Facile preparation of divalent sialoside derivatives by olefin metathesis reaction

Article abstract of DOI:10.1016/S0040-4020(00)00034-X

Olefin metathesis catalyzed by RuCl₂(CHPh)(PCy₃)₂ (1) has been used to synthesize homodimers of O- and S-alkenyl α-sialoside derivatives. The reactions afforded reasonable to good yields under mild reaction conditions. Tra

Full text of DOI:10.1016/S0040-4020(00)00034-X

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 1423–1428
Facile Preparation of Divalent Sialoside Derivatives by Olefin
Metathesis Reaction
*
´
Zhonghong Gan and Rene Roy
Department of Chemistry, University of Ottawa, Ottawa, Ontario, Canada KIN 6N5
Received 22 October 1999; revised 6 January 2000; accepted 7 January 2000
Abstract—Olefin metathesis catalyzed by RuCl2(CHPh)(PCy3)2 (1) has been used to synthesize homodimers of O- and S-alkenyl
a-sialoside derivatives. The reactions afforded reasonable to good yields under mild reaction conditions. Trans-geometrical isomers were
preferred in all cases. ᭧ 2000 Elsevier Science Ltd. All rights reserved.
Introduction
toward the synthesis of carbohydrate homodimers.
Recently, we reported an efficient method to synthesize
alkenyl O- and C-carbohydrate homodimers using Grubbs’
ruthenium carbene complex 1.14 To further explore the
scope and generality of this method, we describe herein
the facile synthesis of divalent sialoside derivatives by
olefin metathesis reaction.
N-Acetylneuraminic acid (NeuAc) represents the most
ubiquitous member of the sialic acid family of derivatives
present on cell surface glycoproteins and glycolipids.1 It
plays important roles in many biological processes, such
as regulation of biofluids and mucins viscosity2 and dis-
aggregation of cells by repulsive effects.3 Moreover, as
terminal substituents, sialic acids are ideally suited to partici-
pate in protein–carbohydrate interactions that mediate cell
surface recognition phenomena. Indeed, cell surface sialo-
sides are known to serve as ligands for microbial toxins,4
bacterial and viral adhesins,5,6 and for mammalian lectins
responsible for cell–cell adhesion.7,8
Results and Discussion
The requisite allyl 315 and n-pentenyl O-a-sialoside 416
were readily accessible from the corresponding alcohols
using b-acetochloroneuraminic acid 2 in the presence of
silver salicylate. Allyl thiosialoside 5 was also prepared
from 2 using phase transfer catalysis (PTC) as previously
reported.17 Following improved phase transfer catalyzed
conditions developed in our laboratory,18 the synthesis of
aryl a-sialosyl derivatives 6 and 7 was achieved at room
temperature in a two phase system using ethyl acetate, 1 M
sodium carbonate and tetrabutylammonium hydrogen
sulfate as phase transfer catalyst. The reactions were
entirely stereospecific and provided crystalline 6 and 7 in
64 and 75% yield, respectively (Scheme 1).
Olefin metathesis catalyzed by transition metal has recently
emerged as a powerful tool for the formation of C–C bonds
in organic syntheses.9 Grubbs’ ruthenium carbene complex
110 is specially useful in this area because of its high reac-
tivity, stability to air, and tolerance to many functional
groups. However, only few examples have been reported
in carbohydrate-related ring-closing metathesis,11 cross-
metathesis,12 and ring-opening metathesis13 reactions. It
seemed appealing to apply the olefin metathesis reaction
Scheme 1.
Keywords: olefin metathesis; divalent sialoside; allyl O-a-sialoside.
* Corresponding author. Tel.: ϩ1-613-5625800 ext 6055; fax: ϩ1-613-5625170; e-mail: rroy@science.uottawa.ca
0040–4020/00/$ - see front matter ᭧ 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00034-X

1424
Z. Gan, R. Roy / Tetrahedron 56 (2000) 1423–1428
Scheme 2.
Treatment of allyl O-a-sialoside 3 with 5 mol% of Grubbs’
catalyst 1 in refluxing CH2Cl2 under nitrogen afforded
homodimer 8 in 82% yield as a mixture of 7:1 E and Z
isomers (Scheme 2). Some starting material together with
trace amount of cross-metathesis product from the initially
released styrene was also obtained.
NMR spectrum of 8 showed a downfield shift for C-20 in the
E isomer (d 64.6 ppm, Dd 3.7 ppm) compared to d
60.9 ppm for that of the Z isomer.
