Synthesis of C-disaccharides via a hetero-Diels-Alder reaction and further stereocontrolled transformations

Article abstract of DOI:10.1016/j.carres.2008.03.015

The partial de novo synthesis of two new C-disaccharides containing d-glucosamine is described. The strategy is based on a hetero-Diels-Alder reaction leading to a 1:1 mixture of separable cycloadducts, which have been stereoselectively functionalized and converted into α-d-Galp-(1→3)-C-d-GlcpNAc and α-l-Galp-(1→3)-C-d-GlcpNAc.

Full text of DOI:10.1016/j.carres.2008.03.015

Available online at www.sciencedirect.com
Carbohydrate Research 343 (2008) 1754–1765
Synthesis of C-disaccharides via a hetero-Diels–Alder
reaction and further stereocontrolled transformations
*
´
´
Qian Wan, Andre Lubineau, Regis Guillot and Marie-Christine Scherrmann
ICMMO Universite´ Paris-Sud 11, 91405 Orsay Cedex, France
Received 8 February 2008; received in revised form 5 March 2008; accepted 9 March 2008
Available online 14 March 2008
Abstract—The partial de novo synthesis of two new C-disaccharides containing D-glucosamine is described. The strategy is based on
a hetero-Diels–Alder reaction leading to a 1:1 mixture of separable cycloadducts, which have been stereoselectively functionalized
and converted into a-D-Galp-(1?3)-C-D-GlcpNAc and a-L-Galp-(1?3)-C-D-GlcpNAc.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: C-Glycoside; D-Glucosamine; Krapcho reaction; cis-Dihydroxylation
1. Introduction
of the human pathogen Shigella dysenteriae type 1 con-
tain an a-linked 2-acetamido-2-deoxy-D-glucopyranosyl
residue.8 Many studies have been carried out to achieve
the synthesis of the oligosaccharides that constitute the
repeating units of this lipopolysaccharide to better
understand the interactions between this antigen and
antibodies, with the final goal of developing a synthetic
vaccine.9 Our approach to a C-mimetic of part of this
antigenic determinant is based on a hetero Diels–Alder
reaction using diene 1,10 which could be prepared
efficiently in large scale, followed by stereo-controlled
transformations.
Numerous studies have been devoted to the synthesis of
C-glycosides,1,2 the carbon-linked analogues of natu-
rally occurring sugars, because these compounds are sta-
ble toward both enzymatic and chemical hydrolysis, and
show biological properties similar3 and even better4 than
those of the parent O-glycosides. To this end, several
methodologies were developed by some of us, for exam-
ple, the condensation of the carbanion of b-diketones
and a formyl group of unprotected sugars in aqueous
medium,5 the indium-promoted condensation of bromo-
enopyranosides with formyl C-glucoside,6 or the
Mukaiyama aldol reaction of the latter with silyl enol
ethers.7
2. Results and discussion
The partial de novo synthesis of C-disaccharide ana-
logues may offer the advantage of allowing stereochem-
ical variation leading to molecular diversity. Because
important naturally occurring oligosaccharides feature
a N-acetyl-glucosamine moiety substituted at the posi-
tion 3 by a galactose unit, we planned on synthesizing
carbon linked analogues of the disaccharides D-sugar-
(1?3)-GlcpNAc. In particular, oligosaccharides related
to the antigenic determinant of the O-specific side chain
To construct the heterocycle from diene 1,10 we first
envisaged the use of diethyl mesoxalate as the dienophile
because, due to its symmetry, only two diastereoisomers
resulting from the facial selectivity of the diene can be
obtained. Numerous examples of hetero-Diels–Alder
reactions involving diethyl mesoxalate have been
described,11 some of them being the key step of synthe-
ses of sugars.12 The hetero-Diels–Alder reaction between
1 and diethyl mesoxalate was carried out in toluene at
100 °C for 48 h to afford a 1:1 mixture of cycloadducts
2 and 3 in 82% yield (Scheme 1). The diastereoisomers
were separated by column chromatography followed
*
Corresponding author. Tel.: +33 1 69 15 72 56; e-mail: mcscherr@
icmo.u-psud.fr
0008-6215/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2008.03.015

Q. Wan et al. / Carbohydrate Research 343 (2008) 1754–1765
1755
O
O
EtO2C
O
O
toluene, 100 °C
O
O
O
+
+
O
O
O
CO2Et
82%
EtO2C
AcHN
AcHN
AcHN
OBn
O
OBn
OBn
CO2Et
1
2
3
CO2Et
O
(1 : 1)
CO2Et
Scheme 1. Hetero Diels–Alder reaction of diene 1 with diethyl mesoxalate.
O
O
O
O
O
O
LiCl, H2O
AcHN
OBn
+
2
AcHN
OBn
DMSO, 170 °C
98%
CO2Et
O
O
4
(20 : 1)
5
CO2Et
Scheme 2. Krapcho decarbethoxylation of compound 2.
by crystallization. The stereochemistry at C-10 for both
compounds was deduced from NOE experiments and
then confirmed by X-ray analysis.
of the substituents at positions 10 and 50 of the enopyr-
anoside ring, which adopts a HO half chair conforma-
tion (Fig. 1, R1 = H-50, R2 = CO2Et). In fact, the
alternative half chair conformation shown in Figure 1,
that is, OH5, was not compatible with the above-men-
tioned NOEs. From these observations, we could con-
5
The geminal diester 2 was then subjected to the Krap-
cho decarbethoxylation (Scheme 2).13 Under classical
conditions (LiCl, H2O, DMSO, 170 °C), the reaction
was very clean and gave the two diastereoisomers, 4
and 5, in 98% total yield and in a 20:1 ratio as shown
by 1H NMR analysis. The major diastereoisomer, 4,
was obtained in a pure form by column chromato-
graphy, whereas 5 was recovered together with trace
amounts of 4.
Having proven the absolute configuration at the ano-
meric carbon (C-10) of their precursor 2, the stereochem-
ical outcome of the decarbethoxylation was deduced
from NMR experiments. In the case of 4, the presence
of NOEs between H-7b and H-3, H-7a and H-10, H-10
and H-3 suggested the preferred relative orientation of
the two sugar units (Fig. 1). The NOE observed between
H-7b and H-50 allowed us to establish a trans disposition
clude that the newly formed ring belonged to the
D
stereochemical series. Therefore, 4 was bearing an a-D-
enopyranosidic moiety and 5 was bearing a b-L unit.
O
O
O
O
O
O
CO2Et
AcHN
AcHN
O
O
OBn
OBn
CO2Et
6
7
Treated under the same conditions, the geminal dies-
ter 3 afforded a 20:1 mixture of 6 and 7 in 98% yield.
The two products were isolated in a pure form by chro-
matography. The NOE experiments, confirmed by the
R2
H4
R1
O
H2
H7a
H7b
H4
O
O
O
O
H2
H7a
H7b
O
O
NHAc
H3
H1'
R1
OBn
NHAc
O
H3
H1'
R2
OBn
R1, R2 = CO2Et, H5'
Figure 1. Structure determination of compound 4 by NOE experiments.
5Ho half chair conformation
oH5 half chair alternative conformation

1756
Q. Wan et al. / Carbohydrate Research 343 (2008) 1754–1765
O
O
O
O
O
O
O
AcHN
AcHN
O
CO2Et
OBn
OBn
a or b
CO2Et
6
+
O
O
10
11
a : m-CPBA, CH2Cl2 (10 : 11 = 1 : 7)
O
, acetone (10 : 11 = 0 : 1)
b :
O
Scheme 3. Epoxidation of compound 6.
diffraction analysis. This analysis proved that the epox-
idation took place on the opposite face to the carboxy-
ethyl group (Fig. 3). As none of the conditions tested
to obtain crystals from 9 was satisfying, at this stage it
was assumed that the stereochemical outcome of the
epoxidation of 4 was the same as that for 6. However,
the structure of 9 was confirmed in the following steps
(vide infra). The use of dimethyloxirane gave quantita-
tively 11 from 6, but no improvement of the yield or
the selectivity of the epoxidation was observed when
these conditions were applied to 4.
The next task was to develop a suitable method to
transform the epoxides into allylic alcohols. Several
methods for this transformation are reported in the
literature. These involve, for instance, organoselenium
compounds,14 lithium amide bases,15 dialkylboryl
triflates, and tertiary amines,16 tert-butyldimethylsilyl
iodide,17 trimethylsilyl trifluoromethanesulfonate and
DBU,18 or methylmagnesium N-cyclohexylisopropyl-
amide.19 First, we tried the conditions described by Falk
and co-workers, involving the use of methylmagnesium
N-cyclohexylisopropylamide.19 Unfortunately, under
these conditions a complex mixture of products was
obtained, and the use of LDA or n-BuLi gave the same
results. Then, we turned to the conditions described by
Noyori and co-workers.18 Compound 9 was treated with
Figure 2. ORTEP depiction of compound 6.
X-ray analysis on the major isomer 6 (Fig. 2), led to the
conclusion that a trans orientation for the substituents
at C-10 and C-50 was obtained also in this case. Thus,
the configuration of the enopyranosidic moiety was a-
L in 6 (in a OH5 conformation) and b-D in 7.
Aiming to simplify the synthesis, we envisaged the
replacement of the two previous steps (cycloaddition
and Krapcho reaction) by a unique cycloaddition
involving ethyl glyoxalate. The reaction between the
latter and diene 1 was carried out in toluene at 125 °C
for 48 h to give a mixture of four diastereoisomers in
58% yield. Cycloadducts 4–7 were obtained in a
1:1.7:1:1.3 ratio as determined by 13C NMR analysis.
Unfortunately, these compounds were difficult to
separate and we returned to the two-step protocol.
To functionalize the 20, 30, and 40 positions, we first
planned to oxidize the allylic position (at C-40) and then
to hydroxylate the double bond. Using CrO3 in CH2Cl2,
we observed partial oxidation of the benzyl group into
benzoate, whereas the use of SeO2 as the oxidizing agent
was unsuccessful. Thus, we changed our strategy and
decided to first epoxidize the double bond and then
transform the epoxides into allylic alcohols. The major
isomers 4 and 6 were treated with m-CPBA to give the
diastereomeric epoxides 8 and 9 (1:4 ratio) and 10 and
11 (1:7 ratio, Scheme 3), respectively.
O
O
O
O
O
O
O
AcHN
AcHN
OBn
OBn
O
O
O
CO2Et
CO2Et
8
9
The stereochemistry of the epoxides was rather diffi-
cult to establish by NMR analysis; fortunately, we were
able to obtain 11 in a crystalline form suitable for X-ray
Figure 3. ORTEP depiction of compound 11.

