Synthesis of sulfonic acid-containing maltose-type keto-oligosaccharides by an iterative approach

Article abstract of DOI:10.1016/j.tet.2012.04.067

Two different series of (2→5)-α-linked homologous keto-oligosaccharides up to tri- and tetrasaccharide were synthesized by an iterative approach, using 3,4,7-tri-O-benzyl-5-O-(2-naphthyl)methyl-1-deoxy-1- ethoxysulfonyl-α-d-gluco-hept-2-ulopyranosyl chloride as a key building block. An iterative cycle consisted of a glycosylation step followed by selective cleavage of the (2-naphthyl)methyl group.

Full text of DOI:10.1016/j.tet.2012.04.067

Tetrahedron 68 (2012) 4986e4994
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of sulfonic acid-containing maltose-type keto-oligosaccharides by an
iterative approach
a
a
a
a
b
a,c
ꢀ
ꢀ
ꢀ ꢀ
ꢀ
ꢀ ꢀ ꢀ
ꢀ
ꢀ
ꢀ
Gabor Majer , Magdolna Csavas , Laszlo Lazar , Mihaly Herczeg , Atttila Benyei , Sandor Antus
,
a,d,
*
ꢀ
ꢀ
Aniko Borbas
a Research Group for Carbohydrates of the Hungarian Academy of Sciences, University of Debrecen, H-4010 Debrecen, PO Box 94, Hungary
b Department of Physical Chemistry, Institute of Chemistry, University of Debrecen, H-4010 Debrecen, PO Box 7, Hungary
c Department of Organic Chemistry, University of Debrecen, H-4010, Debrecen, PO Box 20, Hungary
d Department of Pharmaceutical Chemistry, Medical and Health Science Center, University of Debrecen, H-4010 Debrecen, PO Box 70, Hungary
a r t i c l e i n f o
a b s t r a c t
Article history:
Two different series of (2/5)-a-linked homologous keto-oligosaccharides up to tri- and tetrasaccharide
Received 10 January 2012
Received in revised form 26 March 2012
Accepted 16 April 2012
were synthesized by an iterative approach, using 3,4,7-tri-O-benzyl-5-O-(2-naphthyl)methyl-1-deoxy-1-
ethoxysulfonyl- -gluco-hept-2-ulopyranosyl chloride as a key building block. An iterative cycle con-
sisted of a glycosylation step followed by selective cleavage of the (2-naphthyl)methyl group.
a-D
Available online 25 April 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Sulfated malto-oligomers
Carbohydrate sulfonic acids
Iterative glycosylation
Ketopyranosyl glycosides
Maltose-type oligosaccharide series
1. Introduction
formed via elimination of the labile proton next to the electron
withdrawing sulfonic acid moiety. The rate of undesirable
Sulfated cyclodextrins have exhibited anticancer activity,1,2
presumably through an anti-angiogenic mechanism. Sulfated
maltohexaose also has been identified as a potent inhibitor of
in vitro angiogenesis and heparanase activity.3 Highly sulfated
malto-oligosaccharides have the ability to inhibit the biological
activity of basic fibroblast growth factor and heparanase in vivo,
and act as antitumour and antimetastatic agents in in vivo models
of malignancy.4 Because of the great therapeutical potential of the
sulfated malto-oligosaccharides we envisaged the synthesis of their
sulfonic acid analogues possessing higher stability against esterases
and sulfatases.
elimination side-reaction could be decreased by applying the
chlorosugar 2 as a glycosyl donor.7 It has been also shown that
both thioglycoside 1 and chloro derivative 2 gave the
a-linked
ketosyl glycosides exclusively or in high selectivity.5e8 On the
basis of these results, we considered the application of the
1-deoxy-1-ethoxysulfonyl-a-D-gluco-hept-2-ulopyranosyl donor
3 possessing a selectively removable (2-naphthyl)methyl (NAP)
protecting group for the preparation of the sulfonic acid ana-
logues of the sulfated malto-oligosaccharides by an iterative
approach.
Recent work from this laboratory showed that ethyl 3,4,5,7-
tetra-O-benzyl-1-deoxy-1-ethoxysulfonyl-2-thio-a-D-gluco-hept-
2-ulopyranoside 1 (Fig. 1) could be used as glycosyl donor for
the synthesis of sulfonic acid analogues of the sialyl Lewis
X tetrasaccharide, a natural ligand of transmembrane proteins.5,6
However, the yields of glycosylation reactions using 1 were
moderate since a considerable amount of exo-glycal was always
* Corresponding author. E-mail addresses: borbas.aniko@science.unideb.hu,
borbasa@puma.unideb.hu (A. Borbas).
Fig. 1. 1-Deoxy-1-ethoxysulfonyl-D-gluco-hept-2-ulopyranosyl donors 1,5 27 and 3.
ꢀ
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.04.067

ꢀ
G. Majer et al. / Tetrahedron 68 (2012) 4986e4994
4987
2. Results and discussion
than the chlorosugar.7 Indeed, the thioglycoside 9 upon NIS/TfOH
activation proved to be inefficient for glycosylation of the unreac-
tive acceptor 10;7 the rapidly formed glycosylium intermediate was
mainly stabilized via elimination providing 12 as the main product.
Therefore, only compound 3 was used for the further iterative
processes.
Two series of maltose-type keto-oligosaccharides have been
prepared by means of repeating a glycosylation step using 3 as
a donor followed by unmasking of the (2-naphthyl)methyl-ether
function of the obtained glycoside as outlined in Scheme 1.
Scheme 1. Iterative synthesis of maltose-type keto-oligosaccharide sulfonic acids.
Synthesis of the key building block 3 started from the known 4,9
which was benzylated to afford the fully protected 5 carrying or-
thogonal protecting groups at the anomeric center and position 4.
Selective removal of the 4-methoxyphenyl aglycone with ammo-
nium cerium(IV) nitrate10 was insufficient, since the (2-naphthyl)
methyl group being sensitive towards oxidative cleavage was also
affected. Fortunately, acidic hydrolysis produced the hemiacetal 6
in high yield. Compound 6 was oxidised with DesseMartin peri-
odinane11 and the obtained gluconolactone 7 was reacted with
ethyl methanesulfonate anion generated with n-butyllithium. Nu-
cleophilic addition of the sulfonate ester carbanion to the lactone
carbonyl gave the 1-deoxy-1-ethoxysulfonyl-hept-2-ulopyranose
Selective removal of the (2-naphthyl)methyl group of the fully
protected disaccharide 11 could be achieved by oxidative cleavage
using DDQ15 to give 13 in high yield. Subsequent glycosylation of the
disaccharide acceptor 13 with the freshly prepared donor 3 resulted
in the maltose-type ketosyl trisaccharide 14 together with the
elimination product 12. Then, another iterative cycle involving NAP-
cleavage followed by a glycosylation step furnished the tetra-
saccharide 16. The (2-naphthyl)methyl group of 16 could be split off
with high efficacyat a tetrasaccharidelevel affording 17, which might
be applied as an acceptor for further chain-elongation (Scheme 3).
The other set of sulfonic acid-containing maltose-type keto-
oligosaccharides was prepared in form of a methyl glycoside. Re-
action of thioglycoside 9 with methanol gave a mixture of the
methyl glycosides 1816 and 19 in a 4:1 ratio (Scheme 4). The
anomeric configuration of the crystalline major product has been
verified by X-ray crystallography (an ORTEP view of compound 18 is
derivative 8, exclusively in the
a-anomeric form. Reaction of
hemiketal 8 with thionyl chloride and pyridine went to completion
in 20 min affording the glycosyl chloride 3, its purification by col-
umn chromatography on silica, however, led to partial de-
composition. Therefore, the crude reaction product was planned to
be utilized for the glycosylation reactions. Another glycosyl donor,
the thioglycoside 9 could also be prepared from 8 upon treatment
with ethanethiol in the presence of BF3$Et2O (Scheme 2).
shown in Fig. 2). Treatment of the a-isomer 18 with DDQ resulted in
20, which served as an acceptor for the next iterative process.
Glycosylation of 20 with donor 3 gave disaccharide 21 in an
acceptable yield. The elimination product 12 potentially formed
Scheme 2. Synthesis of the glycosyl donors 3 and 9. Reagents and conditions: (i) NaH, BnBr, DMF, 0 ꢁC, 5 h, 95%; (ii) CH3CN/HClaq (10:1), reflux, 3 h, 85%; (iii) DesseMartin
periodinane, CH2Cl2, rt, 20 min, 85%; (iv) (i-Pr)2NH, n-BuLi, CH3SO3Et, ꢂ60 ꢁC, 3 h, 86%; (v) SOCl2, py, CH2Cl2, rt, 20 min; (vi) EtSH, BF3$Et2O, CH2Cl2, ꢂ20 ꢁC, 18 h, 94%.
For the synthesis of one of the oligosaccharide series,
a monosaccharide unit with a free 4-OH group was intended to be
used as an acceptor in the first iterative cycle. Thus, compound
1012 was glycosylated with freshly prepared chlorosugar 3 in the
presence of silver triflate to result in a mixture of the desired
disaccharide 11 and the elimination side-product 12. The
anomeric configurations of ketopyranosyl glycosides can be de-
termined either by the measurement of the NOE interactions
between H-1 and H-3 or H-4,13 or on the basis of the NMR
C1eH3axial three-bond coupling constant, which is dependent on
from the donor was not isolated. The last iterative glycosylation was
carried out by using the fully benzylated chlorosugar 237 as a donor
affording the trisaccharide 24 carrying a sulfonatomethyl moiety at
each anomeric center (Scheme 5).