Olefin metathesis of the longer spacer n-pentenyl O-a-sialo-
side 4 under similar reaction conditions afforded homo-
dimer 9 in 88% yield as a 3:1 mixture of E and Z isomers.
Monomer 4 was more reactive than 3 because of less steric
hindrance around the quaternary anomeric center, as a
consequence, the E and Z stereoselectivity decreased from
7:1 to 3:1.
The ratio of the inseparable E and Z isomers could not be
1
determined from the H NMR spectrum of the dimer 8
because of overlapping signals. However, it could be
assigned after compound 8 was deacetylated under trans-
esterification conditions (NaOMe, MeOH). The 13C NMR
spectrum was more informative to confirm the identity of
the E and Z isomers. It is generally accepted that the carbon
a to the double bond in the Z isomer is more shielded than
that in the E isomer due to the g effect.19 The empirical
relationship daꢀZ†ϽdaꢀE† allowed us to assign the relative
configuration of the E and Z isomers. For instance, the 13C
Sulfur-containing compounds have long been known to
act as poisons for transition metal catalysts because of
their strong coordinating properties, which cause them
to block the reactive sites of the metals.20 So, as
expected, allyl thiosialoside 5 showed less reactivity
toward Grubbs’ catalyst 1 when compared to the
Scheme 3.

Z. Gan, R. Roy / Tetrahedron 56 (2000) 1423–1428
1425
Scheme 4.
Table 1. Olefin self metathesis of alkenyl sialic acids
Entry
Substrate
Product
Catalyst amount (mol %)
Time (h)
Yield (%)a
(E/Z) Ratiob
1
2
3
4
5
3
4
5
6
7
8
9
10
11
12
5
5
10
5
6
2
24
2
82
88
26
78
37
7/1c
3/1c
2.5/1
1.7/1
1/0
10
24
a After purification by column chromatography.
1
b Determined by H NMR.
c The ratio was determined from its deacetylated derivatives.
corresponding O-glycoside analogs (3, 4). However, the
expected homodimer 10 could be obtained in 26% yield
together with recovered starting material 5 by using
more catalyst and prolonged heating.
CDCl3 solutions. Carbon chemical shifts were given relative
to CDCl3 (77.0 ppm). Assignments were based on COSY,
HMQC and DEPT experiments. Mass spectra were obtained
using a Kratos II H instrument (FAB-glycerol). Optical
rotations were measured on a Perkin–Elmer 241 polari-
meter and were run at 23ЊC. Thin layer chromatography
(TLC) was performed on silica gel 60 F-254, and column
chromatography was carried out on silica gel 60.
To further explore the scope of this method, the more rigid
2-allylphenyl sialoside 6 and 4-vinylphenyl sialoside 7 were
treated with Grubbs’ catalyst under similar reaction con-
ditions to give compounds 11 and 12 in 78 and 37% yields,
respectively (Schemes 3 and 4). Interestingly, compound 12
was obtained as a single E isomer. The results and con-
ditions are summarized in Table 1.
General procedure for the preparation of aryl sialosides
by PTC reaction
To a solution of freshly prepared b-acetochloroneuraminic
acid 2 (0.4 g, 0.78 mmol) in ethyl acetate (10 mL) was
added a solution of phenol derivatives (2-allyl phenol or
4-vinyl phenol) (2 equiv.) and tetrabutylammonium hydro-
gen sulfate (265 mg, 0.78 mmol) in 1 M sodium carbonate
(10 mL). The reaction mixture was vigorously stirred at
room temperature until TLC indicated complete transfor-
mation of the starting material (1 h). The reaction was
diluted with ethyl acetate (20 mL). The organic layer was
separated and washed with saturated sodium chloride
solution (20 mL). The organic phase was dried over
Na2SO4 and concentrated under reduced pressure. The
residue was purified by silica gel column chromatography
using dichloromethane–methanol (30:1) as eluant to obtain
pure product.
Each of the a-sialodimers 8–12 were transformed into
single compound by hydrogenation at atmospheric pressure
(10% Pd/C, 1–12 h) to give their corresponding saturated
a-sialodimers 8a–12a, respectively, in quantitative yields.
