examined the preparation of a
benzylthioalkyl glycoside sialic acid (which
contains a carboxylic acid and an N-acetyl
group). Thus, the known 9 was prepared as
the starting material by the method previously
reported [8]. Addition of a benzylsulfide moi-
ety by a radical reaction to the allyl function
of 9 also proceeded efficiently in an anti-
Markovnikov’s manner to afford 10 in 96%
yield. Conventional O-de-acetylation gave the
tetrol 11 in 78% yield, which was further
treated with aqueous NaOH to produce the
benzylthioalkyl glycoside 12 of sialic acid
quantitatively (Scheme 1).
To construct a carbosilane dendrimer func-
tionalized with monosaccharides having a car-
boxyl group, the glucuronic acid derivative 5
was selected for the first test case. Thus, the
known trityl glucoside 1 [6] was converted in
52% yield into its carboxymethyl derivative 2
via the in situ O-de-tritylation followed by
Jones oxidation (CrO3) in a one-pot proce-
dure. The convenient introduction of a sulfide
function into an alkenyl group has been re-
ported by several groups via radical addition
[7]. Thus, the radical addition of a-
toluenethiol to the CꢀC double bond of the
aglycon of 2 was performed in 1,3-dioxolane
in the presence of AIBN as the radical initia-
tor to afford the 3-(benzylthio)propyl gly-
coside 3 in an anti-Markovnikov’s manner in
almost quantitative yield. The structure of the
Given the success of the preparation of
3-(benzylthio)propyl glycosides 5, 8, and 12,
we proceeded to add these derivatives to the
carbosilane dendrimer 13 [5] to produce sugar
clusters. We have recently reported a simple
and convenient method, namely, a one-pot
reaction in liquid NH3 for Birch reduction and
1
sulfide 3 was confirmed by both its H NMR
spectrum and elemental analysis. Zemple´n O-
deacetylation of 3 gave 4 in 69% yield after
purification on a column of silica gel. Sapon-
ification of the methyl ester 4 proceeded
subsequent S 2 reaction producing thioether
N
linkages, for the construction of a carbosilane
dendrimer functionalized with b-cyclodextrin
and globotriaose moieties (sugar residues lack-
ing additional functional groups). In order to
examine the broader applicability of the one-
pot reaction, the 3-benzylthiopropyl gly-
cosides of 5, 8, and 12 were tested. The Birch
reductive removal of the benzyl group of gly-
coside 5 was performed in liquid NH3 in the
presence of Na, generating the thiolate anion
in situ. After neutralization of the excess Na
by the addition of NH4Cl, the thiolate anion
was allowed to react with the dendrimer 13
Fig. 1. An example of a carbosilane dendrimer uniformly
functionalized with sugar moieties.

K. Matsuoka et al. / Carbohydrate Research 329 (2000) 765–772
767
Scheme 1. Reagents and conditions: (i) Jones oxidation, then CH2N2, Et2O; (ii) a-toluenethiol, AIBN, 1,4-dioxane, 50“80 °C;
(iii) NaOMe, MeOH, rt; (iv) 1 M aq NaOH; (v) 0.05 M aq NaOH.
carrying a bromine atom at its v-positions to
provide crude products. Purification by gel
filtration for removal of the by-products, in-
cluding incompletely reacted compounds, gave
coupling reaction. In a second trial, the cou-
pled product 16 was obtained as acetate show-
ing a molecular ion peak by FABMS at m/z
3838 (Scheme 2).
In conclusion, we have demonstrated the
feasibility of a one-pot reaction in liquid NH3
the carbosilane dendrimer 14 having six -glu-
D
curonic acid moieties in 64% yield based on
13, and which had the expected molecular-ion
peak (m/z 2076). The benzyl sulfide 8 was also
treated with dendrimer 13 by the method de-
scribed for the preparation of 14 to afford a
coupled product. Unfortunately, the crude
product was found to be a mixture, including
N-de-acetylated moieties that gave a positive
ninhydrin test for the amino function. There-
fore, an N-selective acetylation of the amino
function of the product was carried out in
MeOH, followed by gel filtration to give the
corresponding O-de-acetylated glycoden-
drimer, accompanied by some impurities.