Q. Wan et al. / Carbohydrate Research 343 (2008) 1754–1765
1757
0
0
TBDMSOTf and DBU in toluene, to obtain the allylic
ether 13 by electrophile-assisted opening of the epoxide
by TBDMSOTf, followed by the DBU-promoted
b-elimination of the triflate. After 20 h at room temper-
ature, we observed the total conversion of 9 (tlc analysis)
but NMR and MS analyses revealed the formation of
intermediate 12, which gave 13 upon further heating in
pyridine. On the basis of this result, we modified Noy-
ori’s procedure using TBDMSOTf and pyridine
(1.25 equiv) in toluene to open the epoxide, the reaction
mixture was then diluted with pyridine and heated to
55 °C to promote triflic acid elimination. This procedure
avoids the use of strong base (DBU) that could give side
reactions such as epimerization.
possessed the galacto configuration (J3 ;4 = 3.5 Hz,
0
0
0
0
J4 ;5 = 2.0 Hz, J2 ;3 = 10.0 Hz). Because this unit
belonged to the L series, as proven by the X-ray analysis
of its precursor, the vicinal coupling constant of the
anomeric proton (J1 ;2 = 5.5 Hz) allowed us to assign
the a-L absolute configuration at this residue.
Similarly, compound 15 was treated with LiBH4 to
reduce the ester, then with Bu4NF to remove the silyl
group at the position 20, and finally with Ac2O in pyridine
to acetylate the four hydroxyl groups. These three
sequential steps allowed us to obtain 20 in 83% yield. Also
in this case, the constructed C-pyranoside moiety adopted
a chair conformation after desilylation. The spectrum of
the acetylated derivative 20 clearly indicated the galacto
0
0
O
O
O
O
O
O
O
O
RO
O
RO
AcHN
AcHN
AcHN
O
OBn
OBn
OBn
CO2Et
RO
OTf
O
O
CO2Et
CO2Et
12
13
14
0
0
0
0
The same protocol applied to 11 gave 14 in 92% yield.
The two allylic silyl ethers 13 and 14 were then subjected
to cis-dihydroxylation (OsO4, NMO) to afford quantita-
tively 15 and 16, respectively, as single diastereoisomer.
At this stage, the stereochemistry of the diols was diffi-
cult to assign by NMR analysis, but it was anticipated
that an anti hydroxylation of the allylic ether occurred
as predicted by the Kishi model.20
relative configuration (J3 ;4 = 3.5, J4 ;5 = 2.0 Hz) and an
0
0
a-D absolute configuration (J1 ;2 = 5.5 Hz).
O
O
O
O
O
O
AcHN
OBn
AcHN
O
OR'
RO
AcO
OBn
O
OAc
R'O
R'O
OAc
AcO
19
17 R = SiMe2tBu; R' = H
18 R = SiMe2tBu; R' = Ac
O
O
O
O
O
O
RO
AcHN
AcHN
O
O
O
OBn
OBn
O
CO2Et
RO
OH
AcO
AcNH
HO
O
OBn
HO
AcO
AcO
15
16
O
CO2Et
HO
OAc
20
Reduction of the ethyl ester at C-50 of 16, performed
by means of LiAlH4 in THF, gave triol 17, characterized
3. Conclusion
1
as the tri-acetate 18. Although all the signals of the H
NMR spectrum could be assigned, the configurations
of C-30 and C-40 could not be established because the
newly formed heterocycle did not adopt a chair confor-
mation as shown by the relevant coupling constants
In this paper, we have shown that the hetero-Diels–
Alder reaction involving benzyl 2-acetamido-2,3-dide-
oxy-4,6-O-isopropylidene-3-C-(10-pentadienyl)-a-D-gluco-
pyranoside 1 and diethyl mesoxalate is a good entry to
the preparation of two C-disaccharides. Each cycload-
duct was transformed in seven stereoselective steps
affording a-D-Galp-(1?3)-C-D-GlcpNAc derivatives 20
in 59% total yield and in a-L-Galp-(1?3)-C-D-GlcpNAc
19 in 62% total yield.
0
0
0
0
0
0
0
0
=
(J1 ;2 = 3.5 Hz, J2 ;3 = 6.8 Hz, J3 ;4 = 3.4 Hz, J4 ;5
4.1 Hz). Treatment of 18 with Bu4NF followed by
acetylation of the free hydroxyl groups gave 19. The
1H NMR spectrum of 19 clearly indicated that the
C-pyranoside unit was in a chair conformation and

1758
Q. Wan et al. / Carbohydrate Research 343 (2008) 1754–1765
4. Experimental
J = 11.5, J7a,7b = 14.5 Hz, H-7b), 1.34 (s, 3H, CH3),
1.26 (t, 3H, J = 7.4 Hz, CH3), 1.24 (t, 3H, CH3);
13C NMR (CDCl3, 100 MHz): d 170.72 (NHCOCH3),
168.6 (CO2Et), 167.8 (CO2Et), 138.0, 128.9 (C-30),
128.1, 127.3, 127.1, 122.1 (C-20), 99.3 (CH3CO), 96.8
(C-1), 79.7 (C-50), 74.3 (C-4), 72.0 (C-10), 69.1
(PhCH2), 65.9 (C-5), 62.8 (C-6), 62.0 (CH2), 61.9
(CH2), 53.0 (C-2), 36.0 (C-3), 33.2 (C-7), 29.2 (CH3),
29.1 (C-40), 22.8 (COCH3), 19.2 (CH3), 14.0
(CH2CH3), 14.0 (CH2CH3). ESIMS m/z: calcd for
[C30H41NO10+Na]+: 598.2628. Found: 598.2620. Anal.
Calcd for C30H41NO10: C, 62.57; H, 7.18; N, 2.43.
Found: C, 62.83; H, 7.25; N, 2.39.
4.1. General
Melting points were determined with a capillary appara-
tus and are uncorrected. NMR spectra were recorded at
rt with Bruker AC 400 spectrometer. Mass spectrometry
was recorded on a MAT 95S instrument. Elemental
analyses were performed at the C. N. R. S. Microanalyt-
ical Laboratory (Gif sur Yvette, France). All moisture-
sensitive reactions were performed under an argon
atmosphere using oven-dried glassware. All solvents
were dried over standard drying agents and freshly dis-
tilled prior to use. Flash column chromatography was
performed with Silica Gel 60A C. C. (6–35 lm, SDS).
Reactions were monitored by TLC using Silica Gel 60
F254 with detection by UV light (254 nm) and by char-
ring with sulfuric acid.
Eluted second was 3 contaminated by 2 (1.07 g). Crys-
tallization from diethyl ether afforded pure 3 (784 mg,
30
32%) as white crystals. ½aꢀD 25 (c 1.15, CHCl3); mp
116 °C; IR (KBr, m cmꢁ1): 3380, 2982, 2934, 2909,
2869, 2843, 1748, 1732, 1674, 1527, 1386, 1371, 1306,
1291, 1263, 1206, 1190, 1129, 1082, 1054, 1035, 958,
1
4.2. Benzyl 2-acetamido-2,3-dideoxy-3-C-[(ethyl (10R)-
20,30,40-trideoxy-50-C-ethoxycarbonyl-hex-20-enopyr-
anosyluronate)methyl]-4,6-O-isopropylidene-a-D-gluco-
pyranoside (2) and benzyl 2-acetamido-2,3-dideoxy-3-C-
[(ethyl (10S)-20,30,40-trideoxy-50-C-ethoxycarbonyl-hex-20-
enopyranosyluronate)methyl]-4,6-O-isopropylidene-a-D-
glucopyranoside (3)
858, 742, 691, 649; H NMR (C6D6, 400 MHz): d 7.41
(d, 1H, JNH,2 = 7.8 Hz, NH), 7.29 (d, 2H, J = 7.8 Hz,
Ph), 7.20–7.14 (m, 3H, Ph), 5.62–5.50 (m, 2H, H-20, H-
30), 5.20 (d, 1H, J1,2 = 2.9 Hz, H-1), 4.62–4.55 (m, 1H,
H-10), 4.58 (d, 1H, J = 12.7 Hz, PhCH2), 4.38 (ddd,
1H, J1,2 = 2.9, JNH,2 = 7.8, J2,3 = 11.7 Hz, H-2), 4.28
(d, 1H, J = 12.7 Hz, PhCH2), 3.97 (dd, 2H, J = 6.8,
J = 13.6 Hz, CH2CH3), 3.94–3.80 (m, 4H, CH2CH3,
H-5, H-6a), 3.66 (t, 1H, J6a,6b ꢂ J5,6b = 10.3 Hz, H-
6b), 3.24 (dd, 1H, J4,5 = 10.3, J3,4 = 9.3 Hz, H-4), 2.80
A solution of diene-E 1 (1.71 g, 4.26 mmol) and
diethyl mesoxalate (3.8 mL, 10.16 mmol) in freshly
distilled toluene (40 mL) was heated at 100 °C for 43
h. The reaction mixture was cooled to room tempera-
ture, diluted with toluene (40 mL), washed with water
until a neutral solution was obtained, dried (MgSO4),
and concentrated. Column chromatography over silica
gel using 20:1?4:1 CH2Cl2–Et2O gave a 1:1 mixture
of the two cycloadducts 2 and 3 (2.01 g, 3.49 mmol,
82%). A second flash chromatography gave first pure
2 (940 mg, 38%). Recrystallization from diethyl ether
or petroleum ether–EtOAc afforded 2 as white crys-
(ddd, 1H, J = 2.9, J = 4.9, J4a0;4b = 17.1 Hz, H-4b0),
0
2.35–2.25 (m, 2H, H-3, H-4a0), 2.20 (s, 3H, NHCOCH3),
1.84 (dt, 1H, J = 4.9, J7a,7b = 14.7 Hz, H-7a), 1.63 (dt,
1H, J = 2.9, J7a,7b = 14.7 Hz, H-7b), 1.40 (s, 3H,
CH3), 1.23 (s, 3H, CH3), 0.91 (t, 3H, J = 6.8 Hz,
CH2CH3), 0.85 (t, 3H, J = 6.8 Hz, CH2CH3); NMR
13C (C6D6, 100 MHz): d 170.3 (NHCOCH3), 169.3
(CO2Et), 168.1 (CO2Et), 138.8, 129.6, 128.4, 127.6,
127.5, 122.7 (C-20), 99.3 (2CH3C), 97.9 (C-1), 80.0
(C-50), 74.0 (C-4), 71.0 (C-10), 69.5 (PhCH2), 66.5
(C-5), 63.1 (C-6), 62.0 (CH2), 61.7 (CH2), 54.0 (C-2),
36.0 (C-3), 34.2 (C-7), 31.7 (CH3), 29.5 (C-40), 23.0
(COCH3), 19.3 (CH3), 14.0 (CH2CH3), 13.8 (CH2CH3);
ESIMS m/z: calcd for [C30H41NO10+Na]+: 598.2628.
Found, 598.2628. Anal. Calcd for C30H41NO10: C,
62.57; H, 7.18; N, 2.43. Found: C, 62.83; H, 7.25; N,
2.39.
30
tals. ½aꢀD 127 (c 1.0, CHCl3); mp 110 °C; IR (KBr, m
cmꢁ1): 3399, 3063, 3034, 2981, 2947, 2928, 2910,
2878, 2848, 1761, 1742, 1672, 1520, 1470, 1455,
1427, 1372, 1259, 1207, 1188, 1145, 1084, 1063,
1001, 955, 855, 739; 1H NMR (CDCl3, 400 MHz): d
7.40–7.23 (m, 5H, Ph), 6.95 (d, 1H, JNH,2 = 8.5 Hz,
NH), 5.82–5.73 (m, 1H, H-20), 5.66–5.58 (m, 1H,
H-30), 4.94 (d, 1H, J1,2 = 3.4 Hz, H-1), 4.77 (d, 1H,
J = 12.5 Hz, PhCH2), 4.52 (d, 1H, PhCH2), 4.39–4.29
(m, 1H, CH2CH3), 4.20–4.29 (m, 2H, CH2CH3),
4.16–4.05 (m, 2H, CH2CH3, H-10), 3.95 (dt, 1H,
J1,2 = 3.4, JNH,2 = 8.5, J2,3 = 12.0 Hz, H-2), 3.85–3.77
(m, 1H, H-6a), 3.75–3.66 (m, 2H, H-5, H-6b), 3.48–
3.40 (m, 1H, H-4), 2.98–2.83 (m, 1H, H-4a0), 2.41–
2.28 (m, 2H, H-3, H-4b0), 1.97 (s, 3H, NCOCH3),
4.3. Benzyl 2-acetamido-2,3-dideoxy-3-C-(ethyl 20,30,40-
trideoxy-a-D-glycero-hex-20-enopyranosyluronate)-
methyl-4,6-O-isopropylidene-a-D-glucopyranoside (4)
and benzyl 2-acetamido-2,3-dideoxy-3-C-(ethyl 20,30,40-
trideoxy-b-L-glycero-hex-20-enopyranosyluronate)methyl-
4,6-O-isopropylidene-a-D-glucopyranoside (5)
0
1.71(td, 1H, J3,7a ꢂ J1 ;7a = 3.5, J7a,7b = 14.5 Hz,
To a solution of compound 2 (950 mg, 1.65 mmol) and
lithium chloride (210 mg, 4.95 mmol, 3 equiv) in freshly
H-7a), 1.47 (s, 3H, CH3), 1.41 (dt, 1H, J = 3.4,

