First O-glycosylation from unprotected 1-thioimidoyl hexofuranosides assisted by divalent cations

Article abstract of DOI:10.1021/jo070741j

(Chemical Equation Presented) The preparation of O-hexofuranosides was accomplished from unprotected 1-thioimidoyl furanosides as donors. The present methodology was first used for the synthesis of octyl galactofuranoside and further extended to D-galacto

Full text of DOI:10.1021/jo070741j

First O-Glycosylation from Unprotected 1-Thioimidoyl
Hexofuranosides Assisted by Divalent Cations
Ronan Euzen, Jean-Paul Gue´gan, Vincent Ferrie`res,* and Daniel Plusquellec
Sciences Chimiques de Rennes, Ecole Nationale Supe´rieure de Chimie de Rennes, CNRS, AVenue du
Ge´ne´ral Leclerc, F-35700 Rennes, France
Vincent.ferrieres@ensc-rennes.fr
ReceiVed April 10, 2007
The preparation of O-hexofuranosides was accomplished from unprotected 1-thioimidoyl furanosides as
donors. The present methodology was first used for the synthesis of octyl galactofuranoside and further
extended to D-galactofuranose-containing disaccharides. Within this study, we emphasized the need for
additional complexing cations to maintain the furanose ring in its initial size. After experimentation,
calcium ion was first used concomitantly with trimethylsilyl trifluoromethanesulfonate, the latter being
able to activate the thioimidate and the former being likely to inhibit ring expansion. Moreover, an
improvement was performed by using copper(II) trifluoromethanesulfonate which could then meet the
requirements as both promoter and complexing agent.
Introduction
the preparation of hexofuranose-containing oligosaccharides as
potential pharmacophores devoted to innovative therapies.16,17
Glycosylation strategies generally require functional arrange-
ments on both glycosyl donor and acceptor. The appropriate
choice of protecting groups allows at the same time (i)
modulation of the reactivity of both partners and (ii) diastereo-
control of the coupling reactions.2 With nonparticipating groups,
control of the stereochemistry of the newly formed glycosidic
bond is more delicate and the glycosylation reactions evolve
according to many parameters, among them solvent, tempera-
ture, and also anomeric and steric effects. Anomeric mixtures
of pyranosides, notably in gluco and galacto series, are thus
Many natural oligosaccharides and polysaccharides are
structurally based on hexoses in a pyranose configuration. This
explains why the wide majority of the related publications both
in glycobiology and in glycochemistry deal with the study and
the synthesis of hexopyranoconjugates.1-5 However, it is also
well-established that only some microorganisms, and not
mammals, are able to biosynthesize and metabolize membrane
components and other bioconjugates that are built up with
hexoses in a thermodynamically less stable furanose form. In
this context, we6-8 and other teams9-15 have contributed to the
development of chemical methodologies specially dedicated to
(1) Toshima, K.; Tatsuta, K. Chem. ReV. 1993, 93, 1503-1531.
(2) Demchenko, A. Lett. Org. Chem. 2005, 2, 580-589.
(3) Pellissier, H. Tetrahedron 2005, 61, 2947-2993.
(4) Gabius, H.-J.; Siebert, H.-C.; Andre´, S.; Jime´nez-Barbero, J.; Ru¨diger,
H. ChemBioChem 2004, 5, 740-764.
(11) Bohn, M. L.; Colombo, M. I.; Stortz, C. A.; Ruveda, E. A.
Carbohydr. Res. 2006, 341, 1096-1104.
(12) Gandolfi-Donadio, L.; Gola, G.; de Lederkremer, R. M.; Gallo-
Rodriguez, C. Carbohydr. Res. 2006, 341, 2487-2497.
(13) Lee, Y. J.; Lee, B. Y.; Jeon, H. B.; Kim, K. S. Org. Lett. 2006, 8,
3971-3974.
(5) Dwek, R. A. Chem. ReV. 1996, 96, 683-720.
(6) Gelin, M.; Ferrie`res, V.; Plusquellec, D. Eur. J. Org. Chem. 2000,
1423-1431.
(14) Zhang, G.; Fu, M.; Ning, J. Tetrahedron: Asymmetry 2005, 16,
733-738.
(7) Ferrie`res, V.; Roussel, M.; Gelin, M.; Plusquellec, D. J. Carbohydr.
