First intramolecular aglycon delivery onto a D-fucofuranosyl entity for the synthesis of α-D-fucofuranose-containing disaccharides

Article abstract of DOI:10.1002/ejoc.200390184

Intramolecular aglycon delivery was performed for the first time starting from n-pentenyl glycofuranoside as a donor. p-Methoxybenzyl-assisted aglycon transfer required very mild reaction conditions and was promoted by N-iodosuccinimide without assistance of any Lewis acid catalyst. As a result, rare α-D-fucofuranose-containing disaccharides were obtained. Moreover, structure elucidation led to the conclusion that an N-succinimidyl residue was still present in the resulting products. Wiley-VCH Verlag GmbH & Co, KGaA, 69451 Weinheim, Germany, 2003.

Full text of DOI:10.1002/ejoc.200390184

FULL PAPER
First Intramolecular Aglycon Delivery onto a
D
-Fucofuranosyl Entity for the
Synthesis of α- -Fucofuranose-Containing Disaccharides
D
[a]
[a]
[a]
[a]
`
Muriel Gelin, Vincent Ferrieres,* Martine Lefeuvre, and Daniel Plusquellec
Keywords: Fucofuranosides / Glycosylation / Hexofuranosides / n-Pentenyl glycosides
Intramolecular aglycon delivery was performed for the first
time starting from n-pentenyl glycofuranoside as a donor. p-
Methoxybenzyl-assisted aglycon transfer required very mild
reaction conditions and was promoted by N-iodosuccinimide
without assistance of any Lewis acid catalyst. As a result, rare
Moreover, structure elucidation led to the conclusion that an
N-succinimidyl residue was still present in the resulting
products.
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2003)
α-
D-fucofuranose-containing disaccharides were obtained.
Introduction
In this context, we became interested in the preparation
of extremely rare fucofuranosides. Unlike mammalian cells
that biosynthesize -fucopyranose-containing oligosacchar-
ides, microorganisms such as Chaetoceros curvisetus[8a] and
Eubacterium saburreum[8c] are able to incorporate the -fu-
cose enantiomer Ϫ in the furanose configuration Ϫ into
heterogeneous polysaccharides. The latter bacterium has
been detected in approximal dental plaque,[8d] and its T19
strain may settle in the human oral cavity and produce a
cell-surface polysaccharide antigen of unique chemical
composition.[8c] The structural backbone of this heterogly-
can 1 is built of a linear chain of branched β--glycero--
galactoheptopyranosyl residues with a difucofuranoside as
an antenna (Figure 1). Moreover, both fucofuranosyl enti-
ties are characterized by an α-anomeric configuration.
Among the numerous carbohydrates involved in biologi-
cal pathways, -fucose holds a special and prominent place.
In fact, natural oligosaccharides containing -fucopyrano-
syl residues are of particular interest for determinants of A
and H blood groups[1] and for Lewis derivatives.[2] There-
fore, chemical synthesis and structureϪactivity relation-
ships of compounds that embody this 6-deoxy sugar have
been widely investigated. In our laboratory, we have devel-
oped a program directed toward the preparation of glyco-
conjugates bearing uncommon hexofuranosyl entities.[3]
Generally speaking, hexofuranosides are found in archaeb-
acteriae[4] that are able to survive under extreme conditions,
or as membrane components of various pathogenic micro-
organisms[5,6] wherein they act as epitopes and warrant cell
survival. Processes by which galacto-, gluco-,[7] and fucofur-
anosides,[8] and their conjugates, are biosynthesized or
metabolized have not yet been clearly elucidated. Neverthe-
less, the biological action and the structure of enzymes,
such as the uridine diphosphogalactopyranose mutase[9]
and some galactofuranosidases,[10] are currently being stud-
ied. To the best of our knowledge, mammalian hexofurano-
conjugates have yet to be identified. Consequently, the hexo-
furanose-containing conjugates are expected to be anti-
genic,[6] which offers interesting prospects for the design of Figure 1. Polysaccharide antigen 1 produced by the T19 strain of
new pharmacophores and of new molecular tools for enzy-
E. saburreum
matic studies.
To study the chemical synthesis of the nonreducing end
[a]
´
Ecole Nationale Superieure de Chimie de Rennes, UMR CNRS
of this backbone structure, we first designed a simplified
trisaccharide-mimicking compound 2 (Scheme 1) in which
the heptaoside was replaced by a galactopyranoside bearing
an ω-amino chain for further linkage to a carrier. The 1,2-
cis relationship, however, was preserved for the furanosyl
entities. The difficulties connected with this endeavor are (i)
`
´
6052 Syntheses et Activations de Biomolecules, Institut de
Chimie de Rennes,
´ ´
Avenue du General Leclerc, 35700 Rennes, France
Fax: (internat.) ϩ 33-2/23238046
E-mail: vincent.ferrieres@ensc-rennes.fr
Synkem,
[b]
ˆ
47 Rue de Longvic, B. P. 50, 21301 Chenove Cedex, France
1285
Eur. J. Org. Chem. 2003, 1285Ϫ1293  2003 WILEY-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim 1434Ϫ193X/03/0407Ϫ1285 $ 20.00ϩ.50/0

`
M. Gelin, V. Ferrieres, M. Lefeuvre, D. Plusquellec
FULL PAPER
Scheme 1. Targeted mimic structures and retrosynthetic approach
the glycosylation of the less reactive axial hydroxy group 4- and deprotection steps, even under moderately acidic con-
OH of the -galactopyranosyl unit, (ii) the preparation of ditions.
new -fucofuranosyl donors, and (iii) the preparation of α-
linked furanosides (i.e., 1,2-cis-furanosides). We anticipated
that the glycosylation reaction could be more easily per-
formed using an intramolecular aglycon delivery (IAD) ap-
proach.[11] The acetal approach requires the discrimination
of the 2-position on both the acceptor and the donor and,
Figure 2. Increased nucleophilicity of 2-OH by intramolecular hy-
thus, the preparation of the disaccharidic acceptor 3 and
the fucofuranosyl donor 4. This disaccharide 3 may also be
obtained from the same donor 4 and the galactopyranoside
5. Therefore, we have synthesized the n-pentenyl fucofur-
anoside 4 bearing a free 2-OH group, which could be pre-
pared from the corresponding galactofuranoside 6, and the
glycosyl acceptor 5. We describe herein the preparation of
new fucofuranosyl donors, α--Fucf-(1,4)-β--Galp and α-
-Fucf-(1,6)-α--Glcp disaccharides, and mechanistic con-
siderations to explain the formation of unexpected inter-
mediates obtained during the aglycon transfer.
drogen bonding
On this consideration, although n-pentenyl glycosides
have never been used in an IAD approach,[11d] we were at-
tracted towards these widespread compounds as potential
donors[15,16] since (i) they allow protecting group manipu-
lations and (ii) α--galactofuranosides can be synthesized
stereospecifically in one step from free galactose.[17] Thus,
we prepared the n-pentenyl α--galactofuranoside (6) by 1-
O-alkylation of unprotected -galactose with 4-penten-1-yl
bromide in N,NЈ-dimethylpropyleneurea (DMPU) in the
presence of sodium iodide (Scheme 2). Owing to its high
solubility in water, the resulting galactofuranoside was puri-
Results and Discussion
Among the few -fucofuranosides previously pre- fied by a quantitative peracetylation/deacylation sequence.
pared,[10c,12] no 1,2-cis derivatives have been specifically Subsequent monotritylation of the primary hydroxy
synthesized. The IAD concept generally involves the intro- group, using (4-methoxyphenyl)diphenylmethyl chloride
duction of an orthogonal protecting group at 2-O on the (MMTrCl) in the presence of sodium hydride and a cata-
glycosyl donor. Considering our strategy starting from - lytic amount of 4-(dimethylamino)pyridine (DMAP),
galactofuranosides, first we needed the protection of the afforded 7. As we expected, 7 was pivaloylated specifically
primary hydroxy group by a sterically demanding group. at position 2 in the presence of triethylamine, and 2,6-dipro-
We then expected that discrimination between the three re- tected galactofuranoside 8 was isolated in 77% yield. The
maining secondary functions could be attained by the in- free hydroxy groups of 8 were then benzylated under basic
creasing 2-O nucleophilicity by an intramolecular hydrogen conditions. The resulting product was not isolated, however,
bond between[13] 2-OH and an exocyclic heteroatom at C-1 since simple neutralization by addition of IR-120 resin
(Figure 2). On this assumption, donors characterized by a (Hϩ form) allowed in situ detritylation and gave 9. After
relative 1,2-cis configuration were required. Although α-thio- efficient 6-O-tosylation, reduction of 10 was smoothly per-
furanosides are readily available,[14] ethyl 1-thio-α--galac- formed with sodium borohydride,[18] followed by a one-pot
tofuranoside proved to be unsuitable for further protection removal of the ester protecting group with sodium meth-
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Eur. J. Org. Chem. 2003, 1285Ϫ1293

Intramolecular Aglycon Delivery onto a D-Fucofuranosyl Entity
FULL PAPER
oxide. This sequence afforded 4 in 36% yield for the last to estimate the nucleophilic potential of 5 toward our fucof-
five steps.
uranosyl donor. Thus, fucoside 4 was treated with p-meth-
oxybenzyl chloride (PMBCl) to afford 15 (Scheme 4) bear-
ing a nonparticipating group at 2-O also suitable for further
tethering. The selectivity of the coupling reaction promoted
by N-iodosuccinimide (NIS) depended on the nature of
Lewis catalyst. Thus, the disaccharide 16 presenting a β-
interglycosidic bond was obtained diastereospecifically in
the presence of trimethylsilyl trifluoromethanesulfonate
(TMSOTf) and isolated in 33% yield, while the milder
Lewis acid Sn(OTf)2 gave an inseparable α,β-mixture of 16
in a slightly lower yield (25%) with the α-isomer being the
major fucofuranoside. These results showed that the 1,2-cis
anomer could be obtained under mild conditions. The α-
furanosyl configuration was established on the basis of the
13C NMR chemical shift of the anomeric center of the non-
reducing fucosyl residue. In fact, α-O-linked furanosides
give resonances at lower fields than do the corresponding
β-products.[21] Our observations were consistent with this
assignment since a difference in chemical shifts of 5.8 ppm
Scheme 2. Synthesis of α--fucofuranoside 4: (a) 4-penten-1-yl bro-
mide, NaH, DMPU; Ac2O, Pyr; MeONa, MeOH (37%); (b)
MMTrCl, DMAP, Pyr (75%); (c) PivCl, Pyr (77%); (d) BnBr,
TBAI, NaH, CH2Cl2; IR 120 (Hϩ form) (85%); (e) TsCl, Et3N,
DMAP, CH2Cl2 (94%), (f) NaBH4, DMF; MeONa, MeOH (77%)
was obtained for C-1b (δ16α ϭ 101.2 ppm; δ16β
107.0 ppm).