Q. Wan et al. / Carbohydrate Research 343 (2008) 1754–1765
1759
dried and distilled DMSO (10 mL) was added 35 lL
water. The mixture was heated at 170 °C for 3 h,
cooled to room temperature, and water was added.
The products were extracted into diethyl ether; the
extracts were dried by Na2SO4 and evaporated to dry-
ness to give 814 mg (98%) of a 20:1 mixture of 4 and 5.
Flash chromatography (1:1 toluene–EtOAc) of the res-
idue led first to 750 mg of compound 4 as a foam
4.4. Benzyl 2-acetamido-2,3-dideoxy-3-C-(ethyl 20,30,40-
trideoxy-a-L-glycero-hex-20-enopyranosyluronate)methyl-
4,6-O-isopropylidene-a-D-glucopyranoside (6) and benzyl
2-acetamido-2,3-dideoxy-3-C-(ethyl 20,30,40-trideoxy-b-D-
glycero-hex-20-enopyranosyluronate)methyl-4,6-O-isopro-
pylidene-a-D-glucopyranoside (7)
Compound 3 (820 mg, 1.42 mmol) was treated as
described for compound 2 to give 700 mg (98%) of a
20:1 mixture of 6 and 7. Flash chromatography (1:1 tol-
25
(1.49 mmol, 90%). ½aꢀD 43 (c 1.1, CHCl3); IR (KBr, m
cmꢁ1): 3331, 2992, 2941, 1738, 1661, 1524, 1456,
1372, 1268, 1207, 1182, 1122, 1080, 1040, 942, 855,
738, 699; 1H NMR (CDCl3, 400 MHz): d 7.32–7.20
(m, 5H, Ph), 5.92 (d, 1H, JNH,2 = 9.8 Hz, NH), 5.73–
5.64 (m, 1H, H-30), 5.60–5.53 (m, 1H, H-20), 4.72 (d,
1H, J1–2 = 2.9 Hz, H-1), 4.65 (d, 1H, J = 11.7 Hz,
PhCH2), 4.44–4.35 (m, 1H, H-10), 4.39 (d, 1H,
J = 11.7 Hz, PhCH2), 4.05–4.18 (m, 3H, H-50,
CH2CH3), 3.93 (ddd, 1H, J1,2 = 2.9, JNH,2 = 9.8,
J2,3 = 12.7 Hz, H-2), 3.75–3.58 (m, 3H, H-5, H-6a,
H-6b), 3.41 (t, 1H, J3,4 ꢂ J4,5 = 9.8 Hz), 2.36–2.26 (m,
1H, H-4a), 2.22–2.09 (m, 2H, H-3, H-4b), 1.83 (s,
3H, NHCOCH3) 1.63–1.54 (m, 1H, H-7b), 1.40 (s,
1H, CH3), 1.41–1.32 (m, 1H, H-7a), 1.29 (s, 3H,
CH3), 1.17 (t, 3H, J = 7.8 Hz, CH2CH3); 13C NMR
(CDCl3, 100 MHz): d 171.5 (CONH), 170.0 (CO),
137.3 (Ph), 129.9 (Ph), 128.5 (Ph), 128.0 (Ph), 127.9
(Ph), 122.3 (C-20, C-30), 99.3 (CH3OCOCH3), 96.4
(C-1), 75.1 (C-4), 72.8 (C-10), 69.5 (CH2Ph), 67.7
(C-50), 65.1 (C-5), 62.7 (C-6), 61.1 (CH3CH2), 51.6
(C-2), 36.9 (C-3), 33.0 (C-7), 29.1 (CH3), 26.9 (C-40),
22.9 (NHCOCH3), 19.1 (CH3), 14.1 (CH2CH3); IR
(KBr, m cmꢁ1): 3331, 2992, 2941, 1738, 1661, 1524,
1456, 1372, 1268, 1207, 1182, 1122, 1080, 1040, 942,
855, 738, 699. ESIMS m/z: calcd for [C27H37NO8+
Na]+: 526.2417. Found: 526.2420. Anal. Calcd for
C27H37NO8: C, 64.40; H, 7.41; N, 2.78. Found: C,
64.19; H, 7.56; N, 2.67.
26
uene–EtOAc) led first to 30 mg (4%) of 7. ½aꢀD 54 (c 1.0,
CHCl3); IR (NaCl, m cmꢁ1): 3368, 3035, 2990, 2928,
2871, 1747, 1673, 1527, 1498, 1456, 1375, 1288, 1268,
1
1218, 1190, 1123, 1082, 1045, 944, 859, 734, 698; H
NMR (CDCl3, 400 MHz): d 7.29–7.16 (m, 5H, Ph),
7.05 (d, 1H, JNH,2 = 8.0 Hz, NHCOCH3), 5.82–5.73
(m, 1H, H-30), 5.53–5.46 (m, 1H, H-20), 4.89 (d, 1H,
J1,2 = 3.5 Hz, H-1), 4.66 (d, 1H, J = 12.4 Hz, PhCH2),
4.41 (d, 1H, J = 12.4 Hz, PhCH2), 4.36–4.29 (m, 1H,
H-10), 4.24–4.10 (m, 3H, CH3CH2, H-50), 3.82 (ddd,
1H, J1,2 = 3.5, JNH,2 = 8.0, J2,3 = 12.0 Hz, H-2), 3.77–
3.66 (m, 1H, H-6a), 3.65–3.54 (m, 2H, H-5, H-6b),
3.33–3.24 (m, 1H, H-4), 2.21–2.13 (m, 2H, H-4a0,
H-4b0), 2.07–1.98 (m, 1H, H-3), 1.96 (s, 3H,
0
NHCOCH3), 1.68 (td, 1H, J1 ;7a = J3,7a = 3.0, J7a,7b
=
15.0 Hz, H-7a), 1.60 (td, 1H, J1,7b = J3,7b = 5.0,
J7a,7b = 15.0 Hz, H-7b), 1.39 (s, 3H, CH3), 1.29 (s, 3H,
CH3), 1.20 (t, 3H, J = 7.5 Hz, CH2CH3); 13C NMR
(CDCl3, 100 MHz): d 171.5, 171.0, 138.1, 130.0, 128.1,
127.3, 127.1, 123.7, 99.2, 96.8, 73.5, 73.0, 71.9, 69.1,
65.8, 62.8, 61.0, 53.7, 33.3, 31.3, 29.2, 27.8, 22.8, 19.1,
14.2. ESIMS m/z: calcd for [C27H37NO8+H]+:
504.2597. Found: 504.2599. Anal. Calcd for
C27H37NO8: C, 64.40; H, 7.41; N, 2.78. Found: C,
64.24; H, 7.54; N, 2.61.
29
Eluted second was 6 (620 mg, 1.24 mmol, 87%). ½aꢀD
129 (c 01.0, CHCl3); mp 142°C; IR (NaCl, m cmꢁ1):
3318, 3035, 2992, 2938, 2874, 1739, 1658, 1538, 1456,
1373, 1291, 1267, 1199, 1183, 1118, 1076, 1041, 943,
857, 736, 700; 1H NMR (CDCl3, 400 MHz): d 7.40–
7.29 (m, 5H, Ph), 5.96 (d, 1H, JNH,2 = 9.4 Hz, NH),
5.82–5.76 (m, 1H, H-30), 5.73–5.76 (m, 1H, H-20), 4.76
(d, 1H, J1,2 = 3.7 Hz, H-1), 4.71 (d, 1H, J = 11.9 Hz,
PhCH2), 4.52 (m, 1H, H-10), 4.45 (d, 1H, J = 11.9 Hz,
PhCH2), 4.36 (dd, 1H, J = 5.3 Hz, J = 7.0 Hz, H-50),
4.20 (q, 2H, J = 7.0 Hz, CH2CH3), 4.09 (ddd, 1H,
J1,2 = 3.7, JNH,2 = 9.4, J2,3 = 11.5 Hz, H-2), 3.81 (dt,
1H, J = 2.5, J = 5.0 Hz, H-6a), 3.73–3.67 (m, 2H, H-5,
H-6b), 3.40 (m, 1H, H-4), 2.35–2.30 (m, 2H, H-4a0,
H-4b0), 2.17–2.07 (m, 1H, H-3), 1.92 (s, 3H,
NHCOCH3), 1.80 (ddd, 1H, J = 4.1, J = 9.4,
0
Eluted second was 5 contaminated by 4 (60 mg, 7%).
1H NMR (CDCl3, 250 MHz): d 7.42–7.22 (m, 5H, Ph),
7.09 (d, 1H, JNH,2 = 8.5 Hz, NHCOCH3), 5.83–5.72
(m, 1H, H-30), 5.66–5.58 (m, 1H, H-20), 4.94 (d, 1H,
J1,2 = 3.5 Hz, H-1), 4.72 (d, 1H, J = 12.0 Hz, PhCH2),
4.52 (d, 1H, J = 12.4 Hz, PhCH2), 4.36–4.29 (m, 1H,
H-10), 4.30–4.10 (m, 3 H, CH3CH2, H-50), 3.89 (ddd,
1H, J1,2 = 3.5, JNH,2 = 8.5 Hz, J2,3 = 12.5 Hz, H-2),
3.83–3.67 (m, 3H, H-6a, H-5, H-6b), 3.43 (t, 1H,
J3,4 ꢂ J4,5 = 9.8 Hz, H-4), 2.40–2.18 (m, 3H, H-4a0,
H-4b0, H-3), 1.95 (s, 3 H, NHCOCH3), 1.72 (td, 1H,
J = 3.5, J7a,7b = 14.5 Hz, H-7a), 1.47 (s, 1H, CH3),
1.37 (s, 3H, CH3), 1.35–1.21 (m, 4H, CH2CH3,
H-7b); 13C NMR (CDCl3, 100 MHz): d 171.5, 169.9,
155.8, 129.8, 128.4, 128.0, 127.9, 122.3, 99.2, 96.3,
75.0, 72.7, 69.4, 67.6, 65.0, 62.6, 61.1, 51.5, 40.8,
36.8, 29.1, 26.8, 22.9, 19.0, 14.1. ESIMS m/z:
calcd for [C27H37NO8+Na]+: 526.2417. Found:
526.2428.
J7a,7b = 14.4 Hz, H-7a), 1.50 (td, 1H, J1 ;7b = J3,7b
=
6.6, J7a,7b = 14.4 Hz, H-7b), 1.47 (s, 3H, CH3), 1.36 (t,
J = 7.0 Hz, CH2CH3), 1.27 (t, J = 7.0 Hz, CH2CH3);
13C NMR (CDCl3, 100 MHz): d 171.8 (CONH), 169.9
(CO), 137.3 (Ph), 129.8 (Ph), 128.5 (Ph), 128.0 (Ph),

