Cross metathesis for the synthesis of novel C-sialosides

Article abstract of DOI:10.1016/j.carres.2008.03.036

Cross metathesis of both anomers of C-allyl sialoside (3α/3β) with styrene catalyzed by the second generation Grubbs or Hoveyda-Grubbs catalysts gave the corresponding aryl derivatives (4α/4β) in virtually quantitative yields. The products were hydrogenat

Full text of DOI:10.1016/j.carres.2008.03.036

Available online at www.sciencedirect.com
Carbohydrate Research 343 (2008) 1824–1829
Note
Cross metathesis for the synthesis of novel C-sialosides
Sebastian Meinke and Joachim Thiem*
University of Hamburg, Faculty of Science, Department of Chemistry, 20146 Hamburg, Germany
Received 19 February 2008; received in revised form 20 March 2008; accepted 30 March 2008
Available online 4 April 2008
Abstract—Cross metathesis of both anomers of C-allyl sialoside (3a/3b) with styrene catalyzed by the second generation Grubbs or
Hoveyda-Grubbs catalysts gave the corresponding aryl derivatives (4a/4b ) in virtually quantitative yields. The products were hydro-
genated to model compounds 5a/5b. Similarly, reaction of the a-anomer 3a with galactose derivative 8 gave the olefin-linked disac-
charide mimetic 9. Following hydrogenation and deprotection, the ethylene-bridged Neu5Aca(2?6)Gal analogue 11 could be
obtained.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Cross metathesis; Ruthenium catalyst; C-Sialosides; Disaccharide mimetics
With the discovery of the important roles that oligosac-
charide structures play in cell biology, the enzymes deal-
ing with those structures also became of increasing
interest to research. Revealing the properties of glycosyl-
transferases as well as glycosidases not only enhances
the understanding of the mechanisms underlying
infections but also leads to effective new strategies in
defeating them. Of particular interest are the enzymes
belonging to the sialidase family (EC 3.2.1.18), because
N-acetyl neuraminic acid (Neu5Ac) plays a pivotal role
in nature as a major constituent of a variety of glycocon-
jugates such as oligosaccharides, glycoproteins and gan-
gliosides that occur in animals and several pathogens.1
In most cases, neuraminic acids are terminally a-(2?3)
or a-(2?6)-linked to a galactose of the oligosaccharide
cell epitope. Due to the terminal position of Neu5Ac
in these oligosaccharide scaffolds, sialylation is associ-
ated with many processes, such as cell recognition and
cell differentiation. In some biological events, the
Neu5Ac allows recognition by a suitable receptor pro-
tein; in others, the presence of Neu5Ac is able to mask
recognition sites.
sialidase (TcTS) causes the transfer of Neu5Ac from a
human host cell to the cell epitope of the pathogen.3
This unusual transfer mechanism enables the pathogen
to protect its own cell surface against recognition by
the human immune system. Because T. cruzi trypo-
mastigotes lacking trans-sialidase are less efficient in cell
invasion,4 this enzyme seems to play a crucial role in T.
cruzi infection. For the investigation of TcTS, we are
interested in substrate analogues that are stable to
hydrolysis by the enzyme to use in affinity measure-
ments. We envisage C-glycosides of Neu5Ac to meet
those demands.
Previous syntheses of C-sialosides employed strategies
such as alkylation of 2-deoxy derivatives,5 samarium-
mediated coupling of carbonyl compounds to 2-sulfonyl
derivatives6 and even de novo synthesis of the C-glycos-
idically linked Neu5Ac scaffold.7 Previous studies by
Paulsen and Matschulat reported on a radical-induced
allylation at the anomeric centre of Neu5Ac, which
opens up possibilities for further derivatization.8 We
decided to focus on cross metathesis reactions, employ-
ing both the Grubbs catalyst (second generation) 1 and
the Hoveyda-Grubbs catalyst (second generation) 2
(Fig. 1).
In the organism causing South American trypanoso-
miasis2 (Chagas disease), Trypanosoma cruzi, a trans-
Olefin metathesis is already established as a method in
carbohydrate synthesis. Applications cover fields such as
homodimerization and linking of allyl glycosides, cross
*
Corresponding author. Fax: +49 404 2838 4325; e-mail: thiem@
chemie.uni-hamburg.de
0008-6215/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2008.03.036

S. Meinke, J. Thiem / Carbohydrate Research 343 (2008) 1824–1829
1825
sons mentioned above. Therefore, we investigated the
potential of cross metathesis in the syntheses of
substrate analogues resistant to hydrolysis by sialic acid
related enzymes.