In summary, olefin metathesis reaction provides a facile
approach toward the synthesis of divalent sialoside deriva-
tives. The reactions afforded reasonable yields under mild
reaction conditions. Vinyl substituted aryl sialosides
provided only the trans isomer as previously expected on
the basis of analogous results.14c
Experimental
General methods
Methyl (2-allylphenyl 5-acetamido-4,7,8,9-tetra-O-ace-
tyl-3,5-dideoxy-d-glycero-a-d-galacto-2-nonulopyranosid)
onate (6). White solid (64%); mp 86–88ЊC; [a]Dˆϩ0.2 (c
1.0, CHCl3); 1H NMR (CDCl3) d 7.09–6.40 (m, 4H,
aromatic H), 5.88–5.81 (m, 1H, –CHv), 5.79 (d, 1H,
Melting points were determined on a Gallenkamp apparatus
and are uncorrected. 1H and 13C NMR spectra were recorded
on a Bruker AMX 500 instrument. Proton chemical shifts
(d) were given relative to internal CHCl3 (7.24 ppm) for

1426
Z. Gan, R. Roy / Tetrahedron 56 (2000) 1423–1428
J5,NHˆ10.1 Hz, NH), 5.31–5.30 (m, 2H, H-7, H-8),
4.99–4.94 (m, 2H, vCH2), 4.87 (m, 1H, H-4), 4.38 (d,
1H, J5,6ˆ10.9 Hz, H-6), 4.23 (dd, 1H, J8,9aˆ2.0 Hz,
J9a,9bˆ12.4 Hz, H-9a), 4.12–4.09 (m, 2H, H-9b, H-5),
3.53 (s, 3H, OCH3), 3.03–3.28 (m, 2H, –CH2CHv), 2.63
(dd, 1H, J3e,4ˆ4.7 Hz, J3a,3eˆ12.9 Hz, H-3e), 2.16 (dd, 1H,
J3a,4ˆ12.4 Hz, H-3a), 2.06, 2.05, 1.96, 1.95, 1.82 (5s, 15H,
NAc, OAc). 13C NMR (CDCl3) d 170.7–169.9 (CvO),
168.1 (C-1), 150.2, 131.1, 129.9, 127.2, 123.8 (aromatic
C), 136.5 (C-20), 115.5 (C-10), 100.1 (C-2), 73.4 (C-6),
69.5 (C-8), 68.9 (C-4), 68.0 (C-7), 62.0 (C-9), 52.7
(CH3O), 49.1 (C-5), 37.9 (C-3), 34.4 (C-30), 23.0, 20.9,
20.7, 20.6 (NAc, OAc); FAB-MS: 608.3 ([Mϩ1]ϩ,
41.1%); Anal. Calcd for C29H37NO13: C, 57.33; H, 6.14;
N: 2.31. Found: C, 57.03; H, 5.99; N, 2.37.
62.30 (C-9 trans), 62.19 (C-9 cis), 60.92 (C-20 cis), 52.59
(OCH3), 49.22 (C-5), 37.94 (C-3 trans), 37.85 (C-3 cis);
FAB-MS: 1035.4 ([Mϩ1]ϩ, 5.3%); Anal. Calcd for
C44H62N2O26: C, 51.06; H, 6.04; N: 2.71. Found: C, 50.67;
H, 5.97; N, 2.72.
(E, Z) 1,8-Di-O-(methyl 5-acetamido-4,7,8,9-tetra-O-ace-
tyl-3,5-dideoxy-d-glycero-a-d-galacto-2-nonulopyrano-
1
sylonate)-oct-4-ene (9). H NMR (CDCl3) d 5.53 (d, 2H,
J5,NHˆ9.5 Hz, NH), 5.36–5.24 (m, 6H, H-10 trans, H-10 cis,
H-8, H-7), 4.77 (m, 2H, H-4), 4.25 (dd, 2H, J8,9aˆ2.6 Hz,
J9a,9bˆ12.4 Hz, H-9a), 4.08–3.86 (m, 6H, H-9b, H-6, H-5),
3.71 (s, 6H, OCH3), 3.69 (m, 2H, –OCH2–), 3.15 (m, 2H,
–OCH2–), 2.51 (dd, 2H, J3e,4ˆ4.6 Hz, J3a, ˆ12.8 Hz,
3e
H-3e), 1.87 (dd, 2H, J3a,4ˆ12.5 Hz, H-3a), 2.07, 2.06,
1.97, 1.96, 1.81 (5s, 30H, NHAc, OAc), 1.98 (m, 4H,
–CH2CHv), 1.52 (m, 4H, –OCH2CH2–); 13C NMR
(CDCl3) d 170.88–169.97 (CvO), 168.45 (C-1), 129.78
(C-10 trans), 129.32 (C-10 cis), 98.68 (C-2), 72.41 (C-6),
69.15 (C-4), 68.86 (C-8), 67.38 (C-7), 64.35 (C-40 trans),
64.29 (C-40 cis), 62.28 (C-9), 52.51 (OCH3), 37.98 (C-3),
29.51 (C-30 cis), 29.43 (C-30 trans), 28.70 (C-20 trans),
23.32 (C-20 cis); FAB-MS: 1091.5 ([Mϩ1]ϩ, 4.3%); Anal.
