Indirect approach to C-3 branched 1,2-cis-glycofuranosides: synthesis of aceric acid glycoside analogues

Article abstract of DOI:10.1016/j.carres.2007.10.035

Aceric acid (3-C-carboxy-5-deoxy-α-l-xylofuranose) residues are present in pectic polysaccharide rhamnogalacturonan II (RG II) in the form of synthetically challenging 1,2-cis-glycofuranosides. To access synthetic fragments of RG II incorporating aceric a

Full text of DOI:10.1016/j.carres.2007.10.035

Available online at www.sciencedirect.com
Carbohydrate Research 343 (2008) 211–220
Indirect approach to C-3 branched 1,2-cis-glycofuranosides:
synthesis of aceric acid glycoside analogues
Marcelo T. de Oliveira,a,b David L. Hughes,a Sergey A. Nepogodieva,b, and
*
Robert A. Fielda,b,
*
aSchool of Chemical Sciences and Pharmacy, University of East Anglia, Norwich NR4 7TJ, UK
bDepartment of Biological Chemistry, John Innes Centre, Colney Lane, Norwich NR4 7UH, UK
Received 14 June 2007; received in revised form 28 August 2007; accepted 2 October 2007
Available online 7 November 2007
Abstract—Aceric acid (3-C-carboxy-5-deoxy-a-L-xylofuranose) residues are present in pectic polysaccharide rhamnogalacturonan II
(RG II) in the form of synthetically challenging 1,2-cis-glycofuranosides. To access synthetic fragments of RG II incorporating acer-
ic acid, a four-step procedure based on C-2 epimerisation of initially prepared 1,2-trans-glycofuranoside was developed. Readily
available derivatives of branched-chain L-lyxofuranose bearing a 3-C-vinyl group as a masked 3-C-carboxyl group were investigated
as potential precursors of aceric acid units. In the first step of the procedure, installation of a participating group at C-2 of the
furanose ring ensured stereocontrol of the O-glycosylation, which was carried out with the thioglycoside of 2-O-acetyl-3,5-di-O-benz-
yl-3-C-vinyl-L-lyxofuranose. After the glycosylation step, the 2-O-acetyl group was removed, the free 2-OH group was oxidised and
the resulting ketone was finally reduced to form the C-3-vinyl-L-xylofuranoside. The use of L-Selectride in the key reduction reaction
was essential to achieve the required stereoselectivity to generate 1,2-cis-furanoside.
ꢀ 2007 Elsevier Ltd. All rights reserved.
Keywords: Glycofuranosides; Branched-chain sugars; Aceric acid; Rhamnogalacturonan II
1. Introduction
development.4,5 This effect is accounted for by a reduced
ability of RG II to form a dimer, which is the predom-
inant form of RG II in plants.6 It is believed that the
dimerisation of RG II is mediated by cross-linking
through a borate diester formation between apiofuran-
osyl residues. Although a common motif, b-L-Rhap-(1-
30)-b-D-Apif-(1-2)-a-L-GalpA, is present in both side
chains A and B, only the residue belonging to side chain
A is thought to be involved in RG II dimerisation. Frag-
ments of both side chains will be useful in the study of
boron complexation and a number of synthetic frag-
ments of RG II has been reported.7 Reading from the
polygalacturonic acid backbone, the first point of differ-
ence between side chains A and B lies in the glycosyla-
tion of b-L-rhamnopyranosyl residue. Side chain B
(Fig. 1) has the branched-chain sugar aceric acid (Acef)
attached to O-3 of b-L-rhamnopyranose. To date, aceric
acid has only been found in nature in the structure of
RG II. The synthesis of this unusual monosaccharide
and of its C-2 epimer has been reported recently,8,9
Rhamnogalacturonan II (RG II), a unique ‘mega-oligo-
saccharide’ present in the primary cell walls of all higher
plants, plays an essential role in plant growth, develop-
ment and resistance to disease.1,2 RG II consists of a
main backbone of 7–9 a-1,4-linked D-galacturonic resi-
dues to which four structurally different oligosaccha-
rides are attached, the so-called side chains A–D. In
total, 16 different kinds of glycosyl residues are present
in RG II and it is believed1 that at least 24 enzymes
may be required for the generation of the requisite gly-
coside linkages. The complex structure of RG II is,
remarkably, conserved throughout the plant kingdom
with only a few known variations depending on the
source.3,4 Mutant plants having an altered RG II sugar
composition showed significant abnormalities in their
*
Corresponding authors. E-mail addresses: Sergey.Nepogodiev@
bbsrc.ac.uk; Rob.Field@bbsrc.ac.uk
0008-6215/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2007.10.035

212
M. T. de Oliveira et al. / Carbohydrate Research 343 (2008) 211–220
α-L-Rhap
2-OMe-α-L-Fucp 4 OAc
α-D-GalpA
1
1
OAc
3
4
O
O
OR
HO
OH
3
2
1
α-L-Arap-(1 4)-β-D-Galp-(1 2)-α-L-Acef-(1 3)-β-L-Rhap-(1 3')-β-D-Apif-(1 2)-α-D-GalpA
4
2
Me
HO
1
1
α-D-GalpA
α-L-Rhap-(1 2)-β-L-Araf
Figure 1. Structure of a fragment of rhamnogalacturonan II representing the side chain B nonasaccharide attached to a trisaccharide region of
polygalacturonan backbone3b (left) and the aceric acid residue, shown as a generic glycoside with naturally occurring a-L-configuration (right).
but thus far no synthetic fragments of RG II containing
this branched-chain pentose are known.
construction of a 1,2-trans-glycofuranosidic bond first,
followed by the inversion of the C-2 configuration of
the glycofuranose residue. This strategy takes advantage
of highly stereoselective glycosylation provided by the
possibility of a neighbouring group participation as well
as more easy access to C-2 epimers of aceric acid.8
Our strategy began with trapping the furanose form of
L-arabinose by selective 5-O-silylation, followed by con-
ventional isopropylidenation which gave the known
alcohol 120 in an overall 48% yield (Scheme 1). Oxidation
of 1 using Dess–Martin periodinane in CH2Cl2 gave
pentafuranos-2-ulose 220 in a 90% yield. The bicylo-
[3.3.0]octane ring system of 2 allows stereoselective
introduction of branching point by nucleophilic addition
from sterically less demanding exo-face of the mole-
cule.21 Following the classical synthesis of streptose,22
a branched sugar which has structural similarity to aceric
Chemical synthesis of side chain B requires the con-
struction of a 1,2-cis-glycofuranosidic bond between
aceric acid and rhamnopyranose units. Stereoselective
formation of this type of glycosidic bond remains one of
the major challenges of synthetic carbohydrate chemistry
because stereoelectronic and steric effects favour the for-
mation of 1,2-trans-glycofuranosides, even in reactions
with glycofuranosyl donors having non-participating
substituents at C-2. Glycofuranosyl fluorides,10 thiogly-
cofuranosides11,12 and trichloroacetimidates13 of glyco-
furanoses have been employed for the synthesis of
1,2-cis-glycofuranosides. Less common reagents such as
ditiocarbamates14 and 2-carboxybenzyl glycosides15 have
also been used for this purpose. Indirect methods based
on 2,3-anhydro-glycofuranosyl donors16 or intramolecu-
lar aglycon delivery17 proved to be useful in syntheses of
1,2-cis-arabinofuranosides. More recently, a remarkable
stereoselectivity in 1,2-cis-arabinofuranosylation was
achieved with the aid of a 3,5-O-di-tert-butylsilyl protect-
ing group.18 However, the whole arsenal of general 1,2-
cis-glycosylating methods19 has not been widely used by
synthetic chemists for the construction of 1,2-cis-furano-
sides, apparently because of the rare occurrence of this
type of glycosides in nature. Since the only access to aceric
acid is via multi-step synthesis, a choice of glycosylation
method for the construction of aceric acid glycosides
depends on the availability of a suitable glycosyl donor
which can serve as an aceric acid precursor. We describe,
herein an application of an indirect approach to the con-
struction of 3-C-branched 1,2-cis-linked glycofurano-
sides via the inversion of C-2 configuration in more
readily available 1,2-trans-linked glycofuranosides. This
methodology is illustrated by the synthesis of protected
methyl 3-C-vinyl-b-L-xylofuranoside and methyl 3-C-
vinyl-b-L-xylofuranosyl-(1!3)-b-L-rhamnopyranoside;
the functionalised core furanose moiety of these com-
pounds has the same stereochemistry as aceric acid and
can be envisaged as an aceric acid precursor.