1760
Q. Wan et al. / Carbohydrate Research 343 (2008) 1754–1765
122.5 (C-20, C-30), 99.4 (2 ꢃ CH3OC), 96.3 (C-1), 73.1
(C-4), 70.6 (C-10), 69.45 (PhCH2), 67.5 (C-50), 65.1
(C-5), 62.7 (C-6), 60.9 (CH2CH3), 52.9 (C-2), 35.5
(C-3), 33.0 (C-7), 29.1 (CH3), 27.3 (C-40), 23.3
(NHCOCH3), 19.1 (CH3), 14.2 (CH2CH3). ESIMS m/
z: calcd for [C27H37NO8+Na]+: 526.2417, found,
526.2418. Anal. Calcd for C27H37NO8: C, 64.40; H,
7.41; N, 2.78. Found: C, 64.11; H, 7.38; N, 2.58.
oxirane in acetone (1.5 mL, 0.09–0.11 M) until complete
disappearance of the starting material by TLC analysis
(1.2:1 EtOAc–CH2Cl2). The reaction mixture was con-
centrated under reduced pressure to afford pure 11
28
(51 mg, 100%) as a white solid. ½aꢀD 116 (c 1.0, CHCl3);
mp 143 °C; IR (NaCl, m cmꢁ1): 3317, 2992, 2926, 1735,
1662, 1533, 1455, 1380, 1267, 1200, 1123, 1071, 1039,
942, 853, 735, 700; 1H NMR (CDCl3, 400 MHz): d
7.49–7.29 (m, 5H, Ph), 5.81 (d, 1H, JNH,2 = 9.7 Hz,
NHCOCH3), 4.75 (d, 1H, J1,2 = 3.7 Hz, H-1), 4.70 (d,
4.5. Benzyl 2-acetamido-2,3-dideoxy-3-C-(ethyl 20,30-
anhydro-40-deoxy-a-D-lyxo-hexopyranosyluronate)-
methyl-4,6-O-isopropylidene-a-D-glucopyranoside (8)
and benzyl 2-acetamido-2,3-dideoxy-3-C-(ethyl 20,30-
anhydro-40-deoxy-a-D-ribo-hexopyranosyluronate)-
methyl-4,6-O-isopropylidene-a-D-glucopyranoside (9)
0
0
1H, J = 12.0 Hz, PhCH2), 4.59 (ddd, 1H, J3 ;5 = 3.5,
J4 b;5 = 7.3, J4 a;5 = 9.5 Hz, H-50), 4.46 (d, 1H,
J = 12.0 Hz, PhCH2), 4.20 (q, 2H, J = 7.1 Hz,
CH3CH2), 4.13 (dd, 1H, J1,7a = 3.5, J = 10.8 Hz, H-10),
4.07 (ddd, 1H, J = 3.7, J = 9.7 Hz, J = 11.5 Hz, H-2),
3.86–3.65 (m, 3H, H-5, H-6a, H-6b), 3.55–3.43 (m, 2H,
0
0
0
0
H-20, H-4), 3.32 (t, 1H, J3 ;5 = 3.5, J = 4.0 Hz, H-30),
0
0
A solution of 4 (78 mg, 0.15 mmol) in CH2Cl2 (2 mL) was
treated with 3-chloroperoxybenzoic acid (53.5 mg) over-
night at room temperature, then additional m-CPBA
(20 mg) was added. After 3 h, the TLC analysis (6:5
EtOAc–CH2Cl2) revealed the complete disappearance
of the starting material. The reaction mixture was diluted
with CH2Cl2, washed with saturated aqueous solution of
NaHCO3 and brine, dried (MgSO4) and concentrated.
Flash chromatography (1:3 EtOAc–CH2Cl2) of the resi-
due gave a 1:4 mixture of the two epoxides 8 and 9
(73 mg, 0.14 mmol, 91%). Pure 9 (56 mg) was obtained
by a second flash chromatography (1:4 EtOAc–CH2Cl2).
0
2.29 (ddd, 1H, J3,7a = 2.5, J1 ;7a = 3.5 J7a,7b = 14.5 Hz,
H-7a), 2.04–1.91 (m, 2H, H-7b, H-3), 1.97 (s, 3H,
NHCOCH3), 1.86 (ddd, 1H, J = 3.5, J = 9.5,
J4 a;4 b = 13.5 Hz, H-40a), 1.70 (dt, 1H, J4 b;5 = 7.3,
0
0
0
0
J4 a;4 b = 13.5 Hz, H-40b), 1.49 (s, 3H, CH3), 1.36 (s,
3H, CH3), 1.27 (t, 3H, J = 7.1, CH2CH3); 13C NMR
(CDCl3, 100 MHz): d 171.6, 170.1, 137.1, 128.6, 128.1,
128.1, 99.4, 96.2, 74.5, 69.6, 69.6, 65.0, 64.7, 62.7, 61.2,
52.5, 52.0, 51.7, 36.1, 29.9, 29.1, 28.3, 23.3, 19.1 14.1.
ESIMS m/z: calcd for [C27H37NO9+ Na]+: 542.2366.
Found: 542.2376. Anal. Calcd for C27H37NO9: C,
62.41; H, 7.18; O, 27.71; N, 2.70. Found: C, 62.64; H,
7.42; O, 27.58; N, 2.73.
0
0
26
½aꢀD 70 (c 1.0, CH2Cl2); 1H NMR (CDCl3, 400 MHz): d
7.38–7.28 (m, 5H, Ph), 5.87 (d, 1H, JNH,2 = 9.5 Hz,
NHCOCH3), 4.80 (d, 1H, J1,2 = 3.7 Hz, H-1), 4.72 (d,
1H, J = 11.7 Hz, PhCH2), 4.45 (d, 1H, J = 11.7 Hz,
4.7. Benzyl 2-acetamido-2,3-dideoxy-3-C-(ethyl 20-
tbutyldimethylsilyl-30,40-dideoxy-a-D-erythro-hex-30-
enopyranosyluronate)methyl-4,6-O-isopropylidene-
a-D-glucopyranoside (13)
0
0
PhCH2), 4.36 (ddd, 1H, J1 ;7a = 10.5, J1 ;7b = 2.5,
J1 ;2 = 3.0 Hz, H-10), 4.17 ad 4.18 (dq, 2H, J = 1.5,
0
0
0
J = 7.3 Hz, CH2CH3), 4.11 (dd, 1H, J4a0;5 = 3.7,
J4b ;5 = 9.5 Hz, H-50), 4.05 (ddd, 1H, J1,2 = 3.7,
JNH,2 = 9.5, J2,3 = 11.7 Hz, H-2), 3.80 (dd, 1H, J = 3.7,
J = 8.1 Hz, H-6a), 3.77–3.66 (m, 2H, H-5, H-6b), 3.58–
0
0
To a solution of t-butyldimethylsilyl trifluoromethane-
sulfonate (244 mg, 212 lL, 0.924 mmol) in dry toluene
(0.6 mL) was added a solution of epoxide 9 (200 mg,
0.385 mmol) and dry pyridine (61 mg, 62 lL,
0.77 mmol) in dry toluene (1.5 mL). After 10 min at
room temperature, an additional 31 lL of pyridine
was added. The solution was stirred for 1 h until disap-
pearance of the starting material by TLC analysis (3:2
toluene–EtOAc), then diluted with pyridine (10.0 mL),
and heated at 55 °C for 1 h. The solution was concen-
trated and the residue purified by flash chromatography
(95:5?80:20 CH2Cl2–Et2O) to give 13 (192 mg,
3.52 (m, 1H, H-4), 3.41 (m, 1H, J3 ;4a0 = 2.2 Hz, H-30),
0
3.15 (dd, J1 ;2 = 3.0, J2 ;3 = 4.0 Hz, H-20), 2.24 (ddd,
0
0
0
0
J3 ;4 a = 2.2, J4 a;5 = 3.7, J4 a;4 b = 14.7 Hz, H-4a0), 2.20–
2.07 (m, 2H, H-3, H-4b0), 1.96–1.85 (m, 1H, H-7a),
1.87 (s, 3H, NHCOCH3), 1.54–1.45 (m, 1H, H-7b),
1.47 (s, 3H, CH3), 1.37 (s, 3H, CH3), 1.22 (t, 3H,
J = 7.3 Hz, CH2CH3); 13C NMR (CDCl3, 62.9 MHz): d
171.6, 169.9, 137.3, 128.5, 128.0, 127.9, 99.3, 96.3, 74.8,
70.8, 69.4, 65.2, 62.6, 61.4, 53.2, 51.2, 50.6, 36.5, 29.1,
28.5, 27.2, 22.9, 19.4, 14.0. ESIMS m/z: calcd for
[C27H37NO9+Na]+: 542.2366. Found: 542.2378.
0
0
0
0
0
0
27
0.303 mmol, 90%). ½aꢀD 128 (c = 0.7, CHCl3); IR
(KBr, m cmꢁ1): 3300, 2928, 1731, 1664, 1535, 1462,
1370, 1255, 1188, 1120, 1074, 1036.4, 936, 836, 775,
736, 699; 1H NMR (CDCl3, 400 MHz): d 7.37–7.28
(m, 5H, Ph), 6.25 (d, 1H, JNH,2 = 8.5 Hz, NH), 6.05
4.6. Benzyl 2-acetamido-2,3-dideoxy-3-C-(ethyl 20,30-
anhydro-40-deoxy-a-L-ribo-hexopyranosyluronate)-
methyl-4,6-O-isopropylidene-a-D-glucopyranoside (11)
(dd, 1H, J4 ;5 = 3.7, J3 ;4 = 10.1 Hz, H-40), 5.98 (ddd,
0
0
0
0
1H, J3 ;5 = 2.3, J2 ;3 = 5.1, J3 ;4 = 10.1 Hz, H-30), 4.93
0
0
0
0
0
0
A solution of 6 (50 mg, 99 lmol) in CH2Cl2 (7.5 mL)
was treated at 0 °C for 5 h with a solution of dimethyl-
0
0
(d, 1H, J1,2 = 3.5 Hz, H-1), 4.76 (dd, 1H, J3 ;5 = 2.3,