N
N
N
N
Mes
Cl
Mes
Cl
Mes
Mes
Ru
Ru
Cl
Cl
The difficulty in designing a sufficient protocol for
cross metathesis reaction with allyl C-sialosides 3a and
3b8 is the homodimerization that results from self
metathesis of the substrate. To avoid self metathesis,
the reaction was conducted in dilute solutions of the
C-sialosides (0.01 M) with the use of an 8–10-fold excess
of reactant. Under these conditions, in none of the cases
was the formation of any dimerization product of the C-
sialoside observed. For the isolation of the cross metath-
esis product, it was helpful to choose as a reactant a
much more nonpolar compound that can easily be sep-
arated from the desired products.
First, the reaction conditions were optimized by react-
ing the allyl C-sialosides 3a and 3b with styrene, which
meets the above mentioned demands as a reactant, but
might also have the ability to mimic sugar moieties.17
Cross metatheses were conducted with catalysts 1 and
2 in dichloromethane at room temperature and under
refluxing conditions (Table 1). Isolated yields show the
importance of refluxing conditions for shifting the equi-
librium towards the desired products. By using styrene
as a reactant in each case, the formation of (E)-isomers
was observed in excellent yields. It may be assumed that
the products are isomerized by subsequent cross metath-
esis steps to yield the thermodynamically more stable
trans-olefins. Compounds 4a and 4b were deacetylated
and hydrogenated to give the saturated C-sialosides 5a
and 5b (Scheme 1).
O
PCy3
1
2
Figure 1.
metathesis of allyl glycosides and allyl C-glycosides as
well as de novo synthesis of carbohydrates and related
structures.9–13 By dimerization of a methylvinyl C-arabi-
noside, an analogue of a mycobacterial cell wall disac-
charide motif could be synthesized.14 Sialosides were
successfully converted to divalent derivatives by olefin
metathesis.15 The synthesis of disaccharide mimetics by
olefin metathesis16 is of particular interest for the rea-
Table 1.
Ruthenium catalyst
(mol %)
Temperature
(°C)
Product
Yield
(%)
ruthenium catalyst
α
α
+
styrene
4
3
CH2Cl2, 24 h
1 (8)
1 (5)
2 (16)
2 (24)
25
40
25
40
4a
4a
4a
4a
34
92
17
94
Having established the optimal conditions for cross
metathesis, the use of a carbohydrate based olefin as
reactant in cross metathesis with allyl C-sialosides was
explored. The readily available galactose derivative 6
could be oxidized easily by the method of Dess and
Martin18 to give 7 in 63% yield. Wittig olefination
ruthenium catalyst
+
styrene
4
β
3β
CH2Cl2, 24 h
1 (12)
40
4b
100
AcO
OAc
AcO
OAc
AcO
HO
OH
COOMe
COOMe
COOMe
AcO
AcO
AcHN
HO
AcHN
O
O
O
AcHN
AcO
OH
3α
4α
5α
ruthenium catalyst
CH2Cl2, 24 h
1. NaOMe, MeOH
2. Pd/C, H2, MeOH
AcO
OAc
OAc
OH
AcO
HO
AcO
O
COOMe
AcO
AcHN
HO
AcHN
AcHN
O
O
COOMe
COOMe
AcO
AcO
OH
3β
4β
5β
Scheme 1.

1826
S. Meinke, J. Thiem / Carbohydrate Research 343 (2008) 1824–1829
O
OH
H3C
H3C
OAc
AcO
O
H3C
H3C
H3C
H3C
AcO
O
O
MePPh3Br
KOtBu
Dess-Martin-
Periodinan
COOMe
O
O
O
O
O
+
AcO
AcHN
O
H3C
O
H3C
O
H3C
O
CH2Cl2
O
THF
O
O
O
CH3
CH3
CH3
3α
8
7
6
1 (23 mol %) CH2Cl2, reflux
O
AcO
OAc
AcO
O
O
COOMe
AcO
AcNH
O
O
O
9
Pd/C, H2 MeOH
OH
OH
1. NaOMe, MeOH
2. NaOH (0.1 M)
3. H+, H2O
O
AcO
OAc
HO
OH
O
O
O
COOMe
COOH
O
AcO
HO
O
AcNH
AcNH
O
HO
O
OH
AcO
HO
10
11
Scheme 2.
