A short and efficient synthesis of α-C-(1 → 3)-linked disaccharides containing deoxyhexopyranoses

Article abstract of DOI:10.1016/j.tetasy.2004.01.023

Ozonolysis of peracetylated α-D-glucopyranosylprop-2-ene, followed by the reaction of the formed ozonide with (thiazol-2-yl) carbonylmethylenetriphenyl phosphorane, afforded substituted 1-oxa-1,3-butadiene, which by a hetero-Diels-Alder reaction with ethy

Full text of DOI:10.1016/j.tetasy.2004.01.023

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 15 (2004) 1033–1041
A short and efficient synthesis of a-C-(1 fi 3)-linked disaccharides
containing deoxyhexopyranoses
a
Petr Stepanek, Ondrej Vıch, Ladislav Kniezo, Hana Dvorakova and Pavel Vojtısek
a
a,
c
ꢀ ꢁ
ꢀ
ꢁ
ꢀ
ꢀꢁ
ꢁb
ꢁꢀ
*
ꢀ
aDepartment of Chemistry of Natural Compounds, Institute of Chemical Technology, Technickꢁa 5, 166 28 Prague 6, Czech Republic
bNMR Laboratory, Institute of Chemical Technology, Technickꢁa 5, 166 28 Prague 6, Czech Republic
cDepartment of Inorganic Chemistry, Charles University, 128 40 Prague 2, Czech Republic
Received 23 December 2003; accepted 22 January 2004
Abstract—Ozonolysis of peracetylated a-D-glucopyranosylprop-2-ene, followed by the reaction of the formed ozonide with (thiazol-
2-yl)carbonylmethylenetriphenyl phosphorane, afforded substituted 1-oxa-1,3-butadiene, which by a hetero-Diels–Alder reaction
with ethyl vinyl ether gave a 1:1 mixture of two diastereoisomeric dihydropyran derivatives. These, after replacement of the acetyl
protecting groups by benzyl groups, were separated by chromatography and their thiazole substituent converted to an aldehyde
group. Subsequent hydroboration afforded a-C-(1 fi 3)-linked disaccharides in which
D-glucose is linked by a methylene bridge with
2,3-dideoxy-arabino-hexopyranose of - or -configuration. Structures of the obtained compounds have been confirmed by NMR
D
L
spectroscopy and X-ray crystallographic analysis.
ꢀ 2004 Elsevier Ltd. All rights reserved.
1. Introduction
hydrolysis.3 One can therefore expect that C-disaccha-
rides could, for example, form nonhydrolyzable epitopes
of cell surface glycoconjugates, thus disturbing their
interactions with proteins, or they could inhibit the
enzymes involved in the biosynthesis of glycoconjugates.
For these reasons, there is an increased interest in the
search for new synthetic pathways leading to C-disac-
charides and in the study of their properties.4–7 Due to
the great structural variety of disaccharides, where, for
example, one hexopyranose can be attached by an a- or
b-anomeric bond to five different positions (i.e., posi-
tions 1, 2, 3, 4 or 6) of the second hexopyranose, the
existing methods of preparation of C-disaccharides are
usually multistep syntheses, with low overall yields. As a
rule, the hitherto published syntheses make it possible to
prepare only one particular type of C-disaccharide, and
more universal methods enabling synthesis of a wider
variety of C-disaccharides appear only sporadically (see
lit.4u). Therefore, a search for further simple syntheses of
various types of C-disaccharides is desirable, particu-
larly for those which could afford the final compounds
in quantities sufficient for testing their activities.
Interactions of cell-surface oligosaccharides and glyco-
conjugates (glycoproteins or glycolipids) with lectins
represent an essential part of cell communication
system and influence significantly many vital processes,
including cell recognition, cell differentiation and cell
adhesion.1 Although many of these processes are gen-
erally beneficial, glycoconjugates are also involved in a
number of detrimental processes such as inflammation,
viral and bacterial infections, and tumour metastasis. It
is therefore assumed that compounds that could inhibit,
for example, biosynthesis of glycoproteins participating
in the mentioned detrimental processes, and/or disturb
interactions of glycoproteins with lectins, might find use
as compounds with therapeutic effects. One of the more
suitable candidates for such compounds are C-disac-
charides, which are analogues of natural disaccharides
but in which the interglycosidic oxygen atom is replaced
by a methylene group.2 Although this change can
influence the conformational arrangement about the
original C–O–C bonds, it is assumed that C-disaccha-
rides mimic well the structures of the natural disaccha-
rides but unlike them resist acidic as well as enzyme
As concerns C-(1 fi 3)-disaccharides, some types of
C-(1 fi 3)-disaccharides are already known in which the
two monosaccharides are linked by
a
–CH2–,5
–CH(OH)–6 or –CO–7 bridge. Recently, the epi-
meric pair a-C-(1 fi 3)-mannopyranoside of N-acetyl-
galactosamine and a-C-(1 fi 3)-mannopyranoside of
* Corresponding author. Tel.: +420-224-354-265; fax: +420-223-339-
990; e-mail: ladislav.kniezo@vscht.cz
0957-4166/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2004.01.023

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P. Stꢀepꢁanek et al. / Tetrahedron: Asymmetry 15 (2004) 1033–1041
N-acetyltalosamine has been prepared. For the first
isomer, it has been shown experimentally that this type
of C-disaccharide indeed exhibited inhibitory effects
towards several glycosidases and human a-1,3-fucosyl-
transferase.8 In our previous studies we reported a
method of converting a formyl group into a new dide-
oxyhexopyranose. Using this approach, we prepared
compounds in which two monosaccharides were linked
either by a direct C–C bond9 or by a –CH2– bridge.10 In
a preliminary communication11 we have shown that new
a-C-(1 fi 3)-disaccharides containing deoxyhexopyra-
noses can be prepared using the same methodology. We
herein report details of this approach that allows direct
and rapid synthesis of two diastereoisomeric a-C-
O-acetyl-a-D-glucopyranosylethanal 3 in 80% yield, and
this on heating with stabilized ylide 515 in chloroform
and subsequent chromatography gave oxadiene 6 in a
yield of 80%. The trans-configuration of oxadiene 6 was
unequivocally proven on the basis of the vicinal inter-
1
action of olefinic protons H-2/H-3 (15.7 Hz) in the H
NMR spectrum. Cycloaddition reaction of oxadiene 6
with ethyl vinyl ether at room temperature, catalyzed by
Eu(fod)3 (8 mol %), afforded a mixture of the two endo-
cycloadducts 8 and 9 in 90% yield. Similarly to the
synthesis of branched-chain sugars,10 we observed no
chiral induction of the monosaccharide moiety in the
cycloaddition reaction, the endo-cycloadducts 8 and 9
being formed in the ratio 1:1 (as determined by 1H
NMR spectroscopy and HPLC). Moreover, the NMR
spectra did not detect any other (i.e., trans) diastereo-
isomers in the obtained crude cycloadduct mixture.
NMR experiments have shown NOE between protons
H-2 and H-4 in both compounds 8 and 9, which proves
their relative cis-configuration on the dihydropyran ring.