Q. Wan et al. / Carbohydrate Research 343 (2008) 1754–1765
1761
J4 ;5 = 3.7 Hz, H-50), 4.74 (d, 1H, J = 11.8 Hz, PhCH2),
4.48 (d, 1H, J = 11.8 Hz, PhCH2), 4.18 (m, 2H,
CH3CH2), 4.06 (ddd, 1H, J1,2 = 3.5, JNH,2 = 8.5,
J2,3 = 12.0 Hz, H-2), 3.91 (m, 1H, H-10), 3.84–3.66 (m,
J = 2.0,
J2 ;3 = 5.0 Hz,
H-20),
3.37
(t,
1H,
0
0
0
0
J3,4 ꢂ J4,5 = 10.0 Hz, H-4), 2.95 (m, 1H, H-3), 2.75
(m, 1H, H-7a), 1.94 (s, 3H, NHCOCH3), 1.50, 1.35
(2 ꢃ s, 6H, CH3), 1.22 (m, 1H, H-7b), 0.99 (s, 9H,
3 ꢃ CH3), 0.81 (t, J = 7.3 Hz, CH2CH3), 0.05, 0.04
(2 ꢃ s, 6H, CH3); 13C NMR (C6D6, 100 MHz): d
171.7 (NHCO), 169.0 (OCOCH3), 138.8 (Ph), 129.6
(C-30), 128.5 (Ph), 127.8 (Ph), 127.6 (Ph), 126.5 (C-40),
99.7 ((CH3)2CO2), 99.7 (C-1), 73.27 (C-40), 72.90 (C-
10), 72.42 (C0-5), 69.6 (PhCH2), 66.1 (C0-5), 64.5 (C0-
2), 63.4 (C-6), 61.0 (CH3CH2), 54.9 (C-2), 34.1 (C-3),
30.5 (C-7), 29.7 (CH3), 26.1 (Si(CH3)3), 23.0
(NHCOCH3), 19.3 (CH3), 14.0 (CH3CH2), ꢁ3.6, ꢁ4.5
(SiCH3); ESIMS m/z: calcd for [C33H51NO9Si+Na]+:
656.3231. Found, 656.3231. Anal. Calcd for
C33H51NO9Si: C, 62.53; H, 8.11; N, 2.21. Found: C,
62.55; H, 8.35; N, 2.15.
0
0
4H, H-4, H-5, H-6a, H-6b), 3.77 (dd, 1H, J1 ;2 = 2.5,
J2 ;3 = 5.1 Hz, H-20), 2.26–2.16 (m, 1H, H-3), 1.91 (s,
3H, NHCOCH3), 1.78 (ddd, 1H, J = 3.5, J7a,7b = 15.0,
J = 10.0 Hz, H-7a), 1.51 (dd, J = 3.5, J = 15.0 Hz,
H-7b), 1.46 (s, 3H, CH3), 1.36 (s, 3H, CH3), 1.25 (t,
3H, J = 7.2 Hz, CH2CH3), 0.88 (s, 9H, 3 ꢃ CH3), 0.06
(s, 6H, 2 ꢃ CH3); 13C NMR (CDCl3, 100 MHz): d
170.5, 169.9, 137.6, 128.8, 128.4, 127.8, 127.8, 126.1,
99.5, 96.7, 75.2, 73.3, 72.7, 69.5, 65.6, 64.5, 62.9, 61.4,
52.0, 37.8, 19.7, 29.2, 28.9, 25.9, 23.2, 19.1, 18.3, 14.2,
ꢁ4.2, ꢁ4.6. ESIMS m/z: calcd for [C33H51NO9Si+Na]+:
656.3231. Found: 656.3234. Anal. Calcd for
C33H51NO9Si: C, 62.53; H, 8.11; N, 2.21. Found: C,
62.56; H, 8.23; N, 2.11.
0
0
4.9. Benzyl 2-acetamido-2,3-dideoxy-3-C-(ethyl 20-
tbutyldimethylsilyl-a-L-galactopyranosyluronate)methyl-
4,6-O-isopropylidene-a-D-glucopyranoside (16)
4.8. Benzyl 2-acetamido-2,3-dideoxy-3-C-(ethyl 20-
tbutyldimethylsilyl-30,40-dideoxy-a-L-erythro-hex-30-
enopyranosyluronate)methyl-4,6-O-isopropylidene-
a-D-glucopyranoside (14)
To a solution of 14 (80 mg, 126 lmol) and NMO
(35 mg, 258 lmol) in 8:1 acetone–water (4 mL) was
Epoxide 11 (32 mg, 0.06 mmol) was treated as de-
scribed for 9 to give, after flash chromatography
added
a
solution of OsO4 (3.1 lmol, 15.5 lL,
0.025 equiv) in THF (0.2 M). The mixture was stirred
at room temperature for 48 h and then concentrated.
Flash chromatography of the residue (2:100 MeOH–
CH2Cl2) gave 16 (82 mg, 123 lmol, 97%) as a white
27
(19:1?4:1 CH2Cl2–Et2O), 35 mg of 14 (92%). ½aꢀD
129 (c 0.7, CHCl3); IR (KBr, m cmꢁ1): 3376, 2930,
2905, 2858, 1738, 1677, 1531, 1463, 1373, 1261, 1191,
1143, 1122, 1059, 1025, 939, 858, 837, 776, 735, 698;
1H NMR (CDCl3, 400 MHz): d 7.39–7.25 (m, 5H,
Ph), 7.23 (d, 1H, JNH,2 = 9.8 Hz, NHAc), 6.04–5.94
(m, 2H, H-30, H-40), 4.87–4.84 (m, 1H, H-50), 4.76 (d,
1H, J = 11.7 Hz, PhCH2), 4.74 (d, 1H, J1,2 = 2.9 Hz,
H-1), 4.50 (d, 1H, J = 11.7 Hz, PhCH2), 4.23 (dq, 2H,
J = 6.8, J = 3.9 Hz, CH3CH2), 4.10 (ddd, 1H,
J1,2 = 2.9, J2,3 = 12.5, JNH,2 = 9.8 Hz, H-2), 4.06 (m,
1H, H-10), 3.85–3.78 (m, 1H, H-6a), 3.70–3.65 (m,
27
solid; mp 88 °C; ½aꢀD 12 (c 0.7, CHCl3); IR (NaCl, m
cmꢁ1): 3357, 2951, 1737, 1654, 1379, 1254, 1207, 116,
1049, 941, 837, 777; 1H NMR (C6D6, 400 MHz): d
7.66 (d, 1H, JNH,2 = 9.5 Hz, NHCOCH3), 7.27–7.23
(m, 2H, Ph), 7.17–7.10 (m, 3H, Ph), 4.90 (d, 1H,
J1,2 = 3.5 Hz, H-1), 4.80 (s, 1H, OH), 4.64 (m, 1H,
H-10), 4.56 (d, 1H, J = 12.5 Hz, PhCH2), 4.55–4.49 (m,
1H, H-40), 4.45 (ddd, 1H, J1,2 = 3.5, JNH,2 = 9.5,
J2,3 = 12.5 Hz, H-2), 4.30 (d, 1H, J = 12.5 Hz, PhCH2),
H-20,
H-6b),
3.37
(dd,
1H,
4.27 (d, 1H, J4 ,OH = 6.0 Hz, OH), 4.10 (dd, 1H,
0
3H,
H-5,
J3,4 ꢂ J4,5 = 9.5 Hz, H-4), 2.63–2.42 (m, 2H, H-3, H-
7a), 1.85 (s, 3H, NHCOCH3), 1.45, 1.37 (2 ꢃ s, 6H,
CH3), 1.30 (t, 3H, J = 6.8 Hz, CH2CH3), 1.08 (ddd,
J2 ,3 = 2.5, J = 3.5 Hz, H-30), 3.97 (ddd, 1H,
J5,6a = 5.0, J4,5 = 10.1, J5,6b = 10.3 Hz, H-5), 3.95 (dd,
1H, J = 7.0, J = 10.0 Hz, CH3CH2), 3.92–3.78 (m, 3H,
H-6a, H-20, CH3CH2), 3.78–3.70 (m, 2H, H-50, H-6b),
3.47 (t, 1H, J3,4 = J4,5 = 10.1 Hz, H-4), 2.92 (dddd,
J3,7b = 2.5, J3,4 = 10.1, J2,3 = 12.5, J3,7a = 13.0 Hz,
H-3), 2.75 (t, 1H, J = 13.0 Hz, H-7a), 2.0 (s, 3H,
NHCOCH3), 1.50, 1.41 (2s, 6H, 2CH3), 1.2–1.06 (m,
1H, H-7b), 1.03 (s, 9H, 3CH3), 0.90 (t, J = 7.0 Hz,
CH2CH3), 0.24, 0.21 (2s, 6H, 2CH3); 13C NMR
(C6D6, 62.9 MHz): d 172.9, 170.9, 138.3, 128.5, 127.9,
127.0, 99.7, 97.2, 74.5, 73.4, 73.0, 72.8, 69.4, 68.3, 68.0,
66.0, 63.3, 61.0, 55.2, 34.2, 30.4, 29.6, 26.0, 22.8, 19.2,
18.4, 13.9, ꢁ4.0, ꢁ4.7. ESIMS m/z: calcd for
[C33H53NO11Si+Na]+: 690.3286. Found: 690.3286.
Anal. Calcd for C33H53NO11Si: C, 59.35; H, 8.00; N,
2.10. Found: C, 59.44; H, 8.04; N, 1.94
0
0
0
1H, J1 ;7b = 2.9, J3,7b = 9.7, J7a,7b = 12.7 Hz, H-7b),
0.89 (s, 9H, 3 ꢃ CH3), 0.064, 0.059 (2 ꢃ S, 6H, SiCH3);
1H NMR (C6D6, 400 MHz):
d
7.33 (d, 1H,
JNH,2 = 9.3 Hz, NHAc), 7.29–7.26 (m, 1H, Ph), 7.20–
7.08 (m, 4H, Ph), 5.83 (ddd, 1H, J = 2.5, J2 ;3 = 5.0,
0
0
J3 ;4 = 10.3 Hz, H-30), 5.77 (dd, 1H, J3 ;4 = 10.3,
J = 3.3 Hz, H-40), 5.01 (d, 1H, J1,2 = 3.5 Hz, H-1),
4.60 (d, 1H, J = 12.2 Hz, PhCH2), 4.55 (ddd, 1H,
J1,2 = 3.5, JNH,2 = 9.3, J2,3 = 12.5 Hz), 4.48 (t, 1H,
J = 2.5 Hz, H-50), 4.31 (d, 1H, J = 12.2 Hz, PhCH2),
4.28 (m, 1H, J = 12.5 Hz, J = 1.4 Hz, H-10), 3.98
(ddd, 1H, J5,6a = 5.0, J5,6b = 9.0, J4,5 = 10.0 Hz, H-5),
3.88 (dd, 1H, J5,6a = 5.0, J6a,6b = 10.3 Hz, H-6a),
3.76–3.68 (m, 3H, CH3CH2, H-6b), 3.56 (dd, 1H,
0
0
0
0