Next, the crude O-de-acetylated 15 was acetyl-
ated completely to provide the corresponding
dendrimer 15 having six per-O-acetylated N-
for Birch reduction and the subsequent S 2
N
replacement to construct carbosilane den-
drimers bearing three kinds of monosacchar-
ide derivatives containing carboxylic acid and
amide functional groups. Further applications
of this procedure for assembling complex
oligosaccharides, using a series of carbosilane
dendrimers as the core frame, are now under
way.
3. Experimental
Materials and methods.—Unless otherwise
stated, all commercially available solvents and
reagents were used without further purifica-
tion. Pyridine, 1,4-dioxane, and tetrahydro-
furan (THF) were stored over molecular sieves
acetyl- -glucosamine moieties in 46% yield,
D
based on 13; it showed the expected molecular
ion peak at m/z 2973.
,
(4 A MS), and methanol (MeOH) was stored
,
An initial trial coupling of 12 with 13, using
the same conditions as those described for 15,
was carried out. Unfortunately, pure 16 was
not obtained because of difficulties in removal
of impurities. As the impurity seemed to con-
sist of incompletely coupled products, the sto-
ichiometric ratio of 12:13 was raised to 18:1 in
over 3 A MS before use. Melting points
were measured with a Laboratory Devices
Meltemp II apparatus and were uncorrected.
The optical rotations were determined with a
Jasco DIP-1000 digital polarimeter. The IR
spectra were obtained using a Jasco FT/IR-
300E spectrophotometer. The H NMR spec-
tra were recorded at 400 MHz with a Bruker
1
order to enhance the efficiency of the S
N
2

768
K. Matsuoka et al. / Carbohydrate Research 329 (2000) 765–772
AM-400 or at 200 MHz with a Varian Gem-
ini-2000 spectrometer in chloroform-d or D2O.
Tetramethylsilane (Me4Si) and MeOH (3.3
ppm) were used as internal standards. Ring-
proton assignments in NMR were made by
first-order analysis of the spectra and were
supported by the results of homonuclear de-
coupling experiments. Elemental analyses
were performed with a Fisons EA1108 instru-
ment on samples extensively dried at 50–
60 °C over P2O5 for 4–5 h. Fast atom
bombardment mass (FABMS) spectra were
recorded with a Joel JMS-HX110 spectrome-
ter. Reactions were monitored by thin-layer
chromatography (TLC) on precoated plates of
Silica Gel 60F254 (layer thickness, 0.25 mm; E.
Merck, Darmmstadt, Germany). For detec-
tion of the intermediates, TLC sheets were
sprayed with (a) a solution of 85:10:5 (v/v/v)
MeOH–p-anisaldehyde–H2SO4, and heated
for a few minutes (for carbohydrate) or (b) an
aqueous solution of 5 wt% KMnO4 and
heated similarly (for CꢀC double bond).
Column chromatography was performed on
silica gel (Silica Gel 60; 63–200 mm, E.
Merck). Flash column chromatography was
performed on silica gel (Silica Gel 60, spheri-
cal neutral; 40–100 mm, E. Merck). All extrac-
tions were conducted below 45 °C under
diminished pressure.