Unfortunately, the obtained mixture of cycloadducts
was not separable by simple preparative column chro-
matography on silica gel. Therefore, we repeated the
(1 fi 3)-disaccharides in which
methylene bridge with 2,3-dideoxy-arabino-hexopyra-
nose in the - and -configuration, respectively.
D-glucose is linked by a
D
L
2. Results and discussion
For starting compounds in the synthesis, we used per-
acetylated and perbenzylated a- -glucopyranosylprop-
reaction with 1-(20,30,40,60-tetra-O-benzyl-a-
pyranosyl)-prop-2-ene 2.
D-gluco-
D
2-enes 1 and 2, respectively, which are accessible even in
multigram quantities and with ozonolysis can readily
afford the respective peracetylated and perbenzylated
In the case of this compound, the pure a-anomer 2 was
not accessible by simple crystallization as in the case of
the peracetylated derivative 1. However, the undesired
minor b-anomer could be removed by repeated chro-
matography on silica gel in light petroleum containing
2.7% of ethyl acetate. Ozonolysis of the thus obtained
pure diastereoisomer 2 (mp 59–60 ꢁC) afforded aldehyde
4 in a somewhat lower yield (71%) than in the case of
peracetylated derivative 1. The subsequent Wittig reac-
tion with ylide 5 afforded, after chromatography on
a-D
-glucopyranosylethanal 312 and 413 (Scheme 1).
First we used 1-(20,30,40,60-tetra-O-acetyl-a-
D-glucopyr-
anosyl)-prop-2-ene 1,14 which can be easily separated
from the minor b-anomer by crystallization from a
ether/light petroleum or chloroform/hexane mixture.
The thus obtained pure diastereoisomer 1 (mp 108 ꢁC)
on ozonolysis in dichloromethane afforded 2,3,4,6-tetra-
N
OR
OR
9
S
OR
10
Ph3P
RO 8
O
5
O
O
O
RO
RO
RO
RO
5
4
N
RO
6RO
RO
2
7
RO
i
1
O
S
ii
3
O
6 R = Ac
7 R = Bn
1 R = Ac
2 R = Bn
3 R = Ac
4 R = Bn
iii
OR
6'
7'
OR
5'
O
RO
O
RO
2'
N
RO
N
RO
3' RO
1'
5
4'
RO
S
6
S
4
+
O
2
O
3
OEt
OEt
8 R = Ac
10 R = Bn
iv
9 R = Ac
11 R = Bn
iv
Scheme 1. Reagents and conditions: (i) O3, CH2Cl2, )80 ꢁC, 40 min, then Me2S, 2 d; (ii) 5, CHCl3, 60 ꢁC, 24 h; (iii) ethyl vinyl ether, Eu(fod)3
(8 mol %), CH2Cl2, rt, 6 h; (iv) (a) KCN/MeOH, rt, 1 h, (b) NaH, BnBr, THF, 50 ꢁC, 5 h.

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P. Stꢀepꢁanek et al. / Tetrahedron: Asymmetry 15 (2004) 1033–1041
1035
silica gel, oxadiene 7 in a yield of 70%. In this case,
however, it was not possible to prove the trans-config-
uration of the C@C bond in the oxadiene 7 directly from
decomposition of the deacetylation products. Sub-
sequent benzylation in tetrahydrofuran20 gave a mixture
of compounds 10 and 11, thus proving that the pairs 8
and 9 and 10 and 11 have identical configurations.
1
the coupling constants in the H NMR spectrum, since
in this region the spectrum was overlapped by signals of
aromatic protons. The oxadiene 7 was assigned a trans-
configuration because in the cycloaddition reaction with
ethyl vinyl ether, it afforded only two perbenzylated
cycloadducts, 10 and 11, of the same configuration as
the peracetylated cycloadducts 8 and 9 arising from
trans-oxadiene 3 (vide infra).
Concerning the economy of the synthesis, the optimal
method consists at the combined use of both the pro-
tecting groups. We have found that when starting with
the easily accessible peracetylated a-D-glucopyranosyl-
prop-2-ene 1, it is not necessary to isolate the arising
aldehyde 3, as the intermediary ozonide can be decom-
posed directly with the thiazole ylide 5, analogously as
already described for decomposition of ozonides with
other stabilized ylides.21 In this way, we converted the
starting compound 1 into trans-oxadiene 6 in 75% yield
without isolating aldehyde 3. Further synthetic steps,
consisting of cycloaddition, deacetylation and finally
benzylation of the mixture of cycloadducts 8 and 9 (see
Scheme 1), afforded a chromatographically well sepa-
rable 1:1 mixture of diastereoisomers 10 and 11. Thus,
the starting compound 1 was converted in four reaction
steps into 10 and 11 in an overall yield of 56%.
At this stage, we tried to prepare another oxadiene, 12,
substituted by an ester group, which also represents a
suitable reactant in the cycloaddition reaction with ethyl
vinyl ether. Although we have previously prepared such
oxadienes in good yields16 from other sugar aldehydes
by a Wittig reaction with ylide 13,17 the reaction with
aldehyde 4 under the same conditions afforded only a
complex mixture of several compounds. Equally unsat-
isfactory results (complex reaction mixture) were also
obtained in the attempted preparation of oxadiene 12 by
a Mukayiama modification of the aldol reaction, that is,
by the reaction of dimethylacetal of aldehyde 4 with
methyl 2-(trimethylsilyloxy)acrylate18 (Scheme 2). For
this reason we only further studied the cycloaddition
reactions of oxadiene 6 or 7.
After separation on silica gel, the individual diastereo-
isomers 10 and 11 were converted to the C-(1 fi 3)-di-
saccharides. First, the thiazole ring was converted into
an aldehyde group using a known procedure.22 Thus,
compounds 10 and 11 gave the respective aldehydes 14
and 15, which were characterized by NMR spectra but,
as potentially unstable compounds, they were immedi-
ately, without purification, subjected to hydroboration.
Use of an excess of BH3ÆS(CH3)2 resulted in the simul-
taneous reduction of the aldehyde group and hydro-
boration of the C@C bond, which proceeded
stereoselectively from the less hindered side of the di-
hydropyran ring. In this way, cycloadduct 14 was con-
verted into partially benzylated C-(1 fi 3)-disaccharide
16 and 15 into 17 (Scheme 3).
Cycloaddition of perbenzylated oxadiene 7 with ethyl
vinyl ether under the same conditions as for the reaction
with peracetylated oxadiene 6, afforded a 1:1 mixture of
two cycloadducts which, unlike the pair 8 and 9, could
be separated well by preparative flash chromatography
on silica gel. As shown by mass and NMR spectra, the
products were diastereoisomeric compounds 10 and 11.