Chem. 2001, 20, 855-865.
(15) Zhang, G.; Fu, M.; Ning, J. Carbohydr. Res. 2005, 340, 155-159.
(16) Joe, M.; Sun, D.; Taha, H.; Completo, G. C.; Croudace, J. E.;
Lammas, D. A.; Besra, G. S.; Lowary, T. L. J. Am. Chem. Soc. 2006, 128,
5059-5072.
(8) Gelin, M.; Ferrie`res, V.; Lefeuvre, M.; Plusquellec, D. Eur. J. Org.
Chem. 2003, 1285-1293.
(9) Bai, Y.; Lowary, T. L. J. Org. Chem. 2006, 71, 9672-9680.
(10) Bai, Y.; Lowary, T. L. J. Org. Chem. 2006, 71, 9658-9671.
(17) Mennink-Kersten, M. A. S. H.; Ruegebrink, D.; Wasei, N.; Melchers,
W. J. G.; Verweij, P. E. J. Clin. Microbiol. 2006, 44, 1711-1718.
10.1021/jo070741j CCC: $37.00 © 2007 American Chemical Society
Published on Web 06/28/2007
J. Org. Chem. 2007, 72, 5743-5747
5743

Euzen et al.
TABLE 1. Glycosylation of 1-Octanol by Remote Activation of Thioimidate 1
entry
C8H17OH (equiv)
solvent
promoter (equiv)
additive (equiv)
time (h)
yield (%)
2/3c
2R/2âc
1
2a
3b
4
5
6
7
8
9
10
11
12
13
14
2
10
10
10
10
10
20
20
20
20
20
20
20
20
DMF
DMF
DMF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
TMSOTf (0.1)
TMSOTf (0.02)
TMSOTf (0.1)
TMSOTf (0.1)
TMSOTf (0.5)
TMSOTf (1.0)
TMSOTf (0.1)
TMSOTf (0.5)
TMSOTf (1.0)
TMSOTf (1.0)
Cu(OTf)2 (0.1)
Cu(OTf)2 (1.0)
Cu(OTf)2 (1.0)
Cu(OTf)2 (2.0)
2
2
2
2
2
2
2
2
2
2
24
2
24
24
18
38
41
33
52
79
28
53
98
65
38
47
65
43
100:0
100:0
100:0
100:0
79:21
73:27
100:0
89:11
88:12
97:3
1:1.3
1:1.4
1:1.5
1:1
1:1
1:4.9
1:1
1:1.1
1:3.7
1:5.6
1:0.6
1:1.2
1:5.1
1:6.2
CaCl2 (1.0)
100:0
100:0
100:0
100:0
a Donor 1 was added over 12 min. b Donor 1 was added over 1 h. c Ratios were calculated by 1H NMR from integrations corresponding to the anomeric
protons.
obtained. In the field of hexofuranosides, the conformational
furanosyl 1-phosphates in only one step by remote activation
of various 1-thioimidoyl furanosides directly by phosphoric acid
and concluded that the corresponding 2-benzimidazolyl 1-thio-
D-galacto-, D-fuco-, D-gluco-, and D-mannofuranosides were the
most appropriated donors under these conditions.26 Herein, we
report on the direct access to O-furanosides from free thioimi-
dates, alcohols and underline how divalent cations efficiently
contribute to keep the glycoside in its initial five-membered
ring configuration.
flexibility of the five-membered ring plays a stronger role than
those observed with the pyranose counterparts,18 so that dias-
tereoselectivity of the coupling is generally highly influenced
by steric hindrance.8 While benzyl ethers are often used as a
nonparticipating protecting group, a free hydroxyl could also
be regarded as nonstereodirecting function. Such an approach
was initiated by Ferrier19 and nicely complemented through
recent research.20-23 Thioglycosides and 2-thiopyridinyl deriva-
tives were first proposed as unprotected pyranosyl donors which
led to the desired alkyl pyranosides under activation assisted
by mercuric salts. A few years later, Hanessian extended this
strategy and developed the MOP technology (3-methoxy-2-
pyridyloxyl glycosides) as well as the remote activation
process.24 The main advantages of this strategy rely on (i) the
absence of protecting group manipulations at the end of a
synthetic scheme, which is highly desirable for charged targets
and the removal of undesired side products such as orthoesters,
and (ii) a greater reactivity of the glycosyl donors.