Calcd for C48H70N2O26: C, 52.84; H, 6.47; N: 2.57.
Found: C, 52.49; H, 6.46; N, 2.59.
Methyl (4-vinylphenyl 5-acetamido-4,7,8,9-tetra-O-ace-
tyl-3,5-dideoxy-d-glycero-a-d-galacto-2-nonulopyranosid)
onate (7). White solid (75%); mp 81–82ЊC; [a]Dˆϩ14.8 (c
1
1.2, CHCl3); H NMR (CDCl3) d 7.23 (d, 2H, Jˆ8.8 Hz,
aromatic H), 6.93 (d, 2H, aromatic H), 6.57 (dd, 1H,
–CHv), 5.77 (d, 1H, J5,NHˆ11.1 Hz, NH), 5.58 (d, 1H,
Jtransˆ17.6 Hz, CH2v), 5.30 (m, 2H, H-7, H-8), 5.10 (d,
1H, Jcisˆ11.0 Hz, CH2v), 4.87 (ddd, 1H, H-4), 4.36 (dd,
1H, J5,6ˆ10.7 Hz, J6,7Ͻ1 Hz, H-6), 4.25 (dd, 1H,
J8,9aˆ1.5 Hz, J9a,9bˆ12.7 Hz, H-9a), 4.10 (dd, 1H,
J8,9bˆ2.6 Hz, H-9b), 4.04 (ddd, 1H, J4,5ˆ10.4 Hz, H-5),
3.57 (s, 3H, OCH3), 2.62 (dd, 1H, J3e,4ˆ4.7 Hz,
J3a,3eˆ13 Hz, H-3e), 2.14 (dd, 1H, J3a,4ˆ12.7 Hz, H-3a),
2.07, 2.05, 1.96, 1.95, 1.82 (5s, 15H, NAc, OAc); 13C
NMR (CDCl3) 170.8–169.9 (CvO), 168.1 (C-1), 153.3,
133.4, 127.1, 119.8 (aromatic C), 135.9 (C-20), 113.0
(C-10), 99.9 (C-2), 76.8 (C-6), 69.5 (C-8), 68.8 (C-4), 67.4
(C-7), 62.0 (C-9), 52.8 (CH3O), 49.1 (C-5), 38.0 (C-3), 23.0,
20.9, 20.7, 20.6 (NAc, OAc); FAB-MS: 594.3 ([Mϩ1]ϩ,
28.7%); Anal. Calcd for C28H35NO13: C, 56.66; H, 5.94;
N: 2.36. Found: C, 56.42; H, 5.86; N, 2.48.
Compound (10). 1H NMR (CDCl3) d 5.54 (t, 1.14H,
Jˆ3.9 Hz, H-10 trans), 5.48 (t, 0.86H, Jˆ5.2 Hz, H-10
cis), 5.36–5.18 (m, 6H, H-8, H-7, NH), 4.83 (m, 2H,
H-4), 4.28–4.25 (m, 2H, H-9a cis, H-9a trans), 4.08–4.06
(m, 2H, H-9b cis, H-9b trans), 4.00 (ddd, 2H, Jˆ10.4 Hz,
H-5), 3.71–3.76 (m, 2H, H-6), 3.78 (s, 1.71H, OCH3 cis),
3.76 (s, 4.29H, OCH3 trans), 3.34–3.18 (m, 2H, H-20 cis,
H-20 trans), 2.69–2.65 (m, 2H, H-3e cis, H-3e trans), 1.93
(m, 2H, H-3a), 2.12, 2.10, 1.99, 1.98, 1.83 (5s, 30H, NHAc,
OAc); 13C NMR (CDCl3) d 170.84–169.97 (CvO), 168.46
(C-1 cis), 168.22 (C-1 trans), 128.39 (C-10 trans), 127.89
(C-10 cis), 83.25 (C-2 cis), 82.87 (C-2 trans), 74.20 (C-6
cis), 74.02 (C-6 trans), 69.53 (C-4), 68.70 (C-8 cis), 68.44
(C-8 trans), 67.34 (C-7 cis), 67.25 (C-7 trans), 62.16 (C-9),
53.01 (OCH3 trans), 52.99 (OCH3 cis), 49.36 (C-5), 37.82
(C-3), 30.41 (C-20 trans), 25.40 (C-20 cis); FAB-MS: 1067.4
([Mϩ1]ϩ, 3.9%); Anal. Calcd for C44H62N2O24S2: C, 49.52;
H, 5.86; N: 2.63. Found: C, 49.41; H, 5.97; N, 2.63.