Methyl (allyl 2,3,4-tri-O-acetyl-i- -glu-
D
copyranosid)uronate (2) [9].—To a solution of
the known allyl 2,3,4-tri-O-acetyl-6-O-trityl-b-
D-glucopyranoside (1, 5.00 g, 8.49 mmol) [6]
in acetone (100 mL) was added a solution of
CrO3 (17.0 g, 170 mmol) in 3.5 M aq H2SO4
(23 mL) at 0 °C, and the mixture was kept
warm at rt for 50 min. When TLC indicated
the complete conversion of 1, the resultant
mixture was poured into ice–water and ex-
tracted with CHCl3. The organic solution was
washed with brine, dried (NaSO4), and evapo-
rated. The residual syrup was dissolved in
CH2Cl2 (100 mL), and the solution was
treated with ethereal CH2N2. Conventional
work-up gave 2 (1.65 g, 51.9%) after crystal-
lization from 2-propanol; mp 136–137 °C; IR
(KBr) 2952 (wCꢁH), 1758 (wCꢀO) cm−1
;
1H
NMR (400 MHz, CDCl3) l 2.02 (s, 6 H, 2
Ac), 2.05 (s, 3 H, Ac), 3.76 (s, 3 H, Me), 4.04
(m, 1 H, H-5), 4.24 (m, 2 H, OCH2), 4.61 (d,
1 H, J1,2 7.6 Hz, H-1), 5.04 (m, 1 H, H-2), 5.45
Scheme 2. The one-pot reaction, reagents and conditions: (i) Na; (ii) NH4Cl; (iii) acetylation; (vi) CH2N2, ether.

K. Matsuoka et al. / Carbohydrate Research 329 (2000) 765–772
769
3-Benzylthiopropyl
i-
D
-glucopyranosyl-
(m, 4 H, H-3, H-4, ꢀCH2), 5.84 (m, 1 H, CHꢀ).
Methyl (3-benzythiopropyl 2,3,4-tri-O-ace-
uronic acid (5).—A solution of methyl ester 4
(389 mg, 1.04 mmol) in 1 M aq NaOH (5 mL)
was stirred for 15 min at rt. To the solution
was added an IR-120B (H+) resin to remove
Na+, and the suspension was filtered and
concentrated to give 5 (354 mg, 94.7%) as an
amorphous solid, [h]2D7 −33.4° (c 1.13,
MeOH); IR (KBr) 3304 (wOꢁH), 2923 (wCꢁH),
tyl-i-D
-glucopyranosid)uronate (3).—To
a
stirred solution of 2 (102 mg, 0.272 mmol) and
a-toluenethiol (479 mL, 4.08 mmol) in 1,4-
dioxane (0.5 mL) was added 2,2%-azobisisobu-
tyronitrile (AIBN; 22.3 mg, 0.136 mmol) at
50 °C under an Ar atmosphere. The mixture
was stirred for 1.5 h at 80 °C at which time
cyclohexene (413 mL, 40.8 mmol) was added,
and the mixture was stirred at rt for 15 min.
After evaporation, silica gel chromatography
of the residual syrup (8:1 (v/v) toluene–
EtOAc) yielded sulfide 3 (134 mg, 98.5%) as
crystals: mp 75–77 °C, [h]2D8 −16.6° (c 0.44,
1741 (wCꢀO) cm−1
;
1H NMR (400 MHz,
Me2SO-d6 with D2O) l 1.74 (m, 2 H, CH2),
2.46 (t, 2 H, J 7.2 Hz, SCH2), 2.95 (t, 1 H, J2,3
8.6 Hz, H-2), 3.15 (t, 1 H, H-3), 3.26 (t, 1 H,
J3,4 9.3, J4,5 9.4 Hz, H-4), 3.70 (s, 2 H, CH2Ph),
4.18 (d, 1 H, J1,2 7.8 Hz, H-1), 7.22–7.30 (m,
5 H, Ph). Anal. Calcd for C16H22O7S·0.2 H2O:
C, 53.08; H, 6.24. Found: C, 53.09; H, 6.17.
3-Benzylthiopropyl 2-acetamido-3,4,6-tri-O-
CHCl3); IR (neat) 2951 (wCꢁH), 1755 (wCꢀO
)
cm−1; 1H NMR (400 MHz, CDCl3) l 1.82 (m,
2 H, CH2), 2.00, 2.02, 2.02 (each s, 9 H, 3 Ac),
2.46 (t, 2 H, J 7.1 Hz, SCH2), 3.68 (s, 3 H,
Me), 3.74 (s, 2 H, CH2Ph), 3.76 (m, 2 H,
OCH2), 4.02 (d, 1 H, J4,5 9.4 Hz, H-5), 4.51 (d,
1 H, J1,2 7.8 Hz, H-1), 4.98 (dd, 1 H, J2,3 9.2
Hz, H-2), 5.21 (t, 1 H, J3,4 9.3 Hz, H-4), 5.24
(t, 1 H, H-3), 7.22–7.33 (m, 5 H, Ph). Anal.