The presence of NOE between protons H-2 and H-4 in
both compounds proved a relative cis-configuration of
substituents on the dihydropyran ring, similarly to the
pair 8 and 9. In order to compare the configuration of
the peracetylated cycloadducts 8 and 9 with that of the
perbenzylated cycloadducts 10 and 11, we decided to
convert the mixture of 8 and 9 into a mixture of 10 and
11 by deacetylation followed by benzylation. For
deacetylation, treatment with a solution of KCN in
methanol19 appeared to be the optimal method. This
method led to only two diastereoisomeric deacetylated
products (according to NMR spectra). Repeated
We decided to characterize both the obtained products
as peracetylated derivatives. To this end, the crude
products were debenzylated by hydrogenation on pal-
ladium and subsequently acetylated. In both cases we
obtained crystalline products 18 (mp 160–162 ꢁC, overall
yield 53% from 10) and 19 (mp 149–151 ꢁC, overall yield
55% from 11). According to NMR spectra, all substit-
uents in both the new deoxypyranoses are in equatorial
positions. This follows from the existence of NOE
between protons H-1, H-3 and H-5 in both compounds,
as well as from the well discernible coupling constants
of protons H-1 and H-4, identical for both 18 and 19
ꢁ
experiments using classical Zemplen deacetylation
methods (CH3ONa in CH3OH) have shown that in the
final neutralization of the alkaline reaction mixture only
very small excesses of the acid is needed for partial
COOC2H5
OBn
Ph3P
O
O
BnO
BnO
13
BnO
4
4
COOR
ii
i
12
O
R = Me or Et
Scheme 2. Reagents and conditions: (i) 13, CHCl3, 60 ꢁC; (ii) (a) trimethyl orthoformate, TsOH, (b) methyl 2-(trimethylsilyloxy)acrylate, TMSOTf.

ꢀ
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P. Stꢀepꢁanek et al. / Tetrahedron: Asymmetry 15 (2004) 1033–1041
OBn
O
OR
BnO
BnO
O
O
OR1
RO
RO
BnO
RO
O
10
OEt
ii
i
O
R1O
OEt
16 R = Bn, R1 = H
18 R = R1 = Ac
14
iii
OAc
O
AcO
AcO
AcO
AcO
AcO
OBn
OR
7'
5'
O
O
6'
O
BnO
BnO
RO
RO
O
2'
1'
OEt
3'RO
BnO
20
4'
4
11
2
3
OEt
R1O
R1O
i
ii
O
O
6
1
5
OEt
15
17 R = Bn, R1 = H
19 R = R1 = Ac
iii
Scheme 3. Reagents and conditions: (i) (a) MeOTf, MeCN, rt, 15 min, (b) NaBH4, MeOH, rt, 15 min, (c) AgNO3, MeCN/H2O, rt, 20 min; (ii) (a)
Me2SÆBH3, THF, rt, 18 h, (b) NaOH, H2O2, rt, 40 min; (iii) (a) H2/Pd–C, MeOH, rt, 8 h, (b) Ac2O, pyridine, DMAP, rt, 1 h.
(J1;2ax ¼ 9.3 Hz, J3;4 ¼ J4;5 ¼ 10.0 Hz). These data confirm
that the new deoxypyranoses in compounds 18 and 19
have the same relative configuration (arabino) and must
be in an enantiomeric relationship. In one experiment,
debenzylation of compound 17 was performed on Pd on
carbon catalyst, contaminated by traces of acid, and
after acetylation we obtained compound 19, mixed with
its anomer 20. Repeated crystallization of this mixture
from acetone/light petroleum afforded an analytical
sample of pure compound 20, mp 137–139 ꢁC. Its NMR
spectra confirmed an axial position of the ethoxy group
(J1;2ax ¼ 3.4 Hz, J1;2eq ꢀ 0 Hz). Both compounds gave
monocrystals suitable for X-ray crystallographic analy-
sis. The obtained structures of compounds 19 and 20 are
given in Figure 1. As can be seen, the X-ray analysis
confirms the relative configuration of the dideoxy-ara-
bino-hexopyranose ring as has been determined by the
NMR spectra and shows unequivocally that the dide-
oxy-arabino-hexopyranose moiety in compounds 19 and
20 has the -configuration. From this fact it follows that
the dideoxy-arabino-hexopyranose moiety in compound
18 has the -configuration.
L
D
3. Conclusion
In summary, we have described a short and efficient
route to a-C-(1 fi 3)-disaccharides in which either
glucose is linked with ethyl 2,3-dideoxy-arabino-hexo-
pyranoside of - or -configuration. The starting
compound is the easily accessible peracetylated a-
D
-
D
L
D
-
glucopyranosylprop-2-ene. The key step of the synthesis
is the endo-selective cycloaddition reaction affording,
after the exchange of the protecting groups, a mixture of
Figure 1. ORTEP drawing of 19 and 20 (30% probability ellipsoids). The hydrogen atoms (except ring hydrogens) are omitted for clarity.

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P. Stꢀepꢁanek et al. / Tetrahedron: Asymmetry 15 (2004) 1033–1041
1037
only two cis-cycloadducts 10 and 11, which upon sepa-
ration by flash chromatography on silica gel, gave in two
reaction steps a-C-(1 fi 3)-disaccharides 16 and 17. The
structure of the obtained a-C-(1 fi 3)-disaccharides was
unequivocally determined by the NMR spectra of
compounds 18, 19 and 20 and X-ray crystallographic
analysis of compounds 19 and 20. Since pyranosylprop-
2-enes of other configurations (e.g., galacto and manno)
are also easily available, we suppose that our strategy
enables the preparation of a wider series of C-(1 fi 3)-
disaccharides in quantities sufficient enough for
extended screenings of their properties.
H-10a), 4.04 (dd, 1H, J ¼ 12.2 Hz, J ¼ 2.1 Hz, H-10b),
4b), 2.06, 2.05, 2.04, 2.00 (s, 4 · 3H, 4 · O@C–CH3). 13
3.92 (m, 1H, H-9), 2.85 (m, 1H, H-4a), 2.63 (m, 1H, H-
C
NMR (125 MHz, CDCl3) d (ppm): 180.85 (C-1), 170.55,
196.88, 169.5, 169.41, 169.37 (4 · O@C–CH3), 167.65
(thiazole C-2), 144.68 and 126.46 (2 · CH-thiazole),
144.62 (C-2), 126.94 (C-3), 71.16 (C-5), 69.87 (C-7),
69.73 (C-6), 69.17 (C-9), 68.40 (C-8), 61.90 (C-10), 29.74
(C-4), 20.49, 20.47, 20.44, 20.38 (4 · O@C–CH3). MS
(ESI): 484.2 (M+H)þ. Anal. Calcd for C21H25NO10S
(MW 483.50): C, 52.17; H, 5.21; N, 2.90; S, 6.63. Found:
C, 51.93; H, 5.11; N, 2.99; S, 6.85.
4.3. 5,9-Anhydro-6,7,8,10-tetra-O-benzyl-2,3,4-trideoxy-
1-C-(2-thiazolyl)-
D
-glycero-D-ido-dec-2-enose 7
4. Experimental
4.1. General
To a solution of aldehyde 413 (5.1 g, 9.0 mmol) in chlo-
roform (40 mL) was added ylide 5 (7.3 g, 18.8 mmol) and
the reaction mixture then heated at 60 ꢁC for 24 h. The
solvent was evaporated in vacuo and the residue was
purified by chromatography on silica gel in light petro-
leum/ethyl acetate (15:1). Yield 4.2 g (70%) of com-
pound 7 as oil. RF ¼ 0:8 (light petroleum/ethyl acetate,
Melting points are not corrected. TLC was performed
on HF254 plates (Merck) with detection by UV light or
by spraying with a solution of 5 g Ce(SO4)2(H2O)4 in
500 mL 10% H2SO4 and subsequent heating. Flash col-
umn chromatography was performed on silica gel
(Merck, 100–160 lm) in solvents, distilled prior to use.