Typical procedure for the preparation of divalent
sialoside derivatives 8–12 by olefin metathesis reaction
To a solution of alkenyl glycoside (100 mg) in dry dichloro-
methane (2 mL) was added ruthenium catalyst (5–10
mol%). The reaction mixture was refluxed under nitrogen
for 2–24 h. The reaction was monitored by TLC. The reac-
tion mixture was concentrated and purified by silica gel
column chromatography using dichloromethane–methanol
(20:1) as eluant to obtain pure product.
1
Compound (11). H NMR (CDCl3) d 7.24–6.93 (m, 8H,
aromatic H), 5.60 (t, 0.74H, Jˆ5.2 Hz, H-10 cis), 5.56 (t,
1.26H, Jˆ3.7 Hz, H-10 trans), 5.50 (d, 2H, J5,NHˆ10.1 Hz,
NH), 5.35–5.31 (m, 4H, H-7, H-8), 4.92–4.87 (m, 2H, H-4),
4.48–4.37 (m, 2H, H-6 cis, H-6 trans), 4.26 (dd, 2H,
J8,9aˆ2.3 Hz, J9a,9bˆ12.8 Hz, H-9a), 4.12 (dd, 2H,
J8,9bˆ4.7 Hz, H-9b), 4.09–4.05 (m, 2H, H-5 cis, H-5
trans), 3.55 (s, 2.22H, OCH3 cis), 3.53 (s, 3.78H, OCH3
trans), 3.41 (t, 1.48H, H-20 cis), 3.29 (t, 2.52H, H-20
trans), 2.65 (dd, 0.74H, H-3e cis), 2.68 (dd, 1.26H,
J3e,4ˆ4.7 Hz, J3a,3eˆ13.0 Hz, H-3e trans), 2.20–2.11 (m,
2H, H-3a cis, H-3a trans), 2.06, 2.05, 1.96, 1.95, 1.82 (5s,
30H, NHAc, OAc). 13C NMR (CDCl3) d 170.73–169.87
(CvO), 168.06 (C-1 cis), 168.02 (C-1 trans), 129.74
(C-10 trans), 128.34 (C-10 cis), 100.23 (C-2), 73.34 (C-6
cis), 73.31 (C-6 trans), 69.40 (C-8 trans), 69.36 (C-8 cis),
68.80 (C-4 trans), 68.76 (C-4 cis), 67.42 (C-7), 61.96 (C-9),
52.80 (CH3O cis), 52.75 (CH3O trans), 49.25 (C-5), 37.94
(E, Z) 1,4-Di-O-(methyl 5-acetamido-4,7,8,9-tetra-O-ace-
tyl-3,5-dideoxy-d-glycero-a-d-galacto-2-nonulopyrano-
1
sylonate)-but-2-ene (8). H NMR (CDCl3) 5.66 (m, 2H,
H-10 trans, H-10 cis), 5.51–5.23 (m, 6H, NH, H-8, H-7),
4.76 (m, 2H, H-4), 4.23–4.18 (m, 4H, H-9a, –CH2Cv),
4.04–3.96 (m, 6H, H-9b, H-6, H-5), 3.77–3.71 (m, 2H,
–CH2Cv), 3.70 (s, 6H, OCH3), 2.52 (dd, 2H,
J3e,4ˆ4.5 Hz, J3a,3eˆ12.8 Hz, H-3e), 1.87 (dd, 2H,
J3a,4ˆ12.6 Hz, H-3a), 2.06, 1.96, 1.95, 1.79 (5s, 30H,
NHAc, OAc); 13C NMR (CDCl3) 170.85–169.97 (CvO),
168.26 (C-1 cis), 168.18 (C-1 trans), 128.18 (C-10 cis),
128.14 (C-10 trans), 98.56 (C-2 cis), 98.28 (C-2 trans),
72.46 (C-6 cis), 72.39 (C-6 trans), 69.14 (C-4 cis), 69.02
(C-4 trans), 68.55 (C-8), 67.25 (C-7), 64.58 (C-20 trans),

Z. Gan, R. Roy / Tetrahedron 56 (2000) 1423–1428
1427
(C-3 cis), 37.80 (C-3 trans), 32.99 (C-20 trans), 27.67 (C-20
cis); FAB-MS: 1187.5 ([Mϩ1]ϩ, 11.1%); Anal. Calcd for
C56H70N2O26: C, 55.64; H, 5.95; N: 2.36. Found: C, 55.38;
H, 5.98; N, 2.30.