The prepared ketosyl glycosides up to trisaccharides were
deprotected in a two-step procedure. The sulfonic acid esters were
transformed into sodiumsulfonato derivatives via nucleophilic
substitution using sodium iodide, subsequently, the benzyl pro-
tecting groups were removed by catalytic hydrogenation affording
the sulfonic acid-containing saccharides 25e29 (Scheme 6).
In conclusion, two different series of sulfonic acid-containing
3
5e7,13b,14
the dihedral angle in a manner similar to JH,H
.
Applying
the latter method the -interglycosidic linkage of 11 was un-
a
(2/5)-a-linked homologous keto-oligosaccharides were synthe-
ambiguously determined by the recorded small coupling constant
sized using the ketosyl donor 3 possessing a selectively removable
(2-naphthyl)methyl group as the key building block. Although an
elimination product was formed from the donor in each glycosyl-
ation step, three cycles of the iterative process could be carried out
(3JC1 H3 ꢀ1 Hz).
0
0
Synthesis of disaccharide 11 was also attempted by utilising the
thioglycoside 9, although it was expected to be a less potent donor

ꢀ
G. Majer et al. / Tetrahedron 68 (2012) 4986e4994
4988
Scheme 3. Synthesis of the first set of sulfonic acid-containing maltose-type keto-oligosaccharides. Reagents and conditions: (i) AgOTf, CH2Cl2/toluene (4:1), 4 A MS, 0 ꢁC, 5 days,
from 10: 11 (49%) and 12 (25%), from 13: 14 (37%) and 12 (26%), from 15: 16 (38%) and 12 (not isolated); (ii) NIS/TfOH, CH2Cl2, ꢂ40 ꢁC, 75 min, 10% for 11, 37% for 12; (iii) DDQ,
CH2Cl2/H2O (9:1), rt, 25 min, 87% for 13, 79% for 15, 71% for 17.
ꢁ
Scheme 4. Synthesis of acceptor 2. Reagents and conditions: (i) MeOH, NIS/TfOH,
CH2Cl2, 3 A MS, ꢂ50 ꢁC, 20 min, 76% for 18, 20% for 19; (ii) DDQ, CH2Cl2/H2O (9:1), rt,
ꢁ
20 min, 89%.
Scheme 5. Synthesis of the second set of sulfonic acid-containing maltose-type keto-
oligosaccharides Reagents and conditions: (i) AgOTf, CH2Cl2/toluene (4:1), 0 ꢁC, 5 days,
59% for 21, 34% for 24; (ii) DDQ, CH2Cl2/H2O (9:1), rt, 25 min, 78%.
3. Experimental
3.1. General
Optical rotations were measured at room temperature with
a PerkineElmer 241 automatic polarimeter. Melting points were
determined on a Kofler hot-stage apparatus and are uncorrected.
All reactions were performed under anhydrous conditions (using
argon) and monitored by TLC on Kieselgel 60 F254 (Merck) visual-
ized under UV light and charred with 5% sulfuric acid in ethanol.
Column chromatography was performed on Silica Gel 60 (Merck
0.062e0.200 nm). Chemicals were purchased from Aldrich and
Fluka and used without further purification. Molecular sieves were
activated by heating to 360 ꢁC overnight and were cooled over P2O5
in vacuo. The organic solutions were dried over MgSO4, and
Fig. 2. ORTEP view of compound 18 at 50% probability level.
in acceptable yields. The prepared compounds can be regarded as
sulfonic acids analogues of the sulfated malto-oligomers. Biological
evaluation of the derivatives as well as the synthesis of higher keto-
oligosaccharides are in progress in our laboratory.

ꢀ
G. Majer et al. / Tetrahedron 68 (2012) 4986e4994
4989
Scheme 6. (i) Deprotection procedures. Reagents and conditions: NaI, acetone, 3 h, reflux, then Pd/C, H2, AcOH, EtOH/H2O, 62% for 25, 68% for 26, 64% for 27, 61% for 28, 59% for 29.
concentrated in vacuum. The 1H (200, 360 and 500 MHz) and 13C
NMR (50, 90 and 125 MHz) spectra were recorded with Bruker WP-
200SY, Bruker AM-360 and Bruker DRX-500 spectrometers.
Chemical shifts are referenced to Me4Si (0.00 ppm for 1H) or to the
residual solvent signals (77.00 ppm for 13C). The 13C/1H long-range
coupling constants were measured from 1H-coupled 13C NMR
spectra. IR spectra were recorded on a PerkineElmer 16 PC FTIR
spectrometer. X-ray data collection was performed using a Bruker-
3.4. General method C for deprotection
To a solution of the starting material (0.05 mmol) in acetone, NaI
(1.2 equiv/sulfonate ester functional group) was added and stirred
for 2 days. The mixture was then concentrated and the crude
product was purified by column chromatography in CH2Cl2/MeOH
8:2. The obtained sodium salt was dissolved in EtOH/H2O/EtOAc
(9:1:0.5, 5 mL), 10% Pd/C (60e100 mg) was added and it was stirred
in an autoclave under a H2 atmosphere at 20 bar until TLC indicated
a complete conversion. The catalyst was filtered off through a pad
of Celite, and the filtrate was concentrated. The product was puri-
fied by column chromatography in CH2Cl2/MeOH/H2O¼5:4:1.
Nonius MACH3 diffractometer equipped with a point detector us-
ꢁ
ing graphite-monochromated Mo K
a
radiation,
l¼0.71073 A. The
structure was solved using direct methods by the SIR-92 program17
and refined by full-matrix least-squares method on F2, with all non-
hydrogen atoms refined with anisotropic thermal parameters.
A few benzyl carbon atoms were regulated using several restraints.
Refinement was performed using the SHELXL-97 package.18 Publi-
cation material was prepared with the WINGX suite.19 Hydrogen
atoms were located geometrically. MALDI-TOF MS spectra were
recorded on a Bruker Biflex III spectrometer in the positive, linear
mode using satd 2,4,6-trihydroxyacetophenone in water as matrix.
Elemental analyses (C, H, S) were performed using an Elementar
Vario MicroCube instrument.
3.5. p-Methoxyphenyl 2,3,6-tri-O-benzyl-4-O-(2-naphthyl)
methyl-b-D-glucopyranoside (5)
Compound 4 (4.87 g, 8.03 mmol) was dissolved in dry N,N-
dimethylformamide (80 mL) and 60% NaH (0.48 g, 12.05 mmol,
1.5 equiv) was added to the cooled mixture (0 ꢁC). After 30 min
benzyl bromide (15 mL, 9.64 mmol 1.2 equiv) was added and it was
stirred for 5 h. Then MeOH was added, and the reaction mixture
was concentrated. The residue was diluted with CH2Cl2, washed
twice with water, dried, filtered and concentrated. The crude
product was crystallized from EtOH to yield 5 (5.30 g, 95%) as white
3.2. General method A for removal of (2-naphthyl)methyl-
ether
needles. Mp 98e100 ꢁC; [
a]
ꢂ15.4 (c 0.81, CHCl3); Rf 0.65 (n-hex-
D
To a stirred solution of the starting material (0.5 mmol) in
a mixture of CH2Cl2 and water (9:1, 10 mL/mg), DDQ (0.75 mmol,
1.5 equiv) was added and it was vigorously stirred at room tem-
perature. When TLC showed complete conversion (20e25 min) the
mixture was diluted with CH2Cl2, washed twice with satd aq
NaHCO3 and water, dried, filtered and concentrated.
ane/EtOAc 7:3); 1H NMR (360 MHz, CDCl3):
d 7.84e7.21 (m, 22H,
arom.), 7.04, 6.81 (2d, 4H, PMP arom.), 5.06 (d, 1H, J¼10.9 Hz,
CH2Ar), 4.99 (d, 1H, J¼11.1 Hz, CH2Ar), 4.97 (d, 1H, J¼10.9 Hz,
CH2Ar), 4.92e4.88 (m, 1H, skeleton), 4.84 (d, 1H, J¼11.0 Hz, CH2Ar),
4.83 (d,1H, J¼11.0 Hz, CH2Ar), 4.72 (d,1H, J¼11.1 Hz, CH2Ar), 4.60 (d,
1H, J¼12.0 Hz, CH2Ar), 4.51 (d, 1H, J¼12.1 Hz, CH2Ar), 3.84e3.78 (m,
1H, skeleton), 3.77 (s, 3H, OCH3), 3.76e3.67 (m, 4H, skeleton),
3.65e3.55 (m, 1H, skeleton); 13C NMR (90 MHz, CDCl3):
d 155.2,
3.3. General method B for glycosylation using donor 3
151.5 (2C-quat., PMP), 138.5, 138.2, 138.1 (3C-quat., Ph), 135.4, 133.2,
132.9 (3C-quat., NAP), 128.5e125.6 (arom.), 118.4 (2ꢃ), 114.5 (2ꢃ)
(4C-arom., PMP), 102.8 (C-1), 84.7, 82.1, 77.7, (C-2, C-3, C-4), 75.0 (C-
5), 75.7, 75.1, 75.0, 73.4 (4CH2Ar), 68.8 (C-6), 55.6 (OCH3). Anal.
Calcd for C45H44O7 (696.83 g/mol): C, 77.56; H, 6.36. Found: C,
77.44; H, 6.48.
To a solution of the acceptor (0.6 mmol) in toluene (1.5 mL) and
CH2Cl2 (4.5 mL), 4 A powdered molecular sieves and AgOTf
ꢁ
(0.6 mmol) were added and it was stirred overnight. The reaction
mixture was cooled to 0 ꢁC, then donor 3 (0.3 mmol) in dry CH2Cl2
(1.5 mL) was added, and the temperature was kept at 0 ꢁC until TLC
showed complete conversion of the donor (w5 days). The in-
soluble materials were removed by filtration; the filtrate was di-
luted with CH2Cl2, washed with 10% aq Na2S2O3 and water, dried,
filtered and concentrated. The crude product was purified by col-
umn chromatography. The remaining acceptor was recovered in
each case.