ϭ
Next we considered the synthetic route to galactopyrano-
side acceptor 5 (Scheme 3). The preparation began with the
galactosylation of the N-protected aminohexanol 11.[19]
Amongst peracetylated galactopyranosyl donors (i.e., the
bromide, trichloroacetimidate, and thioglycoside deriva-
tives) best results were obtained with the known trichlo-
roacetimidate 12.[20] It is interesting to note that the use of
tin() bis(trifluoromethanesulfonate) [Sn(OTf)2] as a very
mild Lewis acid catalyst provided a fine tuning between the
reactivities of both substrates 11 and 12 and resulted in the
optimal coupling yield. Finally, the glycosylation procedure
was significantly improved by a one-pot transesterification/
deprotection step under Zemplen conditions so that the
yield of this two-step sequence was raised to 87%. Ensuing
4,6-O-benzylidenation with benzaldehyde dimethylacetal in
the presence of camphorsulfonic acid (CSA), followed by
standard benzylation, yielded the fully O- and N-protected
compound 14. Finally, selective opening of the benzylidene
ring was performed with sodium cyanoborohydride in the
presence of trifluoromethanesulfonic acid (TfOH) and pro-
vided the target acceptor 5 in 73% yield.
Encouraged by the latter result, we further examined this
approach, this time by connecting the acceptor and donor
through a bifunctional group. The preparation of a silicon-
tethered disaccharide was first performed, but the resulting
silyl acetal unit proved to be chemically too sensitive. There-
fore, our attention was turned to the use of an acetal as
tether; more specifically, a p-methoxybenzyl acetal.[11c] Oxi-
dation of 2-O-PMB fucoside 15 by 2,3-dichloro-5,6-dicy-
ano-p-benzoquinone (DDQ) in the presence of 5 went to
completion slowly, owing to the low reactivity of the axial
hydroxy group of 5. Nevertheless, the alternative route, con-
sisting in oxidation of 4-O-PMB-protected galactopyrano-
side 17 with C-2-unprotected fucofuranosyl donor 4 me-
diated by DDQ, successfully afforded the desired intermedi-
ate 18 (Scheme 5). Although the tether was rather unstable,
18 could be purified by flash chromatography and charac-
terized by 1H and 13C NMR analysis. The structural assign-
ment was based on the notably downfield chemical shift of
the PMB methylene carbon atom (from δ ϭ 73.0 ppm for
17 to δ ϭ 104.5 ppm for 18). Attempted activation of the
pentenyl donor by NIS and a catalytic amount of either
TMSOTf or Sn(OTf)2 resulted in degradation of both the
donor and acetal linkages, with the release of the acceptor
even in the presence of 2,6-di-tert-butyl-4-methylpyridine
(DTBMP). Nevertheless, when using NIS only,[22] p-meth-
oxybenzyl-assisted aglycon delivery occurred efficiently.
After workup and purification, we isolated a disaccharide
whose structure was assigned on the basis of significant sig-
nals in NMR spectra. Structure elucidation was compli-
cated, however, since the creation of a new stereogenic
center was manifested by the splitting of signals. Neverthe-
less, spectral analysis led us to the following observations:
(i) the signals of the n-pentenyl chain had disappeared; (ii)
three 13C NMR signals are present at δ ϭ 104.0/103.9 and
Scheme 3. Synthesis of β--galactopyranoside 5: (a)
HO(CH2)6NHCbz (11), Sn(OTf)2, CH2Cl2; MeONa, MeOH
(87%); (b) PhCH(OMe)2, CSA, DMF; BnBr, NaH, DMF (54%);
(c) NaBH3CN, TfOH, THF (73%)
Having the fucofuranosyl donor and the acceptor in 99.9 ppm, signifying β-Galp and α-Fucf configurations,
hand, first we investigated intermolecular fucosylation of 5 respectively; (iii) a methoxy group is present (δOCH3 ϭ 55.1
Eur. J. Org. Chem. 2003, 1285Ϫ1293
1287

`
M. Gelin, V. Ferrieres, M. Lefeuvre, D. Plusquellec
FULL PAPER
Scheme 4. Intermolecular glycosidic coupling: (a) PMBCl, NaH, DMF (91%); (b) 5, NIS, Lewis catalyst, CH2Cl2
and 55.2 ppm); (iv) a signal at δ ϭ 176.4 ppm characterizes from fucofuranoside 15 and the glucopyranoside acceptor
carbonyl functions. On the basis of this analysis, we pre- 21 bearing a free primary hydroxy group (Scheme 6). The
sume that aglycon transfer was efficient and that sub- tethering was carried out with DDQ and intramolecular
sequent trapping of the intermediate benzylic cation by the glycosylation occurred smoothly under the action of NIS
poorly nucleophilic N-succinimidyl anion resulted in the over 19 h at room temperature. Once again, the resulting
formation of an O,N-acetal at position 2b. To obtain clear disaccharide 22, isolated in a moderate 21% yield, was
proof of the stereoorientation of the intramolecular glycos- characterized by the presence of an N-succinimidyl residue
ylation, hydrogenolysis of 19 in the presence of catalytic linked to the methylene carbon atom of the PMB group.
amount of palladium acetate was carried out under a high The α-configuration of the reducing entity is suggested by
pressure of hydrogen, then followed by standard peracety- both the chemical shift of C-1a (δC-1a ϭ 97.7 ppm) and a
lation, to yield 20.[23] The chemical structure of this disac- small coupling constant between 1a-H and 2a-H (J1a,2a
ϭ
charide was deduced by high-resolution mass spectrometry 3.6 Hz). When considering the nonreducing carbohydrate
(m/z ϭ 777.3249 for [C34H53NO17 ϩ Na]ϩ) and from the residue, the similar chemical shifts for C-1b in fucofuranos-
1
correlated H-13C signals at δ ϭ 5.14 ppm and 102.1 ppm, ides 22 (δC-1b ϭ 100.5 ppm) and fucofuranosides previously
respectively. The latter value, quite different from that ob- synthesized during this study indicate the same α-configura-
tained for 16β (δC-1b ϭ 107.0 ppm) but similar to 16α (δC- tion for all products. This conclusion was unambiguously
1b ϭ 101.2 ppm), and a high coupling constant between 1b- corroborated by a value for J1b,2b of 4.0 Hz. The presence
H and 2b-H (J1b,2b ϭ 4.6 Hz), are consistent with an α- of a substituted PMB group was established by the specific
1
configuration for the nonreducing fucofuranosyl unit.
signals at δ ϭ 5.65 ppm (s, 1 H) in the H NMR spectrum
and at δ ϭ 80.0 ppm in the 13C NMR spectrum. The large
upfield shift of the benzylic carbon atom signal
(∆δCHPhOMe ϭ δ18 Ϫ δ22 ϭ 34 ppm) is more indicative of
an O,N-acetal than of an O,O-acetal. The succinimidyl moi-
ety was identified owing to its carbonyl and methylene func-
tions. These observations were also corroborated by high-
resolution mass spectrometry. The molecular ion of 22 was
characterized as its sodium adduct (m/z ϭ 1030.4354 for
[C60H65NO3 ϩ Na]ϩ) and as its cation having lost one hy-
drogen atom (m/z ϭ 1006.4380 for [C60H64NO3]ϩ). More-
over, a fragment was measured at 909.4213, corresponding
to the departure of a C4H4NO2 entity. Finally, an abundant
fragment ion at 218.0819, resulting from the release of a
C12H12NO3 residue, enabled us to deduce the presence of a
covalent link between the N-succinimide unit and the
benzylic carbon atom of the PMB group.
Scheme 5. Tethering and intramolecular aglycon transfer: (a)
PMBCl, NaH, DMF (90%); (b) 4, DDQ, CH2Cl2; (c) NIS, CH2Cl2
(34% for two steps); (d) H2 (30 atm), Pd(OAc)2; Ac2O, Py (25%)
To be certain of the proposed structure and mechanism,
we also synthesized a second α-fucofuranose-containing di-
saccharide according to a similar procedure, but starting CH2Cl2; (b) NIS, CH2Cl2 (21% for 2 steps)
Scheme 6. Synthesis of α--fucofuranoside 22: (a) 15, DDQ,
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Intramolecular Aglycon Delivery onto a D-Fucofuranosyl Entity
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Conclusions
reduced pressure. Flash chromatography, eluting with light petro-
leum/ethyl acetate (3:2), gave the peracetylated galactofuranoside
(TLC: Rf ϭ 0.45), which was then deacetylated in methanolic so-
dium methoxide (0.1 , 46 mL, 4.6 mol). Neutralization with IR
120 (Hϩ form) after 2 h at room temperature, filtering, and concen-
tration, provided 4 (2.01 g) in 37% yield. TLC: Rf ϭ 0.53 (dichloro-
methane/methanol, 4:1). [α]D20 ϭ ϩ67.3 (c ϭ 1.0, dichloromethane).
