Synthesis of di- and trisaccharides incorporating a crown ether macrocycle

Article abstract of DOI:10.1016/S0008-6215(99)00151-2

Di- and trisaccharides incorporating a non-reducing hexopyranose residue linked to a sugar bearing a 18-crown-6-ether were synthesized by the trichloroacetimidate method. Mainly β-glycosides were isolated when secondary alcohols were used as acceptors in

Full text of DOI:10.1016/S0008-6215(99)00151-2

www.elsevier.nl/locate/carres
Carbohydrate Research 320 (1999) 147–160
Synthesis of di- and trisaccharides incorporating a crown
ether macrocycleꢀ,ꢀꢀ
Be´atrice Dumont-Hornebeck a, Jean-Pierre Joly a,*, Joe¨l Coulon b, Yves Chapleur a
a Groupe Sucres, UMR 7565 CNRS, Uni6ersite´ Henri Poincare´-Nancy I, Case Officielle 79, BP 239,
F-54506 Nancy-Vandœu6re, France
b Laboratoire de Biochimie Microbienne, Faculte´ des Sciences Pharmaceutiques et Biologiques,
Uni6ersite´ Henri Poincare´-Nancy I, 5 rue A. Lebrun, BP 403, F-54501 Nancy, France
Received 17 October 1998; revised 10 May 1999; accepted 24 May 1999
Abstract
Di- and trisaccharides incorporating a non-reducing hexopyranose residue linked to a sugar bearing a 18-crown-6-
ether were synthesized by the trichloroacetimidate method. Mainly b-glycosides were isolated when secondary
alcohols were used as acceptors in the presence of (C2H5)2O·BF3. Deprotection left four novel structures which were
on one hand able to complex cationic species and on the other hand were able to be recognized by lectins. They are
the first representatives of a new class of water-soluble cation vectors. © 1999 Elsevier Science Ltd. All rights
reserved.
Keywords: Trichloroacetimidates; Crown ethers; Glycosylation; Lectin recognition
be involved in the progression of complicated
1. Introduction
diseases such as chronic inflammation [6], are
gaining more and more importance as cellular
adhesion models [7]. For some years we have
been interested in the development of sugar-
derived crown ethers as complexing agents for
cationic species. Thus, crown ethers were suit-
ably modified in the sugar ring to accept
catecholamines as guests [8,9]. One may ex-
pect that such macrocyclic hosts may also
complex other types of biomolecules and in-
teract directly with a number of RNA se-
quences via a 1,3-hydroxyamine functionality
[10]. The next step should be the targeting of
the supramolecular assembly of the macrocy-
cle and its guest to a selected type of cell able
to recognize a specific marker linked to the
crown ether. In this regard, lectins (or se-
lectins) expressed on the target cell should
interact specifically with mono- or oligosac-
Lectins are widespread carbohydrate-bind-
ing proteins found in plants and vertebrate
tissues [1]. They interact with the cell wall and
with glycoproteins of the plasma membrane in
order to mediate cell recognition, the aggrega-
tion process, and signal transduction [2]. This
specificity for simple and complex oligosac-
charidic structures plays a crucial role in
recognition between putative biotic and target
cells [3]. According to their biological status,
lectins [4] and selectins [5], which are likely to
ꢀ Part 1 of the series: Lectin-targeted crown ethers.
ꢀꢀ Part of the University Thesis of B. Dumont-Hornebeck
(Nancy, 1997), presented in part at the 16th International
Lectin Meeting (Interlec 16) held in Toulouse, France, August
8–13, 1995, Abstr. B 127.
* Corresponding author. Fax: +33-383-912479.
E-mail address: joly@meseb.uhp-nancy.fr (J.-P. Joly)
0008-6215/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(99)00151-2

148
B. Dumont-Hornebeck et al. / Carbohydrate Research 320 (1999) 147–160
charides attached to the supramolecular as-
sembly [11]. On this basis, we recently em-
barked on the synthesis of glycosylated crown
ethers to be tested against a galactose-specific
lectin associated with the cell wall of K. bul-
garicus [12]. This paper describes the details of
the chemical synthesis of oligosaccharidic
crown ethers using the trichloroacetimidate
methodology [13].
The anomeric ratio and the overall yields
for the syntheses of trichloroacetimidates 4
[16], 5 [17], and 6 [18] are summarized in
Table 1.
Hydrazine acetate in dimethylformamide in-
stead of ammonia in THF at 0 °C allowed an
easier 1-O-deacetylation control; cesium car-
bonate as a base (method B, M=Cs) led to
shorter reaction times, cleaner reaction mix-
tures and a better yield in 4. We gave up
trying to isolate the thermodynamically fa-
vored a-imidates, since both anomers were
believed to mainly yield the sole b-glycosidic
linkage as expected from the neighboring-
group participation of the 2-O-acetyl group
[13,14]. However, an attempt with the primary
alcohol 13 [19] as acceptor and the
trichloroacetimidates 4 as donors in the pres-
ence of a catalytic amount of trimethylsilyl
triflate [20] and finely ground molecular sieves
(MS) in dichloromethane yielded after 2 h at
2. Results and discussion
The imidate method initiated by Pougny
and Sinay¨ [14] and developed by Schmidt and
co-workers [15] was employed throughout this
work for the convergent synthesis of novel
oligosaccharidic crown ethers. This strategy is
outlined in Scheme 1.
Trichloroacetimidates were prepared as sta-
ble crystalline mixtures of anomers by two
0 °C a mixture of a- and b-
D
-galactopyra-
methods from per-O-acetylated
D
-galactose
nosyl-(1“6)-a- -glucopyranosides (3:1, 57%,
D
(1), lactose (2), and -glucose (3) (Scheme 2).
D
Scheme 1. Synthesis of glycosylated crown ethers from
D-glucose, D-galactose or lactose.

B. Dumont-Hornebeck et al. / Carbohydrate Research 320 (1999) 147–160
149
Scheme 2. Syntheses of trichloroacetimidates.
not represented here) according to the 400
room temperature in the presence of a large
excess of boron trifluoride etherate in
dichloromethane. The disaccharide 22, which
could not be detected in the reaction medium
of 10 with 1 [22] in the conditions of Paulsen
and Paal [23] after 2 h at room temperature,
was readily obtained (62%) from the
trichloroacetimidate 4 as donor with two
equivalents of boron trifluoride etherate as
‘catalyst’. This yield could even be raised up
to 84% with the same b-selectivity if one
equivalent of dried potassium tetrafluorobo-
rate was added to the reaction mixture prior
to addition of the donor. It has been estab-
lished that the complexation of a potassium
cation by similar crown ethers induces signifi-
cant conformational changes of the fused
sugar moiety [24]. Moreover, weaker interac-
tions between the Lewis acid and the oxygen
atoms of the crown ether should exist in its
complex with the potassium cation involving
altogether a better reactivity of the system.
In the same way, but without potassium
tetrafluoroborate as the template agent, cou-
pling 16 with two equivalents of 4 for 17 h at
room temperature gave the expected disaccha-
ride 23, but only in 11% yield, and the disac-
charide 24 in 23% yield from acceptor 17. In
all cases, the b-(1“4)-glycosidic linkage could
1
MHz H NMR. One must admit that this
Lewis acid involves a rapid in situ anomeriza-
tion of the donor in dichloromethane and that
the displacement of the b-trichloroacetimidate
by more reactive nucleophiles (such as pri-
mary alcohols) acquires a leading SN2 charac-
ter [21].
The synthesis of secondary alcohols 10 and
14 from 9 [19] has already been reported [13].
The acceptor 16 could be obtained either by
nucleophilic displacement of bromine from 10
by an excess of sodium azide (99%) or from 9
by the same reaction followed by saponifica-
tion of the intermediate 15 (aq NaOH,
toluene, room temperature). In the same way,
the nucleophilic displacement of the bromine
atom by potassium phthalimide in dimethyl-
formamide yielded the phthalimidate 17 (97%)
from 10. In the galactose series, the reduction
of bromide 11 with lithium aluminum hydride
yielded a separable mixture of alcohols 12 and
19 (14 and 56.5%, respectively) beside a trace
of the ester 18 (ꢀ4%). The formation of both
by-products 12 and 18 was ascribed to the
bulky cis-substituents which hinder the ap-
proach of aluminohydride ion aggregates to-
ward the galactose b-side (Scheme 3).
Secondary alcohols 10, 12, 14, 16, 17, and
19 were glycosylated by different donors to
give di- or trisaccharides 20, 22, 23, 24, 27, 29,
30, 32, 33, and 35. More precisely, glycosyla-
tion of 14 with 1.5 equivalents of 4 yielded the
first target compound 20 (44%) after 5 h at
1
be ascertained by H NMR (J1–2 ]7.0 Hz) of
the major product isolated after one or two
chromatographic sequences on silica gel (see
Section 3). The two disaccharides 27 and 29,
which displayed the b- -galactopyranosyl-
D