3.6. 2,3,6-Tri-O-benzyl-4-O-(2-naphthyl)methyl-a,b-D-
glucopyranose (6)
To a solution of compound 5 (2.36 g, 3.39 mmol) in acetonitrile
(40 mL) a mixture of cc. HCl/water (1:1, 4 mL) was added and it

ꢀ
G. Majer et al. / Tetrahedron 68 (2012) 4986e4994
4990
was heated at reflux temperature for 3 h. After cooling it was
concentrated, the residue was dissolved in CH2Cl2, washed twice
with water, 1 M aq NaOH (10 mL) and water, dried, filtered and
concentrated. The crystalline crude product was recrystallized
1002, 928, 862, 823, 734, 698, 618, 547, 477, 419 cmꢂ1
;
1H NMR
(200 MHz, CDCl3): 7.78e7.09 (m, 22H, arom.), 4.92e4.52 (m, 6H,
d
CH2Ar), 4.43 (d, 1H, J¼12.0 Hz, CH2Ar), 4.34 (d, 1H, J¼12.0 Hz,
CH2Ar), 4.10 (q, 2H, J¼7.1 Hz, SO3CH2CH3), 4.06e3.91 (m, 2H,
skeleton), 3.74e3.51 (m, 3H, skeleton), 3.31 (d, 1H, J3,4¼9.0 Hz,
H-3), 3.30 (d, 1H, J¼15.0 Hz, H-1a), 2.89 (d, 1H, J¼15.0 Hz, H-1b),
1.18 (t, 3H, J¼6.7 Hz, SO3CH2CH3); 13C NMR (50 MHz, CDCl3):
from EtOH to yield 6 (1.70 g, 85%) as a mixture of the
a
and
b
anomers (
a
/
b
w3:2). Mp 96e98 ꢁC (EtOH); [
a]
D
ꢂ2.1 (c 0.24;
CHCl3), Rf 0.42, 0.48 (n-hexane/EtOAc 6:4); IR nmax (KBr) 3398,
3087, 3060, 3029, 2917, 2861, 1603, 1508, 1496, 1453, 1401, 1362,
1326, 1271, 1258, 1208, 1147, 1086, 1045, 1027, 1001, 945, 905, 854,
d
138.3, 137.8, 137.3 (3C-quat. Ph), 135.4, 133.2, 132.9 (3C-quat.,
NAP), 128.7e125.7 (arom.), 95.8 (C-2), 82.9, 80.9, 77.9 (C-3eC-5),
75.6, 75.1, 75.0, 73.4 (4CH2Ar), 71.9 (C-6), 68.3 (C-7), 67.9
817, 780, 735, 696, 620, 608, 550, 475, 418 cmꢂ1
;
1H NMR
3
(200 MHz, CDCl3):
J¼3.0 Hz, H-1 ), 5.11e4.52 (m, 12.5H), 4.22e4.16 (m, 1H), 4.13
(t, 1H, J¼9.0 Hz, skeleton- ), 4.01 (br s, 0.5H, OH- ) 3.84e3.62 (m,
6.5H, skeleton), 3.53 (t, 0.5H, J¼7.5 Hz, skeleton- ), 3.44 (br s, 1H,
OH- 138.7e137.8 (6C-quat., Ph),
); 13C NMR (50 MHz, CDCl3):
135.7e132.9 (3C-quat., NAP), 128.4e125.8 (arom.), 97.5 (C-1 ), 91.3
(C-1 ), 84.6, 83.1 (C-2 , C-3 or C-4 ), 81.8, 80.0, 77.7, 70.3 (skel-
eton), 75.6e73.2 (CH2Ar), 68.9 (C-6 ), 68.6 (C-6 ). Anal. Calcd for
d
7.92e7.37 (m, 33H, arom.), 5.35 (d, 1H,
(SO3CH2CH3), 55.2 (C-1, JC1,H3ꢀ2.0 Hz), 14.9 (SO3CH2CH3). Anal.
a
Calcd for C41H44O9S (712.85 g/mol): C, 69.08; H, 6.22; S, 4.50.
Found: C, 69.01; H, 6.28 S, 4.52.
a
b
b
a
d
3.9. 3,4,7-Tri-O-benzyl-5-O-(2-naphthyl)methyl-1,2-dideoxy-
1-ethoxysulfonyl-a-D-gluco-hept-2-ulopyranosyl chloride (3)
b
a
b
b
b
b
a
To a stirred solution of compound 8 (213 mg, 0.30 mmol) in dry
CH2Cl2 (2 mL), pyridine (26 L, 0.33 mmol, 1.1 equiv) and SOCl2
(24 L, 0.33 mmol, 1.1 equiv) were added. After 20 min the reaction
C38H38O6 (590.70 g/mol): C, 77.26; H, 6.48. Found: C, 77.39; H,
6.35.
m
m
mixture was diluted with CH2Cl2, washed with 2 M aq HCl, water,
satd NaHCO3 and water, the organic layer was dried, filtered and
concentrated. The crude product was used without further purifi-
cation. Rf 0.80 (CH2Cl2/acetone 98:2); 1H NMR (360 MHz, CDCl3):
3.7. 2,3,6-Tri-O-benzyl-4-O-(2-naphthyl)methyl-D-glucono-
1,5-lactone (7)
To a stirred solution of compound 6 (2.20 g, 3.72 mmol) in dry
CH2Cl2 (20 mL) DesseMartin periodinane (3.16 g, 7.44 mmol,
2.0 equiv) was added at room temperature and stirred for 30 min.
After 30 min it was diluted with diethyl ether, 1.3 M aq NaOH
(25 mL) was added and stirred for 20 min. The organic layer was
separated, washed with 1.3 M aq NaOH (20 mL) and water, dried,
filtered and concentrated. The product was purified by column
chromatography (CH2Cl2/acetone 98:2) to yield 7 (1.73 g, 85%) as
d
7.45e7.78 (m, 22H, arom.), 5.06 (d, 1H, J¼11.5 Hz, CH2Ar), 4.98
(d, 1H, J¼11.0 Hz, CH2Ar), 4.96e4.88 (m, 3H, CH2Ar, skeleton), 4.78
(d, 1H, J¼11.0 Hz, CH2Ar), 4.59, 4.44 (2d, each 1H, J¼11.9 Hz, CH2Ar),
4.36 (d, 1H, J3,4¼9.1 Hz, H-3), 4.28e4.19 (m, 2H, skeleton), 4.13 (q,
2H, J¼8.0 Hz, SO3CH2CH3), 4.00 (d, 1H, J¼15.1 Hz, H-1a), 3.97e3.84
(m, 3H, skeleton), 3.72 (d, 1H, J¼11.1 Hz), 1.22 (t, 3H, J¼7.1 Hz,
SO3CH2CH3); 13C NMR (90 MHz, CDCl3):
d 138.1, 137.8, 137.7
(3C-quat. Ph), 135.2, 133.1, 132.9 (3C-quat., NAP), 128.5e125.7
(arom.), 104.3 (C-2), 83.6, 79.7, 76.6 76.4, (C-3eC-6), 75.6, 75.3, 75.1,
73.3 (4CH2Ar), 68.1 (C-7), 67.8 (SO3CH2CH3), 57.8 (C-1, 3JC1,H3ꢀ1 Hz),
15.0 (SO3CH2CH3).
white needles. Mp 45e47 ꢁC (EtOH); [
0.36 (CH2Cl2/acetone 98:2); 1H NMR (360 MHz, CDCl3):
7.81e7.21 (m, 22H, arom.), 4.99 (d, 1H, J¼11.4 Hz, CH2Ar), 4.84
a
]
ꢂ0.6 (c 0.17, CHCl3); Rf
D
d
(d, 1H, J¼11.4 Hz, CH2Ar), 4.72 (d, 1H, J¼11.3 Hz, CH2Ar), 4.66
(d, 1H, J¼11.1 Hz, CH2Ar), 4.64 (d, 1H, J¼11.3 Hz, CH2Ar), 4.58
(d, 1H, J¼11.3 Hz, CH2Ar), 4.51 (d, 1H, J¼12.0 Hz, CH2Ar),
4.49e4.45 (m, 1H, H-5), 4.40 (d, 1H, J¼12.0 Hz, CH2Ar), 4.13 (d,
1H, J¼6.6 Hz, H-2), 4.01 (t, 1H, J¼6.8 Hz, H-4), 3.94 (t, 1H,
J¼6.7 Hz, H-3), 3.71 (dd, 1H, J5,6¼2.4 Hz, Jgem¼11.0 Hz, H-6a), 3.65
(dd, 1H, J5,6¼3.2 Hz, Jgem¼11.0 Hz, H-6b); 13C NMR (90 MHz,
3.10. Ethyl 3,4,7-tri-O-benzyl-5-O-(2-naphthyl)methyl-1-
deoxy-1-ethoxysulfonyl-2-thio-
ulopyranoside (9)
a-D-gluco-hept-2-
Compound 8 (8.37 g, 11.74 mmol) was dissolved in CH2Cl2
(80 mL) then EtSH (1.3 mL, 17.61 mmol, 1.5 equiv) and BF3$Et2O
(3.6 mL, 29.35 mmol, 2.5 equiv) were added at 0 ꢁC and stirred for
18 h. The product was purified by column chromatography
(n-hexane/EtOAc 3:2) to yield 12 (8.36 g, 94%) as white needles. Mp
CDCl3):
d
169.2 (C-1), 137.5 (2ꢃ), 136.9, 134.9, 133.1, 132.9
(6C-quat., arom.), 128.4e125.8 (arom.), 80.9, 78.1, 77.3, 75.9 (C-2,
C-3, C-4, C-5), 73.9, 73.6 (2ꢃ), 73.4 (4CH2Ar), 68.2 (C-6). Anal.