1H NMR (CD3OD): δ ϭ 1.62Ϫ1.74 (m, 2 H, CH2), 2.11Ϫ2.17 (m,
2 H, CH2), 3.46 (dt, J ϭ 9.7, J ϭ 7.1 Hz, 1 H, OCH2CH2), 3.54
(dd, J6a,6b ϭ 12.2, J5,6b ϭ 8.1 Hz, 1 H, 6-Hb), 3.59Ϫ3.65 (m, 1 H,
5-H), 3.63 (dd, 1 H, J5,6a ϭ 4.6 Hz, 6-Ha), 3.71 (dd, J3,4 ϭ 7.1,
J4,5 ϭ 5.6 Hz, 1 H, 4-H), 3.82 (dt, 2J ϭ 9.7, 3J ϭ 6.6 Hz, 1 H,
OCH2CH2), 3.94 (dd, J1,2 ϭ 4.6, J2,3 ϭ 7.6 Hz, 1 H, 2-H), 4.09 (t,
J ϭ 6.3 Hz, 1 H, 3-H), 4.84 (d, 1 H, 1-H), 4.92Ϫ4.97 (m, 1 H,
The synthesis of α--fucofuranose-containing disacchar-
ides was investigated by using an internal glycosylation pro-
cedure. Our strategy relied on the mild activation of an n-
pentenyl fucosyl donor by N-iodosuccinimide. To promote
p-methoxybenzyl-assisted aglycon transfer, any traces of a
Lewis acid other than NIS were prohibited. This mildly ac-
tivated reaction highlights a new mechanistic pathway in
which the poorly nucleophilic N-succinimidyl anion
quenches the benzylic cation after intramolecular aglycon
delivery. This study resulted in the formation and charac-
terization of mixed α-fucofuranosides presenting an O,N-
acetal function at position 2 of the donor moiety. Our ob-
servations underline (i) the requirement for finding tuned
reactive species as glycosyl donors and acceptors in every
glycosylation reaction and (ii) that substantial efforts are
still needed to efficiently synthesize complex glycoconju-
gates bearing 1,2-cis-hexofuranosyl entities.
2
3
CHϭCH2), 5.00Ϫ5.06 (m, 1 H, CHϭCH2), 5.84 (ddt, J4Ј,5Јa
ϭ
16.8, J4Ј,5Јb ϭ 10.2, J3Ј,4Ј ϭ 6.6 Hz, 1 H, CHϭCH2) ppm. 13C NMR
(CD3OD): δ ϭ 30.0, 31.3 [(CH2)2], 64.1 (C-6), 68.9 (OCH2CH2),
74.5 (C-5), 76.3 (C-3), 78.8 (C-2), 83.4 (C-4), 102.8 (C-1), 115.2
(CHϭCH2), 139.5 (CHϭCH2) ppm. C11H20O6 (248.28): calcd. C
53.22, H 8.12; found C 52.83, H 8.21.
α-D-Galactofuranoside 7: DMAP (0.47 g, 3.87 mmol) and (4-meth-
oxyphenyl)diphenylmethyl chloride (11.94 g, 38.7 mmol) were ad-
ded to a solution of compound 6 (3.20 g, 12.9 mmol) in dry pyri-
dine (60 mL). After 2 h, the mixture was diluted with ethyl acetate
and washed with 20% aqueous HCl, a saturated solution of aque-
ous NaHCO3, and finally a saturated solution of aqueous NaCl.
The aqueous layers were extracted twice with ethyl acetate and the
combined organic layers dried (MgSO4) and concentrated. Purifi-
cation by flash chromatography (light petroleum/ethyl acetate, 13:7)
afforded 7 (5.03 g) in 75% yield. TLC: Rf ϭ 0.48 (dichloromethane/
methanol, 9:1). [α]2D0 ϭ ϩ24.5 (c ϭ 1.0, dichloromethane). 1H NMR
(CDCl3 ϩ D2O): δ ϭ 1.64Ϫ1.71 (m, 2 H, CH2), 2.05Ϫ2.11 (m, 2
H, CH2), 3.15 (dd, J6a,6b ϭ 9.6, J5,6b ϭ 6.6 Hz, 1 H, 6-Hb), 3.30
Experimental Section
General Remarks: Dichloromethane and N,N-dimethylformamide
(DMF) were dried with phosphorus pentoxide and distilled, while
tetrahydrofuran (THF) and toluene were dried with sodium/benzo-
phenone before distilling. Anhydrous pyridine and methanol were
obtained after drying and distilling from calcium hydride and mag-
nesium, respectively. Chemicals and the solvent DMPU were com-
mercially available and used as received. All reactions were per-
formed under nitrogen. Thin layer chromatographic (TLC) analyses
were carried out on precoated nonactivated plates (E. Merck 60
2
3
(dd, 1 H, J5,6a ϭ 6.1 Hz, 6-Ha), 3.47 (dt, J ϭ 9.6, J ϭ 6.6 Hz, 1
F254) with detection by UV absorption (254 nm), when applicable,
2
3
H, OCH2CH2), 3.73 (dt, J ϭ 9.6, J ϭ 6.6 Hz, 1 H, OCH2CH2),
3.78 (s, 3 H, OMe), 3.75Ϫ3.79 (m, 1 H, 5-H), 3.94 (dd, J3,4 ϭ 7.1,
J4,5 ϭ 4.6 Hz, 1 H, 4-H), 4.06 (dd, J1,2 ϭ 4.6, J2,3 ϭ 7.6 Hz, 1 H,
2-H), 4.16 (t, J ϭ 7.1 Hz, 1 H, 3-H), 4.88 (d, 1 H, 1-H), 4.95Ϫ5.04
and charring with 5% H2SO4 in EtOH. For column chromatogra-
phy, E. Merck 60H (5Ϫ40 µm) Silica Gel was used. Filtrations were
performed with Celite 521. Optical rotations were determined with
a PerkinϪElmer 341 polarimeter at 20 °C using a 1-dm cell. 1H
and 13C NMR spectra were recorded with a Bruker ARX 400 spec-
trometer at 400 and 100 MHz, respectively. Chemical shifts are
given in ppm (δ) and coupling constants (J) in Hertz (Hz). The
terms m, s, d, and t signify multiplets, singlets, doublets, and trip-
lets, respectively. CDCl3 and tetramethylsilane were used as solvent
and internal standard, respectively. In order to avoid ambiguity, we
consistently use these designations: C-1a ϭ C atom 1 of ring a; C-
2b ϭ C atom 2 of ring b; 1a-H ϭ H atom at C atom 1 of ring a;
2b-H ϭ H atom at C atom 2 of ring b; 6-Ha ϭ H atom a at C
atom 6; 6-Hb ϭ H atom b at C atom 6; etc. Microanalyses were
performed by the Service de Microanalyses de l’ICSN (Gif sur
Yvette, France).
(m, 2 H, CHϭCH2), 5.77 (ddt, J4Ј,5Јa ϭ 16.8, J4Ј,5Јb ϭ 10.2, J3Ј,4Ј
ϭ
6.6 Hz, 1 H, CHϭCH2), 6.83 (d, 3J ϭ 9.2 Hz, 2 H, o-H of
C6H4OMe), 7.19Ϫ7.45 (m, 12 H, C6H5, C6H4) ppm. 13C NMR
(CDCl3 ϩ D2O): δ ϭ 28.6, 30.1 [(CH2)2], 55.2 (OMe), 64.7 (C-6),
68.6 (OCH2CH2), 70.7 (C-5), 75.8 (C-3), 77.8 (C-2), 82.9 (C-4),
86.8 (CPh2C6H4OMe), 101.1 (C-1), 113.2 (C-o of C6H4OMe), 115.2
(CHϭCH2), 127.0, 127.9, 128.2, 128.3, 130.3 (C6H5, C6H4), 135.3
(C-p of C6H4OMe), 137.7 (CHϭCH2), 144.0, 144.1 (C-i of PhC),
158.5 (C-i of C6H4OMe) ppm. C31H36O7 (520.63): calcd. C 71.51,
H 6.97; found C 71.40, H 7.01.
α-D-Galactofuranoside 8: Triethylamine (1.4 mL, 10.0 mmol),
DMAP (61 mg, 0.50 mmol) and (dropwise) pivaloyl chloride
(0.59 mL, 4.81 mmol) were successively added to a solution of 7
(1.67 g, 3.21 mmol) in THF (5 mL) at 0 °C. After stirring at this
temperature for 1 h, the reaction mixture was diluted with ethyl
Preparation of
D-Fucofuranosides
α-D-Galactofuranoside 6: A 60% suspension of sodium hydride in
oil (0.88 g, 21.9 mmol), n-pentenyl bromide (2.6 mL, 21.9 mmol) acetate (50 mL), washed with 20% aqueous HCl, a saturated solu-
and sodium iodide (3.28 g, 21.9 mmol) were successively added to a
suspension of -galactose (3.95 g, 21.9 mmol) in DMPU (120 mL).
After 5 d at room temperature, one-pot acetylation was carried out
tion of aqueous NaHCO3, and brine. The aqueous layers were ex-
tracted with ethyl acetate, then the resulting organic layers were
combined, dried with MgSO4, and concentrated. Flash chromatog-
by adding at 0 °C dry pyridine (83 mL, 1.03 mol) and acetic anhy- raphy provided 8 (1.49 g) in 77% yield. TLC: Rf ϭ 0.30 (light petro-
dride (83 mL, 0.90 mmol) and then stirring for 24 h. The reaction
mixture was further diluted with ethyl acetate (300 mL), washed
with 20% aqueous HCl and a saturated solution of aqueous NaCl.
The organic layer was then dried (MgSO4) and concentrated under
leum/ethyl acetate, 3:1). [α]D20 ϭ ϩ30.1 (c ϭ 1.0, dichloromethane).