Results and Discussion
On the assumption that 2-benzimidazolyl thiofuranosides are
suitable donors in the formation of anomeric furanosyl phos-
phates, our study began with the galactofuranosylation of
1-octanol with donor 126 (Table 1). In order to mimic the
conditions of the previous phosphorylation, the hard Lewis acid
such trimethylsilyl trifluoromethansulfonate (TMSOTf) was first
studied as a promoter in N,N-dimethylformamide (DMF). After
2 h at room temperature, an anomeric mixture of the target
furanoside 2 was obtained in a low 18% yield but without any
formation of the more stable pyranoside 3 (entry 1). This
moderate yield was ascribed to degradation of the thioimidoyl
donor. To overcome this side reaction, the reactions were
performed either by using only 0.02 molar equiv of the Lewis
acid or by increasing the amount of the aliphatic acceptor, and
by slow adding of 1 (entries 2 and 3). Nevertheless, the latter
precaution was no more required by substituting DMF by the
less polar tetrahydrofuran (THF) (entry 4). It is rather likely
that such new conditions modulate the dissociation of activated
species thus limiting degradation processes. Subsequent im-
proved glycosidic couplings were obtained by concomitantly
increasing amounts of 1-octanol and TMSOTf (entries 5-9),
so that conversion of donor 1 to the desired galactoside was
interestingly performed in a near quantitative yield (entry 9).
These modifications also impacted, first, the stability of the
desired furanosides 2R,â, since they were contaminated by octyl
Considering our interest in the chemistry of glycofuranoconju-
gates,25-27 we have recently performed the synthesis of hexo-
(18) Kirby, A. J. The Anomeric Effect and Related Stereoelectronic
Effects at Oxygen; Springer-Verlag: Berlin, Heidelberg, New York, 1983.
(19) Ferrier, R. J.; Furneaux, R. H. Carbohydr. Res. 1976, 52, 63-68.
(20) Hanessian, S.; Bacquet, C.; Lehong, N. Carbohydr. Res. 1980, 80,
C17-C22.
(21) Ferrie`res, V.; Blanchard, S.; Fischer, D.; Plusquellec, D. Bioorg.
Med. Chem. Lett. 2002, 12, 3515-3518.
(22) Demchenko, A. V.; Malysheva, N. N.; De Meo, C. Org. Lett. 2003,
5, 455-458.
(23) Demchenko, A. V.; Pornsuriyasak, P.; De Meo, C.; Malysheva, N.
N. Angew. Chem., Int. Ed. 2004, 43, 3069-3072.
(24) Hanessian, S.; Lou, B. Chem. ReV. 2000, 100, 4443-4463.
(25) Euzen, R.; Ferrie`res, V.; Plusquellec, D. Carbohydr. Res. 2006, 341,
2759-2768.
(26) Euzen, R.; Ferrie`res, V.; Plusquellec, D. J. Org. Chem. 2005, 70,
847-855.
(27) Euzen, R.; Lopez, G.; Nugier-Chauvin, C.; Ferrie`res, V.; Plusquellec,
D.; Re´mond, C.; O’Donohue, M. Eur. J. Org. Chem. 2005, 4860-4869.
5744 J. Org. Chem., Vol. 72, No. 15, 2007

First O-Glycosylation from Unprotected 1-Thioimidoyl Hexofuranosides
TABLE 2. Glycosylation of 1-Octanol by Remote Activation of Thioimidates 4-7
R-D-galactopyranoside (3) until 27% (entry 6), and second, the
diastereoselectivity of the furanosylation. Indeed, a more acidic
media resulted in an increased amount of the most stable 1,2-
trans-furanoside 2â as shown by the 2R/2â ratio which started
from 1:1 to attain 1:4.9 or 1:3.7 (entries 4-6 and 7-9,
respectively).
by a â configuration, first proceeded with inversion of config-
uration (entry 11, 2R/2â, 1:0.6) and that anomerization occurred
with increased reaction times and/or acidity. Consequently, one
can hypothesized that copper(II) was not only involved as a
mild activating agent but also presented the expected coordina-
tion properties required to fully inhibit the ring expansion as a
side reaction. In order to explain this phenomenon, we hypoth-
esized that both calcium and copper were likely to interact with
either the starting furanosyl thioimidate or the resulted O-
furanoside or with both compounds. More precisely, we assumed
that free OH-5 of the furanosidic derivatives was involved in
such a bond. Owing to heterogeneity of the reaction media,
complexation was qualitatively studied by NMR using calcium
chloride or copper(II) triflate as source of divalent cation and
octyl â-D-galactofuranoside (2â) as a complexing agent in
deuterated dimethylformamide. Thus, the most relevant results
were obtained with cupric ions by proton decoupled 13C NMR.