Calcd for C38H36O6 (588.69 g/mol): C, 77.53; H, 6.16. Found: C,
77.44; H, 6.25.
84e85 ꢁC (ethanol); [
a
]
þ61.1 (c 0.31, CHCl3); Rf 0.77 (n-hexane/
D
EtOAc 3:2); IR nmax (KBr) 3060, 3029, 2979, 2931, 2886, 2865, 2348,
2309, 1496, 1454, 1395, 1350, 1281, 1308, 1207, 1177, 1158, 1124,
1082, 1043, 1027, 1005, 943, 860, 822, 757, 735, 698, 556, 478,
3.8. 3,4,7-Tri-O-benzyl-5-O-(2-naphthyl)methyl-1-deoxy-1-
ethoxysulfonyl-
a
-D
-gluco-hept-2-ulopyranose (8)
457 cmꢂ1; 1H NMR (360 MHz, CDCl3):
d 7.82e7.20 (m, 22H, arom.),
To a solution of (i-Pr)2NH (42
m
L, 0.3 mmol,1.5 equiv) in dry THF
5.04 (d, 1H, J¼11.9 Hz, CH2Ar), 4.99 (d, 1H, J¼11.1 Hz, CH2Ar), 4.92
(d, 1H, J¼11.1 Hz, CH2Ar), 4.87 (d, 1H, J¼11.9 Hz, CH2Ar), 4.86 (d, 1H,
J¼11.1 Hz, CH2Ar), 4.77 (d, 1H, J¼11.1 Hz, CH2Ar), 4.61 (d, 1H,
J¼12.1 Hz, CH2Ar), 4.59 (d, 1H, J¼9.2 Hz, skeleton), 4.50 (d, 1H,
J¼12.1 Hz, CH2Ar), 4.28e4.13 (m, 3H, skeleton), 4.13e4.06 (m, 1H,
skeleton), 3.84 (d, 1H, J¼15.1 Hz, H-1a), 3.82e3.72 (m, 3H, skele-
ton), 3.69 (d, 1H, J¼15.1 Hz, H-1b), 2.47 (m, 2H, J¼7.2 Hz, SCH2CH3),
1.23 (t, 3H, J¼7.5 Hz, SCH2CH3), 1.22 (t, 3H, J¼7.1 Hz, SO3CH2CH3);
(5 mL), 2.5 M n-BuLi (120 mL, 0.3 mmol, 1.5 equiv) was added at
ꢂ15 ꢁC and stirred for 15 min. The reaction mixture was cooled to
ꢂ60 ꢁC, CH3SO3Et (320
mL, 0.3 mmol, 1.5 equiv) was added and
stirred for further 15 min. Then it was cooled to ꢂ78 ꢁC and the
solution of compound 7 (1.18 g, 0.20 mmol) in dry THF (1 mL) was
added. After 3 h stirring at ꢂ60 ꢁC the mixture was allowed to
warm up to room temperature, and concentrated. The residue was
diluted with 5 mL of water and extracted with dichloromethane
(3ꢃ20 mL). The collected organic solution was dried, filtered and
concentrated. The product was purified by column chromatogra-
phy (n-hexane/EtOAc 6:4) to yield 8 (1.43 g, 86%) as white crystals.
13C NMR (90 MHz, CDCl3):
d 138.3, 138.2, 138.1 (3C-quat. Ph), 135.3,
133.1, 132.8 (3C-quat., NAP), 128.5e125.7 (arom.), 89.0 (C-2), 83.9,
79.5, 77.9 (C-3eC-5), 75.4, 75.2, 75.1 (3CH2Ar), 74.0 (C-6), 73.2
3
(CH2Ar), 68.8 (C-7), 67.2 (SO3CH2CH3), 55.9 (C-1, JC1,H3ꢀ2.7 Hz),
Mp 97e98 ꢁC (ethanol); [
ane/EtOAc 6:4); IR nmax (KBr) 3474, 3060, 3031, 2981, 2916, 2864,
a
]
ꢂ65.8 (c 0.5, CHCl3); Rf 0.46 (n-hex-
19.8 (SCH2CH3), 15.0 (SO3CH2CH3), 13.7 (SCH2CH3). Anal. Calcd for
C43H48O8S2 (756.97 g/mol): C, 68.23; H, 6.39; S, 8.47. Found: C,
68.34; H, 6.32; S, 8.44.
D
2368, 2309, 1496, 1454, 1350, 1335, 1308, 1271, 1154, 1084, 1027,

ꢀ
G. Majer et al. / Tetrahedron 68 (2012) 4986e4994
4991
3.11. p-Methoxyphenyl 3,4,7-tri-O-benzyl-5-O-(2-naphthyl)
methyl-1-deoxy-1-ethoxysulfonyl- -gluco-hept-2-
ulopyranosyl-(2/4)-2,3,4-tri-O-benzyl- -glucopyranoside
(11) and 2,6-anhydro-3,4,7-tri-O-benzyl-5-O-(2-naphthyl)
methyl-1-deoxy-1-ethoxysulfonyl- -gluco-hept-1-enitol (12)
ulopyranosyl-(2/5)-3,4,7-tri-O-benzyl-1-deoxy-1-
ethoxysulfonyl- -gluco-hept-2-ulopyranosyl-(2/4)-2,3,6-
tri-O-benzyl- -glucopyranoside (14)
a
-
D
a-D
b-D
b-D
a-
D
Acceptor 13 (987 mg, 0.89 mmol, 1.0 equiv) was glycosylated
with donor 3 (605 mg, 0.88 mmol, 1.0 equiv) according to general
method B to give 14 (590 mg, 37%) as a syrup; [
CHCl3); Rf 0.51 (CH2Cl2/acetone 98:2); 1H NMR (200 MHz, CDCl3):
7.80e6.70 (m, 56H, arom.), 5.06 (d, 1H, J¼7.1 Hz, H-1), 5.00e3.58
(m, 46H), 3.67 (s, 3H, OCH3), 1.11, 1.03 (2t, 6H, 2SO3CH2CH3); 13C
NMR (50 MHz, CDCl3): 155.1, 151.2 (2C-quat., PMP), 138.6, 138.4,
138.3, 138.2, 138.2, 138.1, 138.1 (2ꢃ), 138.0 (9C-quat., Ph), 135.3,
133.1, 132.9 (3C-quat., NAP), 128.4e125.8 (arom.), 118.3 (2ꢃ), 114.4
(2ꢃ) (4C-arom, PMP), 102.0 (C-1), 100.2 (C-20), 99.3 (C-200), 82.6,
82.4, 81.7, 80.3, 80.1, 78.6, 78.3, 76.0, 73.6, 73.1, 73.1, 72.4 (C-2eC-5,
C-30eC-60, C-300eC-600), 75.3 (2ꢃ), 75.2, 74.9, 74.5, 74.0, 73.9, 73.5,
73.3, 73.2, (10 CH2Ar), 69.6, 69.5, 68.8 (C-6, C-700, C-700), 66.9, 66.5
(2SO3CH2CH3), 55.4 (OCH3), 52.3, 51.4 (C-10, C-100), 14.8, 14.7
(2SO3CH2CH3); MALDI-MS: m/z calcd for C105H112NaO23S2þ
[MþNa]þ: 1827.67; found: 1828.51.
a
]
þ28.2 (c 0.22,
D
Acceptor 1012 (6.26 g, 11.25 mmol) was coupled with donor 3
(4.11 g, 5.63 mmol, 0.5 equiv) according to the general method B.
d
The obtained mixture of the
gel chromatography (CH2Cl2/acetone 98:2) to yield 11 (2.48 g, 49%):
and 12 976 mg (25%). Compound 11: [
]D þ9.0 (c 0.19, CDCl3); Rf 0.85
(CH2Cl2/acetone 98:2). 1H NMR (200 MHz, CDCl3):
7.85e6.75 (m,
a and b anomers was separated by silica
d
a
d
41H, arom.), 5.09e4.35 (m, 15H), 4.28e4.11 (m, 4H), 4.02e3.93 (m,
3H), 3.90 (q, 2H, SO3CH2CH3), 3.80e3.58 (m, 7H), 3.76 (s, 3H, OCH3),
1.10 (t, 3H, J¼7.1 Hz, SO3CH2CH3); 13C NMR (50 MHz, CDCl3):
d 155.2,
151.3 (2C-quat., PMP), 138.5, 138.3 (2ꢃ), 138.3, 138.1, 138.0 (6C-quat.
Ph), 135.5, 133.2, 132.9 (3C-quat., NAP), 128.5e125.8 (arom.), 118.2
(2ꢃ),114.5 (2ꢃ) (4C-arom., PMP), 102.1 (C-1), 100.2 (C-20), 82.6, 82.6,
80.6, 80.1, 78.3, 76.7 (C-2eC-4, C-30eC-50), 75.3, 75.2, 75.1, 74.6, 74.2,
73.4, 73.3 (7CH2Ar), 73.4, 73.3 (C-5, C-60), 70.2 (SO3CH2CH3), 68.9,
67.0 (C-6, C-70), 55.6 (OCH3), 51.9 (C-10, JC1 ,H3 ꢀ1 Hz), 14.9
(SO3CH2CH3). Anal. Calcd for C75H78O15S (1251.48 g/mol): C, 71.98;
H, 6.28; S, 2.56. Found: C, 71.89; H, 6.33; S, 2.59.