1H NMR (CDCl3 ϩ D2O): δ ϭ 1.23 [s, 9 H, C(CH3)3], 1.56Ϫ1.63
(m, 2 H, CH2), 2.02Ϫ2.07 (m, 2 H, CH2), 3.13 (dd, J6a,6b ϭ 9.2,
J5,6b ϭ 7.1 Hz, 1 H, 6-Hb), 3.31 (dd, 1 H, J5,6a ϭ 5.6 Hz, 6-Ha),
Eur. J. Org. Chem. 2003, 1285Ϫ1293
1289

`
M. Gelin, V. Ferrieres, M. Lefeuvre, D. Plusquellec
FULL PAPER
3.36 (dt, 2J ϭ 9.6, 3J ϭ 6.6 Hz, 1 H, OCH2CH2), 3.64 (dt, 2J ϭ 4.1 Hz, 6-Ha), 4.33 (t, J ϭ 7.3 Hz, 1 H, 3-H), 4.39Ϫ4.62 (m, 4 H,
3
9.6, J ϭ 6.6 Hz, 1 H, OCH2CH2), 3.78 (s, 3 H, OMe), 3.77Ϫ3.80 OCH2Ph), 4.85 (dd, J1,2 ϭ 4.6, J2,3 ϭ 7.6 Hz, 1 H, 2-H), 4.91Ϫ4.98
(m, 1 H, 5-H), 4.09 (dd, J3,4 ϭ 6.1, J4,5 ϭ 4.6 Hz, 1 H, 4-H), 4.51
(t, J ϭ 6.9 Hz, 1 H, 3-H), 4.76 (dd, J1,2 ϭ 4.6, J2,3 ϭ 7.1 Hz, 1 H, J4Ј,5Јb ϭ 10.2, J3Ј,4Ј ϭ 6.6 Hz, 1 H, CHϭCH2), 7.24Ϫ7.31 (m, 12
2-H), 4.94Ϫ5.10 (m, 2 H, CHϭCH2), 5.15 (d, 1 H, 1-H), 5.75 (ddt,
H, C6H5, C6H4), 7.73 (d, 3J ϭ 8.2 Hz, 2 H, C6H5, C6H4) ppm. 13C
J4Ј,5Јa ϭ 16.8, J4Ј,5Јb ϭ 10.2, J3Ј,4Ј ϭ 6.6 Hz, 1 H, CHϭCH2), 6.83 NMR (CDCl3): δ ϭ 21.6 (CH3PhSO2), 27.0 [C(CH3)3], 28.5, 30.0
(m, 2 H, CHϭCH2), 5.15 (d, 1 H, 1-H), 5.73 (ddt, J4Ј,5Јa ϭ 16.8,
(d, 3J ϭ 8.6 Hz, 2 H, o-H of C6H4OMe), 7.19Ϫ7.46 (m, 12 H,
[(CH2)2], 38.4 [C(CH3)3], 67.4 (OCH2CH2), 69.7 (C-6), 72.2, 73.7
C6H5, C6H4) ppm. 13C NMR (CDCl3 ϩ D2O): δ ϭ 27.1 [C(CH3)3], (OCH2Ph), 77.3 (C-5), 78.8 (C-2), 78.9 (C-4), 79.1 (C-3), 99.7 (C-
28.6, 29.9 [(CH2)2], 38.6 [C(CH3)3], 55.2 (OMe), 64.7 (C-6), 68.4 1), 114.8 (CHϭCH2), 127.6Ϫ128.4, 129.8 (C6H5, C6H4), 132.7 (C-
(OCH2CH2), 70.7 (C-5), 73.2 (C-3), 79.8 (C-2), 83.1 (C-4), 86.8 p of C6H4SO2), 137.3 (CHϭCH2), 137.9, 138.0 (C-i of Ph), 144.8
(CPh2C6H4OMe), 100.3 (C-1), 113.1 (C-o of C6H4OMe), 115.1
(CHϭCH2), 126.9, 127.9, 128.2, 128.3, 130.3 (C6H5, C6H4), 135.3
(C-p of C6H4OMe), 137.6 (CHϭCH2), 144.1, 144.2 (C-i of Ph),
158.5 (C-i of C6H4OMe), 178.8 [COC(CH3)3] ppm. C36H44O8
(604.75): calcd. C 71.50, H 7.73; found C 71.38, H 7.45.
(C-i of C6H4SO2), 177.6 [COC(CH3)3] ppm. C37H46O9S (666.84):
calcd. C 66.64, H 6.95; found C 66.66, H 7.05.
α-
D-Fucofuranoside 4: Sodium borohydride (0.570 g, 15.0 mmol)
was added to
a
solution of galactofuranoside 10 (2.50 g,
3.75 mmol) in DMF (50 mL). After stirring at room temperature
for 44 h, sodium methoxide in methanol (0.5 , 15 mL, 7.5 mmol)
was added, and the mixture stirred for an additional 2 h. The basic
mixture was neutralized by the addition of acetic acid in methanol,
and then diluted with water (50 mL) and extracted with diethyl
ether (4 ϫ 20 mL). The combined organic layers were then dried
α-D-Galactofuranoside 9: Benzyl bromide (5.0 mL, 42.0 mmol),
tetrabutylammonium iodide (0.155 g, 0.42 mmol) and a 60% sus-
pension of sodium hydride in oil (0.168 g, 4.20 mmol) were added
successively to a solution of 8 (1.27 g, 2.10 mmol) in dichlorometh-
ane (13 mL), cooled to 0 °C. The reaction mixture was heated un-
der reflux for 24 h, cooled to 0 °C for a second addition of sodium (MgSO4), concentrated and purified by chromatography, eluting
hydride (0.168 g, 4.20 mmol), and then heated under reflux for an
additional 4 d. After quenching with some drops of methanol, a
one-pot detritylation was performed using IR 120 resin (Hϩ form,
pH ϭ 1) over a period of 1 h. Filtration, neutralization with tri-
with light petroleum/ethyl acetate (9:1), to afford the desired fucof-
uranoside 4 (1.20 g) in 77% yield. TLC: Rf ϭ 0.35 (light petroleum/
ethyl acetate, 4:1). [α]2D0 ϭ ϩ11.6 (c ϭ 1.0, dichloromethane). 1H
NMR (CDCl3 ϩ D2O): δ ϭ 1.17 (d, J5,6 ϭ 6.6 Hz, 3 H, 6-H),
ethylamine, and concentration, afforded a crude product that was 1.60Ϫ1.68 (m, 2 H, CH2), 2.04Ϫ2.09 (m, 2 H, CH2), 3.43 (dt, 2J ϭ
3
purified by chromatography, eluting with light petroleum/ethyl
9.6, J ϭ 6.6 Hz, 1 H, OCH2CH2), 3.51Ϫ3.57 (m, 1 H, 5-H), 3.77
acetate (4:1), to give 9 (0.915 g, 85%) as a colorless oil. TLC: Rf (dt, J ϭ 9.6, 3J ϭ 6.6 Hz, 1 H, OCH2CH2), 3.84 (t, J ϭ 6.3 Hz, 1
2
(light petroleum/ethyl acetate, 4:1) ϭ 0.26. [α]2D0 ϭ ϩ63.7 (c ϭ 1.0,
dichloromethane). 1H NMR (CDCl3 ϩ D2O): δ ϭ 1.26 [s, 9 H,
H, 3-H), 3.87 (t, J ϭ 6.3 Hz, 1 H, 4-H), 4.24 (t, J ϭ 5.3 Hz, 1 H,
2-H), 4.51Ϫ4.85 (m, 4 H, OCH2Ph), 4.93 (d, J1,2 ϭ 4.6 Hz, 1 H,
C(CH3)3], 1.54Ϫ1.61 (m, 2 H, CH2), 2.01Ϫ2.07 (m, 2 H, CH2), 1-H), 4.94Ϫ5.03 (m, 2 H, CHϭCH2), 5.78 (ddt, J4Ј,5Јa ϭ 16.8,
2
3
3.33 (dt, J ϭ 9.7, J ϭ 6.6 Hz, 1 H, OCH2CH2), 3.54Ϫ3.58 (m, 1 J4Ј,5Јb ϭ 10.2, J3Ј,4Ј ϭ 6.6 Hz, 1 H, CHϭCH2), 7.24Ϫ7.35 (m, 10
H, 5-H), 3.63 (dd, J5,6b ϭ 5.1, J6a,6b ϭ 11.7 Hz, 1 H, 6-Hb), 3.69 H, C6H5) ppm. 13C NMR (CDCl3 ϩ D2O): δ ϭ 15.6 (C-6), 28.6,
(dt, 2J ϭ 9.7, 3J ϭ 6.6 Hz, 1 H, OCH2CH2), 3.73 (dd, 1 H, J5,6a
ϭ
30.3 [(CH2)2], 67.7 (OCH2CH2), 71.1, 71.7 (OCH2Ph), 76.3 (C-5),
3.6 Hz, 6-Ha), 4.10 (t, J ϭ 6.8 Hz, 1 H, 4-H), 4.41 (t, J ϭ 7.1 Hz, 77.8 (C-2), 83.8 (C-3), 84.3 (C-4), 101.2 (C-1), 114.9 (CHϭCH2),
1 H, 3-H), 4.50Ϫ4.73 (m, 4 H, OCH2Ph), 4.92 (dd, J1,2 ϭ 4.6, 127.4, 127.6, 127.7, 127.9, 128.2, 128.3 (C6H5), 137.9, 138.0, 138.7
J2,3 ϭ 7.6 Hz, 1 H, 2-H), 4.93Ϫ5.01 (m, 2 H, CHϭCH2), 5.25 (d, (C-i of Ph, CHϭCH2) ppm. C25H32O5 (412.53): calcd. C72.79, H
1 H, 1-H), 5.76 (ddt, J4Ј,5Јa ϭ 16.8, J4Ј,5Јb ϭ 10.2, J3Ј,4Ј ϭ 6.6 Hz,
1 H, CHϭCH2), 7.25Ϫ7.37 (m, 10 H, C6H5) ppm. 13C NMR
(CDCl3 ϩ D2O): δ ϭ 27.1 [C(CH3)3], 28.7, 30.1 [(CH2)2], 38.5
[C(CH3)3], 61.5 (C-6), 67.8 (OCH2CH2), 72.3, 72.8 (OCH2Ph), 78.8
(C-2), 79.9 (C-3), 80.2 (C-4), 80.5 (C-5), 100.1 (C-1), 114.9 (CHϭ
CH2), 127.7, 127.8, 127.9, 128.1, 128.4, 128.5 (C6H5), 137.3 (CHϭ
CH2), 137.9, 138.3 (CipsoPh), 177.7 [COC(CH3)3] ppm. C30H40O7
(512.65): calcd. C 70.29, H 7.86; found C 70.04, H 7.86.
7.82; found C 72.74, H 7.82.