Optical rotations were measured at 25 ꢁC on a spectro-
polarimeter JASCO DIP-370. 1H and 13C NMR spectra
were taken on a Bruker DRX 500 Avance spectrometer
1
5:1). ½aꢁ ¼ þ59:5 (c 1.0, CHCl3). H NMR (500 MHz,
D
CDCl3): d (ppm) 7.98 (d, 1H, J ¼ 2.9 Hz, CH-thiazole),
7.63 (d, 1H, J ¼ 2.9 Hz, CH-thiazole), 7.38–7.13 (m,
22H, 4 · C6H5, H-2, H-3), 4.95–4.41 (m, 8H, 4 · –O–
CH2–Ph), 4.28 (ddd, 1H, J ¼ 9.7 Hz, J ¼ 4.9 Hz,
J ¼ 4.9 Hz, H-5), 3.81–3.59 (m, 6H, H-6, H-7, H-8, H-9,
H-10a, H-10b), 2.78 (m, 2H, H-4a, H-4b). 13C NMR
(125 MHz, CDCl3) d (ppm): 181.14 (C-1), 168.06 (thia-
zole C-2), 147.35, (C-3), 144.59 and 126.16 (2 · CH-thi-
azole), 128.39–126.36 (aromatic C, C-2), 82.17, 79.59,
77.45, 71.49 (C-6, C-7, C-8, C-9), 75.37, 74.93, 73.37,
73.28 (4 · –O–CH2–Ph), 73.18 (C-5), 68.59 (C-10), 29.33
(C-4). MS (ESI): 676.4 (M+H)þ. Anal. Calcd for
C41H41NO6S (MW 604.61): C, 72.86; H, 6.11; N, 2.07; S,
4.74. Found: C, 73.08; H, 6.32; N, 1.95; S, 4.52.
1
at 500.132 MHz for H NMR and at 125.767 MHz for
13C NMR. The spectra obtained in that CDCl3 solutions
1
and chemical shifts in H and 13C NMR spectra are
given in parts per million (d) relative to the peaks of
CHCl3 (7.27 and 77.0, respectively) in CDCl3. H and
1
13C NMR signal assignments were confirmed by 2D
COSY and HMQC when necessary. NOE connectivities
were obtained using 1D 1H DPFGSE-NOE experi-
ment.23 Mass spectra were measured on a Waters Q-
TOF micromass spectrometer operating at a direct inlet
system.
4.4. (2R,4R)- and (2S,4S)-4-(20,60-Anhydro-30,40,50,70-tetra-
4.2. 5,9-Anhydro-6,7,8,10-tetra-O-acetyl-2,3,4-trideoxy-
-ido-dec-2-enose 6
O-benzyl-10-deoxy-
ethoxy-6-(2-thiazolyl)-3,4-dihydro-2H-pyran 10 and 11
D
-glycero-
-ido-heptitol-10-yl)-2-
D
1-C-(2-thiazolyl)-
D
-glycero-
D
A solution of compound 114 (9 g, 24.2 mmol) in dichloro-
methane (150 mL) was ozonized at )80 ꢁC to a persist-
ing blue colouration (about 40 min). Ylide 5 (14.1 g,
36.4 mmol) was added and the mixture stirred at room
temperature for 16 h. The mixture was then partitioned
between water and dichloromethane. The organic phase
was dried, the solvent evaporated in vacuo and the
residue chromatographed on silica gel. Product 6 (8.77 g,
75%) was obtained as a pale yellow oil. RF ¼ 0:4 (light
4.4.1. From oxadiene 6. Ethyl vinyl ether (5.3 mL,
55.4 mmol) and Eu(fod)3 (1.1 g, 1.1 mmol) were added to
a solution of 6 (6.7 g, 13.8 mmol) in dichloromethane
(35 mL) and the reaction mixture sonicated for 6 h at
room temperature. The solvent and any excess ethyl
vinyl ether were evaporated. Chromatography of the
residue (light petroleum/ether, 1:4) afforded 6.95 g of a
1:1 mixture of compound 8 and 9, RF ¼ 0:4 (dichloro-
methane/light petroleum/ether, 4:1:1). ESI MS: 556.2.
(M+H)þ. To a solution of the thus obtained mixture of 8
and 9 in methanol (60 mL) was added KCN (0.41 g,
6.2 mmol) and the mixture stirred at room temperature
until the starting compound disappeared (TLC analysis,
about 1 h). The solvent was evaporated, the residue
dissolved in a chloroform/methanol (5:1) mixture, fil-
tered through a short column of silica gel and the sol-
vent evaporated again. The residue (4.60 g, 11.9 mmol)
was dissolved in tetrahydrofuran (350 mL) and NaH
petroleum/ethyl acetate, 2:1). ½aꢁ ¼ þ94:5 (c 1.0,
D
1
CHCl3). H NMR (500 MHz, CDCl3): d (ppm) 8.02 (d,
1H, J ¼ 2.9 Hz, CH-thiazole), 7.70 (d, 1H, J ¼ 2.9 Hz,
CH-thiazole), 7.41 (d, 1H, J ¼ 15.7 Hz, H-2), 7.25 (ddd,
1H, J ¼ 15.7 Hz, J ¼ 7.1 Hz, J ¼ 3.0 Hz, H-3), 5.34 (dd,
1H, J ¼ 9.2 Hz, J ¼ 8.9 Hz, H-7), 5.13 (dd, 1H,
J ¼ 8.9 Hz, J ¼ 5.5 Hz, H-6), 4.96 (dd, 1H, J ¼ 8.9 Hz,
J ¼ 8.8 Hz, H-8), 4.42 (ddd, 1H, J ¼ 4.9 Hz, J ¼ 4.8 Hz,
J ¼ 5.5 Hz, H-5), 4.25 (dd, 1H, J ¼ 12.2 Hz, J ¼ 6.0 Hz,

ꢀ
1038
P. Stꢀepꢁanek et al. / Tetrahedron: Asymmetry 15 (2004) 1033–1041
(3.55 g of 60% suspension in mineral oil, 88.9 mmol)
added. After stirring at room temperature for 1.5 h,
benzyl bromide (8.46 mL, 71.1 mmol) was added drop-
wise, followed by tetrabutylammonium iodide (0.98 g,
2.7 mmol), and the mixture then heated at 50 ꢁC for 5 h.
Methanol (10 mL) was added and the reaction mixture
partitioned between dichloromethane and water. The
organic phase was dried, evaporated and the residue
chromatographed on silica gel (light petroleum/ethyl
acetate, 15:1 fi 4:1), yielding 3.73 g (36%) of 10 and
3.91 g (38%) of 11.