HO
O
a, b
c
L-Arabinose
TBDPSO
TBDPSO
O
O
Me
Me
Me
1
O
O
d
e
TBDPSO
O
O
HO
O
O
O
Me
Me
Me
3
2
O
O
f
g, h
HO
BnO
BnO
O
O
HO
BnO
O
O
Me
Me
Me
Me
4
5
O
O
OAc
STol
i
BnO
BnO
BnO
OAc
OAc
Me
6
7
Scheme 1. Synthesis of glycosyl donor 7. Reagents and conditions: (a)
TBDPSCl, imidazole, DMF, 65 ꢁC; (b) Me2C(OMe)2, Me2CO, I2, 48%
over two steps; (c) Dess–Martin periodinane, CH2Cl2, 90%; (d)
CH2@CHMgBr, THF, ꢀ78!20 ꢁC, 81%; (e) TBAF, THF, 90%, (f)
BnBr, NaH, Bu4NI, DMF, 75%; (g) TFA–H2O 9:1; (h) Ac2O,
pyridine, 72% over two steps; (i) p-CH3C6H4SH, BF3ÆEt2O, CH2Cl2,
0 ꢁC, 92%.
2. Results and discussion
The synthesis of 1,2-cis-glycosides of aceric acid (Fig. 1)
was approached by an indirect strategy consisting of the

M. T. de Oliveira et al. / Carbohydrate Research 343 (2008) 211–220
213
acid, we made use of vinyl magnesium bromide as a
nucleophile. Addition to ketone 2 was highly stereoselec-
tive and proceeded with the formation of a single product
3 in 81% yield. The desired stereochemistry of the vinyl
adduct 3 was confirmed by X-ray structural analysis
which showed that this compound has the lyxo-configu-
ration (Fig. 2). It should be noted that other nucleo-
philes, such as thiazolyl lithium,8 can also be applied
for the introduction of the C-3 branch point. The vinyl
group was chosen in this instance because it was
expected, due to its relatively small size, not to interfere
with subsequent glycosylation steps required for the con-
struction of RG II side chain B. Deprotection of O-5 in 3
under acidic conditions afforded diol 4, which was benzyl-
ated to give dibenzyl ether 5 in overall 68% yield. Several
attempts to benzylate the tertiary alcohol in compound 3
prior to desilylation were unsuccessful, leading only to
the recovery of starting material. If more vigorous benzy-
lation conditions were applied, including a large excess of
reagent and temperature increased to 40 ꢁC, compound 3
was converted into desilylated product 4. A similar lack
of reactivity of a tertiary alcohol having an adjacent silyl
group was observed recently in benzylation of a com-
pound with unrelated structure.23
measured for individual samples of a-7 (minor product)
and b-7 (major product) isolated from the mixture.
Values of these coupling constants (5.6 Hz for a-7
and 7.3 Hz for b-7) were notably higher than typical
3JH-1,H-2 values for O-glycofuranosides (0–2 Hz for
1,2-trans and 3–5 Hz for 1,2-cis-glycofuranosides).25
This observation is in agreement with previous findings
that the presence of sulfur at the anomeric position, in
particular, in the case of some thioglycofuranosides
(e.g. 7.1 Hz for trans- and 6.8 Hz for cis-isomer of per-
benzylated phenylthiomannofuranoside),11 substantially
3
increases JH-1,H-2 values.
With the donor 7 in hand, NIS/TMSOTf-promoted
glycosylation of methanol and known methyl a-L-
rhamnopyranoside derivative 1226 were executed giving
methyl glycofuranoside 8 and disaccharide 13 in 76%
and 81% yields, respectively (Scheme 2). The a-L-stereo-
chemistry of the furanosyl residue in these compounds
was established from the values of dC-1 in 13C NMR
spectra of 8 (111.0 ppm) and 13 (107.8 ppm) which lie
in the characteristic range of dC-1 for 1,2-trans-glycofur-
anosides. Coupling constants 3JH-1,H-2 for 8 and 13 were
3.1 Hz and 3.7 Hz, respectively. These values are some-
3
what higher than JH-1,H-2 values (0–2 Hz), which are
Taking into account that the preparation of 5-deoxy-
L-arabinose as a precursor of aceric acid will demand
a tedious multistep synthesis,8,24 in these studies, we
proceeded with the investigation of the glycosylation
methodology required for the construction of 1,2-cis-
glycofuranosidic bond using the 5-hydroxy analogue
of aceric acid. The isopropylidene group of the dibenzyl-
ated derivative 5 was hydrolysed in 90% CF3CO2H and
the resulting diol was acetylated to an anomeric mixture
of 1,2-diacetates 6. Treatment of 6 with p-thiocresol-
BF3ÆEt2O produced thioglycoside 7 as a 1:8 mixture
of anomers in 92% yield. The ratio of anomers was
characteristic25 for 1,2-trans-furanosides and usually
allow unambiguous assignment of the anomeric confi-
guration in glycofuranosides.
The key step in the synthesis of target 1,2-cis-glycofur-
anosides from 8 and 13 was the inversion of the C-2 con-
figuration. Epimerisation of C-2 in carbohydrates can be
performed by nucleophilic displacement of a 2-triflate
with nitrate,27 acetate28 or benzoate29 ions. An alterna-
tive approach includes stereoselective reduction of
corresponding 2-uloses.30 This reduction process has
been particularly well studied in the course of the devel-
opment of indirect b-mannosylation methodology31 but
it has not previously been reported for the synthesis of
1,2-cis-glycofuranosides. Application of the 2-ulose
reduction procedure required conversion of 2-acetates
8 and 13 into derivatives 10 and 15, respectively (Scheme
2). After deacetylation of compounds 8 and 13, which
proceeded in 91% yield, 2-hydroxy-derivatives 9 and
14 were subjected to oxidation with Dess–Martin peri-
odinane in CH2Cl2 to afford 2-uloses 10 and 15 in 87%
and 86% yield, respectively. The X-ray crystal structure
obtained for methyl glycofuranosid-2-ulose 10 con-
firmed successful installation of keto group and the cor-
rect C-1 stereochemistry of the furanose unit (Fig. 3).
In attempts to reduce the keto group in methyl glyco-
side 10 using a standard NaBH4 procedure, only the
undesired lyxo-configured alcohol 9 was obtained. In
the pyranose series, a dramatic improvement of the ste-
reoselectivity of C-2 reduction was achieved32 with the
use of sterically demanding LiB(iBu)3H (L-Selectride).