150
B. Dumont-Hornebeck et al. / Carbohydrate Research 320 (1999) 147–160
ence of palladium on charcoal in methanol to
(1“4)-b- -galactopyranosyl linkage, were ob-
D
give the trisaccharide 34. Alternatively we em-
barked on Gabriel synthesis from 22 and 35,
which were converted to the phthalimides 24
and 37, and then deprotected to the previously
isolated amino alcohols 26 and 39. The overall
yields were rather improved in this way; how-
ever, it did not allow us to isolate the pure
intermediates 25 and 38, which were recovered
partially deacetylated by hydrazine after this
penultimate step. For that reason, we did not
apply the Gabriel synthesis to bromides 29
and 32.
tained in lower yields than their corresponding
epimers 20 and 22. In the same way, coupling
the donor 5 with acceptors 14, 10, and 16 gave
the trisaccharides 30, 32, and 33 (in 14, 55,
and 14% yields, respectively). Here again, a
unique b-(1“4)-glycosidic linkage was ob-
served in the isolated reaction products. At
least, coupling the donor 6 with the alcohol 10
afforded the disaccharide 35 in a fair yield
(55%) after purification. The glycosylation
yield seemed to be more dependent on the
nature of the acceptor than on the nature of
the donor: e.g., the azido group at C-6 of the
6-deoxysugar lowered the glycosylation rates
and yields which became rather good (\52%)
when R% was a bromine atom whatever the
donor engaged. All acetylated disaccharides
In summary, ten new acetylated oligosac-
charides incorporating either a non-reducing
galactose residue (compounds 20, 22, 23, 24,
27, 29, 30, 32, and 33) or a glucose residue
(disaccharide 35) have been synthesized in ac-
ceptable yields by the trichloroacetimidate
method. Mainly, if not solely, b-glycosides
were isolated when secondary alcohols were
used as acceptors. These glycosylated crown
ethers may find applications in drug delivery.
The in vitro recognition by a specific lectin of
four selected deprotected oligosaccharides (21,
26, 28, and 31) will be discussed in Part II of
this series [25].
1
could be fully characterized by H NMR,
2D-COSY and mass spectrometry. On the
other hand, deacetylated oligosaccharides
bearing a free amino function at C-6 of the
1
sugar scaffold displayed H NMR spectra
with very poor resolution, suggesting a high
level of self-association. Some transformations
were performed on these oligosaccharides to
isolate the target compounds 21, 26, 28, 31,
and 39. For example, disaccharides 22 and 35
could be reacted with an excess of sodium
azide in dimethylformamide near 100 °C to
give the azido compounds 23 and 36 (ꢀ80%).
The azide group was then hydrogenated over
palladium to give the amines 25 and 38, which
were finally fully deacylated under the Zem-
ple´n conditions to yield the deprotected com-
pounds 26 and 39. As for 23 and 36, the azide
33 could be reduced by hydrogen in the pres-
3. Experimental
General methods.—All reactions (except
two-phase systems) were carried under a dried
argon atmosphere. Chemicals were from
Aldrich (France) and solvents from Prolabo
(France). Methanol was distilled over Mg,
toluene and THF over Na/benzophenone.
Table 1
Synthesis of trichloroacetimidates 4–6
Starting material and method
Reaction time (h)
Product Overall yield (%)
a:b ratio a
i
ii (equiv of CCl3CN/M2CO3)
1 A
1 B
1 B
1 B
2 A
2 B
3 A
3 B
0.7
1.8
24 (2.0/2.0)
19 (1.5/0.1)
4.5 (1.5/1.5)
0.7 (2.0/2.0)
5.5 (2.0/2.0)
1.0 (1.5/1.5)
24 (2.0/2.0)
5 (1.5/1.5)
4
4
4
4
5
5
6
6
52
15
70
85
70
68
72
66
3:1
1:1
9:1
13:1
14:1
20:1
13:1
16:1
1.0
2.0
1.0
0.5
1
a By comparison of H NMR NH signals between 8.5 and 9.0 ppm.

B. Dumont-Hornebeck et al. / Carbohydrate Research 320 (1999) 147–160
151
Scheme 3.
MeOH) before heating at 270 °C. Anhydrous
MgSO4 was used to dry the organic solutions
during work-up. Yields refer to pure isolated
compounds after preparative chromatography
on Silica Gel (E. Merck, particle size 40–63
mM). Melting points were taken in capillary
tubes on a Bu¨chi apparatus and are uncor-
Dimethylformamide was distilled over CaH2
and CH2Cl2 over P2O5 and stored over 4 A
,
MS under argon. All reactions were moni-
tored by thin-layer chromatography (TLC)
carried out on 0.25 mm E. Merck Silica Gel
plates (60 F254). Visualization was achieved
under a UV lamp at 254 nm and development
with a spray of H2SO4 solution (50% in
1
rected. Unless otherwise stated, H and 13C

152
B. Dumont-Hornebeck et al. / Carbohydrate Research 320 (1999) 147–160
79
+
81
+
’
’
506. Found 506 [ BrM] and 508 [ BrM] .
Methyl [2,3-b](11,12-benzo-1,4,7,10,13,16-
hexaoxacyclooctadeca-11-ene)-4-O-benzoyl-6-
NMR spectra were recorded with a Bruker
AC250 spectrometer in CDCl3 or D2O at re-
spectively, 250 and 62.9 MHz at 298 K. EI
mass spectra were recorded on a Nermag R-
1010 spectrometer at 70 eV and ES mass
spectra using a Micromass Platform II of the
UHP-Nancy I. Elemental analyses and LSI
HRMS were performed by the Service Central
de Microanalyse du CNRS (Vernaison,
France), LSI on a Micromass ZAB2-SEQ
from a thioglycerol/NaCl matrix (ionization
Cs+ at 35 kV). CE — abbreviation for crown
ether — is used throughout the experimental
section. Optical rotations were measured on a
Perkin–Elmer 141 automatic polarimeter in a
1 dm cell at ambient temperature. Water used
for HPLC was deionized and distilled prior to
use. The HPLC-grade MeCN solvent from
Carlo Erba was used without further purifica-
tion for the same purpose. The HPLC used a
C18 column: Cosmosil®, 250×4.6 mm i.d., 5
mm particle size (ref. 378-62 from Promochem,
Germany) with UV detection at 275 nm, 0.1
AUFS, flow rate of 1 mL/min.
bromo-2,3,6-trideoxy-i- -galactopyranoside
D
(11).—To a stirred dispersion of methyl [2,3-
b]-(11,12-benzo-1,4,7,10,13,16-hexaoxacyclo-
octadeca-11-ene)-4,6-O-benzylidene-2,3-dide-
oxy-b- -galactopyranoside (8) [19] (4.00 g, 7.5
D
mmol) in abs CCl4 (200 mL) was added dry
CaCO3 (1.88 g, 2.5 equiv) and NBS (1.67 g,
1.25 equiv). The resulting dispersion was im-
mediately heated to reflux by an incandescent
500 W lamp for 30 min, cooled to 5 °C, and
filtered through a sintered glass under the
fume board. The remaining succinimide and
calcium salts were exhaustively rinsed with
CH2Cl2 and the combined organic phases
washed successively with 0.2 M Na2S2O5 (10
mL), 5% aq NaHCO3 (10 mL) and water (10
mL), dried, and finally evaporated under re-
duced pressure. The residue was chro-
matographed (2:1“1:1 n-hexane–EtOAc) to
yield the bromide 11 (3.88 g, 85%) as white
crystals: mp 119–120 °C (i-Pr2O); [h]D +22.3°
1
Methyl [2,3-b](11,12-benzo-1,4,7,10,13,16-
hexaoxacyclooctadeca-11-ene)-6-bromo-2,3,6-
(c 1, CHCl3); H NMR (CDCl3): l 7.61–7.39
(m, 5 H, Ar), 6.88 (bs, 4 H, catechol), 5.76 (d,
1 H, J4–5 3.0 Hz, H-4), 4.32 (d, 1 H, J1–2 7.5
Hz, H-1), 4.25–3.63 (m, 17 H, 8×OCH2,
H-5), 3.6 (s, 3 H, OCH3), 3.54 (dd, 1 H, J2–3
9.5, J3–4 3.0 Hz, H-3), 3.48–3.39 (m, 3 H, H-2,
-6, -6%); EIMS: m/z Calcd for C288H1 35BrO10
trideoxy-h-
lution of
1,4,7,10,13,16-hexaoxacyclooctadeca-11-ene)-
4-O-benzoyl-6-bromo-2,3,6-trideoxy-a- -glu-
D
-glucopyranoside (10).—To a so-
methyl [2,3-b]-(11,12-benzo-
D
copyranoside (9) [19] (4.70 g, 7.68 mmol) in
toluene (50 mL) was added 50% aq NaOH (50
mL), and the mixture was vigorously stirred
for 16 h, the reaction was monitored by TLC
(1:1 EtOAc–n-hexane). Chilled water (100
mL) was added and the aq phase was ex-
tracted with CH2Cl2 (3×50 mL). The organic
phases were combined, washed with water un-
til neutral, dried, and concentrated to a gum
which solidified on standing. Preparative crys-
tallization from Et2O–i-PrOH gave the alco-
hol 10 (3.80 g, 97%) as a white solid: mp
79
+
+
’
’
610. Found 610, [ BrM] and 612 [ BrM] .
Methyl [2,3-b](11,12-benzo-1,4,7,10,13,16-
hexaoxacyclooctadeca-11-ene)-2,3,6-trideoxy-
h- -glucopyranoside (14).—A solution of
D
crown ether 9 [19] (3.35 g, 5.47 mmol) in THF
(25 mL) was dropped over 20 min onto a
stirred suspension of LiAlH4 (0.88 g, 4 equiv)
in THF (25 mL) at 0 °C. After 10 h of stirring
at rt, the suspension was refluxed for 2 h, so
that TLC (EtOAc) showed the complete re-
duction of the bromide 9. EtOAc (5 mL) was
dropped at rt to react with hydride excess and
the hydrolysis was completed with satd aq
Na2SO4 (1 mL). The solution was filtered
through a sintered glass under the fume board
and the remaining salts rinsed twice with THF
(25 mL). The solution was concentrated under
reduced pressure and the residue dissolved in
CH2Cl2 (50 mL), washed twice with water (20
mL), dried, and concentrated to a syrup
1
104–105 °C; [h]D +50.1° (c 2, CHCl3); H
NMR (CDCl3): l 6.82 (bs, 4 H, catechol), 4.77
(d, 1 H, H-1), 4.2–3.98 (m, 6 H, 3×OCH2),
3.96–3.58 (m, 12 H, 5×OCH2, H-3, -5), 3.5
(dd, 1 H, J5–6% 7.0, J6–6% 10.0 Hz, H-6%), 3.49 (t,
1 H, J3–4 ꢀJ4–5 9.0 Hz, H-4), 3.39 (dd, 1 H,
J5–6 2.0 Hz, H-6), 3.36 (s, 3 H, OCH3), 3.34
(dd, 1 H, J1–2 3.0, J2–3 9.0 Hz, H-2), 2.96 (bs,
1 H, OH); EIMS: m/z Calcd for C21H31BrO9