J3a,4ˆ12.5 Hz, H-3a), 2.10, 2.09, 2.00, 1.98, 1.84 (5s,
30H, NHAc, OAc), 1.48 (m, 4H, –OCH2CH2–), 1.29–
1.21 (m, 8H, –O(CH2)2(CH2)2–); 13C NMR (CDCl3) d
171.0–168.5 (CyO), 98.7 (C-2), 72.4 (C-6), 69.1 (C-4),
68.7 (C-8), 67.3 (C-7), 65.0 (OCH2(CH2)2), 62.3 (C-9),
52.6 (OCH3), 49.4 (C-5), 37.7 (C-3), 29.3 (OCH2CH2CH2),
25.8 (O(CH2)2CH2), 23.1 (NHAc), 21.1, 20.8, 20.7 (OAc);
HRMS calcd for C48H73N2O26 (MHϩ) m/z 1093.4452, found
1093.4441.
Compound (12). White solid (CH2Cl2–Hexane); mp 110–
1
111ЊC; [a]Dˆϩ201Њ (c 1.0, CHCl3); H NMR (CDCl3) d
7.36 (d, 4H, Jˆ8.8 Hz, aromatic H), 7.01 (d, 4H, aromatic
H), 6.93 (s, 2H, –CHv), 5.37–5.33 (m, 6H, NH, H-7, H-8),
4.94 (ddd, 2H, H-4), 4.40 (dd, 2H, J5,6ˆ10.8 Hz,
J6,7ˆ1.7 Hz, H-6), 4.30 (dd, 2H, J8,9aˆ2.4 Hz,
J9a,9bˆ12.5 Hz, H-9a), 4.15 (dd, 2H, J8,9bˆ4.7 Hz, H-9b),
4.07 (ddd, 2H, J4,5ˆ10.4 Hz, J5,NHˆ11.1 Hz, H-5), 3.63 (s,
Compound (10a). Mp 88–90ЊC (CH2Cl2–Hexane);
1
[a]Dˆϩ27.5Њ (c 1.0, CHCl3); H NMR (CDCl3) d 5.34–
5.28 (m, 4H, H-8, H-7), 5.20 (d, 2H, JNH,5ˆ10.1 Hz, NH),
4.84 (m, 2H, H-4), 4.27 (dd, 2H, J8,9aˆ2.4 Hz,
J9a,9bˆ12.4 Hz, H-9a), 4.08 (dd, 2H, J8,9bˆ4.7 Hz, H-9b),
4.00 (ddd, 2H, Jˆ10.4 Hz, H-5), 3.82–3.80 (m, 2H, H-6),
3.78 (s, 6H, OCH3), 2.70 (m, 2H, –SCH2–), 2.68 (dd, 2H,
J3e,4ˆ4.7 Hz, J3a,3eˆ12.7 Hz, H-3e), 2.54 (m, 2H, –SCH2–),
1.94 (dd, 2H, J3a,4ˆ12.4 Hz, H-3a), 2.13, 2.11, 2.01, 2.00,
1.85 (5s, 30H, NHAc, OAc), 1.57 (m, 4H, –SCH2CH2–);
13C NMR (CDCl3) d 171.0–170.0 (CvO), 83.0 (C-2), 74.0
(C-6), 69.6 (C-4), 68.5 (C-8), 67.2 (C-7), 62.1 (C-9), 53.0
(OCH3), 49.4 (C-5), 38.0 (C-3), 28.4 (–SCH2–), 28.3
(–SCH2CH2–), 23.2 (NHAc), 21.2, 20.9, 20.8 (OAc);
HRMS calcd for C54H65N2O24S2 (MHϩ) m/z 1069.3369,
found 1069.3352.