Mindful of this precedent, L-Selectride was investigated
with substrates 10 and 15. For the former, a mixture of
1
determined on the basis of intensities of signals in H
NMR spectra, specifically resonances of CH@CH2 and
p-CH3C6H4S groups, which were not overlapping.
Anomeric configurations were assigned tentatively on
3
the basis of JH-1,H-2 coupling constants, which were
Figure 2. X-ray crystal structure of exo-vinyl derivative 3.

214
M. T. de Oliveira et al. / Carbohydrate Research 343 (2008) 211–220
OMe
OMe
OMe
HO
O
OMe
O
a
O
O
c
O
b
d
STol
BnO
BnO
BnO
BnO
BnO
BnO
OAc
O
BnO
BnO
BnO
OAc
OH
BnO
7
8
9
10
11
OMe
Me
BnO
O
e
HO
OBn
12
OMe
OMe
OMe
OMe
Me
BnO
Me
BnO
Me
BnO
Me
BnO
O
O
O
O
b
c
d
O
O
O
O
HO
OBn
OBn
OBn
OBn
O
O
O
O
BnO
BnO
BnO
BnO
BnO
OAc
BnO
BnO
O
BnO
OH
14
13
15
16
˚
Scheme 2. Synthesis of methyl glycofuranoside 11 and disaccharide 16. Reagents and conditions: (a) MeOH, NIS, TMSOTf, 3 A mol sieves, CH2Cl2,
ꢀ30 ꢁC, 76%; (b) NaOMe, MeOH, 91% (for 9), 89% (for 14); (c) Dess–Martin periodinane, CH2Cl2, 87% (for 10), 86% (for 15); (d) L-Selectride,
˚
THF, ꢀ65 ꢁC, 72% (for 11), 80% (for 16); (e) NIS, TMSOTf, 4 A mol sieves, CH2Cl2, ꢀ30 ꢁC, 81%.
can further reduce accessibility to the a-face of ketone
disaccharide 15.
3. Conclusion
In summary, an indirect four-step procedure has been
developed for the construction of 1,2-cis-glycofurano-
sides in relation to the synthesis of aceric acid-containing
fragments of rhamnogalacturonan II. The procedure in-
volves stereospecific 1,2-trans-glycosylation, 2-OH
group deprotection followed by oxidation to ketone
and final reduction with L-Selectride. This sequence of
reactions has been successfully applied to the synthesis
of methyl glycoside 11 and disaccharide 16. The
branched-chain pentofuranosyl units in these com-
pounds have the correct anomeric configuration and pos-
sess the potential to be transformed into aceric acid
derivatives present in the natural pectic polysaccharide
RG II. Introduction of the 5-deoxy group into the pento-
furanosyl unit can be achieved by a variety of methods,
as it has been described earlier.8 The 3-C-vinyl group in
our scheme represents a precursor for the carboxyl group
and it is convenient for the construction of larger frag-
ments of RG II incorporating aceric acid. The carboxyl
group can be unmasked via ozonolysis and subsequent
aldehyde oxidation at a later stage of the oligosaccharide
assembly. The described epimerisation procedure also
conveniently leads to a free C-2 hydroxyl group, which
is required for further extension of the oligosaccharide
chain by chemical glycosylation. Synthesis of larger frag-
ments of side chain B of RG II (Fig. 1) employing this
strategy is currently under way in our laboratories.
Figure 3. X-ray crystal structure of 2-keto derivative 10.
C-2 epimers was obtained in 77% yield, favouring the
desired xylo-configured alcohol 11 (xylo:lyxo ꢁ 14:1)
when the reaction was performed at ꢀ65 ꢁC. Conve-
niently, the disaccharide 2-ulose 15 was reduced under
these conditions into alcohol 16 in 80% yield with the
formation of the undesired epimer being not observed.
These results can be rationalised on the basis of
the assumption that the attack by bulky borohydride
nucleophile on the carbonyl group occurs preferen-
tially from the (slightly) less hindered b-face of C-3-
branched glycofuranosid-2-ulose. This suggestion is sup-
ported by higher stereoselectivity of the reduction of
glycofuranosid-2-ulose 15 compared to glycoside 10.
The former has a bigger aglycon than the latter that

M. T. de Oliveira et al. / Carbohydrate Research 343 (2008) 211–220
215
4. Experimental
(9:1!6:4 petroleum ether–EtOAc) to afford compound
1 as a colourless oil (13.8 g, 48% over two steps); Rf
0.41 (hexane/EtOAc 7:3); [a]D ꢀ4.7 (c 1.2, CHCl3),
All solvents were used as supplied, except for CH2Cl2,
which was freshly distilled from CaH2. Cation-exchange
resin (Amberlite IRA120, H+-form, Fluka) was pre-
washed with water and dry MeOH before use. Dess–
Martin periodinane was prepared according to the
literature procedures.33 Reagents and dry solvents were
added via syringes through septa. Solns of reaction
products were dried with MgSO4. Evaporation of
solvents was performed under reduced pressure at 30–
40 ꢁC. Thin-layer chromatography was performed on
1
lit.20 ꢀ5; H NMR (300 MHz, CDCl3): d 1.06 (s, 9H,
t-Bu), 1.28 (s, 3H, CH3), 1.32 (s, 3H, CH3), 2.08 (s, 1H,
OH), 3.80–3.84 (m, 2H, H-5a, H-5b), 4.03–4.08 (m,
1H, H-4), 4.34–4.45 (m, 1H, H-3), 4.54 (d, 1H,
J1,2 = 3.9 Hz, H-2), 5.88 (d, 1H, H-1), 7.36–7.43 (m,
6H, Ph), 7.65–7.68 (m, 4H, Ph); 13C NMR (75 MHz,
CDCl3): d 19.1 (C(CH3)3), 26.0 (C(CH3)2), 26.8 (4C,
C(CH3)3, C(CH3)2), 63.7 (C-5), 76.4 (C-4), 87.1 (C-3),
87.4 (C-2), 105.6 (C-1), 112.6 (C(CH3)2), 127.8, 129.9
(2C), 133.3 (2C), 135.7 (2C).
aluminium-backed, pre-coated Silica gel plates 60 F254
,
(E. Merck); spots were detected by charring plates trea-
ted with 5% H2SO4 in EtOH. Products were purified by
column chromatography on silica gel (40–63 lm) using
SP4 flash purification system (Biotage). Melting points
were determined using Gallenkamp melting point appa-
ratus and are uncorrected. Optical rotations were mea-
sured at 20–21 ꢁC using Perkin–Elmer 341 polarimeter.
IR spectra were recorded on Perkin Elmer Spectrum
BX FT IR Spectrometer equipped with SensiIR dia-
4.2. 5-O-tert-Butyldiphenylsilyl-1,2-O-isopropylidene-b-
L-threo-pentofuranos-3-ulose (2)
Dess–Martin periodinane (3.4 g, 8.0 mmol) was added
to stirred soln of alcohol 1 (2.0 g, 4.7 mmol) in dry
CH2Cl2 (50 mL), the mixture was stirred for 2 h at
20 ꢁC, then poured into stirred satd aq NaHCO3 soln
(70 mL) containing Na2S2O3 (6.6 g, 16 mmol), and ex-
tracted with CH2Cl2 (2 · 60 mL). The combined organic
extracts were dried and the solvent was removed by
evaporation. The resulting residue was purified by
column chromatography (9:1!7:3 petroleum ether–
EtOAc) to give 2 as an amorphous solid (1.79 g, 90%);
Rf 0.35 (8:2 hexane–EtOAc); [a]D ꢀ12 (c 1.0, CHCl3),
lit.20 ꢀ12.0; mp 31–33 ꢁC (hexane–petroleum ether),
1
mond ATR accessory. H and 13C NMR spectra were
recorded at 20–21 ꢁC with a Varian Gemini 2000 spec-
trometer at 300 and 75 MHz, respectively, or with a
Varian Unity Plus spectrometer at 400 and
100.6 MHz, respectively, using Me4Si as an internal
standard. Resonance allocations were made with the
aid of COSY and HSQC experiments when necessary.