B. Dumont-Hornebeck et al. / Carbohydrate Research 320 (1999) 147–160
153
H-3), 3.51 (dd, 1 H, J5–6 2.5 Hz, H-6), 3.44 (d,
1 H, J1–2 3.0, J2–3 9.0 Hz, H-2), 3.43 (s, 3 H,
OCH3), 3.42 (bt, 1 H, J3–4 9.0, J4–5 7.5 Hz,
H-4), 3.39 (dd, 1 H, J5–6% 6.0, J6–6% 13.0 Hz,
which solidified on standing. Preparative crys-
tallization from i-PrOH–n-hexane afforded
the alcohol 14 (2.04 g, 87%) as a white solid:
1
mp 126–128 °C, [h]D +52.8° (c 1, CHCl3); H
H-6%), 3.15 (bs, 1 H, OH); EIMS: m/z Calcd
NMR (CDCl3): l 6.89 (bs, 4 H, catechol), 4.74
(d, 1 H, H-1), 4.32–4.1 (m, 5 H, 2.5×OCH2),
4.03–3.71 (m, 11 H, 5.5×OCH2), 3.65 (m, 1
H, H-5), 3.52 (t, 1 H, J2–3 9.0 Hz, H-3), 3.41
(dd, 1 H, J1–2 3.5 Hz, H-2), 3.39 (s, 3 H,
OCH3), 3.17 (t, 1 H, J3–4 ꢀJ4–5 9.0 Hz, H-4),
1.7 (bs, 1 H, OH), 1.26 (d, 3 H, J5–6 5.5 Hz,
+
’
for C21H31N3O9 469. Found 469 [M] .
Methyl [2,3-b](11,12-benzo-1,4,7,10,13,16-
hexaoxacyclooctadeca-11-ene)-2,3,6-trideoxy-
6-N-phthalimido-h- -glucopyranoside (17).—
D
To a stirred solution of 10 (1.00 g, 1.97 mmol)
in DMF (20 mL) was added potassium ph-
thalimide (0.548 g, 1.5 equiv) and the reaction
mixture was immediately heated to 135 °C.
The reaction was monitored by TLC (1:1
EtOAc–n-hexane) and was complete after 5 h.
The solvent was evaporated, the residue dis-
solved in CH2Cl2 (70 mL), washed twice with
water (20 mL), dried, and concentrated to a
gum (1.10 g, 97%) which solidified on stand-
ing: mp 137–139 °C (i-PrOH); IR (NaCl) w
1717 cm−1 (CꢀO); [h]D+56.7° (c 1, CHCl3);
1H NMR (CDCl3): l 7.9–7.7 (m, 4 H, Ar),
6.88 (bs, 4 H, catechol), 4.75 (d, 1 H, H-1),
4.3–3.7 (m, 20 H, 8× OCH2, H-4, -5, -6, -6%),
3.57 (t, 1 H, J3–4 9.0 Hz, H-3), 3.46 (bs, 1 H, OH),
3.5, J2–3 9.0 Hz, H-2), 3.34 (dd, 1 H, J1–2 3.5 Hz,
CH3); EIMS: m/z Calcd for C21H32O9 428.
+
’
Found 428 [M] .
Methyl
6-azido-[2,3-b](11,12-benzo-1,4,7,
10,13,16-hexaoxacyclooctadeca-11-ene)-4-O-
benzoyl - 2,3,6 - trideoxy - h -
D
- glucopyranoside
(15).—To a stirred solution of crown ether 9
[19] (3.07 g, 5.0 mmol) in DMF (80 mL) was
added NaN3 (0.651 g, 2 equiv) and the solu-
tion was heated to 130 °C. The reaction, mon-
itored by TLC (3:2, EtOAc–n-hexane), was
complete after 45 min. The solvent was evapo-
rated, the residue dissolved in CH2Cl2 (70
mL), washed twice with water (20 mL), dried,
and concentrated. Chromatography of the
residue (3:2, EtOAc–n-hexane) yielded the
azide 15 (2.294 g, 80%) as a colorless gum:
[h]D+12.6° (c 1, CHCl3); IR (NaCl): w 2100
J2–3 9.0Hz,H-2),3.31(s,3H,OCH3);EIMS:m/z
+
’
Calcd for C29H35NO11 573. Found 573 [M] .
1
cm−1 (N3); H NMR (CDCl3): l 8.13 (d, 2 H,
Methyl [2,3-b](11,12-benzo-1,4,7,10,13,16-
hexaoxacyclooctadeca-11-ene)-2,3,6-trideoxy-
H-1, -5, Ar), 7.59 (t, 1 H, H-3, Ar), 7.46 (t, 2
H, H-2, -4, Ar), 6.88 (bs, 4 H, catechol), 5.1 (t,
1 H, J4–5 9.5 Hz, H-4), 4.9 (d, 1 H, H-1),
4.22–3.7 (m, 16 H, 8×OCH2), 3.78 (m, 1 H,
H-5), 3.56 (t, 1 H, J3–4 9.5 Hz, H-3), 3.52 (dd,
1 H, J1–2 3.5, J2–3 9.5 Hz, H-2), 3.5 (s, 3 H,
OCH3), 3.37 (dd, 1 H, J5–6% 7.0 Hz, H-6%), 3.25
i- -galactopyranoside (19).—The procedure
D
was similar to that employed for the synthesis
of alcohol 14 except that 8 equiv of LiAlH4 (in
two 0.25 g portions) were used and the reac-
tion time was 6 days at reflux. From 1.00 g
(1.635 mmol) of bromide 11 were successively
isolated by gradient chromatography with
1:1“1:9 n-hexane–EtOAc: (i) 0.148 g (15%)
of starting material 11; (ii) 38 mg (4.4%) of
(dd, 1 H, J5–6 3.0 Hz, H-6); EIMS: m/z Calcd
+
’
for C28H35N3O10 573. Found 573 [M] .
Methyl
10,13,16-hexaoxacyclooctadeca-11-ene)-2,3,6-
trideoxy-h- -glucopyranoside (16).—The pro-
6-azido-[2,3-b](11,12-benzo-1,4,7,
methyl
hexaoxacyclooctadeca-11-ene)-4-O-benzoyl-
2,3,6-trideoxy-b- -galactopyranoside (18) as a
[2,3-b](11,12-benzo-1,4,7,10,13,16-
D
cedure employed was exactly the same as for
the synthesis of alcohol 10. From azide 15
(0.94 g, 1.64 mmol) was obtained the alcohol
16 (0.732 g, 95%) as a white solid after prepar-
ative crystallization from i-Pr2O–i-PrOH: mp
98–99 °C, [h]D +48.5° (c 1, CHCl3); IR (KBr)
w 2098 cm−1 (N3), 3400 cm−1 (OH); 1H NMR
(CDCl3): l 6.87 (bs, 4 H, catechol), 4.81 (d, 1
H, H-1), 4.3–4.1 (m, 5 H, 2×OCH2, H-5),
4.04–3.7 (m, 12 H, 6×OCH2), 3.55 (t, 1 H,
D
1
colorless gum: [h]D +21.5° (c 1, CHCl3); H
NMR (CDCl3): l 8.09 (bd, 2 H, Ar), 7.56 (bt,
1 H, Ar), 7.43 (t, 2 H, Ar), 6.93–6.83 (m, 4 H,
catechol), 5.5 (d, 1 H, H-4, J4–5 B1 Hz), 4.28
(1 H, H-1), 4.23–4.0 (m, 5 H, 2.5×OCH2),
3.97–3.63 (m, 12 H, 5.5×OCH2, H-5), 3.57
(s, 3 H, OCH3), 3.53 (dd, 1 H, J3–4 3.5 Hz,
H-3), 3.42 (dd, 1 H, J1–2 7.5, J2–3 9.5 Hz,
H-2), 1.25 (d, 3 H, J5–6 6.4 Hz, CH3); EIMS:

154
B. Dumont-Hornebeck et al. / Carbohydrate Research 320 (1999) 147–160
5.02 (d, 1 H, J1–2 8.0 Hz, H-1 Gal), 4.97 (dd,
1 H, J2–3 10.3, J3–4 3.2 Hz, H-3 Gal), 4.71 (d,
1 H, H-1 Glc), 4.25–3.6 (m, 16 H, 8×OCH2),
4.02 (m, 1 H, J4–5 1.0 Hz, H-5 Gal), 3.74 (dd,
2 H, J5–6 6.0 Hz, H-6, -6% Gal), 3.71 (t, 1 H,
J3–4 9.0 Hz, H-3 Glc), 3.66 (m, 1 H, H-5 Glc),
3.4 (d, 1 H, J1–2 3.5, J2–3 9.0 Hz, H-2 Glc),
3.37 (s, 3 H, OCH3), 3.28 (t, 1 H, J3–4 ꢀJ4–5
9.0 Hz, H-4 Glc), 2.14, 2.06, 1.99, 1.98 (4 s,
each 3 H, 4×OAc), 1.17 (d, 3 H, J5–6 6.3 Hz,
m/z Calcd for C28H36O10 532. Found 532
+
’
[M] ; (iii) 0.114 g (13.8%) of methyl [2,3-
b](11,12 - benzo - 1,4,7,10,13,16-hexaoxacyclo-
octadeca-11-ene)-6-bromo-2,3,6-trideoxy-b- -
D
galactopyranoside (12) as white crystals: mp
100–101 °C (i-Pr2O); [h]D −3.0° (c 1, CHCl3);
1H NMR (CDCl3): l 6.9 (bs, 4 H, Ar), 4.19
(d, 1 H, H-1), 4.19–3.7 (m, 17 H, 8×OCH2,
H-4) 3.65–3.5 (m, 3 H, H-5, -6, -6%), 3.52 (s, 3
H, OCH3), 3.43 (t, 1 H, J1–2 7.2 Hz, H-2), 3.34
(dd, 1 H, J2–3 9.5, J3–4 3.0 Hz, H-3), 2.55 (bs,
1 H, OH); EIMS: m/z Calcd for C21H31BrO9
CH3 Glc); IEMS: m/z Calcd for C35H50O18
+
’
758. Found 758 [M] ; Anal. Calcd for
79
+
81
+
’
’
506. Found 506 [ BrM] and 508 [ BrM] ;
(iv) 0.395 g (56.5%) of target compound 19 as
a white solid: mp 147–149 °C (i-PrOH–n-
C35H50O18 C, 55.40; H, 6.64. Found: C, 55.27;
H, 6.59.
Methyl i-
b](11,12 - benzo - 1,4,7,10,13,16 - hexaoxacyclo-
octadeca-11-ene)-2,3,6-trideoxy-h- -glucopy-
D
-galactopyranosyl-(1“4)-[2,3-
1
hexane), [h]D −1.0° (c 1, CHCl3); H NMR
D
(CDCl3): l 6.88 (bs, 4 H, catechol), 4.23–4.05
(m, 5 H, H-1, 2×OCH2), 4.0–3.68 (m, 13 H,
6×OCH2, H-4), 3.50 (m, 1 H, H-5), 3.49 (s, 3
H, OCH3), 3.36 (d, 1 H, J1–2 6.5 Hz, H-2),
3.32 (dd, 1 H, J2–3 6.5, J3–4 3.0 Hz, H-3), 2.4
(bs, 1 H, OH), 1.33 (d, 3 H, J5–6 6.7 Hz, CH3);
ranoside (21).—To a solution of 20 (64 mg, 88
mmol) in abs MeOH (10 mL) under argon,
was added MeONa (ꢀ20 mg) and the mix-
ture was stirred at rt until TLC (1:1, EtOAc–
n-hexane) showed that the deacetylation was
complete (ꢀ30 min). The mixture was de-
mineralized for 15 min with Dowex (H+)
cation-exchange resin (ꢀ0.8 mL) and filtered.
The resin was washed with MeOH and the
solvents evaporated under reduced pressure to
yield 21 (49 mg, 98%) as a colorless solid: mp
145–147 °C (MeOH); [h]D +42.5° (c 0.2,
EIMS: m/z Calcd for C21H32O9 428. Found
+
’
428 [M] .
Methyl (2,3,4,6-tetra-O-acetyl-i- -galacto-
D
pyranosyl) - (1“4) - [2,3-b](11,12-benzo-1,4,7,
10,13,16-hexaoxacyclooctadeca-11-ene)-2,3,6-
trideoxy-h- -glucopyranoside (20).—To a so-
D
lution of acceptor 14 (0.25 g, 0.58 mmol) and
donor 4 (0.46 g, 1.5 equiv) in CH2Cl2 (6 mL)
1
H2O); H NMR (D2O): l 7.0–6.9 (m, 4 H,
,
was added crushed 4 A MS (ꢀ1 g, activated
catechol), 4.7 (d, 1 H, J1–2 3.0 Hz, H-1 Glc),
4.45 (d, 1 H, J1–2 7.5 Hz, H-1 Gal), 4.16 (t, 3
H, 1.5×OCH2), 4.05–3.55 (m, 20 H, 6.5×
OCH2, H-3, -4, -5 Glc, H-2, -3, -4, -5 Gal),
3.5–3.4 (m, 3 H, H-2 Glc, H-6, -6% Gal), 3.32
(s, 3 H, OCH3), 1.3 (d, 3 H, J5–6 6.1 Hz, CH3);
ESMS: m/z Calcd for C27H42O14 590. Found
613 [M+Na]+; Anal. Calcd for C27H42O14 C,
54.90; H, 7.17. Found: C, 54.72; H, 7.20; tr
(HPLC) 14.6 min (4:1 water–MeCN as
eluent).
at 105 °C for 24 h and stored in vacuo over
P2O5) and the suspension was magnetically
stirred under argon for 30 min at rt. Boron
trifluoride etherate (1.5 mL, 20 equiv) in
CH2Cl2 (6 mL) was then added dropwise over
a period of 15 min. The reaction was moni-
tored by TLC (1:1, EtOAc–n-hexane) and
was diluted after 5 h with CH2Cl2 (20 mL).
The suspension was filtered and the filtrate
neutralized by slow addition of satd NaHCO3
(ꢀ20 mL) at 0 °C. The isolated organic phase
was then washed twice with water (5 mL),
dried with MgSO4, and concentrated under
reduced pressure. Chromatography (2:1,
EtOAc–n-hexane) of the residue on silica gel
afforded the disaccharide 20 (0.191 g, 44%) as
a white solid: mp 167–168 °C (EtOAc),
[h]D+38.5° (c 1, CHCl3); 1H 2D-NMR
(CDCl3): l 6.95–6.82 (m, 4 H, catechol), 5.37
(d, 1 H, H-4 Gal), 5.18 (dd, 1 H, H-2 Gal),
Methyl (2,3,4,6-tetra-O-acetyl-i- -galac-
D
topyranosyl)-(1“4)-[2,3-b](11,12-benzo-1,4,7,-
10,13,16 - hexaoxacyclooctadeca - 11 - ene) - 6-
bromo - 2,3,6 - trideoxy - h -
D
- glucopyranoside
(22).—The same procedure was used as for
the synthesis of 20 except 2 equiv of donor 4
(0.98 g) and catalyst (C2H5)2O·BF3 (0.25 mL)
were used. Yield after 21 h of reaction at rt
from 0.507 g of 10 (1.0 mmol), similar work-
up as 20, and chromatography (1:1“9:1,