3.14. p-Methoxyphenyl 3,4,7-tri-O-benzyl-1-deoxy-1-
0
0
ethoxysulfonyl-
tri-O-benzyl-1-deoxy-1-ethoxysulfonyl-
ulopyranosyl-(2/4)-2,3,6-tri-O-benzyl-a-D
a
-
D
-gluco-hept-2-ulopyranosyl-(2/5)-3,4,7-
-gluco-hept-2-
-glucopyranoside
a-D
Compound 12: Rf 0.58 (CH2Cl2/acetone 98:2); IR nmax (KBr) 3032,
2925, 2868, 2368, 2349, 2309, 1670, 1635, 1456, 1354, 1219, 1071,
1074, 1027, 1006, 916, 843, 820, 772, 698, 671, 598, 569, 526, 475,
(15)
418 cmꢂ1; 1H NMR (200 MHz, CDCl3):
d 7.84e7.15 (m, 22H, arom.),
5.67 (s, 1H, H-1), 4.84 (d, 1H, J¼11.4 Hz, CH2Ar), 4.74 (s, 1H, CH2Ar),
4.69 (s, 1H, CH2Ar), 4.67e4e52 (s, 4H, CH2Ar), 4.51 (d, 1H, J¼12.1 Hz,
CH2Ar), 4.36e4.28 (m, 1H), 4.16 (q, 2H, J¼7.1 Hz, SO3CH2CH3),
4.00e3.75 (m, 5H), 1.21 (t, 3H, SO3CH2CH3); 13C NMR (50 MHz,
Prepared from 14 (444 mg, 0.25 mmol) according to general
method A and purified by column chromatography (CH2Cl2/ace-
tone 99:1) to yield 15 (287 mg, 79%) as a syrup; [
a
]
D þ25.2 (c 0.21,
CHCl3); Rf 0.38 (CH2Cl2/acetone 99:1). 1H NMR (500 MHz, CDCl3):
7.36e7.02 (m, 45H, Ph), 7.00, 6.78 (2m, 4H, PMP arom.), 5.08 (d, 1H,
J¼7.1 Hz, H-1), 5.99e4.35 (m, 18H, CH2Ph), 4.34e3.52 (m, 26H), 3.74
(s, 3H, OCH3), 2.58 (s, 1H, OH), 1.12, 1.10 (2t, 6H, J¼7.1 Hz,
2SO3CH2CH3); 13C NMR (125 MHz, CDCl3): 155.2, 151.2 (2C-quat.,
PMP), 138.7, 138.5 (2ꢃ), 138.3, 138.1 (3ꢃ), 138.0, 137.9 (9C-quat., Ph),
128.6e126.9 (Ph), 118.5 (2ꢃ), 114.6 (2ꢃ) (4C-arom, PMP), 102.2
(C-1), 100.3 (C-20), 99.4 (C-200), 82.6, 82.1, 81.8, 80.6, 79.8, 76.2, 74.8,
73.9, 73.3, 73.1, 72.6, 72.2 (C-2eC-5, C-30eC-60, C-300eC-600), 75.3,
75.3, 75.2, 74.6, 74.3, 73.8, 73.7, 73.4, 73.0 (9CH2Ph), 70.5, 69.6 (2ꢃ)
(C-6, C-70, C-700), 66.9, 66.7 (2SO3CH2CH3), 55.6 (OCH3), 51.5 (2ꢃ)
(C-10, C-100), 15.0, 14.9 (2SO3CH2CH3); MALDI-MS: m/z calcd for
C94H104NaO23Sþ2 [MþNa]þ: 1687.63; found: 1688.73.
CDCl3): d 161.9 (C-2), 137.9, 137.3, 136.5, 134.9, 133.1, 133.0 (6C-quat.,
arom.), 128.6e125.8 (arom.), 104.1 (C-1), 82.2, 78.4, 76.8, 76.4 (C-3,
C-4, C-5, C-6), 73.7, 73.4, 73.2, 72.3 (4CH2Ar), 67.8 (C-7), 66.7
(SO3CH2CH3), 14.8 (SO3CH2CH3); MALDI-MS: m/z calcd for
C41H42NaO8Sþ [MþNa]þ: 717.25; found: 717.61.
Title compounds 11 (10%) and 12 (37%) were also obtained from
the reaction of 10 and 9, upon NIS/TfOH activation.
3.12. p-Methoxyphenyl 3,4,7-tri-O-benzyl-1-deoxy-1-
ethoxysulfonyl- -gluco-hept-2-ulopyranosyl-(2/4)-2,3,6-
a-
D
tri-O-benzyl-b-D-glucopyranoside (13)
Compound 11 (1.29 g, 1.03 mmol) was treated with DDQ
according to general method A and the product was purified by
column chromatography (n-hexane/EtOAc 6:4), to yield 13 (0.90 g,
3.15. p-Methoxyphenyl 3,4,7-tri-O-benzyl-5-O-(2-naphthyl)
methyl-1-deoxy-1-ethoxysulfonyl-
ulopyranosyl-(2/5)-3,4,7-tri-O-benzyl-1-deoxy-1-
ethoxysulfonyl- -gluco-hept-ulopyranosyl-(2/5)-3,4,7-tri-
O-benzyl-1-deoxy-1-ethoxysulfonyl- -gluco-hept-
-glucopyranoside
a-D-gluco-hept-2-
87%) as a syrup; [
a
]
þ5.7 (c 0.11, CHCl3); Rf 0.49 (n-hexane/EtOAc
D
a-D
6:4); 1H NMR (500 MHz, CDCl3)
d
7.38e7.02 (m, 30H, Ph), 6.97, 6.80
a-D
(2m, each 2H, PMP arom.), 5.12e5.04 (m, 1H, skeleton), 4.97 (d, 1H,
J¼11.6 Hz, CH2Ph), 4.89 (d, 1H, J¼11.1 Hz, CH2Ph), 4.86 (d, 1H,
J¼11.5 Hz, CH2Ph), 4.82e4.47 (m, 7H, CH2Ph), 4.45 (s, 2H, CH2Ph),
4.24e4.07 (m, 3H, skeleton), 4.02e3.53 (m, 11H, skeleton), 3.85 (2q,
2H, J¼7.1 Hz, SO3CH2CH3), 3.75 (s, 3H, OCH3), 2.54 (s, 1H, OH), 1.10
ulopyranosyl-(2/4)-2,3,6-tri-O-benzyl-b-D
(16)
Acceptor 15 (320 mg, 0.19 mmol, 1.0 equiv) was glycosylated
with donor 3 (605 mg, 0.88 mmol, 1.0 equiv) according to general
(t, 3H, J¼7.1 Hz, SO3CH2CH3); 13C NMR (125 MHz, CDCl3)
d 155.2,
method B to give tetrasaccharide 16 (610 mg, 38%) as a syrup; [a]
D
151.2 (2C-quat., PMP), 138.4 (2ꢃ), 138.2, 138.0, 138.0, 137.9,
(7C-quat., Ph), 128.7e127.1 (Ph), 118.2 (2ꢃ), 114.5 (2ꢃ) (4C-arom,
PMP), 102.1 (C-1), 100.2 (C-20), 82.5, 82.0, 80.6, 79.8, 76.6, 73.1, 72.6,
72.0 (C-2eC-5, C-30eC-60); 75.1 (2ꢃ), 74.5, 74.2, 73.5, 73.3 (6CH2Ph),
70.4, 70.0 (C-6, C-70), 66.8 (SO3CH2CH3), 55.5 (OCH3), 51.8 (C-10),
14.8 (SO3CH2CH3); MALDI-MS: m/z calcd for C64H70NaO15Sþ
[MþNa]þ: 1133.43; found: 1133.08.
þ36.8 (c 0.2, CHCl3); Rf 0.54 (CH2Cl2/acetone 98:2). 1H NMR
(200 MHz, CDCl3):
d 7.76e6.71 (m, 71H, arom.), 5.04 (d, 1H,
J¼7.1 Hz, H-1), 4.94e3.50 (m, 62H), 3.65 (s, 3H, OCH3), 1.07, 1.01,
0.99 (3t, 9H, 3SO3CH2CH3); 13C NMR (50 MHz, CDCl3):
d
155.2, 151.3
(2C-quat., PMP), 138.7 (2ꢃ), 138.4 (2ꢃ), 138.4, 138.3, 138.2, 138.2,
138.0 (2ꢃ), 138.0, 137.9 (12C-quat., Ph), 135.5, 133.2, 133.0 (3C-quat.,
NAP), 128.5e125.8 (arom.), 118.3 (2ꢃ), 114.5 (2ꢃ) (4C-arom., PMP),
102.2 (C-1), 100.3, 99.5, 99.3 (C-20, C-200, C-2000), 82.9, 82.3, 81.7, 81.5,
81.2, 81.0, 80.6, 79.9, 78.1, 76.2, 74.4, 73.5, 73.3, 72.6, 71.8, 71.6
(C-2eC-5, C-30eC-60, C-300eC-600, C-3000eC-6000), 75.3 (2ꢃ), 75.2, 75.0,
3.13. p-Methoxyphenyl 3,4,7-tri-O-benzyl-5-O-(2-naphthyl)
methyl-1-deoxy-1-ethoxysulfonyl-a-D-gluco-hept-2-

ꢀ
G. Majer et al. / Tetrahedron 68 (2012) 4986e4994
4992
74.7, 74.5, 74.4, 74.1, 73.6, 73.5, 73.4 (2ꢃ), 73.2 3 (13CH2Ar), 69.6,
69.3, 69.2, 68.7 (C-6, C-70, C-700, C-7000), 67.1, 66.6, 66.5 (3SO3CH2CH3),
55.5 (OCH3), 52.0 (3ꢃ) (C-10, C-100, C-1000), 15.0, 14.9 (2ꢃ)
(3SO3CH2CH3). Anal. Calcd for C135H146O31S3 (2360.78 g/mol): C,
68.68; H, 6.23; S, 4.07. Found: C, 68.51; H, 6.26; S, 4.13.