Indeed, a selective and apparent disappearance of C-5 and C-6
signals was observed when 1 molar equiv concentration of Cu2+
ions was used. This was attributed to the broadening of the
corresponding signals which is indicative for a metal interaction
with O-5 and O-6. These results are in good agreement with
those demonstrating complexation of cupric ions by pyrimidine
nucleotides and nucleosides.30 In our study, the 13C NMR
spectrum therefore confirmed the assumption according to which
the aforementioned preservation of the five-membered ring of
the starting furanosyl thioimidate donor during O-glycosylation
reaction is assisted by copper(II) ions.
Although conversion was thus ensured in THF in the presence
of 1 molar equiv of TMSOTf, the limitation of our approach
seemed to rely on the production of the unwanted pyranoside
3. Nevertheless, in order to avoid its formation, we hypothesized
that free hydroxyl could interact with alkaline earth or metal
cations to inhibit the undesired ring expansion. Indeed, additives
such as calcium or barium chloride have already shown their
potential in a revisited Fischer glycosylation reaction from
unprotected reducing monosaccharides.28,29 The resulting speci-
ficity of this approach toward the hexofuranosides was con-
nected with reversible complexation phenomena that are likely
to stabilize substrates, intermediates, and/or products in a
furanose configuration. As expected, the presence of calcium
cations in the reaction media allowed significant decrease of
galactopyranoside 3 (entry 10). This experiment also strength-
ened better affinity of calcium for the 1,2-trans-furanoside since
2â represented 85% of the resulting anomeric mixture of
galactofuranosides (2R/2â, 1:5.6).
Subsequent improvement brought us to also consider the
ability of metal and rare earth cations which have acidic
properties and exhibit higher solubility in THF than calcium
chloride. Among silver, ytterbium, zinc, scandium, tin, and
copper triflates, the last three Lewis acids showed the desired
smooth activation of thioimidate 1 and the more interesting
results were observed with copper(II) triflate. The set of
experiments (entries 11-14), led with metallic promoter,
allowed us to show that glycosidation of donor 1, characterized
Having an efficient method in hand, we further studied the
reactivity of known benzothiazolyl, pyridinyl, thiazolinyl, and
pyrimidinyl galactofuranosides 4, 5, 6, and 7,26 respectively, in
order to highlight the scope of the remote activation of
unprotected thioimidoyl furanosides. Each of these donors was
studied under conditions similar to those previously used with
donor 1 (Table 2). Whatever the nature of the aglycon, it is
(28) Bertho, J.-N.; Ferrie`res, V.; Plusquellec, D. Chem. Commun. 1995,
1391-1393.
(29) Ferrie`res, V.; Bertho, J.-N.; Plusquellec, D. Tetrahedron Lett. 1995,
36, 2749-2752.
(30) Kotowycz, G. Can. J. Chem. 1974, 52, 924-929.
J. Org. Chem, Vol. 72, No. 15, 2007 5745

Euzen et al.
SCHEME 1. Synthesis of Galactofuranose-Containing
Disaccharides 10 and 11
conditions, the desired D-galactofuranosides were synthesized
with limited or no ring expansion toward the most stable
pyranosides.