α- -Fucofuranoside 15: A 60% suspension of sodium hydride in oil
D
(0.087 g, 2.18 mmol) and p-methoxybenzyl chloride (316 µL,
2.18 mmol) were successively added to a solution of 4 (0.748 g,
1.81 mmol) in DMF (15 mL), cooled to 0 °C. After stirring at room
temperature for 1.5 h, water was carefully added at 0 °C and the
mixture was extracted with diethyl ether (5 ϫ 15 mL). The com-
bined organic layers were then washed with saturated aqueous am-
α-
D-Galactofuranoside 10: Triethylamine (0.58 mL, 7.11 mmol), monium chloride and brine, dried (MgSO4), and concentrated un-
DMAP (9 mg, 0.07 mmol) and tosyl chloride (0.407 g, 2.13 mmol) der reduced pressure. The resulting crude oil was submitted to
were successively added to a solution of 9 (0.730 g, 1.42 mmol) in
dichloromethane (7.3 mL). The mixture was heated under reflux
for 4 h, then cooled to room temperature, diluted with dichloro-
methane (50 mL), and washed successively with water, a saturated
aqueous solution of ammonium chloride, and brine. The organic
layer was dried (MgSO4) and concentrated, and the residue purified
by chromatography (light petroleum/ethyl acetate, 19:1 Ǟ 9:1). The
desired product 10 (0.893 g) was isolated in 94% yield. TLC: Rf ϭ
chromatographic purification, eluting with light petroleum/ethyl
acetate (9:1), to give 15 (0.877 g) in 91% yield. TLC: Rf ϭ 0.43
(light petroleum/ethyl acetate, 4:1). [α]2D0 ϭ ϩ38.2 (c ϭ 1.0, di-
chloromethane). H NMR (CDCl3): δ ϭ 1.16 (d, J5,6 ϭ 6.6 Hz, 3
H, 6-H), 1.62Ϫ1.70 (m, 2 H, CH2), 2.06Ϫ2.12 (m, 2 H, CH2), 3.31
1
2
3
(dt, J ϭ 9.6, J ϭ 6.6 Hz, 1 H, OCH2CH2), 3.55Ϫ3.61 (m, 1 H,
2
3
5-H), 3.69 (dt, J ϭ 9.6, J ϭ 6.6 Hz, 1 H, OCH2CH2), 3.80 (s, 3
H, OMe), 4.04 (dd, J1,2 ϭ 4.1, J2,3 ϭ 5.3 Hz, 1 H, 2-H), 3.84 (t,
J ϭ 7.1 Hz, 1 H, 4-H), 4.11 (t, J ϭ 5.3 Hz, 1 H, 3-H), 4.48Ϫ4.79
0.39 (light petroleum/ethyl acetate, 4:1). [α]2D0 ϭ ϩ39.2 (c ϭ 1.0,
1
dichloromethane). H NMR (CDCl3): δ ϭ 1.25 [s, 9 H, C(CH3)3], (m, 6 H, OCH2Ph), 4.84 (d, 1 H, 1-H), 4.94Ϫ5.04 (m, 2 H, CHϭ
1.46Ϫ1.54 (m, 2 H, CH2), 1.96Ϫ2.01 (m, 2 H, CH2), 2.40 (s, 3 H, CH2), 5.80 (ddt, J4Ј,5Јa ϭ 16.8, J4Ј,5Јb ϭ 10.2, J3Ј,4Ј ϭ 6.6 Hz, 1 H,
2
3
CH3C6H4SO2), 3.22 (dt, J ϭ 9.6, J ϭ 7.1 Hz, 1 H, OCH2CH2),
CHϭCH2), 6.86Ϫ6.89 (m, 2 H, o-H of C6H4OMe), 7.24Ϫ7.36 (m,
3.57 (dt, J ϭ 9.6, J ϭ 6.6 Hz, 1 H, OCH2CH2), 3.68Ϫ3.72 (m, 1 12 H, C6H5, C6H4) ppm. 13C NMR (CDCl3): δ ϭ 15.5 (C-6), 28.6,
2
3
H, 5-H), 3.89 (dd, J3,4 ϭ 7.1, J4,5 ϭ 5.1 Hz, 1 H, 4-H), 4.08 (dd, 30.3 [(CH2)2], 55.3 (OMe), 67.2 (OCH2CH2), 71.1, 72.0, 72.2
J6a,6b ϭ 10.7, J5,6b ϭ 7.1 Hz, 1 H, 6-Hb), 4.20 (dd, 1 H, J5,6a
ϭ
(OCH2Ph), 77.3 (C-5), 82.0 (C-3), 83.5 (C-4), 84.1 (C-2), 100.0 (C-
Eur. J. Org. Chem. 2003, 1285Ϫ1293
1290

Intramolecular Aglycon Delivery onto a D-Fucofuranosyl Entity
1), 113.8 (C-o of C6H4OMe), 114.8 (CHϭCH2), 127.4Ϫ129.8 C6H5), 156.1, 156.6 (NCϭO) ppm. C48H53O8N (771.96): calcd. C
FULL PAPER
(C6H5, C6H4), 138.1, 138.2, 138.8 (C-i of Ph, CHϭCH2), 159.4 (C-
i of C6H4OMe) ppm. C33H40O6 (532.68): calcd. C 74.41, H 7.57;
found C 7.14, H 7.61.
74.68, H 6.92; found C 74.81, H 7.01.
β- -Galactopyranoside 5: Sodium cyanoborohydride (0.581 g,
D
9.25 mmol) and trifluoromethanesulfonic acid (818 µL, 9.25 mmol)
were successively added to a solution of 14 (1.02 g, 1.32 mmol) in
Preparation of the Glycosyl Acceptor
˚
THF (20 mL) containing 4-A molecular sieves (1.00 g) cooled to 0
°C. After stirring for 15 min, neutralization was effected by the
addition of triethylamine. The mixture was filtered through a bed
of Celite, eluting with dichloromethane, then washed with water
and brine, dried (MgSO4), and concentrated. Chromatographic
purification (light petroleum/ethyl acetate, 3:1) gave 5 (0.743 g) in
73% yield. TLC: Rf ϭ 0.63 (light petroleum/ethyl acetate, 1:1).
β-D-Galactopyranoside 13: The trichloroacetimidate 12 (4.77 g,
9.7 mmol) and tin() ditrifluoromethanesulfonate (0.404 g,
0.97 mmol) were successively added to a solution of 11 (4.87 g,
˚
19.4 mmol) in dichloromethane (96 mL) containing 4-A molecular
sieves (4.8 g) at 0 °C. After stirring for 10 min, the reaction mixture
was neutralized by adding a few drops of triethylamine. A meth-
anolic solution of sodium methoxide (0.1 , 78 mL) was added to
the mixture without further workup. Neutralization was carried out
by adding IR 120 (Hϩ form) and then stirring for 1 h at room
temperature. After filtration and concentration, chromatographic
purification, eluting with dichloromethane/methanol (9:1 Ǟ 17:3),
gave the product 13 (3.48 g) which was isolated in 87% yield. TLC:
Rf ϭ 0.15 (dichloromethane/methanol, 9:1). [α]2D0 ϭ Ϫ8.3 (c ϭ 1.0,
methanol). 1H NMR (CD3OD): δ ϭ 1.31Ϫ1.44 (m, 2 H, CH2),
[α]2D0 ϭ ϩ0.5 (c ϭ 1.0, dichloromethane). 1H NMR (CDCl3
ϩ
D2O): δ (ppm):; 1.17Ϫ1.40 [m, 4 H, (CH2)2], 1.41Ϫ1.66 [m, 4 H,
(CH2)2], 3.13Ϫ3.20 (m, 1 H, CH2CH2N), 3.20Ϫ3.28 (m, 1 H,
CH2CH2N), 3.42Ϫ3.49 (m, 1 H, OCH2CH2), 3.48 (dd, J2,3 ϭ 9.4,
J3,4 ϭ 3.4 Hz, 1 H, 3-H), 3.55 (t, J ϭ 6.0 Hz, 1 H, 5-H), 3.63 (dd,
1 H, J1,2 ϭ 7.7 Hz, 2-H), 3.72 (dd, 1 H, J6a,6b ϭ 9.8 Hz, 6-Hb),
3.79 (dd, 1 H, 6-Ha), 3.86Ϫ3.94 (m, 1 H, OCH2CH2), 4.01 (d, 1
2
H, 4-H), 4.33 (d, 1 H, 1-H), 4.47 (d, J ϭ 8.0 Hz, 2 H, NCH2Ph),
4.58Ϫ4.90 (m, 6 H, OCH2Ph), 5.16 (d, 2J ϭ 6.4 Hz, 2 H, OC-
OCH2Ph), 7.13Ϫ7.34 (m, 25 H, C6H5) ppm. 13C NMR (CDCl3 ϩ
D2O): δ ϭ 25.9, 26.6, 27.6, 28.0, 29.6 [(CH2)4], 46.1, 47.1
(CH2CH2N), 50.1, 50.4 (NCH2Ph), 66.7 (C-4), 67.1
(NCO2CH2Ph), 69.1 (C-6), 69.8 (OCH2CH2), 72.4 (OCH2Ph), 73.0
(C-5), 73.7, 75.1 (OCH2Ph), 78.9 (C-2), 80.5 (C-3), 103.6 (C-1),
127.1Ϫ128.5 (C6H5), 136.8, 137.9, 137.9, 138.6 (C-i), 156.2, 156.7
(NCϭO) ppm. C48H55O8N (773.97): calcd. C 74.49, H 7.16; found
C 74.65, H 7.19.
2
1.46Ϫ1.53 (m, 2 H, CH2), 1.58Ϫ1.65 (m, 2 H, CH2), 3.10 (t, J ϭ
9.7 Hz, 2 H, 3J ϭ 6.8 Hz, CH2CH2NH), 3.44 (dd, J2,3 ϭ 9.7, J3,4 ϭ
3.0 Hz, 1 H, 3-H), 3.48Ϫ3.50 (m, 2 H, 5-H, 2-H), 3.51 (dt, 1 H,
2J ϭ 9.6 Hz, 3J ϭ 6.6 Hz, OCH2CH2), 3.71 (dd, J6a,6b ϭ 11.7,
J5,6b ϭ 5.6 Hz, 1 H, 6-Hb), 3.74 (dd, 1 H, J5,6a ϭ 7.1 Hz, 6-Ha),
2
3
3.82 (dd, 1 H, J4,5 Ͻ 1 Hz, 4-H), 3.89 (dt, J ϭ 9.7, J ϭ 6.7 Hz,
1 H, OCH2CH2), 4.19 (d, J1,2 ϭ 7.1 Hz, 1 H, 1-H), 5.49 (s, 2 H,
OCH2Ph), 7.28Ϫ7.34 (m, 5 H, C6H5) ppm. 13C NMR (CD3OD):
δ ϭ 26.7, 27.6, 30.7, 30.8 [(CH2)4], 41.7 (CH2CH2NH), 62.5 (C-6),
67.3 (OCH2Ph), 70.3 (C-4), 70.6 (OCH2CH2), 72.6 (C-2), 75.0 (C-
3), 76.6 (C-5), 105.0 (C-1), 128.7, 128.9, 129.4, (C6H5), 138.5 (C-i
of C6H5), 158.9 (NHCO) ppm. C20H31NO8 (413.47): calcd. C
58.10, H 7.56; found C 58.32, H 7.70.