(arom.), 100.1 (C-2), 82.9, 78.4, 76.8 (C-3eC-5), 74.7, 74.0 (2CH2Ar),
73.7 (C-6), 73.3 (2ꢃ) (2CH2Ar), 68.5 (C-7), 66.7 (SO3CH2CH3), 48.7
(C-1, JC1,H3¼2.6 Hz), 47.8 (OCH3), 14.9 (SO3CH2CH3). Anal. Calcd for
C42H46O9S2 (726.87 g/mol): C, 69.40; H, 6.38; S, 4.41. Found: C,
69.28; H, 6.45; S, 4.48.
3.16. p-Methoxyphenyl 3,4,7-tri-O-benzyl-1-deoxy-1-
3.18. Methyl 3,4,7-tri-O-benzyl-1-deoxy-1-ethoxysulfonyl-
-gluco-hept-2-ulopyranoside (20)
a-
ethoxysulfonyl-
tri-O-benzyl-1-deoxy-1-ethoxysulfonyl-
ulopyranosyl-(2/5)-3,4,7-tri-O-benzyl-1-deoxy-1-
ethoxysulfonyl- -gluco-hept-2-ulopyranosyl-(2/4)-2,3,6-
tri-O-benzyl- -glucopyranoside (17)
a
-D
-gluco-hept-2-ulopyranosyl-(2/5)-3,4,7-
D
a-D
-gluco-hept-
Prepared from 18 (364 mg, 0.50 mmol) according to general
method A and purified by column chromatography (CH2Cl2/ace-
tone 98:2) to yield 20 (261 mg, 89%) as a syrup; [
D þ17.2 (c 0.14,
CHCl3); Rf 0.20; 1H NMR (200 MHz, CDCl3)
7.44e7.14 (m, 15H, Ph),
a-D
b-D
a
]
d
Prepared from 16 (163 mg, 0.69 mmol) according to general
method A and purified by column chromatography (CH2Cl2/ace-
5.00 (d, 1H, J¼11.3 Hz, CH2Ph), 4.90 (d, 1H, J¼11.6 Hz, CH2Ph),
4.86e4.74 (m, 2H, CH2Ph), 4.61 (d, 1H, J¼12.1 Hz, CH2Ph), 4.53
(d, 1H, J¼11.9 Hz, CH2Ph), 4.29e4.05 (m, 3H, skeleton, and
SO3CH2CH3), 3.92 (t, 1H, J¼8.6 Hz, skeleton), 3.81e3.46 (m, 6H,
skeleton), 3.25 (s, 3H, OCH3), 2.72 (s, 1H, OH), 1.24 (t, 3H, J¼7.1 Hz,
tone 99:1) to yield 17 (109 mg, 71%) as a syrup; [
a
]
D ꢂ8.95 (c 0.04,
CHCl3); 1H NMR (500 MHz, CDCl3): 7.37e6.73 (m, 64H, arom.), 5.05
(d, 1H, J¼7.3 Hz, H-1), 4.96e3.46 (m, 60H), 3.68 (s, 3H, OCH3), 2.67
(br s, 1H, OH), 1.10, 1.03, 1.02 (3t, each 3H, J¼7.1 Hz, 3SO3CH2CH3);
13C NMR (125 MHz, CDCl3): 155.5e114.6 (arom.), 102.2 (C-1), 100.2
(C-20), 99.6 (C-200, C-2000), 83.1, 82.1, 81.9 (2ꢃ), 81.1, 79.8, 75.9, 74.8,
73.9, 73.3, 73.1, 72.6, 72.2 (C-2eC-5, C-30eC-60, C-300eC-600), 75.3,
75.3, 75.2, 74.6, 74.3, 73.8, 73.7, 73.4, 73.0 (9CH2Ph), 70.5, 69.6 (2ꢃ)
(C-6, C-70, C-700), 66.9, 66.7 (2SO3CH2CH3), 55.6 (OCH3), 51.5 (2ꢃ)
(C-10, C-100), 15.0, 14.9 (2SO3CH2CH3); MALDI-MS: m/z calcd for
C124H138NaO31Sþ3 [MþNa]þ: 2242.84; found: 2243.13.
SO3CH2CH3); 13C NMR (50 MHz, CDCl3):
d
138.3, 137.8 (2ꢃ)
(3C-quat., Ph), 128.4e127.2 (Ph), 98.8 (C-2), 82.5, 79.2, 72.4, 71.2
(C-3eC-6), 75.2, 75.0, 73.3 (3CH2Ph), 69.5 (C-7), 67.1 (SO3CH2CH3),
50.1 (C-1), 47.7 (OCH3), 14.8 (SO3CH2CH3). Anal. Calcd for C31H38O9S
(586.69 g/mol): C, 63.46; H, 6.53; S, 5.47. Found: C, 63.69; H, 6.48; S,
5.43.
3.19. .19Methyl 3,4,7-tri-O-benzyl-5-O-(2-naphthyl)methyl-1-
deoxy-1-ethoxysulfonyl-a-D-gluco-hept-2-ulopyranosyl-
3.17. Methyl 3,4,7-tri-O-benzyl-5-O-(2-naphthyl)methyl-1-
(2/5)-3,4,7-tri-O-benzyl-1-deoxy-1-ethoxysulfonyl-
a-D-
deoxy-1-ethoxysulfonyl-
and methyl 3,4,7-tri-O-benzyl-5-O-(2-naphthyl)methyl-1-
deoxy-1-ethoxysulfonyl- -gluco-hept-2-ulopyranoside (19)
a-D-gluco-hept-2-ulopyranoside (18)
gluco-hept-2-ulopyranoside (21)
b-D
Acceptor 20 (690 mg, 1.18 mmol) was glycosylated with donor 3
(860 mg, 1.18 mmol, 1.0 equiv) according to general method B. The
crude product was purified by column chromatography (CH2Cl2/
To a solution of thioglycoside donor 9 (2.27 g, 3.00 mmol) in
ꢁ
CH2Cl2 (45 mL) were added successively 3 A molecular sieves (3 g)
acetone 98:2) to give 21 (890 mg, 59%) as a syrup; [
a
]
D þ18.4 (c 0.13,
and dry MeOH (1.83 mL, 45 mmol, 15 equiv), and the mixture was
CDCl3); Rf 0.73; 1H NMR (200 MHz, CDCl3):
d
7.86e7.03 (m, 37H,
stirred at rt for 3 h. The mixture was then cooled to ꢂ20 ꢁC and
arom.), 5.19 (d,1H, J¼11.6 Hz, CH2Ar), 5.00 (d,1H, J¼10.9 Hz, CH2Ar),
4.91 (s, 2H, CH2Ar), 4.90 (d,1H, J¼11.1 Hz, CH2Ar), 4.80e4.50 (m, 9H,
CH2Ar), 4.50e3.95 (m, 12H), 3.94e3.78 (m, 2H), 3.77e3.54 (m, 6H),
3.25 (s, 3H, OCH3), 1.19, 1.09 (2t, 6H, 2SO3CH2CH3); 13C NMR
a solution of NIS (0.81 g, 3.60 mmol, 1.2 equiv) and TfOH (107 mL,
1.21 mmol, 0.4 equiv) in dry THF was added. The mixture was kept
at ꢂ20 ꢁC until the TLC showed complete conversion of the donor
(20e30 min). The reaction was quenched by addition of Et3N
(0.5 mL), insoluble materials were removed by filtration, the filtrate
was diluted with CH2Cl2, extracted three times with water, dried
and concentrated. The residue was then purified by column chro-
matography (n-hexane/EtOAc 7:3) to yield 18 (1.65 g, 76%) as white
(50 MHz, CDCl3):
d
139.2, 138.9, 138.6, 138.6, 138.4 (2ꢃ) (6C-quat.,
Ph), 135.5, 133.6, 133.3 (3C-quat., NAP), 128.8e126.3 (arom.), 100.4
(C-2), 98.8 (C-20), 82.9, 82.6, 80.8, 79.5, 79.0, 74.0, 73.6, 73.5
(C-3eC-6, C-30eC-60), 76.0, 75.8, 75.7, 75.6 (2ꢃ), 73.8, 73.7
(7CH2Ar), 69.6, 69.5 (C-7, C-70), 67.2, 67.1 (2SO3CH2CH3), 51.1, 50.6
(C-1, C-10), 48.7 (OCH3), 15.4, 15.2 (2SO3CH2CH3); MALDI-MS m/z
calcd for C72H80NaO17Sþ2 [MþNa]þ: 1303.47; found: 1302.98.
needles. Mp 72e74 ꢁC (ethanol); [
a
]
D þ22.4 (c 0.11, CHCl3); Rf 0.48;
1H NMR (200 MHz, CDCl3):
d
7.86e7.22 (m, 22H, arom.), 5.08e4.92
(m, 4H, CH2Ar), 4.85 (d,1H, J¼11.3 Hz, CH2Ar), 4.76 (d, 1H, J¼11.0 Hz,
CH2Ar), 4.62 (d, 1H, J¼12.1 Hz, CH2Ar), 4.50 (d, 1H, J¼12.1 Hz,
CH2Ar), 4.314.04 (m, 4H), 3.87e3.67 (m, 4H), 3.57 (s, 2H), 3.27
(s, 3H, OCH3), 1.23 (t, 3H, J¼7.1 Hz, SO3CH2CH3); 13C NMR (50 MHz,
3.20. Methyl 3,4,7-tri-O-benzyl-1-deoxy-1-ethoxysulfonyl-
-gluco-hept-2-ulopyranosyl-(2/5)-3,4,7-tri-O-benzyl-1-
deoxy-1-ethoxysulfonyl- -gluco-hept-2-ulopyranoside (22)
a-
D
CDCl3):
d
138.4, 138.1, 138.0 (3C-quat., Ph), 135.4, 133.1, 132.9
a-D
(3C-quat., NAP), 128.4e125.7 (arom.), 99.0 (C-2), 83.1, 79.7, 78.0
(C-3eC-5), 75.5, 75.4, 75.1, 73.3 (4CH2Ar), 72.9 (C-6), 68.5 (C-7), 67.4
(SO3CH2CH3), 50.4 (C-1, JC1,H3ꢀ1 Hz), 47.8 (OCH3), 15.0
(SO3CH2CH3). Anal. Calcd for C42H46O9S2 (726.87 g/mol): C, 69.40;
H, 6.38; S, 4.41. Found: C; 69.24; H, 6.49; S, 4.47.