B. Dumont-Hornebeck et al. / Carbohydrate Research 320 (1999) 147–160
155
1
[h]D +40.4° (c 1, CHCl3); H NMR (CDCl3):
l 7.95–7.7 (m, 4 H, Ar), 6.9 (bs, 4 H, cate-
chol), 5.36 (t, 1 H, J4–5 3.0 Hz, H-4 Gal), 5.22
(t, 1 H, H-2 Gal), 5.0 (dd, 1 H, J2–3 9.5, J3–4
3.0 Hz, H-3 Gal), 4.9 (d, 1 H, J1–2 8.0 Hz, H-1
Gal), 4.63 (d, 1 H, H-1 Glc), 4.34 (dd, 1 H,
J5–6 2.0, J6–6% 11.5 Hz, H-6% Gal), 4.25–3.6 (m,
22 H, 8×OCH2, H-3, -5, -6, -6% Glc, H-5, -6
Gal), 3.54 (t, 1 H, J3–4 ꢀJ4–5 9.0 Hz, H-4
Glc), 3.36 (dd, 1 H, J1–2 3.0, J2–3 9.0 Hz, H-2
Glc), 3.07 (s, 3 H, OCH3), 2.2–1.9 (4 s, each 3
H, 4×OAc); EIMS: m/z Calcd for
C43H53NO20 903. Found 904 [M+H]+.
Method D: the same procedure was used as
for the synthesis of 20. From 0.250 g (0.43
mmol) of 17, after 20 h of reaction at rt, usual
work-up, and chromatography (1:1“9:1,
EtOAc–n-hexane) on silica gel were isolated
EtOAc–n-hexane) on silica gel: 0.517 g (62%)
of 22 as a white solid: mp 153–155 °C
1
(EtOAc); [h]D +46.8° (c 1, CHCl3); H NMR
(CDCl3): l 6.9 (bs, 4 H, catechol), 5.38 (d, 1
H, J4–5 B1.0 Hz, H-4 Gal), 5.17 (dd, 1 H, H-2
Gal), 5.06 (d, 1 H, J1–2 8.0 Hz, H-1 Gal), 4.98
(dd, 1 H, J2–3 10.0, J3–4 3.5 Hz, H-3 Gal), 4.81
(d, 1 H, J1–2 3.5 Hz, H-1 Glc), 4.3–3.4 (m, 25
H, 8×OCH2, H-2, -3, -4, -5, -6, -6% Glc, H-5,
-6, -6% Gal), 3.38 (s, 3 H, OCH3), 2.14, 2.1,
2.03, 1.97 (4 s, each 3 H, 4×OAc); EIMS:
m/z Calcd for C35H49BrO18 836. Found 836
79
+
81
+
’
’
[ BrM] and 838 [ BrM] .
Methyl (2,3,4,6-tetra-O-acetyl-i- -galac-
D
topyranosyl) - (1“4) - 6 - azido - [2,3 - b](11,12-
benzo-1,4,7,10,13,16-hexaoxacyclooctadeca-11-
ene) - 2,3,6 - trideoxy - h -
D
- glucopyranoside
(23).—The same procedure was used as for
the synthesis of 20. From 0.30 g (0.64 mmol)
of acceptor 16, after 17 h of reaction at rt,
pyridine (1 mL) was added and the reaction
mixture was diluted with CH2Cl2 (50 mL) to
give, after the usual work-up and chromatog-
raphy (1:1“9:1, EtOAc–n-hexane) on silica
gel, the azide 23 (57 mg, 11%) as a pale-yellow
gum: [h]D +50.2° (c 1, CHCl3); IR (NaCl) w
1
29 mg (23%) of a gum with H NMR spec-
trum identical to that described above.
Methyl (2,3,4,6-tetra-O-acetyl-i- -galac-
D
topyranosyl) - (1“4) - 6 - amino - [2,3 - b](11,12-
benzo - 1,4,7,10,13,16 - hexaoxacy - clooctadeca-
11 - ene) - 2,3,6 - trideoxy - h - - glucopyranoside
D
(25).—To a solution of the azide 23 (0.121 g)
in 1:1 MeOH–EtOAc (20 mL) under argon
was added palladium on activated charcoal
(10% Pd, 100 mg) and the magnetically stirred
suspension was saturated with H2 (ꢀ780
Torr) at rt. The reaction was monitored by
TLC (EtOAc) and was stopped after 30 h by
filtration through a Celite 521 pad. The
residue was purified by chromatography on
deactivated silica gel (1:1 EtOAc–n-hexane
then 9:1“1:9 EtOAc–EtOH) to yield the
amine 23 (65 mg, 56%) as a pale-yellow solid:
1
2102 cm−1 (N3); H 2D-NMR (CDCl3): l 6.9
(bs, 4 H, catechol), 5.35 (dd, 1 H, J4–5 B2.0
Hz, H-4 Gal), 5.11 (dd, 1 H, H-2 Gal), 5.03
(d, 1 H, J1–2 7.5 Hz, H-1 Gal), 4.95 (dd, 1 H,
J3–4 3.0, J2–3 9.8 Hz, H-3 Gal), 4.78 (d, 1 H,
J1–2 3.5 Hz, H-1 Glc), 4.25–3.7 (m, 22 H,
8×OCH2, H-6, -6%, -5 Gal, H-3, -4, -5 Glc),
3.46 (dd, 1 H, H-6% Glc), 3.41 (d, 1 H, H-2
Glc), 3.4 (s, 3 H, OCH3), 3.25 (dd, 1 H, J6–6%
12.0, J5–6 3.0 Hz, H-6 Glc), 2.14–1.93 (4 s,
1
each 3 H, 4×OAc); EIMS: m/z Calcd for
mp 57–60 °C, [h]D +38.5° (c 0.7, CHCl3); H
+
’
C35H49N3O18 799. Found 799 [M] .
NMR (CDCl3): l 6.93–6.85 (m, 4 H, cate-
chol), 5.37 (d, 1 H, J4–5 B2.0 Hz, H-4 Gal),
5.17 (dd, 1 H, H-2 Gal), 5.06 (d, 1 H, J1–2 8.0
Hz, H-1 Gal), 4.96 (dd, 1 H, J2–3 10.0, J3–4 3.6
Hz, H-3 Gal), 4.78 (d, 1 H, H-1 Glc), 4.25–
3.62 (m, 23 H, 8×OCH2, H-6, -6%, -5 Gal,
H-3, -5, -6, -6% Glc), 3.45 (t, 1 H, J3–4 ꢀJ4–5
9.3 Hz, H-4 Glc), 3.41 (s, 3 H, OCH3), 3.37
(dd, 1 H, J1–2 3.5, J2–3 9.5 Hz, H-2 Glc), 2.45
(d, 2 H, NH2), 2.14, 2.05, 1.99, 1.97 (4 s, each
3 H, 4×OAc); EIMS: m/z Calcd for
C35H51NO18 773. Found 774 [M+H]+.
Methyl (2,3,4,6-tetra-O-acetyl-i- -galac-
D
topyranosyl)-(1“4)-[2,3-b](11,12-benzo-1,4,-
7,10,13,16 - hexaoxacyclooctadeca - 11 - ene) - 6-
N-phthalimido-2,3,6-trideoxy-h- -glucopyran-
D
oside (24).—This compound has been ob-
tained by two methods. Method C: to a solu-
tion of bromine 22 (0.138 g, 0.164 mmol) in
DMF (10 mL) was added potassium phthal-
imide (46 mg, 1.5 equiv) and the reaction
mixture was heated for 1.5 h at 150 °C. Simi-
lar work-up as for 17 and chromatography
(EtOAc“9:1 CH2Cl2–EtOH) on silica gel
yielded 0.105 g (71%) of 24 as a colorless gum:
Methyl
i- -galactopyranosyl-(1“4)-6-
amino - [2,3 - b](11,12 - benzo - 1,4,7,10,13,16-
D

156
B. Dumont-Hornebeck et al. / Carbohydrate Research 320 (1999) 147–160
aspects with the compound prepared by
method E.
hexaoxacyclooctadeca-11-ene)-2,3,6-trideoxy-
h- -glucopyranoside (26).—Method E: to a
D
Methyl (2,3,4,6-tetra-O-acetyl-i- -galac-
D
suspension of K2CO3 (13.4 mg, 1.25 equiv) in
MeOH (10 mL) was added hydrazine hy-
drochloride (13.2 mg, 2.5 equiv) and the mix-
ture was stirred at rt as long as CO2 evolved
(ꢀ45 min). Then, 70 mg (0.8 mmol) of the
disaccharide 24 was added to the resulting
solution and this was heated to gentle reflux.
The reaction was monitored by TLC (EtOAc)
and was stopped after 2 h. The solvent was
evaporated and the residue dissolved in
CH2Cl2 (50 mL) and washed with 1% aq
Li2CO3 (10 mL). The aq phase was extracted
with CH2Cl2 (3×20 mL), the organic phases
combined, dried, concentrated, and purified
by chromatography on silica gel (CH2Cl2“
9:1 CH2Cl2–EtOH) to afford 47 mg of par-
tially deacetylated disaccharide, which was
dissolved in MeOH (10 mL) and treated with
1 M methanolic MeONa (0.2 mL) for 2 h at
rt. The solution was then demineralized for 15
min with Dowex (H+) cation-exchange resin
(ꢀ0.5 mL) and filtered. The beads were
rinsed with MeOH and the solvents evapo-
rated under reduced pressure to yield the
target compound 26 (37 mg, 70% over two
steps) as a pale-yellow gum: [h]D+38.1° (c
topyranosyl)-(1“4)-[2,3-b](11,12-benzo-1,4,7,-
10,13,16-hexaoxacyclooctadeca-11-ene)-2,3,6-
trideoxy-i-
D
-galactopyranoside
(27).—The
same procedure was used as for the synthesis
of the disaccharide 20. From 0.230 g (0.56
mmol) of acceptor 19 and 2 equiv of donor 4,
after 24 h of reaction at rt, usual work-up,
and chromatography on silica gel (1:1“9:1
EtOAc–n-hexane), was isolated 0.114 g (28%)
of disaccharide 27 as a pale-yellow gum:
[h]D +43.9° (c 1.0, CHCl3); 1H NMR
(CDCl3): l 6.94–6.87 (m, 4 H, catechol), 5.35
(dd, 1 H, J4–5 B1.0 Hz, H-4 Gal), 5.19 (dd, 1
H, H-2 Gal), 5.02 (dd, 1 H, J2–3 10.5, J3–4 3.4
Hz, H-3 Gal), 4.64 (d, 1 H, J1–2 7.8 Hz, H-1
Gal), 4.2–4.02 (m, 7 H, 2×OCH2, H-1 CE,
H-6, -6% Gal), 4.0–3.64 (15 H, 6×OCH2, H-4,
-5 CE, H-5 Gal), 3.75 (s, 3 H, OCH3), 3.55
(dd, 1 H, H-3 CE), 3.5 (t, 1 H, J1–2 =J2–3
ꢀ
8.5 Hz, H-2 CE), 2.15, 2.03, 2.02, 1.98 (4 s,
each 3 H, 4×OAc), 1.29 (d, 3 H, J5–6 6.5 Hz,
CH3); 13C HMQC-NMR (CDCl3): l 169.5,
169.4, 168.9 (CH3CO2), 148.0, 147.8 (C-2, -1
catechol), 120.8, 120.6 (C-5, -4 catechol),
113.5, 113.0 (C-6, -3 catechol), 101.3 (C-1
Gal), 101.0 (C-1 EC), 77.3, 75.9, 74.3 (C-3, -5
Gal, C-3 EC), 70.3 (OCH2), 69.9 (C-2 EC),
69.7 (OCH2), 69.4 (C-5 EC), 68.9, 68.7, 68.6
(OCH2), 68.2 (C-4 EC), 67.9 (OCH2), 67.5,
66.1, 60.5 (C-4, -2, -6 Gal), 57.0 (OCH3), 20.0,
1
0.5, CH3CN); H NMR (D2O): l 7.05–6.95
(m, 4 H, catechol); 4.92 (d, 1 H, J1–2 3.5 Hz,
H-1 Glc), 4.45 (d, 1 H, J1–2 7.5 Hz, H-1 Gal),
4.25–4.1 (m, 4 H, 2×OCH2), 4.05–3.2 (m, 27
H, H-6, -6% Glc, OCH3, H-5, -4, -3, -2 Glc,
H-6, -6%, -5, -4, -3, -2 Gal, 6×OCH2); 13C
NMR (3:1 acetone-d6–D2O): l 122.1 (C-4, -5
catechol), 114.3 (C-3 catechol), 114.0 (C-6 cat-
echol), 104.2 (C-1 Gal), 97.4 (C-1 Glc), 79.4
(C-4 Glc), 78.5 (C-5 Gal), 74.0, 73.9 (C-5, -3
Glc), 72.1, 71.9 (C-4, -3 Gal), 71.3, 70.8, 70.6,
69.5 (OCH2), 69.2 (C-2 Gal), 68.9 (C-2 Glc),
61.8 (C-6 Gal), 55.1 (OCH3), 40.8 (C-6 Glc),
LSIHRMS: m/z Calcd for C27H43NO14Na
628.2581. Found 628.2575 [M+Na]+; tr
(HPLC) 14.1 min (H2O as eluent). Method F:
a solution of the amine 25 (40 mg, 0.05 mmol)
was deacetylated in the Zemple´n conditions
(as for disaccharide 20) for 24 h at rt, purified
by elution on basic alumina (Fluka type 5016
A) with 7:3 CH3CN–H2O to yield 25 (31 mg,
99%) as a pale-orange gum identical in all
19.8 (CH3CO2), 15.4 (C-6 EC); EIMS: m/z
+
’
Calcd for C35H50O18 758. Found 758 [M] .
Methyl i-
b](11,12 - benzo - 1,4,7,10,13,16 - hexaoxacyclo-
octadeca-11-ene)-2,3,6-trideoxy-i- -galacto-
D
-galactopyranosyl-(1“4)-[2,3-
D
pyranoside (28).—The same procedure was
used as for the deacetylation of 20. Yield after
24 h of reaction at rt and usual work-up: 87
mg (99%) of disaccharide 28 as a pale-yellow
1
gum: [h]D +37.2° (c 0.2, CH3CN); H NMR
(D2O): l 7.0 (bs, 4 H, catechol), 4.5 (d, 1 H,
J1–2 7.0 Hz, H-1 Gal), 4.1–4.25 (m, 5 H,
2.5×OCH2), 4.0 (d, 1 H, J1–2 7.5 Hz, H-1
CE), 3.9–3.4 (m, 24 H, OCH3, H-6, -6% Gal,
5.5×OCH2, H-2, -3, -4, -5 CE, H-2, -3, -4, -5
Gal), 1.2 (d, 3 H, J5–6 6.0 Hz, CH3); 13C NMR
(CD3CN): l 148.6 (C-1, -2 catechol), 122.5
(C-4, -5 catechol), 114.6, 113.2 (C-3, -6 cate-
chol), 104.9, 103.6, (C-1 CE, C-1 Gal), 78.3,