105.65 (C-5), 99.85 (C-2), 82.53, 79.95, 77.99, 71.45,
71.32 (C-20, C-30, C-40, C-50, C-60), 77.56, 76.36, 73.47,
72.83 (4 · C6H5-CH2), 68.89 (C-70), 64.74 (O-CH2–CH3),
32.36 (C-3), 30.16 (C-10), 27.15 (C-4), 15.28 (–O–CH2–
CH3). MS (ESI): 748.2 (M+H)þ. Anal. Calcd for
C45H49NO7S (MW 747.96): C, 72.26; H, 6.60; N, 1.87; S,
4.29. Found: C, 71.98; H, 6.42; N, 1.73; S, 4.13.
4.5. (2R,4R)-4-(20,60-Anhydro-30,40,50,70-tetra-O-benzyl-
10-deoxy-
formyl-3,4-dihydro-2H-pyran 14
D
-glycero-
-ido-heptitol-10-yl)-2-ethoxy-6-
D
ꢂ
Molecular sieves 4 A (2.6 g) were added to a solution of
4.4.2. From oxadiene 7. Ethyl vinyl ether (1.25 mL,
13.1 mmol) and Eu(fod)3 (0.26 g, 0.26 mmol) were added
to a solution of 7 (2.1 g, 3.1 mmol) in dichloromethane
(15 mL) and the reaction mixture sonicated at room
temperature for 7 h. The solvent and the excess ethyl
vinyl ether were evaporated. Chromatography of the
residue (light petroleum/ethyl acetate, 15:1fi 4:1) afforded
1.02 g (44%) of compound 10 and 1.05 g (46%) of com-
pound 11.
compound 10 (3.8 g, 5.1 mmol) in acetonitrile (70 mL),
and methyl triflate (0.76 mL, 6.7 mmol) added dropwise.
After stirring at room temperature for 15 min, methanol
(3 mL) was added and the solvent evaporated in vacuo.
The residue was treated with methanol (80 mL) and then
NaBH4 (0.66 g, 17.4 mmol) was added in portions. After
stirring at room temperature for 15 min, acetone (7 mL)
was added. The reaction mixture was filtered through
Supercel and the filtrate evaporated in vacuo. The resi-
due was dissolved in acetonitrile (60 mL) and a solution
of AgNO3 (1.4 g) in water (4.6 mL) was added under
vigorous stirring. After stirring for 10 min, phosphate
buffer (20 mL, pH 7) was added and after a further
10 min the acetonitrile was evaporated in vacuo and
the residue partitioned between dichloromethane and
phosphate buffer (pH 7). The organic phase was dried,
the solvent evaporated and the residue flash chromato-
graphed through a short silica gel column in light
petroleum/ethyl acetate (4:1 fi 1:1). Yield 2.47 g (70%)
of aldehyde 14, RF ¼ 0:4 (light petroleum/ethyl acetate,
3:1), which was immediately used in the subsequent
reaction step. 1H NMR (500 MHz, CDCl3): d (ppm)
9.10 (s, 1H, –CH@O), 7.37–7.23 (m, 20H, 4 · C6H5),
5.85 (d, 1H, J ¼ 3.9 Hz, H-5), 5.14 (dd, 1H, J ¼ 4.9 Hz,
J ¼ 2.5 Hz, H-2), 4.92–4.46 (m, 8H, 4 · C6H5–CH2), 4.09
(m, 1H, H-20), 3.90 (dq, 1H, J ¼ 9.6 Hz, J ¼ 7.0 Hz, –O–
CH2–CH3), 3.78–3.55 (m, 7H, H-30, H-40, H-50, H-60, H-
70a, H-70b, –O–CH2–CH3), 2.56 (m, 1H, H-4), 2.01 (m,
3H, H-10a, H-10b, H-3eq), 1.86 (ddd, 1H, J ¼ 13.8 Hz,
J ¼ 4.9 Hz, J ¼ 4.9 Hz, H-3ax), 1.18 (t, 3H, J ¼ 7.1 Hz,
–O–CH2–CH3). 13C NMR (125 MHz, CDCl3) d (ppm):
187.06 (–CH@O), 149.43 (C-6), 138.60, 138.23, 138.10,
137.88 (4 · ipso C6H5–CH2), 128.43–127.64 (20 · C6H5–
CH2), 125.95 (C-5), 98.41 (C-2), 82.37, 80.21, 77.97,
72.07, 71.37 (C-20, C-30, C-40, C-50, C-60), 75.49, 74.99,
2 · 73.49 (4 · C6H5–CH2), 69.03 (C-70), 64.54 (O–CH2–
CH3), 32.49 (C-3), 29.69 (C-10), 27.23 (C-4), 15.12 (–O–
CH2–CH3). MS (ESI): 715.2 (M+Na)þ.