This reaction sequence is short and displayed high
yields as well as easy purification steps. Therefore, it
should be advantageously applied in the synthesis of a
series of various substrate analogues as potential inhi-
bitors or modulators of sialic acid processing enzymes.
HO
OH
COOH
HO
AcNH
O
X
O
HO
OH
OH
HO
HO
X = O
X = CH2CH2
natural disaccharide
disaccharide mimetic 11
1. Experimental
Figure 2.
1.1. General methods
Commercially available starting materials were used
without further purification. Solvents were dried accord-
ing to standard methods. TLC was performed on pre-
coated aluminum plates (Silica Gel 60 F254, Merck
5554) employing UV-absorption and charring with
10% H2SO4 in ethanol for visualization. For column
chromatography Silica Gel 60, 230–400 mesh, 40–
63 lm (Merck) was used. 1H NMR and 13C NMR spec-
tra were recorded on Bruker AMX-400 (400 MHz for
1H, 100.6 MHz for 13C) and on Bruker DRX-500
resulted in the formation of the terminal olefin 8,19
which could undergo cross metathesis with 3a to give
the novel derivative 9 in 95% yield (Scheme 2). In this
case, the lower reactivity of the internal double bond
in C-sialoside 9 leads to a (E/Z)-ratio of 3:1 (based on
NMR). The bulky and nonpolar isopropylidene protect-
ing groups in the reactant facilitated the isolation of the
product in a similar manner as described above. Hydro-
genation under standard conditions and deprotection
(Scheme 2) resulted in an ethylene bridged C-analogue
of a-(2?6)-linked sialyl galactose derivative (Fig. 2).
1
(500 MHz for H, 125.8 MHz for 13C) at 300 K. Chem-
ical shifts were calibrated to solvent residual peaks.20

S. Meinke, J. Thiem / Carbohydrate Research 343 (2008) 1824–1829
1827
The signals were assigned by 1H–1H-COSY, HSQC,
HMBC and if necessary NOESY experiments. Optical
rotations were measured using a Perkin Elmer 241
1.4. Methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-2,6-anhy-
dro-3,5-dideoxy-2-C-(3-phenylprop-2-enyl)-D-erythro-L-
gluco-nononate (4b)
(546 nm) or a Kruss Optronic P8000 (589 nm) at
¨
20 °C. MALDI-TOF-MS was performed on a Bruker
Biflex III with dihydroxybenzoic acid or trihydroxy-
anthracene as matrices in positive reflector mode. ESI-
HRMS was performed on a Thermo Finnigan MAT
95 XL mass spectrometer.
Compound 7 was synthesized using the protocol of
Dess and Martin.18 Compound 8 was synthesized
following a standard procedure. The NMR data of 7
and 8 were consistent with the published data.21
Compound 3b (250 mg; 485 lmol) was reacted with
styrene (0.5 mL, 4 mmol) and catalyst 1 (50 mg 59 lmol,
12 mol %) following GP1 to give 4b (287 mg; 100%):