B. Dumont-Hornebeck et al. / Carbohydrate Research 320 (1999) 147–160
157
22 h with a crystal of 4-DMAP to afford, after
chromatography (1:1 CH2Cl2–Et2O) on silica
gel, the trisaccharide 30 (0.290 g, 14%) as a
white solid: mp 85–87 °C (EtOAc), [h]D +
76.1, 74.5, 73.9, 72.6, 69.6 (C-2, -3, -4, -5 CE,
C-2, -3, -4, -5 Gal), 70.9, 70.6, 70.0, 69.9, 68.9,
68.4, 68.0 (OCH2), 61.8 (C-6 Gal), 57.4
(OCH3), 16.9 (C-6 CE); LSIHRMS: m/z
Calcd for C27H42O14Na 613.2472. Found
613.2508 [M+Na]+.
1
24.0° (c 1, CHCl3); H 2D-NMR (CDCl3): l
6.9–6.8 (m, 4 H, catechol), 5.31 (d, 1 H, J4–5
3.0 Hz, H-4 Gal), 5.1 (t, 1 H, H-2 Glc), 5.07
(dd, 1 H, J2–3 10.5 Hz, H-2 Gal), 4.93 (d, 1 H,
H-1 Glc, J1–2 8.0 Hz), 4.9 (dd, 1 H, J3–4 3.7,
J2–3 10.3 Hz, H-3 Gal), 4.82 (t, 1 H, J3–4 ꢀJ4–
5 9.0 Hz, H-3 Glc), 4.68 (d, 1 H, H-1 CE),
4.42 (d, 1 H, J1–2 7.6 Hz, H-1 Gal), 4.23–3.55
(m, 24 H, H-5 CE, 8×OCH2, H-4, -5, -6, -6%
Glc, H-5, -6, -6% Gal,), 3.61 (t, 1 H, H-3 CE),
3.36 (dd, 1 H, J1–2 3.5, J2–3 9.5 Hz, H-2 CE),
Methyl (2,3,4,6-tetra-O-acetyl-i- -galac-
D
topyranosyl)-(1“4)-[2,3-b](11,12-benzo-1,4,7,-
10,13,16 - hexaoxacyclooctadeca - 11 - ene) - 6-
bromo-2,3,6-trideoxy-i- -galactopyranoside
D
(29).—The same procedure was used as for
the synthesis of the disaccharide 20. From 75
mg (0.15 mmol) of acceptor 12 with 2 equiv of
the donor 4, after 16 h of reaction at rt, usual
work-up, and chromatography on silica gel
(1:1“9:1 EtOAc–n-hexane) 64 mg (52%) of
the disaccharide 29 was isolated as a pale-yel-
low wax: [h]D +18.7° (c 1.0, CHCl3); 1H
NMR (CDCl3): l 6.9 (bs, 4 H, catechol), 5.35
(d, 1 H, H-4 Gal), 5.2 (dd, 1 H, J4–5 B1.5 Hz,
H-2 Gal), 5.02 (dd, 1 H, J2–3 10.5, J3–4 3.5 Hz,
H-3 Gal), 4.64 (d, 1 H, J1–2 7.5 Hz, H-1 Gal),
4.14 (d, 1 H, H-1 CE), 4.25–3.64 (m, 22 H,
8×OCH2, H-5, -6, -6% CE, H-5, -6, -6% Gal),
3.53 (dd, 1 H, H-3 CE), 3.5 (s, 3 H, OCH3),
3.47 (t, 1 H, J3–4 ꢀJ4–5 8.0 Hz, H-4 CE), 3.29
(t, 1 H, J1–2 ꢀJ2–3 7.0 Hz, H-2 CE), 2.12,
2.03, 2.02, 1.97 (4 s, each 3 H, 4×OAc),
EIMS: m/z Calcd for C35H49BrO18 836. Found
3.32 (s, 3 H, OCH3), 3.21 (t, 1 H, J3–4 ꢀJ4–5
9
Hz, H-4 CE), 2.11 (s, 3 H, OAc), 2.04 (s, 3 H,
OAc), 2.0 (bs, 12 H, 4×OAc), 1.93 (s, 3 H,
OAc), 1.14 (d, 3 H, J5–6 6.0 Hz, CH3); ESMS:
m/z Calcd for C47H66O26 1047. Found 1070
[M+Na]+.
Methyl
benzo-1,4,7,10,13,16-hexaoxacyclooctadeca-11-
ene) - 2,3,6 - trideoxy - h - - glucopyranoside
i-lactosyl-(1“4)-[2,3-b](11,12-
D
(31).—To a solution of the trisaccharide 30
(0.233 g, 0.22 mmol) in abs MeOH (15 mL)
under argon was added NaOMe (ꢀ25 mg)
and the mixture was stirred at rt until TLC
(EtOAc) showed that the Zemple´n deacetyla-
tion was complete (2 h). The mixture was
demineralized for 15 min with Dowex (H+)
cation-exchange resin (ꢀ0.8 mL) and filtered.
The beads were rinsed with MeOH and sol-
vents evaporated under reduced pressure to
yield 31 (171 mg, 99%) as a white solid: mp
138–140 °C (MeOH); [h]D +33.5° (c 0.2,
79
+
81
+
’
’
836 [ BrM] and 838 [ BrM] .
Methyl (2,2%,3,3%,4%,6,6%-hepta-O-acetyl-i-
lactosyl)-(1“4)-[2,3-b](11,12-benzo-1,4,7,10,-
13,16 - hexaoxacyclooctadeca - 11 - ene) - 2,3,6-
trideoxy-h- -glucopyranoside (30).—To a so-
D
lution of the acceptor 14 (0.84 g, 1.96 mmol)
and donor 5 (2.14 g, 1.4 equiv) in CH2Cl2 (30
1
,
mL) was added crushed 4 A MS (ꢀ1 g) and
DMF); H NMR (1:1 CD3CN–D2O): l 7.0
the suspension was magnetically stirred under
argon for 30 min at rt. A solution of
trimethylsilyl triflate (80 mL, ꢀ0.2 equiv) in
CH2Cl2 (10 mL) was then added dropwise
over 45 min. The reaction was monitored by
TLC (EtOAc), a new portion of 5 (0.77 g, 0.5
equiv) being added after 22 h of stirring. The
reaction was definitively stopped after 46 h
(total time) by addition of abs pyridine (3
mL). Usual work-up and chromatography on
a silica gel column (EtOAc) afforded a par-
tially deprotected trisaccharide according to
1H NMR. Therefore, the material was reacety-
lated in 1:9 pyridine–Ac2O (10 mL) at rt for
(bs, 4 H, catechol), 4.75 (d, 1 H, J1–2 3.0 Hz,
H-1 CE), 4.44 (d, 1 H, J1–2 7.5 Hz, H-l Gal),
4.08 (t, 4 H, 2×OCH2), 4.0–3.3 (m, 30 H),
3.28 (s, 3 H, OCH3), 3.18 (t, 1 H, J3–4 ꢀJ4–5
8.5 Hz, H-4 EC), 1.23 (d, 3 H, J5–6 6.0 Hz,
CH3); 13C NMR (1:1 CD3CN–D2O): l 149.0
(C-1, -2 catechol), 122.7 (C-4, -5 catechol),
115.1, 114.9 (C-3, -6 catechol), 103.95 (C-1
Gal), 103.1 (C-1 Glc), 97.7 (C-1 CE), 72.7,
71.5, 71.05, 70.4, 70.0, 69.95, 69.7, 69.5 (8×
OCH2), 82.6, 79.8, 79.6, 75.3 (C-2, -3, -5, -4
Glc), 80.6, 73.5, 71.8, 69.4 (C-2, -3, -4, -5 Gal),
76.2, 75.8, 74.4, 67.5, (C-4, -5, -3, -2 CE), 61.9,
61.3 (C-6 Glc, C-6 Gal), 55.5 (OCH3), 17.7