High resolution electrospray ionisation mass spectra
(ESIMS) were obtained on Finnigan MAT 900 XLT
mass spectrometer.
1
IR: m 1772 (CO) cmꢀ1; H NMR (400 MHz, CDCl3): d
1.04–1.06 (m, 9H, t-Bu), 1.36 (s, 3H, CH3), 1.38 (s,
3H, CH3), 3.96–3.97 (m, 2H, H-5a, H-5b), 4.29 (m,
1H, H-4), 4.38 (d, 1H, J1,2 = 6.0 Hz, H-2); 6.03 (d, 1H,
H-1), 7.36–7.44 (m, 6H, Ph), 7.63–7.73 (m, 4H, Ph);
13C NMR (100 MHz, CDCl3): d 19.5 (C(CH3)3), 26.8
(3 C, C(CH3)3), 27.0 (C(CH3)2), 27.7 (C(CH3)2), 64.7
(C-5), 77.0 (C-4), 82.5 (C-2), 102.8 (C-1), 115.0
(C(CH3)2), 128.0, 128.2 (2C), 130.0 (2C), 133.0, 133.3,
135.8, 135.9, 136.0 (C-Ar), 207.4 (C-3).
4.1. 5-O-tert-Butyldiphenylsilyl-1,2-O-isopropylidene-b-
L-arabinofuranose (1)
L-Arabinose (10.0 g, 66.6 mmol) was added to a stirred
solution of tert-butyl(chloro)diphenylsilane (17.5 mL,
67.3 mmol) and imidazole (9.0 g, 132 mmol) in DMF
(120 mL). After 2 h at 60 ꢁC, the reaction mixture was
concentrated, poured into aqueous 1 M HCl (100 mL)
and extracted with CH2Cl2 (3 · 80 mL). The combined
organic extracts were washed with water (2 · 100 mL)
and saturated aqueous NaHCO3 solution (2 · 100 mL),
dried and concentrated. Column chromatography
(8:2!3:7 petroleum ether–EtOAc) gave 5-O-tert-butyl-
diphenylsilyl-a,b-L-arabinofuranose as an oil (14.2 g,
55%); Rf 0.25 (CH2Cl2/MeOH, 9:1); 1H NMR
(400 MHz, CDCl3): d 5.28 (d, 1H, J1,2 = 3.7 Hz, H-1,
b-anomer), 5.40 (s, 1H, H-1, a-anomer). The purified
product was dissolved in a mixture of acetone (150 mL)
and 2,2-dimethoxypropane (6.8 mL, 55.0 mmol) and, I2
(2.6 g, 10.2 mmol) was added. After 1 h, satd aq Na-
HCO3 soln was added until the reaction mixture turned
colourless. The reaction mixture was concentrated and
the residue was purified by column chromatography
4.3. 5-O-tert-Butyldiphenylsilyl-1,2-O-isopropylidene-3-
C-vinyl-b-L-lyxofuranose (3)
A 1.0 M soln of vinylmagnesium bromide in THF
(3.0 mL, 3.0 mmol) was slowly added to a stirred soln
of the ketone 2 (1.00 g, 2.34 mmol) in dry THF
(10 mL) at ꢀ78 ꢁC. After 15 min, the mixture was
allowed to warm to ꢀ20 ꢁC and left at this temperature
for 1.5 h. The reaction was quenched with a mixture
of satd aq NH4Cl soln and crushed ice and then ex-
tracted with CH2Cl2 (3 · 40 mL). The combined organic
extracts were dried and the solvent was removed in
vacuo. The residue was purified by column chromatogra-
phy (1:0!75:25 petroleum ether–EtOAc) to give 3 as a
white solid (0.86 g, 81%); Rf 0.49 (8:2 hexane–EtOAc);
mp 73–75 ꢁC (hexane); [a]D ꢀ4.0 (c 1.0, CHCl3); IR: m

216
M. T. de Oliveira et al. / Carbohydrate Research 343 (2008) 211–220
3507 (OH), 1640 (C@C), no peaks near 1770 cmꢀ1; H
NMR (400 MHz, CDCl3): d 1.05 (s, 9H, t-Bu), 1.36
(s, 3H, CH3), 1.48 (s, 3H, CH3), 3.37 (s, 1H, OH),
3.86–3.94 (m, 2H, H-5a, H-5b), 4.09 (dd, 1H,
J4,5a = 5.0 Hz, J4,5b = 10.3 Hz, H-4), 4.36 (d, 1H,
J1,2 = 4.1 Hz, H-2), 5.18 (dd, 1H, Ja,b = 10.7 Hz,
CH3), 3.98 (m, 2H, H-5a, H-5b), 4.27 (dd, 1H,
J4,5a = 7.3 Hz, J4,5b = 3.9 Hz, H-4), 4.51–4.64 (m, 5H,
2 · CH2Ph, H-2), 5.41 (d, 1H, Ja,b = 11.2 Hz, CHa@
CHbHc), 5.41 (d, 1H, Ja,c = 17.8 Hz, CHa@CHbHc),
1
5.78 (d, 1H, J1,2 = 3.8 Hz, H-1), 6.00 (dd, 1H, Ja,b
,
Ja,c, CHa@CHbHc), 7.26–7.34 (m, 10H, Ph); 13C
NMR (100 MHz, CDCl3): d 26.2 (CH3), 26.7 (CH3),
67.5 (CH2Ph), 70.4 (C-5), 73.5 (CH2Ph), 82.0 (C-2),
84.4 (C-3), 86.0 (C-4), 105.6 (C-1), 113.8 (C(CH3)2),
117.8 (HC@CH2), 127.4, 127.6 (2C), 128.0, 128.5,
138.7 (C-Ar), 138.8 (2C, C-Ar and HC@CH2); HRE-
SIMS: found m/z 414.2275 [M+NH4]+; calcd for
C24H32O5N 414.2276.
Jb,c = 1.2 Hz, CHa@CHbHc), 5.45 (dd, 1H, Ja,c
=
17.2 Hz, Jb,c, CHa@CHbHc), 5.75 (d, 1 H, H-1), 5.86
(dd, 1H, Ja,b, Ja,c, CHa@CHbHc), 7.34–7.43 (m, 6H,
Ph), 7.67–7.70 (m, 4H, Ph); 13C NMR (100 MHz,
CDCl3): d 19.4 (C(CH3)3), 27.0 (3 C, C(CH3)3), 27.1
(C(CH3)2), 27.2 (C(CH3)2), 63.2 (C-5), 78.2 (C-4), 85.6
(2 C, C-2 and C-3), 104.9 (C-1), 114.8 (HC@CH2),
114.9 (C(CH3)2), 127.9 (2C), 129.9, 133.3, 135.9 (2C,
C-Ar), 139.8 (HC@CH2); HRESIMS: found m/z
455.2248; calcd for C26H35O5Si [M+H]+, 455.2248.