Experimental Section
Synthesis of Octyl D-Galactofuranoside (2) in the Presence
of Calcium Chloride (Procedure A). To a solution of donor 1
(59.3 mg, 0.167 mmol) in dry THF (0.5 mL) were successively
added n-octanol (530 µL, 3.35 mmol), calcium chloride (18.6 mg,
0.167 mmol), and TMSOTf (32 µL, 0.167 mmol). The resulting
suspension was stirred for 2 h at rt before being quenched by the
addition of a few drops of triethylamine. After fitration and
concentration under reduced pressure, the target furanoside was
chemically purified. The first step consisted of acetylation using
pyridine (1 mL) and acetic anhydride (1 mL). The media was kept
for 24 h at rt, concentrated, codistilled with toluene, and purified
by chromatography (light petroleum/EtOAc, 4:1). Deacetylation was
further performed under standard conditions: the resulting product
reacted overnight in a 0.1 M solution of sodium methylate in
methanol (1 mL). The solution was further neutralized using resin
IR-120 (H+-form), filtered, and concentrated to afford a mixture
of 2 and 3 in a 65% yield (31.7 mg). NMR spectra were in good
accordance with those previously described.33,34
Synthesis of Octyl D-Galactofuranoside (2) in the Presence
of Copper(II) Triflate (Procedure B). To a solution of donor 7
(50 mg, 0.18 mmol) in anhyd THF (1 mL) were successively added
octanol (575 µL, 3.6 mmol) and copper(II) triflate (66 mg, 0.18
mmol). The reaction was stirred for 24 h at rt, quenched by addition
of triethylamine, and finally diluted with methanol (5 mL). After
filtration of the residual salts, washing with methanol, and
concentration under reduce pressure, the target galactoside 2 was
purified as previously described and isolated in 71% yield (25 mg,
2R/2â ) 1:4.7)
important to emphasize the total conservation of the size of the
initial five-membered ring thanks to the presence of copper ions.
Moreover, 2R, formed under kinetic conditions, smoothly
anomerized to afford 2â, so that the best selectivity toward the
1,2-trans furanoside was observed from the thiazolinyl derivative
6 (entry 7, 2R/2â ) 1:6.7) even if this donor allowed the
synthesis of 2 in a moderate 48% yield. Nevertheless, the desired
galactoside 2 was synthesized and isolated in an excellent 71%
yield starting from the pyrimidinyl furanoside 7 (entry 10). This
result prompted us to prefer donor 7 for subsequent glycosylation
of furanosidic or pyranosidic acceptors 8,31 9,26 and 1032
(Scheme 1). Under these optimal conditions, no coupling could
be performed between 7 and 8 since fast degradation of the
donor was observed. Nevertheless, compounds 9 and 10 were
smoothly glycosylated so that the desired galactofuranose-
containing disaccharides 12 and 13 were isolated in 41-47%
and 41% yield, respectively. Although yields are quite similar,
it is interesting to note that the resulting diastereocontrol of the
reaction slightly depended on the ring size of the saccharidic
acceptor as R/â ratio was 1:3.7 for the furano-furano coupling