Calcd for C23H30O10S: C, 55.41; H, 6.07.
Found: C, 55.67; H, 6.06.
acetyl-2-deoxy-i-
lyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-b-
-glucopyranoside (6) (1.30 g, 3.36 mmol) [7a]
D-glucopyranoside (7).—Al-
D
was treated with a-toluenethiol (5.91 mL, 50.3
mmol) in the same way as that previously
described for the preparation of 3 to afford
white crystalline 7 (1.68 g, 97.8%), mp 136–
137 °C, [h]2D8 −1.77° (c 0.55, CHCl3); IR
Methyl (3-benzylthiopropyl i- -glucopyran-
D
(KBr) 2922 (wCꢁH), 1742 (wCꢀO), 1663 (wC1ꢀO
;
osid)uronate (4).—A solution of acetate 3
(1.60 g, 3.21 mmol) in MeOH was treated with
NaOMe (52.0 mg, 0.962 mmol) at rt under an
Ar atmosphere for 2 h, and then additional
NaOMe (17.3 mg, 0.322 mmol) was added.
After 1 h of stirring at rt, when TLC indicated
the complete conversion of 3, the reaction
mixture was neutralized with IR-120B (H+)
resin until pH 7 and then filtered. The filtrate
was concentrated and the residue was sub-
jected to column chromatography on silica gel
with 10:1 (v/v) CHCl3–MeOH to afford pure
4 (824 mg, 69.0%) as a colorless syrup, [h]D28
−30.0° (c 0.43, MeOH); IR (neat) 3399 (wOꢁH),
amide I), 1538 (lNꢁH; amide II) cm−1; H
NMR (200 MHz, CDCl3) l 1.83 (m, 2 H,
CH2), 1.90 (s, 3 H, NAc), 2.03, 2.03, 2.08
(each s, 9 H, 3 Ac), 2.48 (t, 2 H, J 7.4 Hz,
SCH2), 3.69 (s, 2 H, CH2Ph), 4.12 (dd, 1 H,
J5,6a 2.6, J6a,6b 12.4 Hz, H-6a), 4.23 (dd, 1 H,
J5,6b 4.8 Hz, H-6b), 4.58 (d, 1 H, J1,2 8.2 Hz,
H-1), 5.06 (t, 1 H, J3,4 9.4, J4,5 9.6 Hz, H-4),
5.24 (t, 1 H, J2,3 10.6 Hz, H-3), 5.41 (d, 1 H,
J2,NH 8.8 Hz, NH), 7.22–7.34 (m, 5 H, Ph).
Anal. Calcd for C24H33O9NS: C, 56.35; H,
6.50; N, 2.74. Found: C, 56.60; H, 6.50; N,
2.74.
1
2917 (wCꢁH), 1746 (wCꢀO) cm−1; H NMR (400
3-Benzylthiopropyl 2-acetamido-2-deoxy-i-
-glucopyranoside (8).—A solution of acetate
D
MHz, Me2SO-d6 with D2O) l 1.71 (m, 2 H,
CH2), 2.42 (t, 2 H, J 7.2 Hz, SCH2), 2.99 (t, 1
H, H-2), 3.21 (t, 1 H, J2,3 9.0 Hz, H-3), 3.31 (t,
1 H, J3,4 9.3 Hz, H-4), 3.58 (m, 2 H, OCH2),
3.62 (s, 3 H, Me), 3.65 (s, 2 H, CH2Ph), 3.74
(d, 1 H, J4,5 9.7 Hz, H-5), 4.22 (d, 1 H, J1,2 7.8
Hz, H-1), 7.18–7.30 (m, 5 H, Ph). Anal. Calcd
for C17H24O7S·0.5 H2O: C, 53.53; H, 6.61.