1762
Q. Wan et al. / Carbohydrate Research 343 (2008) 1754–1765
4.10. Benzyl 2-acetamido-2,3-dideoxy-3-C-(ethyl 20-
tbutyldimethylsilyl-a-D-galactopyranosyluronate)methyl-
4,6-O-isopropylidene-a-D-glucopyranoside (15)
13C NMR (MeOD, 100 MHz): d 173.1 (NHCOCH3),
139.0 (Ph), 129.4, 129.2, 128.8 (Ph), 100.8 ((CH3)2CO2),
96.9 (C-1), 74.0, 73.4 (C-4), 72.8 (C-20), 71.9 (C-30), 71.7
(C-10), 70.2 (PhCH2), 69.8 (C-40), 66.4, 63.8 (C-60), 61.4
(C-6), 54.7 (C-2), 35.6 (C-3), 29.6 (OCH3), 26.5
(C(CH3)3), 25.8 (C-7), 22.7 (NHCOCH3), 19.5
(OCH3), ꢁ4.3, ꢁ4.6 (SiCH3). ESIMS m/z: calcd for
[C31H51NO10Si+Na]+: 648.31807. Found: 648.31827.
Anal. Calcd for C31H51NO10Si: C, 59.49; H, 8.21; N,
2.24. Found: C, 59.43; H, 8.34; N, 2.09.
Compound 13 (80 mg, 126 lmol) was treated as
described for 14. Flash chromatography of the residue
(2:100 MeOH–CH2Cl2) gave 15 (82 mg, 123 lmol,
28
97%) as a white solid. ½aꢀD 74 (c 0.1, CHCl3); 1H
NMR (CDCl3, 400 MHz): d 7.40–7.28 (m, 5H, Ph),
5.97 (d, 1H, JNH,2 = 9.0 Hz, NHCOCH3), 4.86 (d, 1H,
J
1,2 = 3.5 Hz, H-1), 4.73 (d, 1H, J = 12.0 Hz, PhCH2),
A solution of triol 17 (29 mg, 46 lmol) in pyridine
(1.5 mL) and acetic anhydride (0.5 mL) was kept at
room temperature overnight, then concentrated. Flash
chromatography of the residue (1:3 EtOAc–toluene)
4.46 (d, 1H, J = 12.0 Hz, PhCH2), 4.34–4.18 (m, 5H,
H-10, H-50, H-40, CH3CH2), 4.13–3.99 (m, 2H, H-2,
H-30), 3.88–3.60 (m, 6H, H-20, H-5, H-6a, H-6b, H-4,
H-40), 3.00 (s, 1H, OH), 2.20–2.08 (m, 2H, H-3, OH),
1.90 (s, 3H, NHCOCH3), 1.70 (ddd, 1H, J = 2.5,
J = 11.0, J = 14.5 Hz, H-7a), 1.45 (s, 3H, CH3), 1.37–
1.30 (m, 1H, H-7b), 1.38 (s, 3H, CH3), 1.31 (t, 3H,
J = 7.0 Hz, CH3CH2), 0.88 (s, 9H, C(CH3)3), 0.06,
0.03 (2s, 6H, 2SiCH3); 13C NMR (CDCl3, 100 MHz):
d 172.8, 169.9, 137.4, 128.4, 127.9, 99.4, 96.5, 73.6,
72.5, 71.8, 71.4, 71.0, 70.4, 69.4, 67.2, 65.4, 62.7, 61.6,
51.6, 37.1, 29.1, 28.0, 25.7, 23.0, 19.0, 17.9, 13.9, ꢁ4.7,
ꢁ4.9. ESIMS m/z: calcd for [C33H53NO11Si+Na]+:
690.32856. Found: 690.3283. Anal. Calcd for
C33H53NO11Si: C, 59.35; H, 8.00; N, 2.10. Found: C,
59.42; H, 8.05; N, 2.04.
29
gave 18 (34 mg, 100%) as a colorless oil. ½aꢀD 70.0 (c
1.0, CHCl3); IR (NaCl, m cmꢁ1): 3373, 2930, 2858,
1751, 1681, 1660, 1535, 1463, 1372, 1234, 1121, 1080,
1
1053, 942, 909, 864, 839, 780, 739 and 700; H NMR
(C6D6, 400 MHz): d 7.24–7.02 (m, 5H, Ph), 6.31 (d,
0
0
1H, JNH,2 = 9.8 Hz, NH), 5.73 (dd, 1H, J4 ;5 = 4.1,
J3 ;4 = 3.4 Hz, H-40), 5.51 (dd, 1H, J3 ;4 = 3.4,
0
0
0
0
J2 ;3 = 6.8 Hz, H-30), 4.98 (dd, 1H, J5 ;6a0 = 9.3 Hz,
H-6a0), 4.76 (d, 1H, J1,2 = 3.5 Hz, H-1), 4.50 (ddd, 1H,
J1,2 = 3.5, J2,3 = 11.6, JNH,2 = 9.8 Hz, H-2), 4.49 (d,
1H, J = 11.7 Hz, PhCH2), 4.33 (td, 1H, J = 11.5,
0
0
0
J1 ;2 = 3.5 Hz, H-10), 4.21 (ddd, 1H, J4 ;5
ꢂ
0
0
0
0
J5 ;6b ¼ 4:1; J5 ;6a0 ¼ 9:3 Hz; H-50, 4.20 (d, 1H, J =
0
0
0
0
0
0
0
11.7 Hz, PhCH2), 4.06 (dd, 1H, J2 ;3 = 6.8, J1 ;2
=
=
4.11. Benzyl 2-acetamido-3-C-(30,40,60-tri-O-acetyl-20-
tbutyldimethylsilyl-a-L-galactopyranosyl)methyl-2,3-
dideoxy-4,6-O-isopropylidene-a-D-glucopyranoside (18)
3.5 Hz, H-20), 3.97 (dd, 1H, J5 ;6 b = 4.1, J6 a;6 b
0
0
0
0
11.5 Hz, H-6b0), 3.95–3.85 (m, 2H, H-5, H-6a), 3.72–
3.63 (m, 1H, H-6b), 3.28 (m, 1H, H-4), 2.47–2.37 (m,
1H, H-7a), 2.33–2.23 (m, 1H, H-3), 1.88 (s, 3H,
NHCOCH3), 1.74 (s, 3H, COCH3), 1.63–1.58 (m, 1H,
H-7b), 1.61 (s, 3H, COCH3), 1.60 (s, 3H, COCH3),
1.43 (s, 3H, CH3), 1.23 (s, 3H, CH3), 1.0 (s, 9H,
3 ꢃ CH3), 0.18 (s, 3H, CH3), 0.10 (s, 3H, CH3); 13C
NMR (C6D6, 100 MHz): d 171.1, 169.2, 169.2, 169.1,
137.9, 128.6, 128.6, 128.2, 128.1, 99.8, 97.4, 73.2, 70.6,
70.1, 69.7, 67.4, 65.8, 63.1, 60.6, 53.9, 35.4, 29.4, 28.4,
25.9, 22.9, 20.5, 20.3, 20.1, 19.1, 18.3, ꢁ4.7, ꢁ4.9.
ESIMS m/z: calcd for [C37H58NO13Si]+: 752.3677.
Found: 752.3673. Anal. Calcd for C37H57NO13Si: C,
59.10; H, 7.64; N, 1.86. Found: C, 59.32; H, 7.66; N,
1.74.
To a stirred, cooled (0 °C) solution of 16 (125 mg,
188 lmol) in dry THF (15 mL) was added a 1 M solu-
tion of LiAlH4 in THF (374 lL). The mixture was stir-
red at 0 °C for 3 h, diluted with a saturated aqueous
solution of NH4Cl, and extracted with EtOAc three
times. The combined organic phases were dried
(Na2SO4) and concentrated. The residue was purified
by flash chromatography (1:99?5:95 MeOH–CH2Cl2)
to give benzyl 2-acetamido-3-C-(20-t-butyldimethylsilyl-
a-L-galactopyranosyl)methyl-2,3-dideoxy-4,6-O-isopro-
pylidene-a-D-glucopyranoside (17) (98 mg, 157 lmol,
84%). 1H NMR (MeOD, 400 MHz): d 7.39–7.26 (m,
5H, Ph), 4.71 (d, 1H, J = 12.2 Hz, PhCH2), 4.68 (d,
1H, J1,2 = 3.5 Hz, H-1), 4.50 (d, 1H, J = 12.2 Hz,
PhCH2), 4.145 (td, 1H, J = 4.0, J = 12.5 Hz, H-10),
4.07 (dd, 1H, J1,2 = 3.5, J2,3 = 11.8 Hz, H-2), 3.94–3.86
4.12. Benzyl 2-acetamido-3-C-(20,30,40,60-tetra-O-acetyl-
a-L-galactopyranosyl)methyl-2,3-dideoxy-4,6-O-isopro-
pylidene-a-D-glucopyranoside (19)
(m, 2H, H-40, H-6a), 3.84 (dd, J1 ;2 = 4.6,
0
0
J2 ;3 = 7.8 Hz, H-20), 3.78–3.65 (m, 5H, H-5, H-50,
To a solution of 18 (12 mg, 16 lmol) in THF (1 mL)
was added a 1 M solution of Bu4NF in THF (16 lL,
1 equiv). After 10 min at room temperature, the solu-
tion was concentrated and the residue was partitioned
between H2O and CH2Cl2. The organic phase was
dried (phase separator filter) and concentrated. A solu-
tion of the residue in pyridine (1 mL) and acetic anhy-
0
0
H-6b, H-6a0, H-6b0), 3.63 (dd, 1H, J2 ;3 = 7.8,
0
0
J3 ;4 = 3.4 Hz, H-30), 3.58 (dd, 1H, J = 9.0,
J = 10.3 Hz, H-4), 2.30–2.20 (m, 1H, H-3), 2.15–2.05
(m, 1H, H-7a), 1.92 (s, 3H, NHCOCH3), 1.51 (s, 3H,
CH3), 1.45 (ddd, 1H, H-7b), 1.36 (s, 3H, CH3), 0.91 (s,
9H, 3 ꢃ CH3), 0.11 (s, 3H, CH3), 0.09 (s, 3H, CH3);
0
0