6H, OCH3), 2.68 (dd, 2H, J3e,4ˆ4.6 Hz, J3a, ˆ12.9 Hz,
3e
H-3e), 2.20 (dd, 2H, J3a,4ˆ12.5 Hz, H-3a), 2.13, 2.11,
2.02, 2.01, 1.89 (5s, 30H, NAc, OAc); 13C NMR (CDCl3)
d 170.9–170.0 (CvO), 168.1 (C-1), 153.2, 133.2, 127.3,
120.0 (aromatic C), 127.1 (–HCv), 100.0 (C-2), 73.3 (C-6),
69.2 (C-8), 68.7 (C-4), 67.3 (C-7), 62.0 (C-9), 52.9 (CH3O),
49.4 (C-5), 38.1 (C-3); FAB-MS: 1159.3 ([Mϩ1]ϩ,
0.4%); Anal. Calcd for C54H66N2O26: C, 56.86; H,
5.74; N: 2.42. Found: C, 56.04; H, 5.66; N, 2.42.
Preparation of divalent sialoside derivatives 8a–12a by
reduction reaction—typical procedure
To a-sialodimer 8 (20 mg,) in ethanol (2 mL) was added
10% Pd/C (2 mg). The mixture was stirred at room tempera-
ture for 1 h under hydrogen atmosphere. The reaction
mixture was filtered and concentrated to yield compound
8a as a white solid (20 mg, 100%).
Compound (11a). Mp 93–94ЊC (CH2Cl2–hexane);
[a]DˆϪ3.0Њ (c 1.0, CHCl3); H NMR (CDCl3) 7.14–6.93
1
(m, 8H, aromatic H), 5.39–5.30 (m, 4H, H-7, H-8), 5.27 (d,
2H, J5,NHˆ10.1 Hz, NH), 4.91 (m, 2H, H-4), 4.41 (dd, 2H,
J6,7ˆ1.8 Hz, J5,6ˆ10.8 Hz, H-6), 4.27 (dd, 2H, J8,9aˆ2.6 Hz,
J9a,9bˆ12.5 Hz, H-9a), 4.14 (dd, 2H, J8,9bˆ4.9 Hz, H-9b),
4.07 (ddd, 2H, J4,5ˆ10.4 Hz, H-5), 3.55 (s, 6H, OCH3),
2.62 (dd, 2H, J3e,4ˆ4.7 Hz, J3a,3eˆ12.9 Hz, H-3e), 2.57
(m, 4H, –Ph–CH2–), 2.18 (dd, 2H, J3a,4ˆ12.6 Hz, H-3a),
2.12, 2.10, 2.01, 2.00, 1.88 (5s, 30H, NHAc, OAc), 1.57 (m,
4H, –Ph–CH2CH2–); 13C NMR (CDCl3) d 170.9–168.1
(CvO), 151.9, 133.4, 126.8, 124.7, 118.9 (6C, aromatic),
100.2 (C-2), 73.3 (C-6), 69.3 (C-8), 68.8 (C-4), 67.4 (C-7),
62.0 (C-9), 52.80 (CH3O), 49.3 (C-5), 37.8 (C-3), 30.2, 29.6
(–CH2CH2–), 23.1 (NHAc), 21.0, 20.8, 20.7 (OAc); HRMS
calcd for C54H73N2O26 (MHϩ) m/z 1189.4452, found
1189.4432.
a-Sialodimers 9a, 11a and 12a were obtained in the same
manner from glycodimers 9, 11 and 12 in quantitative
yields. However, a-thiosialodimer 10 was treated with the
same mass amount of palladium catalyst for 12 h to afford
compund 10a in 100% yield.
Compound (8a). mp 104–105ЊC (CH2Cl2–Hexane);
1
[a]DˆϪ18.2Њ (c 1.0, CHCl3); H NMR (CDCl3) d 5.34
(m, 2H, H-8), 5.29 (dd, 2H, J6,7ˆ2.1 Hz. J7.8ˆ8.2 Hz,
H-7), 5.21 (d, 2H, JNH,5ˆ9.7 Hz, NH), 4.80 (m, 2H, H-4),
4.27 (dd, 2H, J8,9aˆ2.7 Hz, J9a,9bˆ12.4 Hz, H-9a), 4.09–
3.98 (m, 6H, H-9b, H-6, H-5), 3.75 (s, 6H, OCH3), 3.74
(m, 2H, –OCH2–), 3.16 (m, 2H, –OCH2–), 2.53 (dd, 2H,
Compound (12a). Mp 102–103ЊC (CH2Cl2–Hexane);
J3e,4ˆ4.6 Hz, J3a, ˆ12.8 Hz, H-3e), 1.90 (dd, 2H,
3e
1
[a]Dˆϩ3.6Њ (c 1.0, CHCl3); H NMR (CDCl3) d 6.98 (d,
J3a,4ˆ12.6 Hz, H-3a), 2.11, 2.10, 2.00, 1.99, 1.84 (5s,
30H, NHAc, OAc), 1.55 (m, 4H, –OCH2CH2–); 13C NMR
(CDCl3) 170.0–168.3 (CvO), 98.7 (C-2), 72.4 (C-6), 69.1
(C-4), 68.6 (C-8), 67.2 (C-7), 64.7 (–OCH2CH2–),
62.2 (C-9), 52.7 (OCH3), 49.4 (C-5), 38.0 (C-3), 26.1
(–OCH2CH2–), 23.2 (NHAc), 21.0, 20.8, 20.7 (OAc);
HRMS calcd for C44H65N2O26 (MHϩ) m/z 1037.3826,
found 1037.3836.