Found: C, 53.70; H, 6.58.
7 (1.50 g, 2.93 mmol) in MeOH (30 mL) was
treated with NaOMe (47.5 mg, 0.88 mmol) at
rt for 1.5 h under an Ar atmosphere. To the
resulting mixture was added IR-120B (H+)
resin for neutralization, and then the mixture
was filtered. The filtrate was evaporated in
vacuo to give 8 (1.12 g, 99.0%) as white
crystals, mp 160–162 °C, [h]2D7 −23.8° (c 0.99,

770
K. Matsuoka et al. / Carbohydrate Research 329 (2000) 765–772
1
amide I), 1561 (lNꢁH; amide II) cm−1; H
NMR (200 MHz, Me2SO-d6 with D2O) l 1.52
(t, 1 H, J3ax,3eq =J3ax,4 11.8 Hz, H-3ax), 1.64
(m, 2 H, OCH2CH2), 1.84 (s, 3 H, NAc), 2.34
(t, 2 H, J 7.1 Hz, SCH2), 2.46 (dd, 1 H, J3eq,4
1\Hz, H-3eq), 3.63 (s, 2 H, CH2Ph), 3.68 (s,
3 H, Me), 7.19–7.28 (m, 5 H, Ph). Anal.
Calcd for C22H33O9NS: C, 54.20; H, 6.82; N,
2.87. Found: C, 54.24; H, 6.86; N, 2.80.
Me2SO); IR (KBr) 3277 (wOꢁH), 2921 (wCꢁH),
1653 (wCꢀO; amide I), 1550 (lNꢁH; amide II)
1
cm−1; H NMR (200 MHz, CD3OD) l 1.76
(m, 2 H, CH2), 1.94 (s, 3 H, NAc), 2.47 (t, 2
H, J 7.2 Hz, SCH2), 3.70 (s, 2 H, CH2Ph),
4.36 (d, 1 H, J1,2 8.2 Hz, H-1), 7.24–7.30 (m,
5 H, Ph). Anal. Calcd for C18H27O6NS·0.5
H2O: C, 54.80; H, 7.15; N, 3.55. Found: C,
55.05; H, 7.17; N, 3.51.
3 - Benzylthiopropyl 5 - acetamido - 4,7,8,9-
3-Benzylthiopropyl5-acetamido-3,5-dideoxy-
tetra-O-acetyl-3,5-dideoxy-i-
D
-glycero-
D-
h-
D
-glycero- -galacto-2-nonulopyranosonic
D
galacto-2-nonulopyranosonic acid methyl ester
(10).—Allyl 5-acetamido-4,7,8,9-tetra-O-ace-
acid (12).—A solution of methyl ester 11 (796
mg, 1.63 mmol) in 0.05 M aq NaOH (80 mL)
was stirred at rt for 1 h, at which time an
IR-120B (H+) resin was added to the mixture.
After filtration, the filtrate was concentrated
in vacuo to give amorphous 12 in quantitative
yield, [h]2D3 −18.6° (c 1.12, Me2SO); IR (KBr)
3415 (wOꢁH), 2933 (wCꢁH), 1635 (wCꢀO; amide I),
tyl-3,5-dideoxy-b-
D
-glycero- -galacto-2-nonu-
D
lopyranosonic acid methyl ester (9) (1.30 g,
2.45 mmol) [8] was allowed to react with
a-toluenethiol (4.31 mL, 36.7 mmol) in the
same way as described for the preparation of
3 to afford amorphous 10 (1.54 g, 96.2%),
[h]2D7 −20.6° (c 1.56, CHCl3); IR (KBr) 2959
(wCꢁH), 1748 (wCꢀO), 1660 (wCꢀO; amide I), 1549
1
1562 (lNꢁH; amide II) cm−1; H NMR (400
MHz, D2O) l 1.60 (t, 1 H, J3ax,3eq =J3ax,4 12
Hz, H-3ax), 1.79 (m, 2 H, OCH2CH2), 2.00 (s,
3 H, NAc), 2.50 (t, 2 H, J 7.3 Hz, SCH2), 2.69
(dd, 1 H, J3eq,4 4.7 Hz, H-3eq), 3.74 (s, 2 H,
CH2Ph), 7.28–7.39 (m, 5 H, Ph). Anal. Calcd
for C21H31O9NS·0.7 H2O: C, 51.88; H, 6.72;
N, 2.88. Found: C, 51.84; H, 6.64; N, 2.89.