½aꢀD ꢁ12 (c 1, CHCl3); H NMR (CDCl3, 500 MHz): d
7.33–7.15 (m, 5H, arom. H), 6.51 (d, 1H,
JCH,CH = 15.8 Hz, Ph–CH@), 5.99–5.92 (m, 1H,
20
1
@CH–),
5.38–5.37
(dd,
1H,
J7,8 = 2.5 Hz,
J7,6 = 2.2 Hz, H-7), 5.34–5.28 (m, 2H, H-4, NH), 5.11
(ddd, 1H, J8,9b = 7.9 Hz, J8,7 = 2.5 Hz, J8,9a = 2.2 Hz,
H-8), 4.76 (dd, 1H, J9a,9b = 12.3 Hz, J9a,8 = 2.2 Hz,
H-9a), 4.13 (dd, 1H, J9b,9a = 12.3 Hz, J9b,8 = 7.9 Hz,
H-9b), 4.10 (dd, 1H, J6,5 = 10.7 Hz, J6,7 = 2.2 Hz,
H-6), 3.87 (m, 1H, H-5), 3.76 (s, 3H, OCH3), 3.00–
2.94 (m, 1H, CH2), 2.77–2.72 (m, 1H, CH2), 2.38 (dd,
1H, J3,3 = 13.2 Hz, J3,4 = 5.1 Hz, H-3eq), 2.14 (s, 3H,
COCH3), 2.03 (s, 3H, COCH3), 2.02 (s, 3H, COCH3),
1.96 (dd, 1H, J3,3 = 13.2 Hz, J3,4 = 11.9 Hz, H-3ax),
1.90 (s, 3H, COCH3), 1.85 (s, 3H, COCH3); 13C NMR
(CDCl3, 100.6 MHz): d 171.65, 171.10, 170.95, 170.69,
170.64, 170.41 (C@O), 136.79 (arom. Cquart), 134.68
(Ph–CH@), 128.62, 127.75, 126.49 (arom. C), 122.14
(@CH–), 79.65 (C-2), 73.13 (C-6), 72.00 (C-8), 69.21
(C-7), 69.26 (C-4), 62.75 (C-9), 52.71 (OCH3), 50.51
(C-5), 36.16, 36.13 (C-3, CH2), 23.45, 21.12, 21.07,
20.96, 20.75 (5 ꢂ CH3). MALDI-TOF: m/z 592.1
[M+H] +, 614.1 [M+Na] +, 630.1 [M+K]+. ESIMS:
614.2207 [M+Na] +, calcd: 614.2213.
1.2. General procedure for cross metathesis with
C-sialosides (GP1)
The allyl C-sialoside (0.35 mmol) was dissolved under
nitrogen in anhydrous dichloromethane (35 mL) to yield
an 0.01 M solution and the second reactant (8–10-fold
excess) was added. After the addition of the ruthenium
catalyst, the reaction was stirred at the indicated temper-
ature (Table 1) for 24 h. The removal of the solvent in
vacuo and column chromatography on silica gel (tolu-
ene–acetone) yielded the product as a white foam.
1.3. Methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-2,6-anhy-
dro-3,5-dideoxy-2-C-(3-phenylprop-2-enyl)-D-erythro-L-
manno-nononate (4a)
Various amounts of 3a were reacted with the indicated
catalyst amounts at the given temperature (Table 1)
20
following GP1 to give 4a (yield, see Table 1): ½aꢀ546
1.5. Methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-2,6-
anhydro-3,5-dideoxy-2-C-(3-phenylpropyl)-D-erythro-L-
manno-nononate (5a)
1
ꢁ8.8 (c 1.0, CHCl3); H NMR (CDCl3, 400 MHz): d
7.39–7.19 (m, 5H, arom. H), 6.38 (d, 1H, JCH,CH
=
16.1 Hz, Ph–CH@), 6.19–6.11 (m, 1H, @CH–), 5.41
(ddd, 1H, J8,7 = 6.9 Hz, J8,9b = 6.0 Hz, J8,9a = 2.5 Hz,
H-8), 5.34 (dd, 1H, J7,8 = 6.9 Hz, J7,6 = 1.6 Hz, H-7),
5.19 (br d, 1H, NH), 4.88–4.80 (m, 1H, H-4), 4.43 (dd,
1H, J9a,9b = 12.3 Hz, J9a,8 = 2.5 Hz, H-9a), 4.15 (dd,
1H, J9b,9a = 12.3 Hz, J9b,8 6.0 Hz, H-9b), 4.08–3.98 (m,