Compound 10: RF ¼ 0:29 (light petroleum/ethyl acetate,
1
8:1). ½aꢁ ¼ þ35:2 (c 1.0, CHCl3). H NMR (500 MHz,
D
CDCl3): d (ppm) 7.83 (d, 1H, J ¼ 3.3 Hz, CH-thiazole),
7.17–7.32 (m, 21H, 4 · C6H5, CH-thiazole), 6.08 (d, 1H,
J ¼ 3.4 Hz, H-5), 5.20 (dd, 1H, J ¼ 2.1 Hz, J ¼ 6.8 Hz,
H-2), 4.96–4.48 (m, 8H, 4 · C6H5–CH2), 4.30 (m, 1H, H-
20), 4.02 (dq, 1H, J ¼ 9.6 Hz, J ¼ 7.0 Hz, –O–CH2–CH3),
3.82–3.62 (m, 8H, H-30, H-40, H-50, H-60, H-70a, H-70b,
–O–CH2–CH3), 2.62 (m, 1H, H-4), 2.17 (ddd, 1H,
J ¼ 2.1 Hz, J ¼ 4.6 Hz, J ¼ 11.5 Hz, H-3eq), 1.98 (m, 2H,
H-10a, H-10b), 1.88 (ddd, 1H, J ¼ 6.8 Hz, J ¼ 11.5 Hz,
J ¼ 11.5 Hz, H-3ax), 1.30 (t, 3H, J ¼ 7.0 Hz, –O–CH2–
CH3). 13C NMR (125 MHz, CDCl3) d (ppm): 164.62
(thiazole C-2), 143.73 (C-6), 143.28 (CH-thiazole),
138.36, 138.27, 138.22, 138.12 (4 · ipso C6H5–CH2),
128.36–127.57 (20 · C6H5–CH2), 118.48 (CH-thiazole),
104.24 (C-5), 99.61 (C-2), 82.36, 80.13, 78.07, 72.31,
71.48 (C-20, C-30, C-40, C-50, C-60), 75.42, 74.96, 73.53,
73.14 (4 · C6H5-CH2), 69.1 (C-70), 64.65 (–O–CH2–
CH3), 33.76 (C-3), 30.22 (C-10), 27.67 (C-4), 15.27 (–O–
CH2–CH3). MS (ESI): 748.2 (M+H)þ. Anal. Calcd for
C45H49NO7S (MW 747.96): C, 72.26; H, 6.60; N, 1.87; S,
4.29. Found: C, 72.11; H, 6.37; N, 1.98; S, 4.07.
Compound 11: RF ¼ 0:42 (light petroleum/ethyl acetate,
1
8:1) ½aꢁ ¼ þ39:1 (c 1.0, CHCl3). H NMR (500 MHz,
D
CDCl3): d (ppm) 7.82 (d, 1H, J ¼ 3.3 Hz, CH-thiazole),
7.15–7.38 (m, 21H, 4 · C6H5, CH-thiazole), 5.97 (d, 1H,
J ¼ 3.2 Hz, H-5), 5.20 (dd, 1H, J ¼ 1.7 Hz, J ¼ 6.7 Hz,
H-2), 4.97–4.50 (m, 8H, 4 · C6H5–CH2), 4.25 (m, 1H, H-
20), 4.05 (dq, 1H, J ¼ 9.6 Hz, J ¼ 7.0 Hz, –O–CH2–CH3),
4.08-3.59 (m, 8H, H-30, H-40, H-50, H-60, H-70a, H-70b,
–O–CH2–CH3), 2.67 (m, 1H, H-4), 2.22 (ddd, 1H,
J ¼ 1.7 Hz, J ¼ 2.6 Hz, J ¼ 13.3 Hz, H-3eq), 2.09 (m, 1H,
H-10a), 1.87 (m, 1H, H-10b), 1.75 (ddd, 1H, J ¼ 6.7 Hz,
J ¼ 13.3 Hz, J ¼ 13.3 Hz, H-3ax), 1.30 (t, 3H, J ¼ 7.0 Hz,
O–CH2–CH3). 13C NMR (125 MHz, CDCl3) d (ppm):
164.40 (thiazole C-2), 143.86 (C-6), 143.29 (CH-thia-
zole), 138.68, 138.22, 138.04 (4 · ipso C6H5–CH2),
128.49–127.57 (20 · C6H5–CH2), 118.40 (CH-thiazole),
4.6. (2S,4S)-4-(20,60-Anhydro-30,40,50,70-tetra-O-benzyl-10-
deoxy-
3,4-dihydro-2H-pyran 15
D
-glycero-
-ido-heptitol-10-yl)-2-ethoxy-6-formyl-
D
The title aldehyde 15 was prepared from compound 11
(3.9 g) in the same manner as described in the preceding
experiment. Yield 2.61 g (72%). 1H NMR (500 MHz,
CDCl3): d (ppm) 9.07 (s, 1H, –CH@O), 7.37–7.24 (m,
20H, 4 · C6H5), 5.94 (d, 1H, J ¼ 3.9 Hz, H-5), 5.14 (dd,

ꢀ
P. Stꢀepꢁanek et al. / Tetrahedron: Asymmetry 15 (2004) 1033–1041
1039
1H, J ¼ 5.5 Hz, J ¼ 2.1 Hz, H-2), 4.95–4.43 (m, 8H,
4 · C6H5–CH2), 4.17 (m, 1H, H-20), 3.92 (dq, 1H,
J ¼ 9.6 Hz, J ¼ 7.0 Hz, –O–CH2–CH3), 3.79–3.54 (m,
7H, H-30, H-40, H-50, H-60, H-70a, H-70b, –O–CH2–CH3),
2.58 (m, 1H, H-4), 2.06 (m, 2H, H-10a, H-10b), 1.90 (m,
1H, H-3eq), 1.76 (ddd, 1H, J ¼ 13.8 Hz, J ¼ 5.5 Hz,
J ¼ 5.5 Hz, H-3ax), 1.19 (t, 3H, J ¼ 7.0 Hz, –O–CH2–
CH3). 13C NMR (125 MHz, CDCl3) d (ppm): 186.96
(–CH@O), 149.45 (C-6), 138.57, 138.07, 138.01, 137.79
(4 · ipso C6H5–CH2), 128.50–127.65 (20 · C6H5–CH2,
C-5), 98.57 (C-2), 82.24, 79.73, 78.07, 72.11, 71.38 (C-20,
C-30, C-40, C-50, C-60), 75.47, 75.05, 73.52, 73.06
(4 · C6H5–CH2), 69.12 (C-70), 64.58 (–O–CH2–CH3),
31.82 (C-3), 29.36 (C-10), 27.97 (C-4), 15.15 (–O–CH2–
CH3). MS (ESI): 715.2 (M+Na)þ.
(C-60), 68.79 (C-50), 64.76 (–O–CH2–CH3), 62.88 (C-6),
62.40 (C-70), 37.39 (C-3), 37.23 (C-2), 27.16 (C-10),
20.80–20.58 (6 · O@C–CH3), 15.04 (–O–CH2–CH3). MS
(ESI): 627.3 (M+Na)þ. HRMS (ESI): calcd for
C27H40NaO15 (M+Na)þ 627.2265, found 627.2286.
4.8. Ethyl 2,3-dideoxy-3-C-(20,60-anhydro-30,40,50,70-tetra-
O-acetyl-10-deoxy-
D
-glycero-
-arabino-hexopyranoside 19
D
-ido-heptitol-10-yl)-4,6-di-
O-acetyl-b-
L
The title compound 19 was prepared from aldehyde 15
(2.6 g) in the same manner as described in the preceding
experiment. Yield 1.72 g (76%) of 19, mp 149–151 ꢁC
(acetone/light petroleum).
RF ¼ 0:3 (light petroleum/ether, 1:4). ½aꢁ ¼ þ85:9 (c 1,
D
4.7. Ethyl 2,3-dideoxy-3-C-(20,60-anhydro-30,40,50,70-tetra-
CHCl3). 1H NMR (CDCl3): d (ppm) 5.24 (dd, 1H,
J ¼ 8.9 Hz, J ¼ 9.2 Hz, H-40), 5.06 (dd, 1H, J ¼ 9.2 Hz,
J ¼ 5.8 Hz, H-30), 4.91 (dd, 1H, J ¼ 8.9 Hz, J ¼ 8.9 Hz,
H-50), 4.73 (dd, 1H, J ¼ 10.0 Hz, J ¼ 10.0 Hz, H-4), 4.52
(dd, 1H, J ¼ 1.5 Hz, J ¼ 9.6 Hz, H-1), 4.26 (m, 2H, H-1,
H-6a), 4.18 (m, 2H, H-70a, H-70b), 4.07 (dd, 1H,
J ¼ 2.4 Hz, J ¼ 12.1 Hz, H-6b), 3.94 (dq, 1H, J ¼ 7.1 Hz,
J ¼ 9.3 Hz, –O–CH2–CH3), 3.80 (m, 1H, H-60), 3.59–
3.50 (m, 2H, H-5, –O–CH2–CH3), 2.14–2.01 (m, 19H,
6 · O@C–CH3, H-3), 1.92 (m, 2H, H-2eq, H-10a), 1.40
(ddd, 1H, J ¼ 9.6 Hz, J ¼ 9.6 Hz, J ¼ 12.8 Hz, H-2ax),
1.29–1.20 (m, 4H, –O–CH2–CH3, H-10b). 13C NMR
(125 MHz, CDCl3) d (ppm): 170.85, 170.50, 170.24,
169.92, 2 · 169.51 (6 · O@C–CH3), 101.06 (C-1), 74.73
(C-5), 70.40 (C-4), 70.03 (C-30), 69.90 (C-40), 68.89
(C-50), 68.78 (C-60), 68.60 (C-20), 64.79 (–O–CH2–CH3),
63.06 (C-6), 62.27 (C-70), 35.13 (C-2), 34.55 (C-3),
26.64 (C-10), 20.85–20.61 (6 · O@C–CH3), 15.06 (–O–
CH2–CH3). MS (ESI): 627.3 (M+Na)þ. HRMS (ESI):
calcd for C27H40NaO15 (M+Na)þ 627.2265, found
627.2295.