Prepared from 21 (750 mg, 0.59 mmol) according to general
method A and purified by column chromatography (CH2Cl2/ace-
tone 99:1) to yield 22 (519 mg, 78%) as white needles. Mp
111e112 ꢁC (ethanol);
[a
]
þ23.2 (c 0.13, CHCl3); Rf 0.20
D
Compound 19 was isolated as a colourless syrup (0.47 g, 22%);
(nehexaneeEtOAc 6:4); 1H NMR (360 MHz, CDCl3):
d
7.36e7.09 (m,
[
a
]
D þ42.4 (c 0.14, CHCl3); Rf 0.43; 1H NMR (200 MHz, CDCl3):
d
1H
30H, arom.), 5.20 (d, 1H, J¼11.5 Hz, CH2Ph), 4.88e4.48 (m, 11H,
CH2Ph), 4.40e4.35 (m, 2H), 4.21e3.52 (m, 18H), 3.25 (s, 3H, OCH3),
2.46 (s, 1H, OH), 1.20, 1.10 (2t, 6H, 2CH3); 13C NMR (90 MHz, CDCl3):
NMR (200 MHz):
d
7.84e7.15 (m, 22H, arom.), 4.97 (d, 1H, J¼11.1 Hz,
CH2Ar), 4.87 (d, 1H, J¼11.5 Hz, CH2Ar), 4.80 (d, 1H, J¼11.5 Hz,
CH2Ar), 4.77 (d,1H, J¼11.4 Hz, CH2Ar), 4.74 (d,1H, J¼11.1 Hz, CH2Ar),
4.64 (d, 1H, J¼10.8 Hz, CH2Ar), 4.62 (d, 1H, J¼12.1 Hz, CH2Ar), 4.48
(d, 1H, J¼12.1 Hz, CH2Ar), 4.26 (q, 2H, J¼7.1 Hz, SO3CH2CH3),
4.13e3.55 (m, 8H, skeleton), 3.44 (s, 3H, OCH3), 1.34 (t, 3H,
d
138.8, 138.5, 138.3, 138.0, 138.0, 137.9 (6C-quat. arom.),
128.6e127.0 (arom.), 100.1, 98.5 (C-2, C-20), 82.3, 81.8, 80.2, 79.2,
73.6, 73.4, 72.7, 71.8 (C-3eC-6, C-30eC-60), 75.7, 75.4, 75.3, 75.1, 73.7,
73.5 (6CH2Ph), 70.6, 69.3 (C-7, C-70), 67.0, 66.7 (2SO3CH2CH3), 50.7,
50.2 (C-1, C-10), 48.3 (OCH3), 15.1, 14.9 (2SO3CH2CH3); MALDI-MS
m/z calcd for C61H72NaO17S2þ [MþNa]þ: 1163.41; found: 1163.15.
SO3CH2CH3); 13C NMR (50 MHz, CDCl3):
d
138.2, 138.0, 137.5
(3C-quat., Ph), 135.5, 133.1, 132.8 (3C-quat., NAP), 128.4e125.6

ꢀ
G. Majer et al. / Tetrahedron 68 (2012) 4986e4994
4993
3.21. Methyl 3,4,5,7-tetra-O-benzyl-1-deoxy-1-ethoxysulfonyl-
-gluco-hept-2-ulopyranosyl-(2/5)-3,4,7-tri-O-benzyl-1-
deoxy-1-ethoxysulfonyl- -gluco-hept-2-ulopyranosyl-
(2/5)-3,4,7-tri-O-benzyl-1-deoxy-1-ethoxysulfonyl-a-D-gluco-
hept-2-ulopyranoside (24)
(dd, 1H, J¼12.1, 1.5 Hz), 3.66e3.57 (m, 2H), 3.36e3.27 (m, 3H),
3.23e3.19 (m, 4H, 1H and OCH3); 13C NMR (90 MHz, D2O):
100.6
(C-2), 75.2 (2ꢃ), 74.3, 71.1 (C-3eC-6), 62.2 (C-7), 53.8 (C-1), 48.5
(OCH3). Anal. Calcd for: C8H15NaO9S (310.25 g/mol), C: 30.97, H:
4.87, S: 10.34, Found C: 30.91, H: 4.92, S: 10.39.
a-D
d
a-D
Acceptor 22 (423 mg, 371 mg, 1.0 equiv) was glycosylated with
donor 237 (860 mg, 1.18 mmol, 1.0 equiv) according to general
method B. The product was isolated and purified by column
chromatography (CH2Cl2/acetone 98:2) to obtain 24 (184 mg, 28%)
as a syrup; Rf 0.73 (CH2Cl2/acetone 98:2); 1H NMR (200 MHz,
3.25. Methyl-1-deoxy-1-sodiumsulfonato-a-D-gluco-hept-2-
ulopyranosyl-(2/5)-1-deoxy-1-sodiumsulfonato-a-D-gluco-
hept-2-ulopyranoside (28)
Compound 22 (124 mg, 0.11 mmol) was converted into com-
pound 28 according to general method C. The product was purified
by Sephadex gel G-25 in H2O to give 28 as a syrup (40 mg, 64%);
CDCl3):
d
7.39e6.91 (m, 50H, arom.), 5.15 (d, 1H, J¼11.4 Hz),
4.97e4.46 (m, 19H), 4.36e4.09 (m, 13H), 4.00e3.89 (m, 4H),
3.83e3.79 (m, 13H), 3.15 (s, 3H, OCH3), 1.20, 1.14, 1.04 (3t, 9H,
[a
]
D þ82.0 (c 0.06, H2O); IR nmax (KBr) 3419, 2938, 1636, 1418, 1194,
1144, 1108, 1041, 903, 833, 797, 759, 670, 640, 608, 546 cmꢂ1 1H
NMR (360 MHz, D2O):
4.19 (d, 1H, J¼9.7 Hz), 4.14 (d, 1H, J¼9.2 Hz),
3.97e3.72 (m, 8H), 3.64e3.55 (m, 3H), 3.49e3.40 (m, 3H), 3.29
(s, 3H, OCH3); 13C NMR (90 MHz, D2O): 101.3, 100.3, (C-2, C-20),
3SO3CH2CH3); 13C NMR (50 MHz, CDCl3):
d
138.8, 138.7, 138.5 (2ꢃ),
;
138.4, 138.2, 138.1 (2ꢃ), 138.0 (2ꢃ) (10C-quat., arom.), 128.4e127.1
(arom.), 100.2 (C-2), 99.5 (C-20), 98.6 (C-200), 82.8, 82.3, 81.5, 80.2,
79.7 (2ꢃ), 79.2, 78.6, 74.0, 73.9, 73.4 (2ꢃ) (C-3eC-6, C-30eC-60,
C-300eC600), 75.6, 75.4 (5ꢃ), 75.3, 75.2, 73.8, 73.7 (10CH2Ph), 69.7,
69.4, 68.8 (C-7, C-70, C-700), 67.0, 67.0, 66.6 (3SO3CH2CH3), 50.4 (3ꢃ)
(C-1, C-10, C-100), 48.2 (OCH3), 15.1, 14.9, 14.8 (3SO3CH2CH3);
MALDI-MS m/z calcd for C98H112NaO25Sþ3 [MþNa]þ: 1807.65;
found: 1808.28.
d
d
75.0, 74.9 (2ꢃ), 74.2, 74.1, 73.1, 72.9, 70.9 (C-3eC-6, C-30eC-60), 62.5,
62.1 (C-7, C-70), 54.4, 52.9 (C-1, C-10), 49.1 (OCH3). Anal. Calcd for
C15H26Na2O17S2 (588.47 g/mol): C, 30.62; H, 4.45; S,10.90. Found: C,
30.55; H, 4.51; S, 10.86.