1
(lNꢁH; amide II) cm−1; H NMR (400 MHz,
CDCl3) l 1.80 (m, 2 H, OCH2CH2), 1.88 (s, 3
H, NAc), 1.93 (dd, 1 H, J3ax,3eq 12.8, J3ax,4 12.4
Hz, H-3ax), 2.03, 2.04, 2.12, 2.15 (each s, 12
H, 4 Ac), 2.48 (t, 2 H, J 7.2 Hz, SCH2), 2.56
(dd, 1 H, J3eq,4 4.6 Hz, H-3eq), 3.56 (m, 2 H,
OCH2), 3.70 (s, 2 H, CH2Ph), 3.77 (s, 3 H,
Me), 4.06 (q, 1 H, H-5), 4.09 (dd, 1 H, J8,9b
5.5, J9a,9b 12.5 Hz, H-9b), 4.11 (dd, 1 H, J5,6
10.6, J6,7 2.2 Hz, H-6), 4.30 (dd, 1 H, J8,9a 2.7
Hz, H-9a), 4.84 (ddd, 1 H, J4,5 9.8 Hz, H-4),
5.17 (d, 1 H, J5,NH 9.6 Hz, NH), 5.32 (dd, 1 H,
J7,8 8.4 Hz, H-7), 5.40 (ddd, 1 H, H-8), 7.15–
Carbosilane dendrimer carrying six
D
-glu-
curonic acid moieties (14).—To a stirred solu-
tion of 5 (229 mg, 0.639 mmol) in liquid NH3
(ꢀ30 mL) was added Na (147 mg, 6.39
mmol) at −30 °C, and the mixture was
stirred for 1 h. The stirred mixture was treated
with NH4Cl (273 mg, 5.11 mmol) for 10 min,
and then a solution of bis[(3-bromopropyl-
silyl)propyl]dimethylsilane (13) (53 mg, 57
mmol) [5] in THF (2 mL) was added dropwise.
The mixture was stirred overnight and then
evaporated to dryness. The residue was
purified by Sephadex G-25 with 5% aq AcOH
as an eluent to give 14 (80 mg, 64.0%) as an
amorphous solid. An analytical sample was
treated with IR-120B (H+) resin for 20 min at
rt. After filtration, the filtrate was lyophilized
to give pure 14 as white powder, [h]2D2 −36.4°
(c 0.98, water); IR (KBr) 3377 (wOꢁH), 2913
(wCꢁH), 1732 (wCꢀO) cm−1; 1H NMR (400 MHz,
D2O) l −0.05 (s, 6 H, 2 Me), 0.65 (m, 20 H,
10 SiCH2), 1.37 (m, 4 H, 2 CH2), 1.61 (m, 12
H, 6 CH2), 1.93 (m, 12 H, 6 CH2), 2.61 (m, 24
H, 12 SCH2), 3.39 (t, 6 H, J2,3 8.5 Hz, H-2),
7.33 (m,
5
H, Ph). Anal. Calcd for
C30H41O13NS: C, 54.95; H, 6.30; N, 2.14.
Found: C, 54.91; H, 6.29; N, 2.14.