4.6. 1,2-Di-O-acetyl-3,5-di-O-benzyl-3-C-vinyl-a,b-
L-lyxofuranose (6)
4.4. 1,2-O-Isopropylidene-3-C-vinyl-b-L-lyxofuranose (4)
A soln of compound 5 (1.4 g, 3.5 mmol) in CH2Cl2
(1 mL) was treated with 90% aq CF3CO2H (5 mL) at
0 ꢁC and the mixture was stirred at 20 ꢁC for 1 h, diluted
with water (5 mL) and extracted with CH2Cl2
(2 · 30 mL). The organic extracts were dried, solvent
was evaporated and the residue was purified by chroma-
tography (8:2!6:4 petroleum ether–EtOAc) to give 1,2-
diol as an oil (1.10 g, 88%). Rf 0.45 (1:1 hexane–EtOAc);
A 1 M soln of TBAF in THF (15 mL, 15 mmol) was
added to a stirred soln of the silyl ether 3 (3.0 g,
6.6 mmol) in THF (15 mL). The mixture was stirred
for 2 h at 20 ꢁC, concentrated and the residue was puri-
fied by column chromatography (8:2!1:1 petroleum
ether–EtOAc) to afford the title compound 4 as an oil
(1.28 g, 90%); Rf 0.35 (6:4 hexane–EtOAc); [a]D +2.0
IR: m 3399 (OH), 1640 (C@C) cmꢀ1
;
13C NMR
1
(c 0.9, CHCl3); H NMR (400 MHz, CDCl3): d 1.41
(100 MHz, CDCl3): d 97.8 (C-1b), 104.4 (C-1a); HRE-
SIMS: found m/z 374.1962 [M+NH4]+; calcd for
C21H28O5N 374.1962. The purified product (0.60 g,
1.68 mmol) was dissolved in pyridine (2 mL), Ac2O
(2.0 mL, 32 mmol) was added and the mixture was kept
for 17 h at 20 ꢁC. The mixture was repeatedly diluted
with toluene and concentrated. The residual solid was
dissolved in 15 mL of CH2Cl2, and the soln was washed
with 0.1 M aq HCl soln (2 · 5 mL) and saturated aq
NaHCO3 soln (5 mL), dried over MgSO4 and concen-
trated. Purification of the residue by column chromato-
graphy (9:1!7:3 petroleum ether–EtOAc) gave 6 (0.60 g,
71%) as a 8.5:1 mixture of anomers. Minor anomer of 6:
Rf 0.22 (8:2 hexane–EtOAc), 1H NMR (400 MHz,
(s, 3H, CH3), 1.65 (s, 3H, CH3), 3.87 (d, 2H,
J4,5 = 5.2 Hz, H-5a, H-5b), 3.97 (t, 1H, J4,5, H-4), 4.48
(br s, 2H, OH), 4.40 (d, 1H, J1,2 = 4.2 Hz, H-2), 5.26
(d, 1H, Ja,b = 10.8 Hz, CHa@CHbHc), 5.50 (d, 1H,
Ja,c = 17.2 Hz, CHa@CHbHc), 5.84 (d, 1H, H-1), 5.91
(dd, 1H, Ja,b
,
Ja,c
,
CHa@CHbHc); 13C NMR
(100 MHz, CDCl3): d 27.0 (2C, CH3), 61.6 (C-5), 78.5
(C-4), 85.1 (C-2), 85.7 (C-3), 105.0 (C-1), 114.7
(C(CH3)2), 114.9 (HC@CH2), 139.5 (HC@CH2); HRE-
SIMS: found m/z 234.1335 [M+NH4]+; calcd for
C10H20O5N, 234.1336.
4.5. 3,5-Di-O-benzyl-1,2-O-isopropylidene-3-C-vinyl-b-L-
lyxofuranose (5)
CDCl3): d 2.02 (s, Ac), 2.07 (s, Ac), 5.58 (d,
J1,2 = 4.9 Hz, H-2), 6.40 (d, H-1). Analytical sample of
the major anomer of 6: Rf 0.25 (8:2 hexane–EtOAc);
[a]D ꢀ29.9 (c 1.2, CHCl3); IR: m 1746 (C@O) no peaks
Sodium hydride (60% suspension in mineral oil, 3.6 g,
90 mmol) was added to a stirred soln of the diol 4
(2.1 g, 9.7 mmol), benzyl bromide (3.5 mL, 29 mmol)
and Bu4NI (1.1 g, 3.0 mmol) in DMF (30 mL) at 0 ꢁC.
The mixture was allowed to warm to room temperature
and stirred for 3 h. MeOH (10 mL) was added carefully
and the reaction mixture was concentrated. The residue
was dissolved in CH2Cl2 (100 mL), washed with water
(2 · 20 mL) and saturated aq NaHCO3 soln (2 ·
20 mL), dried and concentrated. Column chromatogra-
phy of the residue (1:0!8:2 petroleum ether–EtOAc)
gave compound 5 as an oil (2.9 g, 75%). Rf 0.45 (8:2
1
near 3650 cmꢀ1; H NMR (400 MHz, CDCl3): d 2.04
(s, 3H, Ac), 2.09 (s, 3H, Ac), 3.78 (dd, 1H, J4,5a
=
6.7 Hz, J5a,5b = 10.8 Hz, H-5a), 3.89 (dd, 1H,
J4,5b = 4.0 Hz, H-5b), 4.41 (dd, 1H, H-4), 4.49 (d, 1H,
Jgem = 12.0 Hz, CHPh), 4.58 (d, 1H, Jgem, CHPh), 4.59
(d, 1H, Jgem, CHPh), 4.68 (d, 1H, CHPh), 5.44 (d, 1H,
Ja,b = 11.1 Hz, CHa@CHbHc), 5.53 (d, 1H, Ja,c
=
17.7 Hz, CHa@CHbHc), 5.71 (d, 1H, J1,2 = 3.6 Hz, H-
2), 5.97 (dd, 1H, Ja,b, Ja,c, CHa@CHbHc), 6.31 (d, 1H,
H-1), 7.26–7.34 (m, 10H, Ph); 13C NMR (100 MHz,
CDCl3): d 21.0 (CH3), 21.4 (CH3), 68.3 (CH2Ph), 68.5
(C-5), 73.7 (CH2Ph), 79.6 (C-2), 85.0 (C-3), 85.7 (C-4),
1
hexane–EtOAc); [a]D ꢀ24.1 (c 1.0, CHCl3); H NMR
(400 MHz, CDCl3): d 1.33 (s, 3H, CH3), 1.51 (s, 3H,

M. T. de Oliveira et al. / Carbohydrate Research 343 (2008) 211–220
217
99.7 (C-1), 119.7 (HC@CH2), 126.9, 127.5, 127.9, 128.0,
128.5 (2C), 128.6, 134.4, 138.1 (C-Ar), 139.2
(HC@CH2), 169.8 (CO), 170.2 (CO); HRESIMS: found
m/z 463.1728 [M+Na]+; calcd for C25H28O7Na
463.1727.