158
B. Dumont-Hornebeck et al. / Carbohydrate Research 320 (1999) 147–160
H-6% CE), 3.48 (dd, 1 H, J1–2 3.5, J2–3 ꢀJ3–4
8.0 Hz, H-2 CE), 3.44 (s, 3 H, OCH3), 3.41
(dd, 1 H, J5–6 2.0, J6–6% 9.0 Hz, H-6), 2.17–
(C-6 CE); FABMS: m/z Calcd for C33H52O19:
752. Found 775 [M+Na]+; Anal. Calcd for
C33H52O19 C, 52.66; H, 6.96. Found C, 52.45;
H, 6.80; tr (HPLC) 16.4 min (80:20 H2O–
CH3CN as eluent).
1.95 (m, 21 H, 7×OAc); EIMS Calcd for
+
’
C47H65N3O26 1087. Found 1087 [M] .
Methyl (2,2%,3,3%,4%,6,6%-hepta-O-acetyl-i-
lactosyl)-(1“4)-6-amino-[2,3-b](11,12-benzo-
1,4,7,10,13,16 - hexaoxacyclooctadeca - 11-ene)-
Methyl (2,2%,3,3%,4%,6,6%-hepta-O-acetyl-i-
lactosyl)-(1“4)-[2,3-b](11,12-benzo-1,4,7,10,-
13,16-hexaoxacyclooctadeca-11-ene)-6-bromo-
2,3,6-trideoxy-h-
D
-glucopyranoside
(32).—
2,3,6-trideoxy-h-
D
-glucopyranoside
(34).—
The same procedure was used as for the syn-
thesis of the disaccharide 20. From 0.45 g
(0.887 mmol) of acceptor 10 with 1.385 g (2
equiv) of the donor 5, after 24 h of reaction at
rt, usual work-up, and chromatography on
silica gel (1:1 EtOAc–n-hexane), was isolated
ꢀ0.60 g of partially deacetylated trisaccharide
The same procedure was used as for the syn-
thesis of the disaccharide 25. From 70 mg (64
mmol) of the azide 33 after 18 h of reaction at
rt, usual work-up, and chromatography on
silica gel (EtOAc“19:1 EtOAc–EtOH) was
isolated 20 mg (30%) of the trisaccharide 34 as
a yellow–orange gum: [h]D +55.8° (c 0.8,
1
1
as a gum according to H NMR. Peracetyla-
CHCl3); H NMR (CDCl3): l 6.87 (bs, 4 H,
tion of this mixture, as for 30, afforded the
trisaccharide 32 (0.549 g, 55%) as a colorless
catechol), 5.37 (d, 1 H, J1–2 7.0 Hz, H-4 Gal),
5.2–4.85 (m, 4 H Lac), 4.78 (d, 1 H, J1–2 3.5
Hz, H-1 CE), 4.48 (d, 1 H, J1–2 8.0 Hz, H-1
1
wax: [h]D +44.1° (c 1.0, CHCl3); H NMR
(CDCl3): l 6.87 (bs, 4 H, catechol), 5.5–4.9
(m, 5 H, Lac), 4.83 (d, 1 H, H-1 EC), 4.79 (t,
1 H, Lac), 4.47 (d, 1 H, J1–2 8.0 Hz, H-1 Gal),
4.43 (d, 1 H, J1–2 8.0 Hz, H-1 Glc), 4.2–3.6
(m, 25 H, 8×OCH2, H-3, -4, -5 CE, H-5, -6,
-6% Gal, H-5, -6, -6% Glc), 3.48–3.33 (m, 5 H,
J5–6% ꢀ5, J1–2 3.5 Hz, H-6% CE, OCH3, H-2
CE), 3.28 (dd, 1 H, J6–6% 11.5, J5–6 8.0 Hz, H-6
CE), 2.15–1.9 (m, 21 H, 7×OAc), ; EIMS:
m/z Calcd for C47H65BrO26 1124. Found 1042
Gal), 4.3–3.5 (m, 25 H), 3.42 (t, 1 H, J3–4 ꢀ
J4–5 9 Hz, H-4 CE), 3.4 (s, 3 H, OCH3), 3.33
(dd, 1 H, J1–2 3.5, J2–3 9.5 Hz, H-2 CE), 2.15
(s, 3 H, OAc), 2.12 (s, 3 H, OAc), 2.06 (bs, 12
H, 4×OAc), 1.95 (s, 3 H, OAc), 1.8 (bs, 2 H,
NH2);
C47H67NO26Na 1084.3849. Found 1084.3855.
Methyl (2,3,4,6-tetra-O-acetyl-i- -glucopyr-
LSIHRMS:
m/z
Calcd
for
D
anosyl)-(1“4)-[2,3-b](11,12-benzo-1,4,7,10,-
13,16-hexaoxacyclooctadeca-11-ene)-6-bromo-
81
+
’
[ BrM−2C2H2O] .
2,3,6-trideoxy-h-
D-glucopyranoside
(35).—
Methyl (2,2%,3,3%,4%,6,6%-hepta-O-acetyl-i-
lactosyl)-(1“4)-6-azido-[2,3-b](11,12-benzo-
1,4,7,10,13,16-hexaoxacyclooctadeca-11-ene)-
The same procedure was used as for the syn-
thesis of 20 except that 2 equiv of the donor 6
(4.07 g) and catalyst ((Et)2O·BF3, 1.0 mL)
were engaged. After 4 h of reaction at rt from
2.10 g of 10 (4.13 mmol), similar work-up,
and chromatography (1:1 EtOAc–n-hexane)
on silica gel: 1.843 g (53%) of 35 as a white
solid: mp 141–142 °C (i-PrOH), [h]D +35.5°
2,3,6-trideoxy-h-
D
-glucopyranoside
(33).—
The same procedure was used as for the syn-
thesis of the disaccharide 20. From 0.47 g (1.0
mmol) of the acceptor 16 with 0.97 g (1.2
equiv) of the donor 5, in the presence of 1.2
equiv (140 mL) of (Et)2O·BF3, after 24 h of
reaction at rt, usual work-up, and chromatog-
raphy on silica gel (1:1 EtOAc–n-hexane),
was isolated 0.15 g (14%) of the trisaccharide
33 as a pale-yellow wax: [h]D +47.8° (c 0.5,
1
(c 1, CHCl3); H NMR (CDCl3): l 6.89 (bs, 4
H, catechol), 5.21–5.05 (m, 2 H, H-2, -3 Glc),
4.97–4.92 (m, 2 H, H-1,-4 Glc), 4.8 (d, 1 H,
H-1 EC), 4.3 (dd, 1 H, J5–6 4.0, J6–6% 12.0 Hz,
H-6 Glc), 4.23–4.02 (m, 7 H, 3×OCH2 CE,
H-5 Glc), 3.98–3.75 (m, 12 H, 5×OCH2, H-5
CE, H-6% Glc), 3.7 (t, 1 H, H-3 CE), 3.68 (dd,
1 H, J5–6% 7.0 Hz, H-6% CE), 3.65 (t, 1 H,
J3–4ꢀJ4–5 9.5 Hz, H-4 CE), 3.53 (dd, 1 H,
J5–6 4.0, J6–6% 11.0 Hz, H-6 CE), 3.41 (s, 3 H,
OCH3), 3.39 (dd, 1 H, J1–2 3.0, J2–3 9.5 Hz,
H-2 CE), 2.13–1.97 (4 s, each 3 H, 4×OAc);
1
CHCl3); IR (NaCl) w 2100 cm−1 (N3), H
NMR (CDCl3): l 6.9 (bs, 4 H, catechol),
5.4–4.9 (m, 6 H, Lac), 4.82 (d, 1 H, H-1 CE),
4.47 (d, 1 H, J1–2 8.0 Hz, H-1 Gal), 4.43 (d, 1
H, J1–2 8.5 Hz, H-1 Glc), 4.3–3.6 (m, 25 H,
8×OCH2, H-3, -4, -5 CE, H-5, -6, -6% Gal,
H-5, -6, -6% Glc), 3.57 (1 H, dd, J5–6% 6.0 Hz,