3-Benzylthiopropyl5-acetamido-3,5-dideoxy-
i-
D
-glycero- -galacto-2-nonulopyranosonic
D
acid methyl ester (11).—A solution of acetate
10 (1.30 g, 1.98 mmol) in MeOH (15 mL) was
stirred in the presence of NaOMe (43.0 mg,
0.793 mmol) at rt for 2 h under an Ar atmo-
sphere. The resulting mixture was treated with
IR-120B (H+) resin, filtered, and concen-
trated. The residual syrup was chro-
matographed on silica gel with 5:1 (v/v)
CHCl3–MeOH to give pure 11 (755 mg,
78.1%) as white crystals: mp 148–150 °C, [h]D27
−27.4° (c 1.77, Me2SO); IR (KBr) 3352
(wOꢁH), 2935 (wCꢁH), 1724 (wCꢀO), 1625 (wCꢀO
;

K. Matsuoka et al. / Carbohydrate Research 329 (2000) 765–772
771
Carbosilane dendrimer carrying six N-
acetylneuraminic acid moieties (16).—Sodium
(148 mg, 6.45 mmol) was added to a solution
of 12 (305 mg, 0.645 mmol) in liquid NH3
(ꢀ30 mL) at −55 °C, and the dark blue
mixture was stirred for 1 h. The mixture was
treated with NH4Cl (276 mg, 5.16 mmol) for 5
min, and then a solution of dendrimer 13 (25
mg, 27 mmol) in THF (2 mL) was added
dropwise to the mixture at −30 °C. The mix-
ture was stirred overnight and evaporated.
The white residue was allowed to react with
Ac2O (5 mL) in pyridine (15 mL) at rt
overnight. After evaporation in vacuo, the
residue was treated with CH2N2 in diethyl
ether. A combination of a gel filtration with
Sephadex LH-20 eluted with MeOH and silica
gel chromatography of the concentrated reac-
tant mixture gave 16 as a colorless solid (42
3.56 (t, 6 H, J3,4 9.1 Hz, H-3), 3.62 (t, 6 H, J4,5
9.2 Hz, H-4), 3.85 (m, 12 H, 6 OCH2), 3.99 (d,
13
6 H, H-5), 4.50 (d, 1 H, J1,2 7.8 Hz, H-1); C
NMR (100.6 MHz, D2O) l −2.19 (Me),
12.02 [SiC (G1)], 17.52 [CH2 (G0)], 18.70 [CH2
(G0)], 20.34 [CH2 (G0)], 24.28, 28.32, 29.56,
35.79, 69.29 (C-4), 71.49 (C-2), 72.92, 74.90,
75.43, 102.65 (C-1), 172.27 (C-6); FABMS
Calcd for [M+]: 2076.7. Found: m/z 2076.5.
Anal. Calcd for C80H144O42S6Si3·2 H2O: C,
45.96; H, 7.14. Found: C, 46.05; H, 7.07.
Carbosilane dendrimer carrying six N-ace-
tyl- -glucosamine moieties (15).—A mixture
D
of 8 (254 mg, 0.658 mmol), Na (151 mg, 6.58
mmol) in liquid NH3 (ꢀ30 mL) was stirred
for 1 h at −30 °C. After adding NH4Cl (317
mg portionwise, 5.92 mmol), the dendrimer 13
(51 mg, 57 mmol) in THF (1 mL) was injected
dropwise to the stirred mixture and the stir-
ring was continued for 19 h. When the TLC of
the reaction mixture indicated N-de-acetyla-
tion of products, as judged by the results of a
ninhydrin test, the reaction mixture was acetyl-
ated in the conventional way in MeOH after
removal of NH3. Chromatographic purifica-