O-acetyl-10-deoxy-
D
-glycero-
-arabino-hexopyranoside 18
D
-ido-heptitol-10-yl)-4,6-di-
O-acetyl-b-
D
A 2 M solution of BH3ÆS(CH3)2 in tetrahydrofuran
(4.5 mL, 9 mmol) was added dropwise to a solution
of aldehyde 14 (2.29 g, 3.3 mmol) in tetrahydrofuran
(70 mL), precooled to 0 ꢁC, and the reaction mixture
stirred at room temperature for 16 h. Then a 30% solu-
tion of NaOH (3.7 mL) and 30% solution of H2O2
(3.7 mL) was added and after stirring at room temper-
ature for 30 min the reaction mixture was partitioned
between ethyl acetate and saturated NaCl solution. The
organic phase was dried, the solvent evaporated in
vacuo and the residue dissolved in ethanol (150 mL) and
hydrogenated over Pd/C (10%, 0.9 g) under atmospheric
pressure. After 8 h, the catalyst was filtered off and the
solvent evaporated. The residue was dissolved in pyri-
dine (25 mL), acetic anhydride (10 mL) and dimethyl-
aminopyridine (0.1 g) then added and the mixture stirred
at room temperature for 1 h. The reaction mixture was
poured onto ice, partitioned between water and ethyl
acetate and the organic phase, after drying and evapo-
ration of the solvent, was chromatographed on silica
gel in light petroleum/ether (1:4). Yield 1.5 g (75%)
of compound 18, mp 159–162 ꢁC (acetone/light petro-
leum).
4.9. Ethyl 2,3-dideoxy-3-C-(20,60-anhydro-30,40,50,70-tetra-
O-acetyl-10-deoxy-
D
-glycero-
-arabino-hexopyranoside 20
D
-ido-heptitol-10-yl)-4,6-di-
O-acetyl-a-
L
Aldehyde 15 was treated as described in Section 4.7,
except that a Pd-catalyst containing traces of acid, was
employed. Crystallization from acetone/light petroleum
of the obtained mixture of 19 and 20 afforded an ana-
lytical sample of the title compound 20, mp 137–139 ꢁC
(acetone/light petroleum). RF ¼ 0:3 (light petroleum/
RF ¼ 0:35 (light petroleum/ether, 1:4). ½aꢁ ¼ þ21:3 (c 1,
D
CHCl3). 1H NMR (CDCl3): d (ppm) 5.23 (dd, 1H,
J ¼ 9.2 Hz, J ¼ 9.6 Hz, H-40), 4.97 (dd, 1H, J ¼ 9.6 Hz,
J ¼ 5.8 Hz, H-30), 4.93 (dd, 1H, J ¼ 9.1 Hz, J ¼ 9.2 Hz,
H-50), 4.74 (dd, 1H, J ¼ 10.0 Hz, J ¼ 10.0 Hz, H-4), 4.52
(dd, 1H, J ¼ 1.3 Hz, J ¼ 9.3 Hz, H-1), 4.27 (dd, 1H,
J ¼ 4.9 Hz, J ¼ 12.1 Hz, H-6a), 4.20 (m, 2H, H-70a, H-
20), 4.11 (dd, 1H, J ¼ 2.1 Hz, J ¼ 12.1 Hz, H-70b), 4.04
(dd, 1H, J ¼ 2.2 Hz, J ¼ 12.1 Hz, H-6b), 3.95 (dq, 1H,
J ¼ 7.2 Hz, J ¼ 9.4 Hz, –O–CH2–CH3), 3.85 (m, 1H, H-
60), 3.59–3.50 (m, 2H, H-5, –O–CH2–CH3), 2.20 (m, 1H,
H-2eq), 2.14–2.01 (m, 18H, 6 · O@C–CH3), 1.90 (m,
1H, H-3), 1.64 (m, 2H, H-10a, H-10b), 1.51 (ddd, 1H,
J ¼ 12.8 Hz, J ¼ 9.3 Hz, J ¼ 9.3 Hz, H-2ax), 1.23 (t, 3H,
J ¼ 7.2 Hz, –O–CH2–CH3). 13C NMR (125 MHz,
CDCl3) d (ppm): 170.86, 170.63, 170.30, 169.91, 169.63,
169.52 (6 · O@C–CH3), 101.00 (C-1), 74.52 (C-5), 73.16
(C-20), 71.42 (C-4), 70.19 (C-30), 69.75 (C-40), 69.01
ether, 1:4). ½aꢁ ¼ þ21:5 (c 1, CHCl3). 1H NMR
D
(CDCl3): d (ppm) 5.24 (dd, 1H, J ¼ 9.1 Hz, J ¼ 9.3 Hz,
H-40), 5.06 (dd, 1H, J ¼ 9.3 Hz, J ¼ 5.9 Hz, H-30), 4.92
(dd, 1H, J ¼ 9.1 Hz, J ¼ 9.1 Hz, H-50), 4.87 (d, 1H,
J ¼ 3.4 Hz, H-1), 4.75 (dd, 1H, J ¼ 10.2 Hz, J ¼ 10.2 Hz,
H-4), 4.28–4.20 (m, 3H, H-20, H-70a, H-6a), 4.11 (dd,
1H, J ¼ 2.1 Hz, J ¼ 12.1 Hz, H-70b), 4.01 (dd, 1H,
J ¼ 2.1 Hz, J ¼ 12.1 Hz, H-6b), 3.88 (ddd, 1H,
J ¼ 2.1 Hz, J ¼ 4.5 Hz, J ¼ 10.2 Hz, H-5), 3.80 (ddd, 1H,
J ¼ 2.1 Hz, J ¼ 5.5 Hz, J ¼ 9.1 Hz, H-60), 3.68 (dq, 1H,
J ¼ 7.1 Hz, J ¼ 9.6 Hz, –O–CH2–CH3), 3.48 (dq, 1H,
J ¼ 7.1 Hz, J ¼ 9.6 Hz, –O–CH2–CH3), 2.23 (m, 1H,
H-3), 2.14–2.01 (m, 19H, 6 · O@C–CH3, H-2eq), 1.89

ꢀ
1040
P. Stꢀepꢁanek et al. / Tetrahedron: Asymmetry 15 (2004) 1033–1041
(ddd, 1H, J ¼ 2.8 Hz, J ¼ 13.5 Hz, J ¼ 13.5 Hz, H-10a),
1.52 (ddd, 1H, J ¼ 3.4 Hz, J ¼ 13.1 Hz, J ¼ 13.1 Hz, H-
2ax), 1.27-1.18 (m, 4H, J ¼ 7.2 Hz, –O–CH2–CH3, H-
10b). 13C NMR (125 MHz, CDCl3) d (ppm): 170.83,
170.61, 170.37, 170.02, 169.65, 169.53 (6 · O@C–CH3),
96.11 (C-1), 70.82 (C-4), 70.27 (C-40), 70.17 (C-30), 69.01
(C-50), 68.95 (C-20), 68.65 (C-60), 68.61 (C-5), 63.01 (C-
6), 62.86 (–O–CH2–CH3), 62.23 (C-70), 34.14 (C-2),
30.91 (C-3), 27.09 (C-10), 20.85–20.66 (6 · O@C–CH3),
15.03 (–O–CH2–CH3). MS (ESI): 627.3 (M+Na)þ.