3.26. Methyl-1-deoxy-1-sodiumsulfonato-
ulopyranosyl-(2/5)-1-deoxy-1-sodiumsulfonato-
a
-
D
-gluco-hept-2-
-gluco-
3.22. p-Methoxyphenyl 4-O-(1-deoxy-1-sodiumsulfonato-
-gluco-hept-2-ulopyranosyl)- -glucopyranoside (25)
a-
a-D
D
b-D
hept-2-ulopyranosyl-(2/5)-1-deoxy-1-sodiumsulfonato-
a-D-
gluco-hept-2-ulopyranoside (29)
Compound 13 (110 mg, 91
25 (colourless syrup, 31 mg, 62%) according to general method C;
þ12.6 (c 0.1, H2O); IR nmax (KBr) 3408, 2938, 1733, 1635, 1559,
mmol) was converted into compound
Compound 24 (135 mg, 76
29 according to general method C. The product was purified by
mmol) was converted into compound
[a]
D
1508, 1418, 1301, 1218, 1106, 1044, 936, 902, 834, 800, 753, 640, 594,
527 cmꢂ1 1H NMR (200 MHz, D2O):
7.13e6.98 (m, 4H, arom.),
5.00 (d, 1H, J¼7.7 Hz), 4.21 (m, 1H), 3.97e3.30 (m, 14H, skeleton),
3.82 (s, 3H, OCH3); 13C NMR (90 MHz, D2O):
154.7, 150.8 (2C-quat.,
Sephadex gel G-25 in H2O to give 29 as a syrup (36 mg, 52%); [a]
D
þ76.4 (c 0.1, H2O); 1H NMR (360 MHz, D2O):
d 4.26 (d, 1H,
;
d
J¼9.7 Hz), 4.20 (d, 1H, J¼9.5 Hz), 4.14 (d, 1H, J¼9.2 Hz), 4.04e3.70
d
(m, 13H), 3.65e3.55 (m, 5H), 3.50e3.40 (m, 3H), 3.29 (s, 3H, OCH3);
13C NMR (90 MHz, D2O):
d
100.9, 100.7, 99.9 (C-2, C-20, C-200), 74.5
PMP), 118.1 (2ꢃ), 115.0 (2ꢃ) (4C-arom., PMP), 101.0 (C-1), 99.9
(C-20), 75.4 (2ꢃ), 73.5, 73.3, 72.5, 72.3, 71.4, 69.4 (C-2eC-5,
C-30eC-60), 61.0, 60.1 (C-6, C-70), 55.7 (OCH3), 52.8 (C-10). Anal.
Calcd for C20H29NaO15S (564.49 g/mol): C, 42.55; H, 5.18; S, 5.68.
Found: C, 42.69; H, 5.07; S, 5.72.
(2ꢃ), 74.4 (2ꢃ), 73.9, 73.7 (2ꢃ), 73.1, 72.6, 72.5 (2ꢃ), 70.5,
(C-3eC-6, C-30eC-60, C-300eC-600), 62.1, 61.6 (2ꢃ), (C-7, C-70, C-700),
53.9 (2ꢃ), 52.5 (C-1, C-10, C-100), 48.6 (OCH3). Anal. Calcd for
C22H37Na3O25S3 (866.68 g/mol): C, 30.49; H, 4.30; S, 11.10. Found C,
30.54; H, 4.25; S, 11.02.
3.23. p-Methoxyphenyl 1-deoxy-1-sodiumsulfonato-
hept-2-ulopyranosyl-(2/5)-1-deoxy-1-sodiumsulfonato-
gluco-hept-2-ulopyranosyl-(2/4)- -glucopyranoside (26)
a-D-gluco-
a-D-
Acknowledgements
b-D
ꢀ
The work is supported by the TAMOP 4.2.1/B-09/1/KONV-2010-
Compound 15 (98 mg, 56 mmol) was converted into compound
26 (colourless syrup, 32 mg, 70%) according to general method C;
0007 project. The project is co-financed by the European Union and
the European Social Fund. Financial support of the Hungarian Re-
search Fund (K 62802) is also acknowledged.
[
a]
D þ39.9 (c 0.1, H2O); 1H NMR (360 MHz, D2O):
d 7.13, 7.00 (2d, 4H,
arom.), 4.99 (d, 1H, J¼7.7 Hz), 4.29 (d, 1H, J¼9.7 Hz), 4.21 (d, 1H,
J¼9.5 Hz), 4.03 (t, 1H, J¼8.9 Hz, J¼9.3 Hz), 3.94e3.69 (m, 12H), 3.83
(s, 3H, OCH3), 3.65e3.57 (m, 6H), 3.43 (t, 1H, J¼9.6 Hz, J¼9.4 Hz);
References and notes
13C NMR (90 MHz, D2O):
d
155.8, 152.1 (2C-quat., PMP), 119.3 (2ꢃ),
1. Islam, T.; Linhardt, R. J. In Carbohydrate-Based Drug Discovery; Wong, C.-H., Ed.;
Wiley-VCH: Weinheim, 2003; Vol. 1, pp 407e439.
2. Mitchell, M. A.; Wilks, J. W. Annual Reports in Medicinal Chemistry; Academic:
San Diego, CA, 1992.
116.0 (2ꢃ) (4C-arom., PMP), 102.3 (C-1), 101.0, 100.9 (C-20, C-200),
76.6, 76.4, 74.6 (2ꢃ), 74.3, 74.0, 73.7, 73.5, 73.1, 72.5 (2ꢃ), 70.5
(C-2eC-5, C-30eC-60, C-300eC-600), 62.1, 61.6, 61.1 (C-6, C-70, C-700),
56.8 (OCH3), 54.0, 53.9 (C-10, C-100). Anal. Calcd for C27H40Na2O23S2
(842.70 g/mol): C, 38.48; H, 4.78; S, 7.61. Found: C, 38.35; H, 4.71; S,
7.57.
3. Parish, C. R.; Freeman, C.; Brown, K. J.; Francis, D. J.; Cowden, W. D. Cancer Res.
1999, 59, 3433e3441.
€
4. Fugedi, P.; Tyrrell, D. J.; Tressler, R. J.; Stack R. J.; Ishihara, M. Pat. WO9609828.
ꢀ
ꢀ
ꢀ
5. Borbas, A.; Szabovik, G.; Antal, Zs.; Herczegh, P.; Agocs, A.; Liptak, A. Tetrahe-
dron Lett. 1999, 40, 3639e3642.
ꢀ
ꢀ
ꢀ ꢀ
ꢀ
6. Borbas, A.; Szabovik, G.; Antal, Zs.; Feher, K.; Csavas, M.; Szilagyi, L.; Herczegh,
ꢀ
P.; Liptak, A. Tetrahedron: Asymmetry 2000, 11, 549e566.
3.24. Methyl-1-deoxy-1-sodiumsulfonato-
ulopyranoside (27)
a-D-gluco-hept-2-
ꢀ ꢀ
ꢀ
ꢀ ꢀ
ꢀ
ꢀ
7. Csavas, M.; Majer, G.; Herczeg, M.; Remenyik, J.; Lazar, L.; Mandi, A.; Borbas, A.;
Antus, S. Carbohydr. Res. 2011, 346, 1527e1533.
8. Borbas, A.; Csavas, M.; Szilagyi, L.; Majer, G.; Liptak, A. J. Carbohydr. Chem. 2004,
23, 133e146.
ꢀ
ꢀ ꢀ
ꢀ
ꢀ
ꢀ
Compound 20 (108 mg, 0.19 mmol) was converted into com-
pound 27 (colourless syrup, 33 mg, 54%) according to general
method C; IR nmax (KBr) 3419, 2946, 2843, 1635, 1471, 1417, 1308,
1198, 1094, 1045, 992, 937, 903, 816, 794, 719, 671, 640, 609, 529,
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
9. Borbas, A.; Szabo, Z. B.; Szilagyi, L.; Benyei, A.; Liptak, A. Tetrahedron 2002, 58,
5723e5732.
10. Fukuyama, T.; Laird, A. A.; Hotchkiss, L. M. Tetrahedron Lett. 1985, 26,
6291e6292.
11. (a) Dess, D. B.; Martin, J. C. J. Org. Chem. 1983, 48, 4155e4156; (b) Ireland, R.;
Longbin, J. J. Org. Chem. 1993, 58, 2899.
503 cmꢂ1
;
1H NMR (360 MHz, D2O):
d
3.92 (d, 1H, J¼9.5 Hz), 3.72

ꢀ
G. Majer et al. / Tetrahedron 68 (2012) 4986e4994
4994
12. Meijer, A.; Ellervik, U. J. Org. Chem. 2004, 69, 6249e6256.
15. (a) Xia, J.; Abbas, S. A.; Locke, R. D.; Piskorz, C. F.; Alderfer, J. L.; Matta, K. L.
Tetrahedron Lett. 2000, 41, 169e173; (b) Wright, J. A.; Yu, J.; Spencer, J. B. Tet-
rahedron Lett. 2001, 42, 4033e4036.
16. The crystal structure of compound 18 has been deposited at the Cambridge
Crystallographic Data Centre and allocated the deposition number CCDC 846877.
17. Altomare, A.; Cascarano, G.; Giacovazzo, C.; Guagliardi, A. J. Appl. Crystallogr.
1993, 26, 343e350.
13. (a) Heskamp, H. M.; Veeneman, G. H.; van der Marel, G. A.; Van Boeckel, C. A. A.;
van Boom, J. H. Tetrahedron 1995, 51, 5657e5670; (b) Dondoni, A.; Marra, A.;
Rojo, I.; Scherrmann, M.-C. Tetrahedron 1996, 52, 3057e3074.
14. (a) Haverkamp, J.; Spoormaker, T.; Dorland, L.; Vliegenthart, J. F. G.; Schauer, R.
J. Am. Chem. Soc. 1979, 101, 4851e4853; (b) Hori, H.; Nakajami, T.; Nishida, Y.;
ꢀ
Ohrui, H.; Meguro, H. Tetrahedron Lett. 1988, 29, 6317e6322; (c) Majer, G.;
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
Borbas, A.; Illyes, T. Z.; Szilagyi, L.; Benyei, A.; Liptak, A. Carbohydr. Res. 2007,
18. Sheldrick, G. M. Acta Crystallogr. 2008, A64, 112e122.
342, 1393e1404 and references cited therein.
19. Farrugia, L. J. J. Appl. Crystallogr. 1999, 32, 837e838.