β-D-Galactopyranoside 17: This compound was obtained as de-
scribed previously for 15, but starting from 5 (0.630 g, 0.81 mmol)
in DMF (13 mL) and using a 60% suspension of sodium hydride
in oil (0.041 g, 0.97 mmol) and p-methoxybenzyl chloride (150 µL,
0.97 mmol). After stirring at room temperature, workup and chro-
matography (light petroleum/ethyl acetate, 17:3), the desired galac-
toside 17 (0.651 g) was isolated in 90% yield. TLC: Rf ϭ 0.65 (light
petroleum/ethyl acetate, 3:2). [α]2D0 ϭ ϩ4.3 (c ϭ 1.0, dichlorometh-
β-D-Galactopyranoside 14: Benzaldehyde dimethylacetal (1.3 mL,
8.70 mmol) and monohydrated camphorsulfonic acid (0.169 g,
0.73 mmol) were successively added to a solution of 13 (3.00 g,
7.30 mmol) in DMF (30 mL). After stirring at 50 °C for 3 h, then
cooling and quenching with some drops of triethylamine, the mix-
ture was diluted with DMF (30 mL). A 60% suspension of sodium
hydride in oil (1.04 g, 26.1 mmol) and benzyl bromide (3.1 mL,
26.1 mmol) were then added. After 2 h at room temperature, neu-
tralization was effected by the addition of methanol. After concen-
tration under reduced pressure at 50 °C, the resulting oil was par-
titioned between ethyl acetate (75 mL) and water (75 mL). The or-
ganic layer was washed with water and a brine, dried (MgSO4),
concentrated and chromatographed (light petroleum/ethyl acetate,
7:3 Ǟ 13:7) to afford target 14 (3.02 g) in 54% overall yield. TLC:
Rf ϭ 0.20 (light petroleum/ethyl acetate, 7:3). [α]2D0 ϭ ϩ23.1 (c ϭ
1.0, dichloromethane). 1H NMR (CDCl3): δ ϭ 1.16Ϫ1.65 [m, 8
H, (CH2)4], 3.13Ϫ3.20 (m, 1 H, CH2CH2N), 3.20Ϫ3.27 (m, 1 H,
CH2CH2N), 3.29 (s, 1 H, 5-H), 3.42Ϫ3.52 (m, 1 H, OCH2CH2),
1
ane). H NMR(CDCl3 ϩ D2O): δ ϭ 1.17Ϫ1.40 [m, 4 H, (CH2)2],
1.41Ϫ1.63 [m, 4 H, (CH2)2], 3.13Ϫ3.26 (m, 2 H, CH2CH2N),
3.42Ϫ3.47 (m, 1 H, OCH2CH2), 3.48 (dd, J2,3 ϭ 7.1, J3,4 ϭ 2.6 Hz,
1 H, 3-H), 3.49Ϫ3.52 (m, 1 H, 5-H), 3.53Ϫ3.57 (m, 2 H, 6-H), 3.76
(s, 3 H, OMe), 3.79 (dd, 1 H, J1,2 ϭ 7.6 Hz, 2-H), 3.86 (d, 1 H, 4-
H), 3.85Ϫ3.90 (m, 1 H, OCH2CH2), 4.31 (d, 1 H, 1-H), 4.45Ϫ4.48
(m, 2 H, NCH2Ph), 4.38Ϫ4.91 (m, 8 H, OCH2Ph), 5.15Ϫ5.17 (m,
2 H, OCOCH2Ph), 6.77Ϫ6.83 (m, 2 H, H-o of C6H4OMe),
7.13Ϫ7.33 (m, 27 H, C6H5, C6H4) ppm. 13C NMR (CDCl3
ϩ
D2O): δ ϭ 25.9, 26.6, 27.7, 28.0, 29.6 [(CH2)4], 46.2, 47.1
(CH2CH2N), 50.1, 50.4 (NCH2Ph), 55.2 (OMe), 67.1
(NCO2CH2Ph), 68.8 (OCH2CH2), 68.9 (C-6), 72.8 (C-4), 73.0
(OCH2C6H4OMe), 73.4 (C-5), 73.5, 73.9, 75.1 (OCH2Ph), 79.8 (C-
2), 82.2 (C-3), 103.9 (C-1), 113.8 (C-o of C6H4OMe), 127.2Ϫ130.8
(C6H5, C6H4), 137.9, 138.6, 138.8 (C-i of Ph), 156.2, 156.7 (NCϭ
O), 159.1 (C-i of C6H4OMe) ppm. C56H63O9N ϩ 0.5 H2O (903.13):
calcd. C 74.48, H 7.14; found C 74.36, 6.97.
3.54 (dd, J2,3 ϭ 9.7, J3,4 ϭ 3.6 Hz, 1 H, 3-H), 3.82 (dd, 1 H, J1,2
7.8 Hz, 2-H), 3.91Ϫ3.98 (m, 1 H, OCH2CH2), 4.00 (d, J6a,6b
ϭ
ϭ
12.3 Hz, 1 H, 6-Hb), 4.09 (d, 1 H, 4-H), 4.29 (d, 1 H, 6-Ha), 4.35
(d, 1 H, 1-H), 4.47 (d, 2J ϭ 9.6 Hz, 2 H, NCH2Ph), 4.76Ϫ4.92 (m,
Glycosidic Coupling Reactions
2
4 H, OCH2Ph), 5.16 (d, J ϭ 6.7 Hz, 2 H, OCOCH2Ph), 5.49 (s, 1
H, CHPh), 7.23Ϫ7.39 (m, 23 H, C6H5), 7.54Ϫ7.57 (m, 2 H, C6H5) Disaccharide 16: NIS (0.014 g, 0.06 mmol) and a Lewis acid
ppm. 13C NMR (CDCl3): δ ϭ 25.8, 26.6, 27.6, 28.0, 29.6 [(CH2)4], [0.01 mmol, either TMSOTf (2 µL) or Sn(OTf)2 (4 mg)] were added
46.1, 47.1 (CH2CH2N), 66.3 (C-5), 50.0, 50.4 (NCH2Ph), 67.1 to a solution of 15 (0.032 g, 0.06 mmol) and 5 (0.039 g, 0.05 mmol)
˚
(NCO2CH2Ph), 69.2 (C-6), 69.8 (OCH2CH2), 71.9 (OCH2Ph), 74.0
in dichloromethane (1 mL) in the presence of 4-A molecular sieves
(C-4), 75.2 (OCH2Ph), 78.4 (C-2), 79.1 (C-3), 101.3 (CHPh), 103.6 (0.1 g). The reaction mixture was stirred at 0 °C for 1 h and at
(C-1), 126.5Ϫ128.9 (C6H5), 137.8, 137.9, 138.4, 138.9 (C-i of room temperature for 22 h, and then quenched by adding triethyl-
Eur. J. Org. Chem. 2003, 1285Ϫ1293
1291

`
M. Gelin, V. Ferrieres, M. Lefeuvre, D. Plusquellec
FULL PAPER
amine. After filtration through a bed of Celite, the resulting solu- (0.024 mL, 0.041 mmol) in ethanol (4 mL) in the presence of pal-
tion was concentrated and chromatographed (light petroleum/ethyl ladium acetate (36 mg). After stirring under hydrogen (1 atm) at
acetate, 4:1) to afford either stereochemically pure 16β (0.020 g, room temperature for 6 d and then for an additional 24 h under a
33%) or a mixture of 16α,β (0.015 g, 25%). 16β: TLC: Rf ϭ 0.40 higher pressure of hydrogen (30 atm), the mixture was neutralized
(light petroleum/ethyl acetate, 7:3). 1H NMR (CDCl3): δ ϭ 1.15 (d, (acetic acid), filtered, and concentrated. The resulting crude oil was
5b,6b ϭ 6.1 Hz, 3 H, 6-Hb), 1.18Ϫ1.55 [m, 8 H, (CH2)4], 3.11Ϫ3.27 then acetylated [acetic anhydride (2 mL), pyridine (2 mL)] at 50
J
(m, 2 H, CH2CH2N), 3.49 (dd, J2a,3a ϭ 6.6, J3a,4a ϭ 2.5 Hz, 1
H, 3a-H), 3.50Ϫ3.52 (m, 1 H, 5a-H), 3.53Ϫ3.56 (m, 2 H, 6-Ha),
°C for 5 h. The solution was diluted with ethyl acetate (10 mL),
successively washed with 20% aqueous HCl, saturated aqueous so-
3.59Ϫ3.64 (m, 1 H, 5b-H), 3.78 (s, 3 H, OMe), 3.76Ϫ3.79 (m, 1 H, dium bicarbonate, and brine. After drying (MgSO4) and removal
2a-H), 3.86 (dd, J4b,5b ϭ 3.6, J3b,4b ϭ 8.2 Hz, 1 H, 4b-H), of the solvent, chromatographic purification gave 20 (0.005 g) in
3.84Ϫ3.88 (m, 1 H, OCH2CH2), 3.93 (dd, 1 H, J2b,3b ϭ 4.1 Hz, 3b-
H), 3.92Ϫ3.96 (m, 1 H, OCH2CH2), 4.11 (dd, 1 H, J1b,2b ϭ 1.0 Hz, leum/ethyl acetate/triethylamine, 4:1:0.05). H NMR (CDCl3): δ ϭ
25% yield. Tethered Disaccharide 18: TLC: Rf ϭ 0.55 (light petro-
1
2b-H), 4.14 (d, 1 H, 4a-H), 4.31 (d, J1a,2a ϭ 7.1 Hz, 1 H, 1a-H),
4.21Ϫ4.95 (m, 12 H, OCH2Ph), 5.16 (d, 3J ϭ 5.1 Hz, 2 H, OC-