2H, H-5, H-6), 3.72 (s, 3H, OCH3), 2.69–2.57 (m, 2H,
CH2), 2.52 (dd, 1H, J3,3 = 12.8 Hz, J3,4 = 4.5 Hz,
H-3eq), 2.12 (s, 3H, COCH3), 2.11 (s, 3H, COCH3),
2.01 (s, 3H, COCH3), 2.00 (s, 3H, COCH3), 1.87 (s,
Compound 4a (83 mg; 0.14 mmol) was dissolved in
methanolic sodium methoxide solution (20 mL, 0.1 M)
and stirred for 5 h at room temperature. The solution
was then neutralized with Dowex 50X8 (H+) resin, fil-
trated and concentrated. The residue was hydrogenated
with a catalytic amount of palladium on charcoal in
MeOH (20 mL) under a hydrogen atmosphere. Filtra-
tion, evaporation of the solvent and flash chromato-
20
graphy (CH2Cl2–MeOH) gave 5a (60 mg, 100%): ½aꢀD
1
3H, COCH3), 1.84 (dd, 1H, J3,3 = 12.8 Hz, J3,4
=
ꢁ172.4 (c 1, MeOH); H NMR (CD3OD, 400 MHz): d
12.3 Hz, H-3ax); 13C NMR (CDCl3, 100.6 MHz): d
171.72, 171.20, 170.85, 170.44, 170.34, 170.22 (C@O),
7.27–7.12 (m, 5H, arom. H), 3.85–3.80 (m, 2H, H-8,
H-9a), 3.75 (s, 3H, OCH3), 3.72–3.54 (m, 3H, H-4,
H-5, H-9b), 3.49 (dd, 1H, J6,5 = 7.5 Hz, J6,7 = 1.5 Hz,
H-6), 3.47 (dd, 1H, J7,8 = 6.0 Hz, J7,6 = 1.5 Hz, H-7),
2.65–2.53 (m, 3H, CH2, H-3eq), 1.99 (s, 3H, COCH3),
1.81–1.68 (m, 3H, CH2), 1.60–1.47 (m, 2H, CH2,
H-3ax); 13C NMR (CDCl3, 100.6 MHz): d 175.62,
(C@O), 143.10 (arom. Cquart), 129.42, 129.38, 126.90
(arom. C), 81.59 (C-2), 75.78 (C-6), 72.88 (C-8), 70.20
(C-7), 69.09 (C-4), 64.61 (C-9), 54.19 (C-5), 53.06
137.06 (arom.
Cquart), 134.27 (Ph–CH@), 128.61,
127.60, 126.51 (arom. C), 122.76 (@CH–), 80.84
(C-2), 73.69 (C-6), 70.31 (C-4), 69.93 (C-8), 68.09
(C-7), 62.56 (C-9), 52.55 (OCH3), 49.75 (C-5), 43.66
(CH2), 37.52 (C-3), 23.32, 21.24, 21.03, 20.92, 20.90
(5 ꢂCH3). MALDI-TOF: m/z 592.4 [M+H] +, 614.3
[M+Na]+, 630.3 [M+K]+. ESIMS: 614.2189 [M+Na] +,
calcd: 614.2213.

1828
S. Meinke, J. Thiem / Carbohydrate Research 343 (2008) 1824–1829
(OCH3), 42.11 (CH2), 40.86 (C-3), 36.58 (CH2),
26.44 (CH2), 22.61 (CH3). MALDI-TOF: m/z 426.2
[M+H] +, 448.2 [M+Na] +, 464.2 [M+K]+. ESIMS:
448.1943 [M+Na] +, calcd: 448.1947.
1H, J3,3 = 12.5 Hz, J3,4 = 12.2 Hz, H-3II ), 1.57 (s, 3H,
ax
CH3), 1.45 (s, 3H, CH3), 1.33 (s, 3H, CH3), 1.32 (s,
3H, CH3); 13C NMR (CDCl3, 100.6 MHz): d 171.58,
171.18, 170.80, 170.32 170.07 (C@O), 130.91, 126.91
(C-6I, C-7I), 109.14, 108.55 (C(CH3)2), 96.51 (C-1I),
80.45 (C-2II), 73.76 (C-6II), 73.31 (C-4I), 70.94, 70.43
(C-2I, C-3I), 70.37 (C-4II), 69.12 (C-8II), 68.70 (C-7II),
67.80 (C-5I), 62.45 (C-9II), 52.54 (OCH3), 49.73 (C-5II),
42.95 (C-8I), 37.49 (C-3II), 26.18, 26.10, 25.05, 24.45
(CCH3), 23.32, 21.19, 21.02 (3 ꢂ CH3), 20.93 (2 ꢂ
CH3). MALDI-TOF: m/z 766.3 [M+Na] +, 782.3
[M+K] +.