but reached 1:7.1 for the furano-pyrano one.
Octyl R,â-D-Galactofuranosyl-(1,6)-2,3,5-tri-O-benzyl-â-D-ga-
lactofuranoside (12). Compound 12 was synthesized according to
a procedure similar to that described for 2 in procedure B starting
from 7 (35 mg, 0.13 mmol), acceptor 925 (1.42 g, 2.52 mmol), and
copper(II) triflate (46.2 mg, 0.13 mmol). Chromatography eluting
with CH2Cl2-MeOH (19:1) gave the desired disaccharide 12 (43
1
mg, 47%, R/â ) 1:3.7): Rf 0.2 (CH2Cl2/MeOH, 19:1); H NMR
(400 MHz, CD3OD) and 13C NMR (400 MHz, CD3OD) for the
â-anomer 12â were similar to those previously described;25 1H
NMR (400 MHz, CD3OD) data for 12R δ 7.36-7.23 (m, 15 H,
C6H5), 5.00 (s, 1 H, H-1a), 4.84 (d, 1 H, J ) 4.6 Hz, H-1b), 4.73-
4.32 (m, 6 H, OCH2Ph), 4.12 (dd, 1 H, J ) 7.4, 7.1 Hz, H-3b),
4.10 (dd, 1 H, J ) 6.9, 3.6, H-4a), 4.00 (dd, 1 H, J ) 10.4, 6.4,
H-6a), 3.99-3.94 (m, 3 H, H-2a, H-3a, H-2b), 3.81 (ddd, 1 H, J )
10.4, 6.4, 6.1 Hz, H-5a), 3.73 (dd, 1 H, J ) 7.1, 5.1 Hz, H-4b),
3.66 (dt, 1 H, J ) 9.6, 6.4 Hz, OCH2CH2), 3.65-3.57 (m, 3 H,
H-6′a, H-5b, H-6b), 3.54 (dd, 1 H, J ) 10.9, 6.1 Hz, H-6′b), 3.39
(dt, 1 H, J ) 9.6, 6.4 Hz, OCH2CH2), 1.61-1.54 (m, 2 H,
OCH2CH2), 1.39-1.25 [m, 10 H, (CH2)5], 0.89 (t, 3 H, J ) 7.1
Hz, CH3); 13C NMR (400 MHz, CD3OD) δ 139.6, 139.2, 139.1
(Cipso), 129.7, 129.4, 129.3, 128.9, 128.8 (C6H5), 107.4 (C-1a), 103.1
(C-1b), 89.3 (C-2a), 84.1 (C-3a), 83.4 (C-4b), 82.2 (C-4a), 78.9
(C-2b), 77.8 (C-5a), 76.1 (C-3b), 74.3 (OCH2Ph), 74.1 (C-5b), 73.0,
72.9 (OCH2Ph), 69.1 (C-6a), 64.1 (C-6b), 68.6 (OCH2CH2), 33.0,
30.6, 30.5, 27.4, 23,8 [(CH2)6], 14.5 (CH3); HRMS calcd for C41H56-
NaO11 [M + Na]+ 747.3720, found 747.3721.
Conclusions
In conclusion, we present herein the first O-glycosidation
performed from unprotected furanosyl donors and neutral
acceptors. Our approach, which required the preservation of the
initial size of five-membered rings, rested on the remote
activation of free thioimidoyl furanosides by an appropriate
Lewis acid and on the complexation of furanosidic reactants
and/or products. Two versatile solutions were developed. They
involved either the combination of TMSOTf and calcium
chloride or the use of only copper(II) triflate to realize the
targeted glycosylation reactions. Under such experimental
Phenyl 2,3,5,6-Tetra-O-acetyl-R,â-D-galactofuranosyl-(1,6)-
2,3,4-tri-O-benzyl-1-thio-R-D-mannopyranoside (13). Disaccha-
ride 13 was synthesized according to a procedure similar to that
previously described for 2 starting from 7 (48 mg, 0.17 mmol),
(31) Pathak, A. K.; Pathak, V.; Seitz, L.; Maddry, J. A.; Gurcha, S. S.;
Besra, G. S.; Suling, W. J.; Reynolds, R. C. Bioorg. Med. Chem. 2001, 9,
3129-3143.
(32) Mart´ın-Lomas, M.; Khiar, N.; Garc´ıa, S.; Koessler, J. L.; Nieto, P.
M.; Rademacher, T. W. Chem. Eur. J. 2000, 6, 3608-3621.
(33) Ferrie`res, V.; Bertho, J.-N.; Plusquellec, D. Carbohydr. Res. 1998,
311, 25-35.
(34) Ferrie`res, V.; Gelin, M.; Boulch, R.; Toupet, L.; Plusquellec, D.
Carbohydr. Res. 1998, 314, 79-83.