Q. Wan et al. / Carbohydrate Research 343 (2008) 1754–1765
1763
dride (0.5 mL) was kept at room temperature over-
4.13. Benzyl 2-acetamido-3-C-(20,30,40,60-tetra-O-acetyl-
night, then concentrated. Flash chromatography of
a-D-galactopyranosyl)methyl-2,3-dideoxy-4,6-O-isopro-
pylidene-a-D-glucopyranoside (20)
the residue (step gradient from 100:0.5?100:2
29
CH2Cl2–MeOH) afforded 19 (10.4 mg, 96%). ½aꢀD 81.0
(c 1.0, CHCl3); 1H NMR (CD3CN, 400 MHz): d
7.36–7.24 (m, 5H, Ph), 6.46 (d, 1H, JNH,2 = 9.8 Hz,
To a stirred, cooled (0 °C) solution of 15 (80 mg,
0.12 mmol) in dry THF (10 mL) was added a 2 M
solution of LiBH4 in THF (70 lL). After 2 d at room
temperature, a 1 M solution of Bu4NF in THF
(480 lL, 4 equiv) was added. After 4 min at room
temperature, the solution was concentrated and the
residue was partitioned between H2O and CH2Cl2. The
organic phase was dried (phase separator filter) and
concentrated. A solution of the residue in pyridine
(3 mL) and acetic anhydride (1.5 mL) was kept at room
temperature overnight, then concentrated. Flash
chromatography of the residue (step gradient from
100:1?100:3 CH2Cl2–MeOH,) afforded 20 (67.5 mg,
NH), 5.36 (dd, 1H, J4 ;5 = 2.0, J3 ;4 = 3.5 Hz, H-40),
0
0
0
0
5.20 (dd, 1H, J3 ;4 = 3.5, J2 ;3 = 10.0 Hz, H-30), 5.06
0
0
0
0
(dd, 1H, J2 ;3 = 10.0, J1 ;2 = 5.5 Hz, H-20), 4.78 (dd,
1H, J5,6a = 5.0, J6a,6b = 11.3 Hz, H-6a), 4.74 (d, 1H,
0
0
0
0
J = 12.0 Hz, PhCH2), 4.71 (ddd, 1H, J5,6b
=
J6a,6b = 11.3 Hz, H-6b), 4.69 (d, 1H, J1,2 = 3.5 Hz, H-
1), 4.53 (d, 1H, J = 12.0 Hz, PhCH2), 4.29–4.21 (m,
2H, H-10, H-50), 4.16–4.08 (m, 2H, H-2, H-60a), 4.06
(dd, 1H, J5 ,6 b = 6.0, J6 a,6 b = 11.5 Hz, H-60b), 3.60
(ddd, 1H, J4,5 = 10.0 Hz, H-5), 3.52 (dd, 1H,
J3,4 = 10.0 Hz, H-4), 1.92–1.79 (m, 2H, H-3, H-7a),
1.99, 1.94, 1.87, 1.85, 1.75 (5s, 15H, 5CH3), 1.34
(ddd, 1H, J = 2.5 Hz, J = 7.0 Hz, J7a,7b = 15.0 Hz,
H-7b), 1.42, 1.24 (2s, 6H, 2CH3); 13C NMR (CDCl3,
100 MHz): d 170.4, 170.2, 170.1, 136.9, 128.6, 128.3,
128.2, 99.7, 96.5, 72.6, 71.7, 69.6, 68.1, 67.7, 67.5,
66.8, 65.5, 62.5, 61.2, 53.1, 35.9, 29.6, 29.2, 28.9,
23.3, 23.1, 20.8, 20.7, 20.6, 19.1. ESIMS m/z: calcd
for [C33H45NO14+Na]+: 702.2732. Found: 702.2749.
Anal. Calcd for C33H45NO14: C, 58.31; H, 6.67; N,
2.06. Found: C, 58.22; H, 6.81; N, 1.94.
0
0
0
0
29
83%). ½aꢀD 63.0 (c 1.0, CHCl3); 1H NMR (CDCl3,
400 MHz): d 7.29–7.40 (m, 5H, Ph), 5.93 (d, 1H,
0
0
JNH,2 = 10.0 Hz, NH), 5.15 (dd, 1H, J2 ;3 = 9.5,
J1 ;2 = 5.5 Hz, H-20), 5.07 (dd, 1H, J3 ;4 = 3.5,
0
0
0
0
J2 ;3 = 9.5 Hz, H-30), 4.78 (d, 1H, J1,2 = 3.5 Hz, H-1),
4.72 (d, 1H, J = 12.0 Hz, PhCH2), 4.66–4.60 (m, 1H,
H-10), 4.46 (d, 1H, J = 12.0 Hz, PhCH2), 4.78 (dd, 1H,
0
0
J5 ;6 a = 8.5, J6 a;6 b = 12.0 Hz, H-60a), 4.13–3.90 (m,
3H, H-5, H-2, H-60b), 3.88–3.80 (m, 1H, H-6a),
3.76–3.65 (m, 2H, H-5, H-6b), 3.48 (dd, 1H,
0
0
0
0
Table 1. Crystallographic data for 3, 2, 6, and 11
6
11
3
2
Formula
Fw
Crystal system
Space group
C
27H37N1O8
C27H37N1O9
519.58
Monoclinic
P21
11.1060(4)
9.3810(3)
14.3592(7)
90
112.552(2)
90
C30H41N1O10
575.64
C30H41N1O10
575.64
503.58
Monoclinic
P21
10.9963(3)
9.3926(3)
14.4351(4)
90
112.017(2)
90
1382.18(7)
2
Orthorhombic
P212121
11.8525(11)
14.1706(15)
18.5722(15)
90
90
90
3119.3(5)
4
Orthorhombic
P212121
10.4979(14)
17.996(3)
16.512(2)
90
90
90
3119.4(7)
4
˚
a (A)
˚
b (A)
˚
c (A)
a (°)
b (°)
c (°)
3
˚
V (A )
1381.62(9)
2
Z
F(000)
k (A)
540
0.71075
293(2)
1.210
0.089
556
0.71075
293(2)
1.249
0.093
1232
0.71075
293(2)
1.226
0.092
1232
0.71075
293(2)
1.226
0.092
˚
T (K)
qcalcd (Mg mꢁ3
)
l(MoKa) (mmꢁ1
)
h Range (° min–max)
No. of data collected
No. of unique data
R(int)
2.93–27.56
5921
5921
1.54–27.38
6015
6015
1.81–23.27
14929
4488
1.81–23.27
15018
4496
0.0
0.0
0.0358
0.0263
No. of variable parameters
No. of obsd Refl (I > 2r(I))
R obsd, all
Rw obsd, all
S
383
4064
0.0472, 0.0813
0.0753, 0.1204
1.011
394
3925
0.0502, 0.0887
0.1268, 0.1483
1.029
423
4119
0.0535, 0.0594
0.1152, 0.1177
1.155
423
3928
0.0337, 0.0425
0.0846, 0.0908
1.066
(D/r)max
(D/q)max,min (e A
0.010
0.140, ꢁ0.144
0.009
0.151, ꢁ0.210
0.000
0.221, ꢁ0.179
0.002
0.165, ꢁ0.130
ꢁ3
˚
)