then cooled to ꢀ30 ꢁC. After addition of N-iodosuccin-
imide (0.12 g, 0.53 mmol) and TMSOTf (16 lL,
0.086 mmol,), the mixture was stirred for 1 h at
ꢀ30 ꢁC and then treated with a few drops of Et3N. Di-
luted aq Na2S2O3 soln (10 mL) was added at 20 ꢁC, the
mixture was stirred for 30 min, extracted with CH2Cl2
(3 · 10 mL), dried and concentrated. The residue was
purified by column chromatography (1:0!8:2 hexane–
EtOAc) to give methyl glycofuranoside 8 as an oil
(0.13 g, 76%); Rf 0.37 (8:2 hexane–EtOAc); [a]D ꢀ51.0
(c 1.0, CHCl3); IR: m 1746 (C@O), no peaks near
4.7. p-Tolyl 2-O-acetyl-3,5-di-O-benzyl-1-thio-3-C-vinyl-
a,b-L-lyxofuranoside (7)
A soln of acetate 6 (0.20 g, 0.45 mmol) and thiocresol
(65 mg, 0.52 mmol) in dry CH2Cl2 (5 mL) was carefully
treated with BF3ÆOEt2 (45 lL, 0.90 mmol) at 0 ꢁC and
the mixture was kept at 5 ꢁC for 1 h. Triethylamine
(0.5 mL) was added and the resulting soln was diluted
with CH2Cl2 and washed with satd aq NaHCO3 soln
and water. The organic layer was dried, filtered and con-
centrated. The product was purified by column chroma-
tography (1:0!9:1 petroleum ether–EtOAc) to yield 7
(0.21 g, 92%, a:b 1:8) as a colourless syrup. Repeated
purification of a small sample of 7 afforded pure b-ano-
mer, Rf 0.28 and a-anomer, Rf 0.21 (9:1 hexane–EtOAc).
3400 cmꢀ1 1H NMR (400 MHz, CDCl3): d 2.02 (s,
;
3H, COCH3), 3.43 (3H, s, OCH3), 3.80 (dd,
1H, J4,5a = 7.1 Hz, J5a,5b = 10.8 Hz, H-5a), 3.90 (dd,
1H, J4,5b = 3.8, H-5b), 4.33 (dd, 1H, H-4), 4.52 (d, 1H,
Jgem = 12.0 Hz, CHPh), 4.58–4.60 (m, 2H, 2 · CHPh),
4.64 (d, 1H, Jgem = 12.0 Hz, CHPh), 5.08 (d, 1H,
J1,2 = 3.1 Hz, H-2), 5.38 (d, 1H, Ja,b = 11.1 Hz,
CHa@CHbHc),
5.50
(d,
1H,
Ja,c = 17.7 Hz,
CHa@CHbHc), 5.52 (d, 1H, H-1), 5.99 (dd, 1H, Ja,b
,
Ja,c, CHa@CHbHc), 7.26–7.34 (m, 10H, Ph); 13C
NMR (100 MHz, CDCl3): d 21.1 (Ac), 55.9 (OCH3),
68.0 (CH2Ph), 70.0 (C-5), 73.6 (CH2Ph), 79.9 (C-2),
84.5 (C-4), 85.3 (C-3), 107.0 (C-1), 118.9 (HC@CH2),
126.8, 127.4, 127.8, 128.0, 128.5, 128.6, 135.4, 138.4
(C-Ar), 139.4 (HC@CH2), 169.9 (CO); HRESIMS:
found m/z 435.1779 [M+Na]+; calcd for C24H28O6Na
435.1778.
1
Thioglycoside b-7: [a]D ꢀ72.0 (c 1.2, CHCl3); H NMR
(400 MHz, CDCl3): d 2.10 (s, 3H, Ac), 2.33 (s, 3H,
CH3C6H4S), 3.74 (dd, 1H, J4,5a = 4.7 Hz, J5a,5b
=
10.8 Hz, H-5a), 3.91 (dd, 1H, J4,5b = 6.3 Hz, H-5b),
4.20 (dd, 1H, H-4), 4.49 (d, 1H, Jgem = 12.0 Hz, CHPh),
4.59 (m, 2H, PhCH), 4.75 (d, 1H, Jgem = 12.0 Hz,
PhCH), 5.36 (d, 1H, Ja,b = 11.2 Hz, CHa@CHbHc),
5.43 (d, 1H, J1,2 = 7.3 Hz, H-1), 5.44 (d, 1H,
Ja,c = 17.8 Hz, CHa@CHbHc), 5.65 (d, 1H, H-2), 5.91
(dd, 1H, Ja,b, Ja,c, CHa@CHbHc), 7.12–7.46 (m, 14H,
Ph); 13C NMR (100 MHz, CDCl3): d 21.2 (CH3C6H4S),
21.4 (OC(O)CH3), 68.2 (C-5), 68.4 (PhCH2), 73.5
(PhCH3), 78.3 (C-2), 84.4 (C-3), 84.6 (C-4), 88.4 (C-1),
119.6 (HC@CH2), 126.9–138.4 (Ph), 139.5 (HC=CH2),
169.6 (CO); HRESIMS: found m/z 522.2309
[M+NH4]+; calcd for C30H40O5NS 522.2309. Thiogly-
coside a-7: 1H NMR (400 MHz, CDCl3): d 2.13 (s,
3H, Ac), 2.31 (s, 3H, CH3C6H4S), 3.91 (dd, 1H,
J4,5a = 4.5 Hz, J5a,5b = 10.7 Hz, H-5a), 4.00 (dd, 1H,
J4,5b = 6.9 Hz, H-5b), 4.24 (dd, 1H, H-4), 4.55 (d,
1H, Jgem = 12.0 Hz, CHPh), 4.57 (2H, m, CHPh), 4.65
(1H, d, Jgem 12.0 Hz, CHPh), 4.69 (1H, d, Jgem, CHPh),
5.63 (d, 1H, H-1 or H-2, J1,2 = 5.8 Hz), 5.67 (d, 1H, H-1
or H-2), 5.46 (d, 1H, Ja,b = 11.2 Hz, CHa@CHbHc),
5.47 (d, 1H, Ja,c = 17.7 Hz, CHa@CHbHc), 6.00 (dd,
1H, Ja,b, Ja,c, CHa@CHbHc), 7.09–7.39 (m, 14H, Ph);
HRESIMS: found m/z 527.1869 [M+Na]+; calcd for
C30H40O5NS 527.1863.
4.9. Methyl 3,5-di-O-benzyl-3-C-vinyl-a-L-lyxofuranoside
(9)
A soln of monoacetate 8 (0.22 g, 0.53 mmol) in CH2Cl2
(2 mL) was treated with 1.0 M NaOMe in MeOH
(0.6 mL), the mixture was stirred for 1 h at 20 ꢁC., di-
luted with MeOH (10 mL) and treated with Amberlite
IRA-120 (H+) ion exchange resin. After removal of
the resin by filtration, the filtrate was concentrated and
the residue was purified by column chromatography
(1:0!8:2 hexane–EtOAc) to afford alcohol 9 as an oil
(0.18 g, 91%). Rf 0.29 (8:2 hexane–EtOAc); [a]D ꢀ64.5
(c 1.1, CHCl3); IR: m 3381 (O–H) cmꢀ1, no peaks near
1750 cmꢀ1
;
1H NMR (400 MHz, CDCl3): d 3.40 (s,
3H, OCH3), 3.69 (dd, 1H, J4,5a = 3.7 Hz, J5a,5b
=
10.5 Hz, H-5a), 3.77 (dd, 1H, J4,5b = 2.9, H-5b), 4.07
(br s, 1H, H-2), 4.23 (d, 1H, J4,5 = 3.2 Hz, H-4), 4.53
(d, 1H, Jgem = 11.8 Hz, PhCH), 4.57–4.60 (m, 2H,
CHPh), 4.64 (d, 1H, Jgem = 11.2 Hz, PhCH), 4.99 (br
s, 1H, H-1), 5.37 (d, 1H, Ja,b = 11.1 Hz, CHa@CHbHc),
5.47 (d, 1H, Ja,c = 17.7 Hz, CHa@CHbHc), 6.20 (dd,
1H, Ja,b, Ja,c, CHa@CHbHc), 7.26–7.33 (m, 10H, Ph);
13C NMR (100 MHz, CDCl3): d 55.8 (OCH3), 67.5
(CH2Ph), 68.8 (C-5), 74.1 (CH2Ph), 77.8 (C-2), 84.2
(C-3), 85.9 (C-4), 111.0 (C-1), 117.3 (HC@CH2), 127.6
(2C), 128.0, 128.1, 128.5, 128.7, 137.5, 137.9 (C-Ar),
4.8. Methyl 2-O-acetyl-3,5-di-O-benzyl-3-C-vinyl-a-L-
lyxofuranoside (8)
A mixture of thioglycoside 7 (0.21 g, 0.42 mmol), MeOH
˚
(175 lL, 4.32 mmol) and 3 A mol sieves (0.5 g) in
CH2Cl2 (12 mL) was stirred for 20 min at 20 ꢁC and

218
M. T. de Oliveira et al. / Carbohydrate Research 343 (2008) 211–220
139.0 (HC@CH2); HRESIMS: found m/z 393.1676
(d, 1H, H-1,), 5.37 (dd, 1H, Ja,c = 17.6 Hz, Jb,c
1.3 Hz, CHa@CHbHc), 5.38 (dd, 1H, Ja,b = 11.3 Hz,
Jb,c Ja,c,
=
[M+Na]+; calcd for C22H26O5Na 393.1672.