1.6. Methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-2,6-anhy-
dro-3,5-dideoxy-2-C-(3-phenylpropyl)-D-erythro-L-gluco-
nononate (5b)
Compound 4b (70 mg; 0.12 mmol) was dissolved in
methanolic sodium methoxide solution (20 mL, 0.1 M)
and stirred for 5 h at room temperature. The solution
was then neutralized with Dowex 50X8 (H+) resin, fil-
trated and concentrated. The residue was hydrogenated
with a catalytic amount of palladium on charcoal in
MeOH (20 mL) under a hydrogen atmosphere. Filtra-
tion, evaporation of the solvent and flash chromato-
1.8. Methyl 50-acetamido-40,70,80,90-tetra-O-acetyl-20,60-
anhydro-30,50-dideoxy-20-C-(6,7,8-trideoxy-1,2;3,4-di-O-
isopropylidene-a-D-galacto-octopyranos-8-yl)-D-erythro-
L-manno-nononate (10)
20
graphy (CH2Cl2–MeOH) gave 5b (46 mg, 92%): ½aꢀD
1
ꢁ33.6 (c 1, MeOH); H NMR (CD3OD, 400 MHz): d
Compound 9 (65 mg; 87 lmol) was hydrogenated with a
catalytic amount of palladium on charcoal in MeOH
(20 mL) under a hydrogen atmosphere. Filtration, evap-
oration of the solvent and flash chromatography (tolu-
7.27–7.12 (m, 5H, arom. H), 3.93 (ddd, 1H,
J4,5 = 11.3 Hz, J4,5 = 9.3 Hz, J4,3 = 4.8 Hz, H-4), 3.85–
3.71 (m, 4H, C-5, C-6, C-8, C-9a), 3.70 (s, 3H, OCH3),
3.69–3.43 (m, 2H, C-7, C-9b), 2.69–2.51 (m, 2H, CH2),
2.19 (dd, 1H, J3,3 = 13.1 Hz, J3,4 = 4.8 Hz, H-3eq),
2.16–2.09 (m, 1H, CH2), 1.99 (s, 3H, COCH3), 1.95–
1.85 (m, 1H, CH2), 1.78–1.70 (m, 1H, CH2), 1.62 (dd,
1H, J3,3 = 13.1 Hz, J3,4 = 11.3 Hz, H-3ax), 1.35–1.24
(m, 1H, CH2); 13C NMR (CDCl3, 100.6 MHz, carbonyl
groups not detected): d 129.48, 129.35, 126.85 (arom. C),
80.82 (C-2), 71.94, 71.75 (C-6, C-8), 70.60 (C-7), 68.12
(C-4), 65.24 (C-9), 54.48 (C-5), 52.96 (OCH3), 41.38
(C-3), 36.56, 32.42, 25.90 (3 ꢂ CH2), 22.84 (CH3). MAL-
DI-TOF: m/z 426.2 [M+H] +, 448.2 [M+Na] +, 464.2
[M+K]+. ESIMS: 448.1948 [M+Na]+, calcd: 448.1947.
20
ene–acetone) gave 10 (62 mg, 95%): ½aꢀD ꢁ50 (c 1.0,
1
CHCl3); H NMR (CDCl3, 400 MHz): d 5.50 (d, 1H,
J1,2 = 5.1 Hz, H-1I), 5.36–5.29 (m, 2H, H-8II, H-7II),
5.13 (br d, 1H, NH), 4.84–4.77 (m, 1H, H-4II), 4.57
(dd, 1H, J3,2 = 7.9 Hz, J3,4 = 2.0 Hz, H-3I), 4.35 (dd,
1H, J9a,9b = 12.2 Hz, J9a,8 = 2.5 Hz, H-9aII), 4.27 (dd,
1H, J2,1 = 5.1 Hz, J2,3 = 2.0 Hz, H-2I), 4.14 (dd, 1H,
J4,3 = 7.9 Hz, J4,5 = 1.8 Hz, H-4I), 4.11 (dd, 1H,
J9b,9a = 12.2 Hz, J9b,8 = 5.4 Hz, H-9bII), 4.02–3.94 (m,
2H, H-5II, H-6II), 3.74 (s, 3H, OCH3), 3.70–3.65 (m,
1H, H-5I), 2.49 (dd, 1H, J3,3 = 12.7 Hz, J3,4 = 4.6 Hz,
H-3II ), 2.12 (s, 6H, 2 ꢂCOCH3), 2.03 (s, 3H, COCH3),
eq
2.02 (s, 3H, COCH3), 1.87 (s, 3H, COCH3), 1.79–1.62
1.7. Methyl 50-acetamido-40,70,80,90-tetra-O-acetyl-20,60-