1764
Q. Wan et al. / Carbohydrate Research 343 (2008) 1754–1765
Beau, J.-M.; Gallagher, T. Top. Curr. Chem. 1997, 187, 1;
(d) Beau, J.-M.; Vauzeilles, B.; Skrydstrup, T. In Glyco-
science. Chemistry and Chemical Biology; Fraser-Reid, B.,
Tatsuta, K., Thiem, J., Eds.; Springer: Heidelberg, 2001;
Vol. 3, p 2679.
J3,4 = J4,5 = 10.0 Hz, H-4), 2.12 (s, 3H, CH3), 2.10–2.00
(m, 1H, H-3), 2.06, 2.02, 1.98, 1.87 (4s, 12H, 4CH3),
1.84–1.73 (m, 1H, H-7a), 1.43, 1.39 (2s, 6H, 2CH3),
1.38–1.25 (m, 1H, H-7b); 13C NMR (CDCl3,
100 MHz): d 170.9, 170.2, 170.1, 169.8, 169.5, 136.9,
128.5, 128.2, 128.1, 99.2, 96.2, 75.7, 70.9, 69.5, 68.6,
67.8, 67.3, 67.1, 64.9, 62.6, 62.0, 51.0, 35.7, 28.9, 25.2,
23.0, 20.7, 20.6, 20.4, 18.9. ESIMS m/z: calcd for
[C33H45NO14+Na]+: 702.2732. Found: 702.2743. Anal.
Calcd for C33H45NO14: C, 58.31; H, 6.67; N, 2.06.
Found: C, 58.64, H, 6.48; N, 1.96.
2. For recent synthesis of C-disaccharides, see: (a) Stichler-
Bonaparte, J.; Vasella, A. Helv. Chim. Acta 2001, 84,
2355–2367; (b) Dondoni, A.; Marra, A.; Mamoru, M.;
Giovannini, P. P. J. Org. Chem. 2002, 67, 4186–4199; (c)
Paterson, D. E.; Griffin, F. K.; Alcaraz, M.-L.; Taylor, R.
J. K. Eur. J. Org. Chem. 2002, 1323–1326; (d) Postema, M.
H. D.; Piper, J. L.; Liu, L.; Shen, J.; Faust, M.; Andreana,
P. J. Org. Chem. 2003, 68, 4748–4754; (e) Mikkelsen, L.
M.; Skrydstrup, T. J. Org. Chem. 2003, 68, 2123–2128; (f)
Kuberan, B.; Sikkander, S. A.; Tomiyama, H.; Linhardt,
R. J. Angew. Chem., Int. Ed. 2003, 42, 2073–2075; (g)
Abdallah, Z.; Doisneau, G.; Beau, J.-M. Angew. Chem.,
Int. Ed. 2003, 42, 5209–5212; (h) Dondoni, A.; Marra, A.
Tetrahedron Lett. 2003, 44, 4067–4071; (i) Demange, R.;
Awad, L.; Vogel, P. Tetrahedron: Asymmetry 2004, 15,
3573–3585; (j) Li, X.; Takahashi, H.; Ohtake, H.; Ikegami,
S. Tetrahedron Lett. 2004, 45, 4123–4126; (k) Chambers,
D. J.; Evans, G. R.; Fairbanks, A. J. Tetrahedron 2005, 61,
7184–7192; (l) Ress, D. K.; Baytas, S. N.; Wang, Q.;
Munoz, E. M.; Tokuzoki, K.; Tomiyama, H.; Lindhardt,
R. J. J. Org. Chem. 2005, 70, 8197–8200; (m) Steunenberg,
P.; Jeanneret, V.; Zhu, Y.-H.; Vogel, P. Tetrahedron:
Asymmetry 2005, 16, 337–346; (n) Cheshev, P.; Marra, A.;
Dondoni, A. Org. Biomol. Chem. 2006, 4, 3225–3227; (o)
Ren, Z.-X.; Yang, Q.; Price, K. N.; Chen, T.; Nygren, C.;
Turner, J. F. C.; Baker, D. C. Carbohydr. Res. 2007, 342,
1668–1679.
4.14. X-ray crystallography
X-ray diffraction data were collected by using a Kappa
CCD Nonius diffractometer with graphite-monochro-
˚
mated MoKa radiation (k = 0.71073 A). The data were
corrected for Lorentz polarization, and absorption
effects. The structures were solved by direct methods
using SHELXS-9721 and refined against F2 by full-matrix
least-squares techniques using SHELXL-9722 with aniso-
tropic displacement parameters for all non-hydrogen
atoms. Hydrogen atoms were located on a difference
Fourier map and introduced into the calculations as a
riding model with isotropic thermal parameters. All
calculations were performed by using the Crystal
Structure crystallographic software package WINGX.23
CCDC 676261, CCDC 676262, CCDC 676263, and
CCDC 676264 contain the Supplementary data for this
paper. These data can be obtained free of charge from
The Cambridge Crystallographic Data Centre via
http://www.ccdc.cam.ac.uk/data_request/cif. The crys-
tallographic data are summarized in Table 1.
3. (a) Xin, Y.-C.; Zhang, Y.-M.; Mallet, J.-M.; Glaudemans,
C. P. J.; Sinay, P. Eur. J. Org. Chem. 1999, 471–476; (b)
¨
Glaudemans, C. P. J. Chem. Rev. 1991, 91, 25–33.
4. Yang, G.; Schmieg, J.; Tsuji, M.; Franck, R. W. Angew.
Chem., Int. Ed. 2004, 43, 3818–3822.
5. (a) Rodrigues, F.; Canac, Y.; Lubineau, A. Chem.
Commun. 2000, 2049–2050; (b) Hersant, Y.; Abou-Jneid,
R.; Canac, Y.; Lubineau, A.; Philippe, M.; Semeria, D.;
Radisson, X.; Scherrmann, M.-C. Carbohydr. Res. 2004,
339, 741–745; (c) Bragnier, N.; Scherrmann, M.-C.
Synthesis 2005, 5, 814–818.
6. (a) Canac, Y.; Levoirier, E.; Lubineau, A. J. Org. Chem.
2001, 66, 3206–3210; (b) Lubineau, A.; Canac, Y.; Le
Goff, N. Adv. Synth. Catal. 2002, 344, 319–327; (c)
Levoirier, E.; Canac, Y.; Norsikian, S.; Lubineau, A.
Carbohydr. Res. 2004, 339, 2737–2747.
Acknowledgments
This work was supported by the CNRS and the Minist-
`
´
ere de l’Education Nationale, de l’Enseignement Superi-
`
eur et de la Recherche. Q. W. thanks the Ministere des
7. (a) Zeitouni, J.; Norsikian, S.; Merlet, D.; Lubineau, A.
Adv. Synth. Catal. 2006, 348, 1662–1670; (b) For a
corrigendum, see: Adv. Synth. Catal. 2006, 348, 2009.
8. Dmitriev, B. A.; Knirel, Y. A.; Kochetkov, N. K. J.
Biochem. 1976, 66, 559–566.
´
`
Affaires etrangeres for an Eiffel fellowship. We thank
Professor N. Ghermani for some X-ray analysis.
´
9. (a) Kovac, P.; Edgar, K. J. J. Org. Chem. 1992, 57, 2455–
Supplementary data
2467; (b) Pozsgay, V.; Coxon, B. Carbohydr. Res. 1995,
277, 171–178; (c) Pozsgay, V. J. Org. Chem. 1998, 63,
5983–5999; (d) Pozsgay, V.; Kubler-Kielb, J.; Schneerson,
R.; Robbins, J. B. Proc. Natl. Acad. Sci. U.S.A. 2007, 104,
14478–14482.
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.carres.
2008.03.015.
10. Wan, Q.; Lubineau, A.; Scherrmann, M.-C. J. Carbohydr.
Chem. 2004, 23, 83–93.
11. (a) Ruden, R. A.; Bonjouklian, R. J. Am. Chem. Soc.
1975, 97, 6892–6893; (b) Achmatowicz, O.; Jurczak, J.;
Pyrek, J. S. Tetrahedron 1976, 32, 2113–2116; (c)
Bonjouklian, R.; Ruden, R. A. J. Org. Chem. 1977, 42,
4095–4103; (d) Schmidt, R.; Wagner, A. Synthesis 1981,
273–275; (e) Salomon, R. G.; Roy, S.; Salomon, M. F.
References
1. Reviews: (a) Postema, M. H. D. C-Glycosides Synthesis;
CRC Press: Boca Raton, 1995; (b) Levy, D. E.; Tang, C.
The Chemistry of C-Glycosides; Elsevier: Oxford, 1995; (c)

Q. Wan et al. / Carbohydrate Research 343 (2008) 1754–1765
1765
Tetrahedron Lett. 1988, 29, 769–772; (f) Robert, H.;
Garrigues, B.; Dubac, J. Tetrahedron Lett. 1998, 39,
1161–1164; (g) Yao, S.; Roberson, M.; Reichel, F.; Hazell,
R. G.; Jørgensen, K. A. J. Org. Chem. 1999, 64, 6677–
6687.
18. (a) Murata, S.; Suzuki, M.; Noyori, R. J. Am. Chem. Soc.
1979, 101, 2738–2739; (b) Murata, S.; Suzuki, M.; Noyori,
R. Bull. Chem. Soc. Jpn. 1982, 55, 247–254.
19. Mosset, P.; Mana, S.; Viala, J.; Falk, J. R. Tetrahedron
Lett. 1986, 27, 299–302.
12. (a) David, S.; Eustache, J.; Lubineau, A. J. Chem. Soc.,
Perkin Trans. 1 1979, 1795–1798; (b) Knapp, S.; Levorse,
A. T.; Potenza, J. A. J. Org. Chem. 1988, 53, 4773–4779;
20. (a) Cha, J. K.; Christ, W. J.; Kishi, Y. Tetrahedron Lett.
1983, 24, 3943–3946; (b) Christ, W. J.; Cha, J. K.; Kishi,
Y. Tetrahedron Lett. 1983, 24, 3947–3950; (c) Cha, J. K.;
Christ, W. J.; Kishi, Y. Tetrahedron 1984, 40, 2247–2255;
For a review see: (d) Cha, J. K.; Kim, N. S. Chem. Rev.
1995, 95, 1761–1795.
´
`
(c) Bataille, C.; Begin, G.; Guillam, A.; Lemiegre, L.; Lys,
C.; Maddaluno, J.; Toupet, L. J. Org. Chem. 2002, 67,
8054–8062.
13. Krapcho, A. P. Synthesis 1982, 805, 893–914.
14. Sharpless, K. B.; Lauer, R. F. J. Am. Chem. Soc. 1973, 95,
2697–2699.
21. Sheldrick, G. M. SHELXS-97, Program for Crystal
Structure Solution, University of Go¨ttingen, Go¨ttingen,
Germany, 1997.
15. O’Brien, P. J. Chem. Soc., Perkin Trans. 1 1998, 1439–
1457.
16. Inoue, T.; Uchimaru, T.; Mukaiyama, T. Chem. Lett.
1977, 1215–1218.
22. Sheldrick, G. M. SHELXL-97, Program for the refinement
of crystal structures from diffraction data, University of
Go¨ttingen, Go¨ttingen, Germany, 1997.
23. Farrugia, L. J. J. Appl. Crystallogr. 1999, 32, 837–
838.
17. Detty, M. R. J. Org. Chem. 1980, 45, 924–926.