,
CHa@CHbHc), 6.06 (dd, 1H, Ja,b
,
4.10. Methyl 3,5-di-O-benzyl-3-C-vinyl-a-L-erythro-
pentofuranosid-2-ulose (10)
CHa@CHbHc), 7.25–7.34 (m, 10H, Ph); 13C NMR
(100 MHz, CDCl3): d 56.1 (CH3), 66.9 (CH2Ph), 68.9
(C-5), 73.6 (CH2Ph), 76.3 (C-2), 83.5 (C-4), 87.1 (C-3),
102.5 (C-1), 117.7 (HC@CH2), 126.6, 127.4, 127.7,
127.9, 128.5 (C-Ar), 133.6 (HC@CH2), 138.5, 139.2
(C-Ar); HRESIMS: found m/z 388.2115 [M+NH4]+;
calcd for C22H30O5N 388.2118.
Dess–Martin periodinane (0.53 g, 1.25 mmol) was added
to a stirred soln of the alcohol 9 (0.23 g, 0.62 mmol) in
dry CH2Cl2 (10 mL) at 20 ꢁC. After 2 h, the reaction
mixture was poured into stirred saturated aq NaHCO3
soln (10 mL) containing Na2S2O3 (1.0 g, 6.3 mmol),
and extracted with CH2Cl2 (2 · 15 mL). The combined
organic extracts were dried, solvent was removed in
vacuo and the residue was purified by column chromato-
graphy (9:1!8:2 petroleum ether–EtOAc) to give 10 as
a white solid (0.20 g, 87%); Rf 0.54 (8:2 hexane–EtOAc);
mp 76–77 ꢁC (hexane); IR: m 1772 (C@O), 1640 (C@C),
no peaks near 3400 cmꢀ1; [a]D +61.0 (c 1.0, CHCl3); 1H
NMR (400 MHz, CDCl3): d 3.50 (s, 3H, OCH3), 3.87
(dd, 1H, J4,5a = 6.2 Hz, J5a,5b = 10.8 Hz, H-5a,), 3.97
(dd, 1H, J4,5b = 4.0 Hz, H-5b), 4.46 (dd, 1H, H-4),
4.51 (d, 1H, Jgem = 11.6 Hz, CHPh), 4.54 (d, 1H, CHPh,
Jgem = 11.6 Hz), 4.62 (d, 1H, Jgem = 12.4 Hz, CHPh),
4.65 (d, 1H, Jgem = 12.4 Hz, CHPh), 4.89 (s, 1H, H-1),
4.12. Methyl 2,4-di-O-benzyl-3-O-(2-O-acetyl-3,5-di-O-
benzyl-3-C-vinyl-a-L-lyxofuranosyl)-a-L-rhamnopyran-
oside (13)
A mixture of thioglycosides 7 (0.20 g, 0.40 mmol),
methyl 2,4-di-O-benzyl-a-L-rhamnopyranoside (12)26
˚
(0.15 g, 0.42 mmol) and 4 A molecular sieves (0.5 g) in
CH2Cl2 (8 mL) was stirred under nitrogen for 20 min
at 20 ꢁC and then cooled to ꢀ30 ꢁC. N-Iodosuccinimide
(0.11 g, 0.49 mmol) and TMSOTf (10 lL, 0.055 mmol)
were added and the mixture was stirred at this tempera-
ture for 40 min. The mixture was treated with Et3N
(0.5 mL) and diluted aq Na2S2O3 soln to remove the yel-
low colour. After dilution with CH2Cl2 (10 mL) the mix-
ture was washed with water (2 · 10 mL), organic layer
was concentrated in vacuo and the residue was purified
by column chromatography (1:0!8:2 petroleum ether–
EtOAc). The disaccharide 13 was obtained as a colour-
less oil (0.24 g, 81%); Rf 0.28 (8:2 hexane–EtOAc); [a]D
ꢀ71.0 (c 1.0, CHCl3); IR: m 1747 (C@O), no peaks near
3400 cmꢀ1; 1H NMR (400 MHz, CDCl3): d 1.31 (d, 3H,
J5,6 = 6.0 Hz, H-6), 1.72 (s, 3H, Ac), 3.28 (s, 3H, OCH3),
5.47 (dd, 1H, Ja,c = 17.6 Hz, Jb,c
=
0.8 Hz,
CHa@CHbHc), 5.53 (dd, 1H, Ja,b = 11.2 Hz, Jb,c
,
CHa@CHbHc), 5.87 (dd, 1H, Ja,b, Ja,c CHa@CHbHc),
7.22–7.34 (m, 10H, Ph); 13C NMR (100 MHz, CDCl3):
d 56.5 (OCH3), 67.1 (CH2Ph), 68.0 (C-5), 73.8 (CH2Ph),
79.8 (C-3), 83.8 (C-4), 99.1 (C-1), 121.7 (HC@CH2),
127.3, 127.8, 127.9 (2C), 128.6, 131.5, 138.2 (C-Ar),
138.2 (HC@CH2), 205.4 (C-2); HRESIMS: found m/z
391.1519 [M+Na]+; calcd for C22H24O5Na 391.1516.