1.04 (d, J5b,6b ϭ 6.1 Hz, 3 H, 6b-Ha), 1.08Ϫ1.54 [m, 10 H, (CH2)4,
CH2], 1.91Ϫ1.97 (m, 2 H, CH2), 2.99 (dt, J ϭ 9.2, J ϭ 7.1 Hz, 1
2
3
OCH2Ph), 5.49 (d, 1 H, 1b-H), 6.76Ϫ6.81 (m, 2 H, o-H of H, OCH2C4H7), 3.04Ϫ3.19 (m, 2 H, CH2CH2N), 3.28 (dd, J2a,3a ϭ
C6H4OMe), 7.06Ϫ7.34 (m, 37 H, C6H5, C6H4) ppm. 13C (CDCl3): 9.7, J3a,4a ϭ 3.0 Hz, 1 H, 3a-H), 3.32Ϫ3.39 (m, 1 H, OCH2C5H10),
δ ϭ 16.1 (C-6b), 25.9, 26.6, 27.7, 28.1, 29.6 [(CH2)4], 46.1, 47.1 3.42Ϫ3.50 (m, 3 H, 5a-H, 5b-H, OCH2C4H7), 3.52 (dd, 1 H,
(CH2CH2N), 50.1, 50.4 (NCH2Ph), 55.3 (OMe), 67.1
J1a,2a ϭ 7.6 Hz, 2a-H), 3.65 (dd, J5a,6Јa ϭ 5.6, J6a,6Јa ϭ 9.6 Hz, 1
(NCO2CH2Ph), 68.9 (C-6a), 70.1 (OCH2CH2), 71.2, 71.3, 71.9 H, H-6a-Hb), 3.70 (s, 3 H, OMe), 3.69Ϫ3.71 (m, 1 H, 4b-H),
(OCH2Ph), 72.5 (C-4a), 73.0 (C-4b), 73.5 (OCH2Ph), 73.7 (C-5a), 3.76Ϫ3.84 (m, 1 H, OCH2C5H10), 3.91 (dd, 1 H, 6a-Ha), 3.95Ϫ3.97
74.2 (C-5b), 75.0 (OCH2Ph), 79.6 (C-2a), 82.2 (C-3a), 83.3 (C-3b),
88.1 (C-2b), 103.9 (C-1a), 107.0 (C-1b), 113.4 (C-o of C6H4OMe), 4a-H, 1b-H), 4.36Ϫ4.38 (m, 2 H, NCH2Ph), 4.39Ϫ4.71 (m, 10 H,
127.2Ϫ130.0 (C6H5, C6H4), 138.0Ϫ138.8 (C-i of CH2Ph), 159.2 (C- OCH2Ph), 4.86Ϫ4.94 (m, 2 H, CHϭCH2), 5.08 (br. s, 2 H, OC-
i of C6H4OMe) ppm. 16α: TLC: Rf ϭ 0.40 (light petroleum/ethyl OCH2Ph), 5.65 (s, 1 H, CHPhOMe), 5.69 (ddt, J4Ј,5Јa ϭ 16.8,
(m, 2 H, 2b-H, 3b-H), 4.21 (d, 1 H, 1a-H), 4.23Ϫ4.26 (m, 2 H,
acetate, 7:3). Characteristic data obtained from the anomeric mix-
J4Ј,5Јb ϭ 10.2, J3Ј,4Ј ϭ 6.1 Hz, 1 H, CHϭCH2), 6.68Ϫ6.71 (m, 2 H,
ture: 13C NMR (CDCl3): δ ϭ 15.8 (C-6b), 25.9, 26.6, 27.6, 28.0, o-H of C6H4OMe), 7.12Ϫ7.25 (m, 37 H, C6H5, C6H4) ppm. 13C
29.7 [(CH2)4], 46.1, 47.1 (CH2CH2N), 50.0, 50.3 (NCH2Ph), 55.2 NMR (CDCl3): δ ϭ 15.5 (C-6b), 25.8, 26.6, 27.6, 28.0, 29.6
(OMe), 67.1 (NCO2CH2Ph), 69.2 (C-6a), 69.9 (OCH2CH2), 71.2
(OCH2Ph), 72.1 (C-4a), 72.2, 73.4 (OCH2Ph), 73.7 (C-5a), 75.1
[(CH2)4], 28.8, 30.3 [(CH2)2], 46.1, 47.1 (CH2CH2N), 50.1, 50.4
(NCH2Ph), 55.3 (OMe), 67.2 (OCH2C4H7, NCO2CH2Ph), 69.2 (C-
(OCH2Ph), 77.1 (C-5b), 79.4 (C-2a), 80.7 (C-3b), 81.4 (C-3a), 83.1 6a), 69.9 (OCH2C5H10), 71.2 (OCH2Ph), 71.5 (C-4a), 72.6, 72.9,
(C-4b), 84.1 (C-2b), 101.2 (C-1b), 104.0 (C-1a), 113.8 (C-o of 73.4 (OCH2Ph), 73.7 (C-5a), 75.0 (OCH2Ph), 77.0 (C-5b), 79.2 (C-
C6H4OMe), 127.2Ϫ129.9 (C6H5, C6H4), 137.9Ϫ138.3 (C-i of 2a), 81.5, 81.8 (C-2b, C-3b), 82.0 (C-3a), 82.9 (C-4b), 99.9 (C-
CH2Ph), 159.3 (C-i of C6H4OMe) ppm.
1b),103.9 (C-1a), 104.5 (CHC6H4OMe), 113.1 (C-o of C6H4OMe),
114.7 (CHϭCH2), 127.3Ϫ128.5 (C6H5, C6H4), 132.0Ϫ138.8 (C-i of
Ph, CHϭCH2), 155.9, 156.7 (NCϭO), 159.7 (C-i of C6H4OMe)
ppm. Disaccharide 19: Selected 13C NMR spectroscopic data
Disaccharide 20: DDQ (0.029 g, 0.127 mmol) was added to a solu-
tion of fucofuranosyl donor 4 (0.035 g, 0.085 mmol) and galactop-
yranoside 17 (0.091 g, 0.102 mmol) in dry dichloromethane (2 mL)
(CDCl3):
δ ϭ 15.5 (C-6b), 25.9Ϫ29.7 (CH2), 46.2, 47.1
˚
containing 4-A molecular sieves (0.2 g) and cooled to 0 °C. After
(CH2CH2N), 50.1, 50.4 (NCH2Ph), 55.1, 55.2 (OMe), 69.1 (C-6a),
73.2 (C-5a), 73.5, 75.0 (OCH2Ph), 76.5 (C-5b), 79.2 (C-2a), 80.3,
80.7, 82.2, 83.0 (C-2b, C-3b, C-4b, C-3a), 100.0 (C-1b), 103.9, 104.0
(C-1a), 113.1 (C-o of C6H4OMe), 158.9 (NCϭO), 159.6 (C-i of
C6H4OMe), 176.4 (CH2CO) ppm. Disaccharide 20: TLC: Rf ϭ 0.28
stirring at room temperature for 1 h, the reaction was quenched by
adding an aqueous solution (0.50 mL) of ascorbic acid (0.7%), cit-
ric acid (1.3%) and sodium hydroxide (0.9%).[24] The mixture was
filtered through a bed of Celite and the resulting solution was
washed with an aqueous solution of ascorbic acid (0.7%), citric
acid (1.3%) and sodium hydroxide (0.9%), then with saturated
aqueous sodium bicarbonate, and then finally with brine. The com-
bined aqueous layers were extracted with dichloromethane and the
resulting organic solution was dried (MgSO4) and concentrated.
For spectral assignments, the desired tether 18 was purified through
a short bed of silica gel eluting with light petroleum/ethyl acetate
(4:1). This eluent was complemented with 1% of triethylamine to
neutralize the acidic centers of the chromatographic material and
so to limit degradation of labile tether 18. This procedure allowed
us to record 1H and 13C NMR spectra. Nevertheless, we rec-
ommend that crude 18 be used without further purification. In this
case, 18 was first dried by co-evaporation with dry toluene under
reduced pressure at 50 °C. The resulting oil was then dissolved in
(dichloromethane/methanol, 19:1). 1H NMR (CDCl3):
δ ϭ
1.25Ϫ1.35 [m, 4 H, (CH2)2], 1.38 (d, J5b,6b ϭ 6.6 Hz, 3 H, 6b-Ha),
1.47Ϫ1.57 [m, 4 H, (CH2)2], 1.96, 1.98, 2.00, 2.01, 2.03, 2.07, 2.11
(7 s, 21 H, OCOCH3), 3.08Ϫ3.14 (m, 2 H, NCH2CH2), 3.29 (t, J ϭ
7.6 Hz, 1 H, 5a-H), 3.40Ϫ3.46 (OCH2CH2), 3.65 (s, 1 H, NH), 3.75
(t, J4b,5b ϭ 6.6 Hz, 1 H, 5b-H), 3.84Ϫ3.90 (m, 2 H, OCH2CH2, 4b-
H), 4.02 (d, J3a,4a ϭ 3.0 Hz, 1 H, 4a-H), 4.12 (dd, J6Јa,6a ϭ 11.2,
J5a,6Јa ϭ 6.1 Hz, 1 H, 6a-Hb), 4.39 (d, J1a,2a ϭ 8.2 Hz, 1 H, 1a-H),
4.41Ϫ4.46 (m, 1 H, 6-Ha), 4.76 (dd, 1 H, J2a,3a ϭ 10.7 Hz, 3a-H),
4.96Ϫ4.99 (m, 2 H, 1b-H, 5b-H), 5.14 (dd, J2b,3b ϭ 8.6, J1b,2b
ϭ
4.6 Hz, 1 H, 2b-H), 5.42 (dd, 1 H, 2a-H), 5.57Ϫ5.62 (m, 1 H, 3b-
H) ppm. 13C NMR (CDCl3): δ ϭ 15.5 (C-6b), 20.5, 20.7, 20.8,
20.9, 21.0, 21.3, (OCOCH3), 22.2 (NHCOCH3), 27.0, 27.1, 29.4,
29.5 [(CH2)4], 40.8 (NCH2CH2), 62.4 (C-6a), 68.4 (C-5b), 69.0 (C-
2a), 70.0 (OCH2CH2), 71.8 (C-5a), 72.3 (C-3b), 73.2 (C-3a), 75.9
(C-2b), 76.5 (C-4a), 80.3 (C-4b), 101.7 (C-1a), 102.1 (C-1b),
˚
dichloromethane (2 mL) containing 4-A molecular sieves (0.2 g).