tion by Sephadex G-25 eluting with 5% aq
AcOH gave crude products. Further manipu-
lation of the products into the complete ac-
etates was accomplished by Ac2O with
pyridine. Chromatography of the resulting ac-
etates on silica gel with 10:1 (v/v) CHCl3–
MeOH afforded pure 15 (75 mg, 46.0%) as an
amorphous solid, [h]2D5 −3.0° (c 0.63, CHCl3);
1
mg, 40.8%): H NMR (400 MHz, CDCl3) l
−0.68 (s, 6 H, 2 CH3), 0.56 (m, 20 H, 10
SiCH2), 1.25 (m, 4 H, 2 CH2), 1.52 (m, 12 H,
6 CH2), 1.80 (m, 12 H, 6 CH2), 1.86 (s, 18 H,
6 NAc), 1.92 (t, 6 H, J3ax,4 12.6 Hz, H-3ax),
2.00, 2.03, 2.12, 2.13 (each s, 72 H, 24 Ac),
2.48 (t, 12 H, J 7.3 Hz, 6 SCH2), 2.53 (t, 12 H,
J 7.2 Hz, 6 SCH2), 2.56 (dd, 6 H, J3ax,3eq 13.2,
J3eq,4 4.6 Hz, H-3eq), 3.56 (m, 12 H, 6 OCH2),
3.78 (s, 18 H, Me), 4.05 (q, 6 H, H-5), 4.10 (m,
6 H, H-6), 4.12 (dd, 6 H, H-9b), 4.29 (dd, 6 H,
J8,9a 2.3, J9a,9b 12.4 Hz, H-9a), 4.83 (ddd, 6 H,
J4,5 9.5 Hz, H-4), 5.30 (d, 6 H, J5,NH 8.9 Hz,
NH), 5.32 (dd, 6 H, J6,7 1.9, J7,8 8.4 Hz, H-7),
5.38 (ddd, 6 H, J8,9b 5.7 Hz, H-8); 13C NMR
(100.6 MHz, CDCl3) l −3.30 (SiMe), 12.11
[SiC (G1)], 20.76 [CH2 (G0)], 20.82 [CH2
(G0)], 20.86 [CH2 (G0)], 21.08, 23.13, 24.23,
28.43, 29.67, 35.88, 38.02, 49.36 (OMe), 52.70,
62.28, 63.36, 67.25, 68.54, 69.10, 72.43, 77.20,
98.76 (C-2), 168.43 (CꢀO), 169.96 (CꢀO),
170.06 (CꢀO), 170.21 (CꢀO), 170.62 (CꢀO),
170.94 (CꢀO); FABMS Calcd for [M+H+]:
3838.42. Found: m/z 3838.20.
IR (KBr) 2920 (wCꢁH), 1748 (wCꢀO), 1661 (wC1ꢀO
;
amide I), 1557 (lNꢁH; amide II) cm−1; H
NMR (400 MHz, CDCl3) l −0.10 (s, 6 H, 2
CH3), 0.53 (m, 20 H, 10 SiCH2), 1.23 (m, 4 H,
2 CH2), 1.50 (m, 12 H, 6 CH2), 1.80 (m, 12 H,
6 CH2), 1.92 (s, 18 H, 6 NAc), 1.98, 2.00, 2.04
(each s, 54 H, 18 Ac), 2.45 (t, 12 H, J 7.1 Hz,
6 SCH2), 2.51 (t, 12 H, J 7.0 Hz, 6 SCH2),
3.72 (ddd, 6 H, J4,5 9.7, J5,6a 2.4, J5,6b 4.7 Hz,
H-5), 3.74 (m, 12 H, 6 OCH2), 3.88 (q, 6 H,
H-2), 4.09 (dd, 6 H, J6a,6b 12.2 Hz, H-6a), 4.23
(dd, 6 H, H-6b), 4.66 (d, 6 H, J1,2 8.3 Hz,
H-1), 5.03 (t, 6 H, J3,4 9.6 Hz, H-4), 5.26 (t, 6
H, J2,3 9.9 Hz, H-3), 6.44 (d, 6 H, J2,NH 8.9
Hz, NH); FABMS Calcd for [M+]: 2973.15.
Found: m/z 2973.07. Anal. Calcd for
C128H210O54N6S6Si3: C, 51.70; H, 7.12; N, 2.83.
Found: C, 52.20; H, 7.19; N, 2.62.
Acknowledgements
This work was partly supported by a grant
in aid from NEDO [New Energy and Indus-
trial Technology Development Organization
(Glycocluster project)].

772
K. Matsuoka et al. / Carbohydrate Research 329 (2000) 765–772
[4] (a) K. Matsuoka, M. Terabatake, Y. Saito, C. Hagihara,
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