5746 J. Org. Chem., Vol. 72, No. 15, 2007

First O-Glycosylation from Unprotected 1-Thioimidoyl Hexofuranosides
acceptor 10 (1.89 g, 3.50 mmol), and copper(II) triflate (61.5 mg,
0.17 mmol). Chromatography eluting with CH2Cl2-MeOH (19:1)
gave the a crude oil (Rf 0.2) which was diluted in pyridine (570
µL, 6.99 mmol) and anhydride acetic (650 µL, 6,92 mmol). After
being stirred at rt for 48 h, the reaction medium was concentrated
and codistilled with toluene. The resulting mixture was finally
purified by flash chromatography eluting with light petroleum-
EtOAc (4:1 f 3:2). An anomeric mixture (R/â ) 1:7.1) of the
target furanose-containing disaccharide 13 was thus obtained in 41%
yield (60 mg, 0.07 mmol): Rf 0.1 (light petroleum-EtOAc, 4:1);
1H NMR (400 MHz, CD3OD) data for 13R δ 7.42-7.18 (m, 20 H,
C6H5), 5.51 (dd, 1 H, J ) 7.5, 7.1 Hz, H-3b), 5.41 (d, 1 H, J ) 1.6
Hz, H-1a), 5.17 (d, 1 H, J ) 4.4 Hz, H-1b), 5.05-5.00 (m, 2 H,
H-2b, H-5b), 4.89-4.85, 4.65-4.52 (2 m, 6 H, OCH2Ph), 4.27-
4.17 (m, 2 H, H-5a, H-6′b), 4.04 (dd, 1 H, J ) 7.1, 4.9 Hz, H-4b),
4.00 (dd, 1 H, J ) 12.0, 6.0 Hz, H-6′b), 3.93 (dd, 1 H, J ) 11.1,
4.2 Hz, H-6a), 3.92-3.89 (m, 2 H, H-2a, H-4a), 3.75 (dd, 1 H, J
) 9.3, 3.1 Hz, H-3a), 3.61 (dd, 1 H, J ) 11.1, 1.5 Hz, H-6′a),
2.01, 1.94, 1.86, 1.78 (4 s, 12 H, CH3CO); 13C NMR (400 MHz,
CD3OD) δ 170.5, 170.4, 169.9 (CO), 138.3, 138.2, 137.9 (Cipso
OCH2Ph), 134.0 (Cipso SPh), 132.8, 129.2, 128.5, 128.2, 128.1,
128.0, 127.9, 127.8 (C6H5), 99.9 (C-1b), 85.8 (C-1a), 80.1 (C-3a),
77.7 (C-4b), 76.4 (C-2a), 76.2 (C-2b), 75.1 (C-4a), 73.5 (C-3b),
72.6 (C-5a), 70.3 (C-5b), 67.2 (C-6a), 62.2 (C-6b), 20.9, 20.8, 20.6,
20.5 (CH3); 1H NMR (400 MHz, CD3OD) data for 13â δ
7.44-7.16 (m, 20 H, C6H5), 5.49 (d, 1 H, J ) 1.6 Hz, H-1a), 5.31
(dd, 1 H, J ) 7.5, 3.8 Hz, H-5b), 5.03 (d, 1 H, J ) 1.6 Hz, H-2b),
4.99 (s, 1 H, H-1b), 4.89-4.85, 4.68-4.51 (2 m, 6 H, OCH2Ph),
4.84 (dd, 1 H, J ) 5.5, 1.6 Hz, H-3b), 4.26 (dd, 1 H, J ) 5.5, 3.5
Hz, H-4b), 4.22 (dd, 1 H, J ) 11.9, 3.8 Hz, H-6b), 4.21-4.18
(m, 1 H, H-5a), 4.08 (dd, 1 H, J ) 11.9, 7.5 Hz, H-6′b), 3.93-
3.92 (m, 1 H, H-2a), 3.90 (dd, 1 H, J ) 9.7, 9.1 Hz, H-4a), 3.85
(dd, 1 H, J ) 10.8, 1.5 Hz, H-6a), 3.77 (dd, 1 H, J ) 9.1, 2.9 Hz,
H-3a), 3.70 (dd, 1 H, J ) 10.8, 6.0, H-6′a), 2.03, 2.00, 1.92, 1.87
(4 s, 12 H, CH3CO); 13C NMR (400 MHz, CD3OD) δ 170.5, 170.2,
170.1, 169.5 (CO), 138.4, 138.1, 137.8 (Cipso OCH2Ph), 134.3 (Cipso
SPh),131.8, 129.1, 128.5, 128.0, 127.9, 127.8, 127.6 (C6H5), 105.4
(C-1b), 85.8 (C-1a), 82.2 (C-3a or C-3b, C-4b), 81.2 (C-2b), 80.1
(C-3a or C-3b), 74.9 (C-4a), 76.2 (C-2a), 72.4 (C-5a), 69.4
(C-5b), 66.7 (C-6a), 63.1 (C-6b), 20.9, 20.8, 20.6 (CH3); HRMS
calcd for C47H52NaO14S [M + Na]+ 895.2976, found 895.2976.
Acknowledgment. We are grateful to the French Ministry
of Education, Research and Technology for a grant to R.E.
Supporting Information Available: 1D- and 2D-correlational
NMR, 1H-1H, and 1H-13C spectra for all products. This material
is available free of charge via the Internet at http://pubs.acs.org.
JO070741J
J. Org. Chem, Vol. 72, No. 15, 2007 5747