After cooling at 0 °C, NIS (0.023 g, 0.10 mmol) was added and the
mixture was warmed slowly to room temperature. After stirring for
19 h, the mixture was neutralized (triethylamine), filtered through
a bed of Celite (dichloromethane), and finally purified by chroma-
168.8Ϫ171.2 (CϭO) ppm. HRMS: m/z ([M
ϩ
Na]ϩ,
C34H53NO17Na): calcd. 770.3211; found 770.3249.
tography (light petroleum/ethyl acetate, 7:3 Ǟ 13:7). Compound 19 Disaccharide 22: The reaction was performed according to a pro-
was isolated in 34% yield. Subsequent hydrogenolysis was carried
out with 19 (0.036 g, 0.028 mmol) in a solution of acetic acid
cedure similar to that described for 19 but using, for the prep-
aration of the intermediate acetal, fucofuranoside 15 (0.040 g,
1292
Eur. J. Org. Chem. 2003, 1285Ϫ1293

Intramolecular Aglycon Delivery onto a D-Fucofuranosyl Entity
FULL PAPER
R. M. de Lederkremer, W. Colli, Glycobiology 1995, 5,
[6]
[7]
0.075 mmol), glucopyranoside 21 (0.029 g, 0.063 mmol) and DDQ
(0.029 g, 0.127 mmol), and for the aglycon transfer, NIS (0.070 g,
0.31 mmol). The resulting disaccharide 22 (0.013 g) was isolated
after chromatography (light petroleum/ethyl acetate, 3:2) in 21%
yield. TLC: Rf ϭ 0.42 (light petroleum/ethyl acetate, 3:2). 1H NMR
(CDCl3): δ ϭ 1.14 (d, J5b,6b ϭ 6.6 Hz, 3 H, 6-Hb), 2.65 [s, 4 H,
(CH2)2], 3.08 (dd, J1a,2a ϭ 3.6, J2a,3a ϭ 9.7 Hz, 1 H, 2a-H), 3.30 (s,
3 H, 1a-OCH3), 3.36 (dd, J4a,5a ϭ 9.2, J3a,4a ϭ 5.1 Hz, 1 H, 4a-H),
3.48Ϫ3.52 (m, 1 H, 5b-H), 3.53Ϫ3.57 (m, 1 H, 5a-H), 3.59 (s, 3 H,
C6H4OCH3), 3.74 (dd, 1 H, J6a,6Јa ϭ 12.2, J5a,6Јa ϭ 2.0 Hz, 6a-Hb),
3.77 (dd, 1 H, J5a,6a ϭ 2.5 Hz, 6a-Ha), 3.78 (dd, 1 H, 3a-H), 3.87
546Ϫ552.
T. Morigushi, T. Wada, M. Sekine, J. Org. Chem. 1996, 61,
9223Ϫ9228.
[8] [8a]
B. Smestad, A. Haug, S. Myklestad, Acta Chem. Scand.,
[8b]
Ser. B 1975, 29, 337Ϫ340.
bohydr. Res. 1977, 58, 439Ϫ442.
J. Hoffman, B. Lindberg, Car-
[8c]
N. Sato, F. Nakazawa, M.
Sato, E. Hoshino, T. Ito, Carbohydr. Res. 1993, 245, 105Ϫ111.
[8d] P. A. Mashimo, Y. Murayama, H. Reynolds, C. Mouton, S.
A. Ellison, R. J. Genco, J. Periodontol. 1981, 52, 374Ϫ379.
[9] [9a]
P. M. Nassau, S. L. Martin, R. E. Brown, A. Weston, D.
Monsey, M. R. McNeil, K. Duncan, J. Bacteriol. 1996, 178,
[9b]
1047Ϫ1052.
2000, 328, 473Ϫ480.
J. N. Barlow, J. S. Blanchard, Carbohydr. Res.
(dd, J3b,4b ϭ 7.1, J4b,5b ϭ 7.6 Hz, 1 H, 4b-H), 4.06 (dd, J1b,2b
ϭ
[9c]
J. N. Barlow, M. E. Girvin, J. S. Blan-
4.0, J2b,3b ϭ 7.1 Hz, 1 H, 2b-H), 4.16 (t, 1 H, 3b-H), 4.59 (d, 1 H,
1a-H), 4.42Ϫ4.87 (m, 10 H, OCH2Ph), 5.37 (d, 1 H, 1b-H), 6.42
(s, 1 H, CHC6H4OMe), 6.77Ϫ6.79 (m, 2 H, o-H of C6H4OMe),
7.13Ϫ7.31 (m, 27 H, C6H5, C6H4) ppm. 13C NMR (CDCl3): δ ϭ
15.6 (C-6b), 28.1 [(CH2)2], 55.0, 55.1 (C6H4OCH3, 1a-OCH3), 64.9
(C-6a), 70.5 (C-5a), 71.2, 71.8, 73.1, 74.7, 75.3 (OCH2Ph), 77.2 (C-
4a), 77.3 (C-5b), 79.9 (CHC6H4OMe), 80.1 (C-2a), 81.2 (C-3b),
81.8 (C-3a), 81.9 (C-2b), 84.0 (C-4b), 113.7 (C-o of C6H4OMe),
97.7 (C-1a), 100.5 (C-1b), 127.0Ϫ128.3 (C6H5, C6H4), 137.9, 138.4,
138.8, 139.2 (C-i of Ph), 152.6 (C-i of C6H4OMe), 176.2 (CϭO)
chard, J. Am. Chem. Soc. 1999, 121, 6968Ϫ6969. [9d] Q. Zhang,
[9e]
H. W. Liu, J. Am. Chem. Soc. 2001, 123, 6756Ϫ6766.
Q.
Zhang, H. W. Liu, J. Am. Chem. Soc. 2000, 122, 9065Ϫ9070.
[9f]
R. E. Lee, M. D. Smith, R. J. Nash, R. C. Griffiths, M.
McNeil, R. K. Grewal, W. Yan, G. S. Besra, P. J. Brennan, G.
W. J. Fleet, Tetrahedron Lett. 1997, 38, 6733Ϫ6736.
[10] [10a] C. Marino, P. Herczegh, R. M. de Lederkremer, Carbohydr.
[10b]
Res. 2001, 333, 123Ϫ128.
C. Marino, K. Marino, L. Mi-
letti, M. J. Manso Alves, W. Colli, R. M. de Lederkremer, Gly-
A. Chiocconi, C. Marino, R.
M. de Lederkremer, Carbohydr. Res. 2000, 323, 7Ϫ13.
[10c]
cobiology 1998, 8, 901Ϫ904.
ppm. HRMS: [M
ϩ ϭ
Na]ϩ, (C60H65NO13Na) calcd. m/z
[11]
[11a]
See, for example:
Soc. 1991, 113, 9377Ϫ9379.
Chem. Soc. 1992, 114, 1087Ϫ1088.
F. Barresi, O. Hindsgaul, J. Am. Chem.
1030.4354, found 1030.4362; [M Ϫ H]ϩ (C60H64NO13) calcd. m/z ϭ
1006.4378; found 1006.4380; [M Ϫ C4H4NO2]ϩ (C56H61O11) calcd.
m/z ϭ 909.4214; found 909.4213: [C12H12NO3]ϩ calcd. m/z ϭ
218.0817; found 218.0819.
[11b]
G. Stork, G. Kim, J. Am.
[11c]
Y. Ito, T. Ogawa, An-
[11d]
gew. Chem. Int. Ed. Engl. 1994, 33, 1765Ϫ1767.
C. Krog-
[11e]
Jensen, S. Oscarson, J. Org. Chem. 1996, 61, 4512Ϫ4513.
H. J. Jung, M. Müller, R. R. Schmidt, Chem. Rev. 2000, 100,
4423Ϫ4442.
Acknowledgments
We gratefully acknowledge the Ministere de l’Education Nationale,
[12]
[13]
J. Thiem, H. P. Wessel, Liebigs Ann. Chem. 1983, 2173Ϫ2184.
V. K. Pogorelyi, Russ. Chem. Rev. 1977, 46, 602Ϫ638.
`
[14] [14a]
[14b]
de la Recherche et de la Technologie, for a grant to M. G., and
M. L. Wolfrom, J. Am. Chem. Soc. 1930, 52, 2464Ϫ2473.
M. L. Wolfrom, Z. Yosizawa, B. O. Juliano, J. Org. Chem.
´
Pierre Guenot, Centre Regional de Mesures Physiques de l’Ouest
(Rennes), for recording HRMS spectra and for his precious help
in interpreting results.
1959, 24, 1529Ϫ1530.
[15]
[16]
B. Fraser-Reid, U. E. Udodong, Z. Wu, H. Ottosson, J. R.
Merritt, C. S. Rao, C. Roberts, R. Madsen, Synlett 1992,
927Ϫ942.
R. Velty, T. Benvegnu, M. Gelin, E. Privat, D. Plusquellec, Car-
bohydr. Res. 1997, 299, 7Ϫ14.
[1]
[1a] U. Schmid, H. Waldmann, Chem. Eur. J. 1998, 4, 494Ϫ501.
[1b]
R. U. Lemieux, H. Driguez, J. Am. Chem. Soc. 1975, 97,
4063Ϫ4075.
[17]
[18]
W. Klotz, R. R. Schmidt, Liebigs Ann. Chem. 1993, 683Ϫ690.
In concentrated media or under the action of lithium alu-
minium hydride, n-pentenyl 3,6-anhydro-2,3-di-O-benzyl-α--
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