4H, Jˆ8.6 Hz, aromatic H), 6.92 (d, 4H, aromatic H), 5.37
(m, 2H, H-8), 5.34 (dd, 2H, J6,7ˆ1.8 Hz. J7.8ˆ8.2 Hz, H-7),
5.31 (d, 2H, J5,NHˆ10.1 Hz, NH), 4.90 (m, 2H, H-4), 4.34
(dd, 2H, J6,7ˆ1.8 Hz, J5,6ˆ10.8 Hz, H-6), 4.30 (dd, 2H,
J8,9aˆ2.5 Hz, J9a,9bˆ12.5 Hz, H-9a), 4.16 (dd, 2H,
J8,9bˆ4.7 Hz, H-9b), 4.05 (ddd, 2H, J4,5ˆ10.4 Hz, H-5),
3.58 (s, 6H, OCH3), 2.80 (m, 4H, –Ph–CH2–), 2.66 (dd,
2H, J3e,4ˆ4.7 Hz, J3a,3eˆ12.9 Hz, H-3e), 2.16 (dd, 2H,
J3a,4ˆ12.6 Hz, H-3a), 2.12, 2.10, 2.03, 2.00, 1.88 (5s,
30H, NHAc, OAc); 13C NMR (CDCl3) d 170.9–168.0
(CvO), 151.8, 137.3, 129.3, 120.0 (aromatic C),
100.2 (C-2), 73.2 (C-6), 69.2 (C-8), 68.9 (C-4), 67.3
(C-7), 62.0 (C-9), 52.9 (CH3O), 49.3 (C-5), 38.0
(C-3), 37.0 (CH2), 23.2 (NHAc), 21.0, 20.8, 21.7
(OAc); HRMS calcd for C54H69N2O26 (MHϩ) m/z
1161.4139, found 1161.4138.
Compound (9a). mp 82–84ЊC (CH2Cl2–Hexane);
1
[a]DˆϪ15.3Њ (c 1.0, CHCl3); H NMR (CDCl3) d 5.35
(m, 2H, H-8), 5.29 (dd, 2H, J6,7ˆ2.0 Hz. J7.8ˆ8.1 Hz,
H-7), 5.24 (d, 2H, JNH,5ˆ9.4 Hz, NH), 4.80 (m, 2H, H-4),
4.27 (dd, 2H, J8,9aˆ2.7 Hz, J9a,9bˆ12.4 Hz, H-9a), 4.09–
3.99 (m, 6H, H-9b, H-6, H-5), 3.75 (s, 6H, OCH3), 3.70
(m, 2H, –OCH2–), 3.15 (m, 2H, –OCH2–), 2.53 (dd, 2H,
J3e,4ˆ4.7 Hz, J3a,3eˆ12.8 Hz, H-3e), 1.90 (dd, 2H,

1428
Z. Gan, R. Roy / Tetrahedron 56 (2000) 1423–1428
10. Schwab, P.; France, M. B.; Ziller, J. W.; Grubbs, R. H. Angew.
Acknowledgements
Chem., Int. Ed. Engl. 1995, 34, 2039.
11. (a) Overkleeft, H. S.; Pandit, U. K. Tetrahedron Lett. 1996, 37,
547; (b) El Sukkari, H.; Gerson, J.-P.; Renoux, B. Tetrahedron
Lett. 1998, 39, 4043; (c) Holt, D. J.; Barker, W. D.; Ghosh, S.
Angew. Chem. 1998, 37, 3298.
We thank the Natural Sciences and Engineering Research
Council of Canada (NSERC) for financial support.
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