anhydro-30,50-dideoxy-20-C-(6,7,8-trideoxy-1,2;3,4-di-O-
isopropylidene-a-D-galacto-oct-6-enopyranos-8-yl)-D-
erythro-L-manno-nononate (9)
(m, 7H, H-3II , H-6I, H-7I, H-8I), 1.53 (s, 3H, CH3),
ax
1.45 (s, 3H, CH3), 1.34 (s, 3H, CH3), 1.32 (s, 3H,
CH3); 13C NMR (CDCl3, 100.6 MHz, carbonyl groups
were not detected): d 109.04, 108.39 (C(CH3)2), 96.63
(C-1I), 80.49 (C-2II), 73.34 (C-6II), 72.76 (C-4I), 71.03
(C-3I), 70.75 (C-2I), 70.44 (C-4II), 69.41 (C-8II), 67.92
(C-7II), 67.29 (C-5I), 62.40 (C-9II), 52.49 (OCH3), 49.94
Compound 3a (75 mg; 0.15 mmol) was reacted with 8
(240 mg; 0.936 mmol) and catalyst 1 (29 mg, 34 lmol;
22 mol %) according to GP1 (refluxing conditions) to
I
(C-5II), 39.83, 38.00, 30.20 (C-3II, C-6 , C-8I), 26.20,
20
give 9 (106 mg, 95%) as a colourless oil: ½aꢀ546 ꢁ45 (c
26.16, 25.12, 24.42 (CCH3), 23.39, 22.09, 21.07, 20.98,
20.96 (5 ꢂCH3), 19.56 (C-7I). MALDI-TOF: m/z 746.3
[M+H] +, 768.3 [M+Na]+, 784.3 [M+K] +. ESIMS:
768.3065 [M+Na]+, calcd: 768.3055.
1.0, CHCl3); 1H NMR (CDCl3, 500 MHz, major isomer
is characterized): d 5.73–5.59 (m, 2H, H-6I, H-7I), 5.52
(d, 1H, J1,2 = 5.1 Hz, H-1I), 5.37–5.30 (m, 2H, H-8II,
H-7II), 5.18 (br d, 1H, NH), 4.85–4.77 (m, 1H, H-4II),
4.59 (dd, 1H, J3,2 = 7.9 Hz, J3,4 = 2.3 Hz, H-3I), 4.34
(dd, 1H, J9a,9b = 12.4 Hz, J9a,8 = 2.6 Hz, H-9aII), 4.31–
4.24 (m, 2H, H-2I, H-5I), 4.20 (dd, 1H, J4,3 = 7.9 Hz,
J4,5 = 1.9 Hz, H-4I), 4.08 (dd, 1H, J9b,9 a = 12.4 Hz,
J9b,8 = 5.6 Hz, H-9bII), 4.01–3.97 (m, 2H, H-5II, H-
1.9. 50-Acetamido-20,60-anhydro-30,50-dideoxy-20-C-(6,7,8-
trideoxy-D-galacto-octopyranos-8-yl)-D-erythro-L-man-
no-nonulosonic acid (11)
Compound 10 (62 mg, 83 lmol) was dissolved in meth-
anolic sodium methoxide solution (20 mL, 0.1 M) and
stirred for 5 h at room temperature. The solution was
then neutralized with Dowex 50X8 (H+) resin, filtrated
6II), 3.71 (s, 3H, OCH3), 2.52–2.43 (m, 3H, H-3II , H-
eq
8I), 2.11 (s, 6H, 2 ꢂ COCH3), 2.03 (s, 3H, COCH3),
2.00 (s, 3H, COCH3), 1.86 (s, 3H, COCH3), 1.77 (dd,

S. Meinke, J. Thiem / Carbohydrate Research 343 (2008) 1824–1829
1829
and concentrated. The residue was dissolved in water
References
and stirred with Dowex 50X8 (H+) resin overnight at
60 °C. After filtration, the solution was treated with
0.1 M sodium hydroxide solution. After stirring for
2 h, the solution was again neutralized with Dowex
50X8 (H+) resin, filtrated, purified over Biogel P2 and
lyophilized to give 11 (24 mg, 60%): mp 162–164 °C
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Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.carres.
2008.03.036.