B. Dumont-Hornebeck et al. / Carbohydrate Research 320 (1999) 147–160
159
was complete after 2 h. The solvent was evap-
orated, the residue dissolved in CH2Cl2 (70
mL), washed twice with water (20 mL), dried,
concentrated, and chromatographed (1:1
EtOAc–n-hexane) to yield the disaccharide 37
(0.143 g, 65%) as a white foam: [h]D+37.5° (c
EIMS: Calcd m/z for C35H49BrO18 836. Found
79
+
81
+
’
’
836 [ BrM] and 838 [ BrM] .
Methyl (2,3,4,6-tetra-O-acetyl-i- -glucopyr-
D
anosyl) - (1“4) - 6 - azido - [2,3-b](11,12-benzo-
1,4,7,10,13,16-hexaoxacyclooctadeca-11-ene)-
2,3,6-trideoxy-h- -glucopyranoside (36).—To
D
1
1, CHCl3); H NMR (CDCl3): l 7.9–7.65 (m,
a solution of 0.40 g (0.477 mmol) of bromide
35 in abs DMF (10 mL) under argon were
added NaN3 (62 mg, 2 equiv) and NH4Cl (100
mg, ꢀ4 equiv). The mixture was then heated
at 130/135 °C for 2 h so that TLC (EtOAc)
showed no more starting material. The solvent
was evaporated and the residue dissolved in
CH2Cl2 (50 mL), washed with water (2×20
mL), dried, and concentrated to yield, after
chromatography, the azide 36 (0.296 g, 78%)
as a colorless gum which crystallized on stand-
ing: mp 63–65 °C (EtOAc); [h]D +52.1° (c 1,
4 H, Ar), 6.9 (bs, 4 H, catechol), 5.02 (d, 1 H,
J1–2 8.0 Hz, H-1 Glc), 5.22–4.95 (m, 3 H, H-2,
-3, -4 Glc), 4.65 (d, 1 H, H-1 CE), 4.33 (dd, 1
H, J5–6 4.0, J6–6% 12.0 Hz, H-6% Glc), 3.98 (m,
1 H, J5–6 3.5, J5–6% 8.0 Hz, H-5 CE), 4.25–3.7
(m, 20 H, 8×OCH2, H-6, -6% CE, H-5, -6
Glc), 3.68 (t, 1 H, H-3 CE), 3.53 (t, 1 H,
J3–4ꢀJ4–5 9.0 Hz, H-4 CE), 3.35 (dd, 1 H,
J1–2 3.5, J2–3 9.0 Hz, H-2 CE), 3.1 (s, 3 H,
OCH3); 2.15–2.0 (m, 12 H, 4×OAc); EIMS:
m/z Calcd for C43H53NO20 903. Found 904
[M+H]+.
1
CHCl3); IR (KBr): w 2099 cm−1 (N3); H
NMR (CDCl3): l 6.89 (bs, 4 H, catechol),
5.2–4.85 (m, 4 H, H-1, -2, -3, -4 Glc), 4.77 (d,
1 H, H-1 CE), 4.27 (dd, 1 H, J5–6 4.0, J6–6%
12.5 Hz, H-6% Glc), 4.22–3.6 (m, 22 H, 8×
OCH2, H-3, -4, -5, -6% CE, H-5, -6 Glc), 3.39
(dd, 1 H, J1–2 3.5, J2–3 9.0 Hz, H-2 CE), 3.38
(s, 3 H, OCH3), 3.23 (dd, 1 H, J5–6 3.5, J6–6%
13.0 Hz, H-6 CE), 2.08–1.95 (4 s, each 3 H,
4×OAc); 13C NMR (CDCl3): l 170.8, 170.3,
169.6, 169.5 (CH3CO2), 148.9, 148.8 (C-1, -2
catechol), 121.7, 121.5 (C-4, -5 catechol),
114.2, 114.0 (C-3, -6 catechol), 100.5 (C-1
Glc), 97.6 (C-1 EC), 80.7 (C-3 CE), 80.6 (C-4
EC), 79.7 (C-5 EC), 78.1 (C-2 EC), 73.2 (C-3,
-5 Glc,), 72.7 (OCH2), 72.2 (C-5 EC), 71.9
(OCH2), 71.7 (C-4 EC), 70.9, 70.8, 70.0, 69.8,
69.6 (OCH2), 69.5 (C-2 Glc), 69.3 (OCH2),
68.0 (C-4 Glc), 61.9 (C-6 Glc), 55.4 (OCH3),
50.6 (C-6 EC), 20.8, 20.7, 20.6 (CH3CO2);
Methyl (2,3,4,6-tetra-O-acetyl-i- -glucopyr-
D
anosyl) - (1“4) - 6 - amino-[2,3-b](11,12-benzo-
1,4,7,10,13,16 - hexaoxacyclooctadeca - 11-ene)-
2,3,6-trideoxy-h-
D-glucopyranoside
(38).—
The same procedure was used as for the syn-
thesis of 25 except that a 1:1 mixture of
MeOH–EtOAc (20 mL) was used as the sol-
vent. From 0.200 g (0.25 mmol) of azide 36 in
the presence of 0.100 g of 10% Pd/C after 14
h of reaction at rt under 780 Torr of H2, was
obtained after usual work-up and chromatog-
raphy on deactivated silica (1% NEt3) 0.112 g
(58%) of the amine 38 as a yellow–orange
1
gum: [h]D +23.0° (c 1, CHCl3); H NMR
(CDCl3): l 6.9 (bs, 4 H, catechol), 5.2–4.9 (m,
3 H, H-2, -3, -4 Glc), 4.85 (d, 1 H, H-1 Glc,
J1–2 8.0 Hz), 4.73 (d, 1 H, H-1 CE), 4.3–3.62
(m, 22 H, 8×OCH2, H-5, -6, -6% CE, H-5, -6,
-6% Glc), 3.51 (t, 1 H, H-3 CE), 3.4 (t, 1 H,
J3–4ꢀJ4–5 9.0 Hz, H-4 CE), 3.38 (dd, 1 H,
J1–2 3.5, J2–3 9.0 Hz, H-2 CE), 3.37 (s, 3 H,
OCH3), 2.15–2.0 (4 s, each 3 H, 4×OAc),
1.27 (bs, 2 H, NH2); EIMS: m/z Calcd for
C35H51NO18 773. Found 774 [M+H]+.
EIMS: m/z Calcd for C35H49N3O18 799.
+
’
Found 799 [M] .
Methyl (2,3,4,6-tetra-O-acetyl-i- -glucopyr-
D
anosyl)-(1“4)-[2,3-b](11,12-benzo-1,4,7,10,-
13,16 - hexaoxacyclooctadeca - 11 - ene) - 2,3,6-
trideoxy-N-phthalimido-h-
D
-glucopyranoside
Methyl i- -glucopyranosyl-(1“4)-6-amino-
D
(37).—The same procedure was used as for
the synthesis of the acceptor 17. To a stirred
solution of the bromide 35 (0.23 g, 0.274
mmol) in abs DMF (10 mL) was added potas-
sium phthalimide (76 mg, 1.5 equiv) and the
reaction mixture was heated to 135 °C. The
reaction was monitored by TLC (EtOAc) and
[2,3 - b](11,12 - benzo - 1,4,7,10,13,16-
hexaoxacyclooctadeca-11-ene)-2,3,6-trideoxy-
h- -glucopyranoside (39).—A first attempt at
Gabriel synthesis from the phthalimide 37
failed. Thus, the same procedure was used as
for the synthesis of 26. From 100 mg (0.129
mmol) of the acetylated precursor 38 after 24
D

160
B. Dumont-Hornebeck et al. / Carbohydrate Research 320 (1999) 147–160
[6] T. Tsukida, Y. Hiramatsu, H. Tsujishita, T. Kiyoi, M.
Yoshida, K. Kurokawa, H. Moriyama, H. Ohmoto, Y.
Wada, T. Saito, H. Kondo, J. Med. Chem., 40 (1997)
3534–3541, and refs cited therein.
[7] (a) H. Ahmed, A. Sharma, R.A. DiCioccio, H.J. Allen,
J. Mol. Recognition, 5 (1992) 1–8. (b) A. Chakrabarti,
S.K. Podder, J. Mol. Recognition, 5 (1992) 69–73.
[8] B. Dumont, M.-F. Schmitt, J.-P. Joly, Tetrahedron Lett.,
35 (1994) 4773–4776.
[9] M.-F. Schmitt-Dubessy, Univ. D. Thesis, Nancy, 1997.
[10] M. Hendrix, P.B. Alper, E. Scott Priestley, C.-H. Wong,
Angew. Chem., Int. Ed. Engl., 36 (1997) 95–98.
[11] M.S. Wadhwa, K.G. Rice, J. Drug Targeting, 3 (1995)
111–127.
[12] S. Al-Mahmood, S. Colin, R. Bonaly, J. Biol. Chem., 266
(1991) 20882–20887. All the biological results are sum-
marized in Part 2 [25].
[13] Part of this work was presented previously; see: (a) B.
Dumont, J.-P. Joly, Y. Chapleur, A. Marsura, Bioorg.
Med. Chem. Lett. 4 (1994) 1123–1126. (b) B. Dumont,
J.-P. Joly, Y. Chapleur, J. Coulon in E. Van Driessche,
P. Rouge´, S. Beeckmans, T.C. Bøg-Hansen (Eds.),
Lectins: Biology, Biochemistry, Clinical Biochemistry,
Textop, Hellerup, Denmark, Vol. 11, 1996, pp. 285–289.
[14] (a) J.-R. Pougny, P. Sinay¨, Tetrahedron Lett., 45 (1976)
4073–4076. (b) J.-R. Pougny, J.-C. Jacquinet, M. Nassr,
D. Duchet, M.-L. Milat, P. Sinay¨, J. Am. Chem. Soc., 99
(1977) 6762–6763.
h stirring were isolated 112 mg (\99%) of the
target compound 39 as a pale-yellow gum:
1
[h]D+16.6° (c 0.2, H2O); H NMR (D2O): l
7.03–6.93 (m, 4 H, catechol), 4.88 (d, 1 H,
H-1 CE), 4.41 (d, 1 H, J1–2 7.7 Hz, H-1 Glc),
4.14 (bt, 4 H, 2×OCH2), 4.0–3.3 (m, 22 H,
H-3, -5, -6, -6 CE, H-2, -3, -5, -4, -6, -6% Glc,
6×OCH2), 3.3 (dd, 1 H, J1–2 3.4 Hz, J2–3 9.0
Hz, H-2 CE), 3.29 (s, 3 H, OMe), 3.19 (t, 1 H,
13
J3–4 ꢀJ4–5 8.7 Hz, H-4 CE); C NMR (D2O):
l 148.9 (C-1, -2 catechol), 122.7 (C-4, -5 cate-
chol), 115.0, 114.8 (C-3, -6 catechol), 102.5
(C-1 Glc), 98.6 (C-1 CE), 71.1, 70.9, 70.8,
69.8, 69.7, 69.2 (OCH2), 80.2, 79.2, 76.8, 76.3,
76.2, 74.4, 70.1, 69.4 (C-4, -5, -3, -2 CE, C-5,
-4, -3, -2 Glc), 61.5 (C-6 Glc), 55.3 (OCH3),
41.5 (C-6 CE); LSIHRMS: m/z Calcd for
C27H43NO14Na 628.2581. Found 628.2577
[M+Na]+; tr (HPLC) 14.7 min (H2O as elu-
ent).
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