HRMS (ESI): calcd for C27H40NaO15 (M+Na)þ
627.2265, found 627.2296.
for 19 and CCDC 230423 for 20) can be obtained free
of charge on application to CCDC, e-mail: deposit@
ccdc.cam.ac.uk.
Acknowledgements
This work was supported by Ministry of Education,
Youth and Sport of the Czech Republic (grant no
223300006) and by Grant Agency of the Czech Republic
(grant no 203/03/0497). The authors are grateful to Dr.
David Sykora for the measurements of mass spectra.
4.10. X-ray structure analysis of compounds 19 and 20
The diffraction-quality crystals of compounds 19 and 20
were grown from acetone solutions by vapour diffusion
of light petroleum at room temperature. Selected col-
ourless crystals were mounted on glass fibres in random
orientations using silicon fat. Diffraction data were
collected using Nonius Kappa CCD diffractometer
(Enraf–Nonius) at 150(1) K (Cryostream Cooler Oxford
Cryosystem) and analyzed using the HKL program
References and notes
1. For recent reviews, see: (a) Glycoscience: Chemistry and
Chemical Biology; Fraser-Reid, B. O., Tatsuta, K., Thiem,
J., Eds.; Springer: Heidelberg, 2001; (b) Carbohydrates in
€
Chemistry and Biology; Ernst, B., Hart, G. W., Sinay, P.,
Eds.; Wiley-VCH: Weinheim, 2000.
2. (a) Levy, D. E.; Tang, C. The Chemistry of C-Glycosides.
In Tetrahedron Organic Chemistry Series; Baldwin, J. E.,
Magnus, P. D., Eds.; Pergamon–Elsevier: Oxford, 1995;
(b) Postema, M. H. D. In: C-Glycoside Synthesis; CRC:
Boca Raton, FL, 1995; (c) Vogel, P.; Ferrito, R.;
Kraehenbuehl, K.; Baudat, A. In Carbohydrate Mimics,
Concept and Methods; Chapleur, Y., Ed.; Wiley-VCH:
Weinheim, 1998; pp 19–48; (d) Du, Y.; Linhardt, R. J.;
Vlahov, I. R.. Tetrahedron 1998, 54, 9913; (e) Vogel, P..
Chimia 2001, 55, 359; (f) Liu, L.; McKee, M.; Postema, M.
H. D. Curr. Org. Chem. 2001, 5, 1133.
package.24 The structures were solved by the direct, and
25
refined by full-matrix least-squares techniques (SIR92
,
SHELXL97.26) Scattering factors for neutral atoms used
were included in the program SHELXL97. The hydrogen
atoms were found on a difference Fourier map and
refined isotropically. Final geometric calculations were
carried out with SHELXL97 and recent version of the
PLATON program.27
ꢁ
3. (a) Mikros, E.; Labrinidis, G.; Perez, S. J. Carbohydr.
Chem. 2000, 19, 1319; (b) Jimenez-Barbero, J.; Espinosa,
Pertinent crystallographic data for compound 19:
C27H40O15, Mw ¼ 604:59, monoclinic, space group P21
ꢁ
~
J. F.; Asensio, J. L.; Canada, F. J.; Poveda, A. Adv.
ꢂ
(no. 4), Z ¼ 2, unit cell parameters a ¼ 12:8390ð3Þ A,
Carbohydr. Chem. Biochem. 2001, 56, 235–284; (c) Goe-
kjian, P. G.; Wei, A.; Kishi, Y. In Carbohydrate-Based
Drug Discovery; Wong, Ch.-H., Ed.; Wiley-VCH: Wein-
heim, 2003; pp 305–340.
ꢂ
ꢂ
b ¼ 8:6060ð2Þ A, c ¼ 13:8230ð3Þ A, a ¼ c ¼ 90ꢁ, b ¼
101:021ð1Þꢁ, V ¼ 1499:17ð6Þ Aꢂ3, Dcalcd ¼ 1:339 g cmꢂ3
,
ꢂ
F ð000Þ ¼ 644, k(Mo Ka) ¼ 0.71073 A, l ¼ 0:11 mmꢂ1, h
in range from 3.24ꢁ to 27.48ꢁ (6755 measured reflections,
6729 unique data), R1 ¼ 0:0318, wR2 ¼ 0:0749 for 6178
observed reflections [ P 4rðF0Þ], goodness-of-fit S ¼
1:058. The residual electron density was found between
ꢂ
4. (a) Witczak, Z. J.; Chabra, R.; Chojnacki, J. Tetrahedron
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)0.138 and 0.220 e Aꢂ3. In the crystal, only van der
Waalsꢀ contact are observed.
ꢂ
Tetrahedron Lett. 1997, 38, 8845; (d) Bornaghi, L.; Utille,
€
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Pertinent crystallographic data for compound 20:
C27H40O15, Mw ¼ 604:59, orthorhombic, space group
P212121 (no. 19), Z ¼ 4, unit cell parameters
ꢂ
ꢂ
ꢂ
a ¼ 8:5050 A, b ¼ 12:6950 A, c ¼ 27:6950 A, a ¼ b ¼
€
Mallet, J.-M.; Sinay, P. Tetrahedron Lett. 1998, 39, 3697;
ꢂ3
c ¼ 90ꢁ, V ¼ 2993:60ð6Þ A
,
Dcalcd ¼ 1:341 g cmꢂ3
,
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ꢂ1
ꢂ
F ð000Þ ¼ 1288, k(Mo Ka)¼ 0.71073 A, l ¼ 0:11 mm , h
in range from 3.24ꢁ to 27.50ꢁ (6835 measured reflections,
6823 unique data), R1 ¼ 0:0312, wR2 ¼ 0:0752 for 6233
€
E. D.; Rubinstenn, G.; Mallet, J.-M.; Sinay, P. Synlett
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observed
reflections
[ P 4rðF0Þ],
goodness-of-fit
S ¼ 1:023. The residual electron density was found
between )0.151 and 0.185 e Aꢂ3. In the crystal, only
ꢂ
van der Waalsꢀ contact are observed.
ꢁ
T.; Espinosa, J.-F.; Jimenez-Barbero, J.; Beau, J.-M.
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All crystallographic data (included cif-files) for the
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Cambridge Crystallographic Data Centre as a supple-
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