4.11. Methyl 3,5-di-O-benzyl-3-C-vinyl-a-L-xylofuran-
oside (11)
3.57 (t, 1H, J3,4 = J4,5 = 9.6 Hz, H-4), 3.68 (dq, 1H, J4,5
,
0
0
0
0
J5,6, H-5), 3.76 (dd, 1H, J4 ;5 a ¼ 6:8 Hz, J5 a;5 b
¼
10:8 Hz, H-50a), 3.87 (dd, 1H, J4 ;5 b ¼ 4:0 Hz, J5 a;5 b
,
0
0
0
0
A 1.0 M soln of lithium tri-sec-butylborohydride (L-
Selectride) in THF (0.53 mL) was added slowly under
nitrogen to a soln of the ulose 10 (150 mg, 0.407 mmol)
in THF (3 mL) at ꢀ55 ꢁC. After 40 min, satd aq NaH-
CO3 soln (10 mL) was added and the mixture was ex-
tracted with CH2Cl2 (3 · 10 mL). The combined
organic extracts were dried, solvent was evaporated
and the residue was purified by column chromatography
(1:0!7:3 hexane–EtOAc) to give alcohol 11 as a colour-
less oil (108 mg, 72%) along with the C-2 epimer 9 (8 mg,
5%). Compound 11: Rf 0.22 (8:2 hexane–EtOAc); [a]D
ꢀ20.1 (c 1.0, CHCl3), IR: m 3521 (OH), no peaks near
H-50b), 3.95 (dd, 1H, J1,2 = 1.5 Hz, J2,3 = 3.0 Hz, H-
0
0
0
0
2), 4.03 (dd, 1H, H-3,), 4.34 (dd, 1H, J4 ;5 a, J4 ;5 b, H-
40), 4.48 (d, 1H, Jgem = 11.6 Hz, CHPh,), 4.51–4.55 (m,
2H, H-20, CHPh), 4.58 (d, 1H, Jgem = 12 Hz, CHPh),
4.59 (d, 1H, Jgem = 11.2 Hz, CHPh,), 4.64 (d, 1H,
Jgem = 12.0 Hz, CHPh), 4.65 (d, 1H, Jgem = 12.4 Hz,
CHPh), 4.81 (d, 1H, Jgem = 12.4 Hz, CHPh), 4.85 (d,
1H, Jgem = 11.6 Hz, CHPh), 5.36 (d, 1H, Ja,b = 11.0 Hz,
CHa@CHbHc), 5.51 (br s, 1H, H-1), 5.53 (d, 1H,
0
0
Ja,c = 17.8 Hz, CHa@CHbHc), 5.75 (d, 1H, J1 ;2
¼
3:7 Hz, H-10), 5.96 (dd, 1H, Ja,b, Ja,c, CHa@CHbHc),
7.36–7.24 (m, 20H, Ph); 13C NMR (100 MHz, CDCl3):
d 17.9 (C-6), 20.4 (OCOCH3), 54.6 (OCH3), 67.7 (C-
5), 67.9 (CH2Ph), 68.9 (C-50), 73.3 (CH2Ph), 73.4
(CH2Ph), 74.9 (CH2Ph), 78.4 (C-20), 79.8 (C-3), 80.2
(C-2), 80.7 (C-4), 84.3 (C-40), 85.0 (C-30), 99.2 (C-1),
107.8 (C-10), 118.9 (HC@CH2), 126.6, 127.2, 127.3,
127.4, 127.5, 127.6, 127.7, 128.2, 128.3 (C-Ar), 134.7
(HC@CH2), 138.2, 138.7, 138.8, 139.2 (C-Ar), 169.5
1770 cmꢀ1 1H NMR (400 MHz, CDCl3): d 3.52 (s,
;
3H, CH3), 3.76 (dd, 1H, J4,5a = 7.4 Hz, J5a,5b = 11.2 Hz,
H-5a), 3.83 (dd, 1H, J4,5b = 2.6 Hz, H-5b), 4.27 (dd, 1H,
H-4), 4.33 (d, 1H, J1,2 = 4.6 Hz, H-2), 4.52 (d, 1H,
Jgem = 12.4 Hz, CHPh,), 4.53 (d, 1H, Jgem = 12.4 Hz,
CHPh), 4.62 (d, 1H, Jgem = 12.2 Hz, CHPh), 4.64 (d,
1H, Jgem = 12.2 Hz, CHPh), 4.83 (br s, 1H, OH), 5.10

M. T. de Oliveira et al. / Carbohydrate Research 343 (2008) 211–220
219
(CO); HRESIMS: found m/z 761.3306 [M+Na]+; calcd
(d, 3H, J5,6, H-6,), 3.28 (s, 3H, OCH3), 3.59 (t, 1H,
for C44H50O10Na 761.3296.
J3,4 = J4,5 = 9.4 Hz, H-4), 3.68 (dq, 1H, J4,5
=
0
0
12.2 Hz, J5,6 = 6.0 Hz, H-5), 3.84 (dd, 1H, J4 ;5 a
¼
0
0
4.13. Methyl 2,4-di-O-benzyl-3-O-(3,5-di-O-benzyl-3-C-
vinyl-a-L-lyxofuranosyl)-a-L-rhamnopyranoside (14)
6:2 Hz, J5 a;5 b ¼ 10:8 Hz, H-50a), 3.87–3.91 (m, 1H,
H-2), 3.94 (dd, 1H, J4 ;5 b ¼ 3:6 Hz, J5 a;5 b, H-50b),
4.11 (dd, 1H, J2,3 = 3.1 Hz, J3,4 = 9.4 Hz, H-3), 4.47–
4.63 (m, 10H, H-1, H-40, 8 · CHPh), 4.76 (d, 1H,
Jgem = 12.1 Hz, PhCH), 5.01 (d, 1H, Jgem = 10.4 Hz,
PhCH), 5.33 (s, 1H, H-10), 5.50 (d, 1H, Ja,c = 17.8 Hz,
0
0
0
0
The disaccharide 13 (0.25 g, 0.34 mmol) was dissolved in
CH2Cl2 (1 mL) and treated with 1.0 M soln of NaOMe
in MeOH (0.30 mL). The resulting soln was stirred at
room temperature for 1 h, diluted with MeOH
(10 mL) and treated with Amberlite IRA-120 (H+) ion
exchange resin. The mixture was filtered and concen-
trated in vacuo. Column chromatography (1:0!8:2
petroleum ether–EtOAc) gave the title compound 14
as an oil (0.21 g, 89%); Rf 0.24 (8:2 hexane–EtOAc);
CHa@CHbHc),
5.51
(d,
1H,
Ja,b = 11.1 Hz,
CHa@CHbHc), 5.89 (dd, 1H, Ja,b, Ja,c, CHa@CHbHc),
7.21–7.43 (m, 20H, Ph); 13C NMR (100 MHz, CDCl3):
d 18.2 (C-6), 54.9 (OCH3), 67.2 (CHPh), 68.1 (2C,
C-5, C-50), 73.5 (CHPh), 73.8 (CHPh), 75.8
(CHPh), 78.8 (C-2), 79.9 (C-4), 80.3 (C-30), 81.4
(C-3), 83.8 (C-40), 99.2 (C-1), 100.1 (C-10), 121.6
(HC@CH2), 127.3, 127.7, 127.8 (2C), 127.9, 128.0,
128.5, 128.6 (3C), 128.7 (C-Ar), 131.8 (HC@CH2),
138.3 (2C), 138.6, 138.8 (C-Ar), 205.0 (C-20); HRE-
SIMS: found m/z 712.3481 [M+NH4]+; calcd for
C42H50O9N 712.3480.
IR thin film: m 3374 (OH), no peaks near 1750 cmꢀ1
;
[a]D +37.4 (c 1.1, CHCl3); 1H NMR (400 MHz, CDCl3):
d 1.33 (d, 3H, J5,6 = 6.0 Hz, H-6), 3.29 (s, 3H, OCH3),
3.58 (t, 1H, J3,4 = J4,5 = 9.4 Hz, H-4), 3.64–3.71 (m,
0
0
0
0
1H, H-5), 3.68 (dd, 1H, J4 ;5 a ¼ 3:4 Hz, J5 a;5 b ¼
0
,
10:4 Hz, H-50a), 3.76 (dd, 1H, J4 ;5 b ¼ 2:9 Hz, J5 a;5 b
0
0
0
H-50b), 3.88 (br s, 1H, H-20), 4.01 (dd, 1H,
J2,3 = 3.1 Hz, H-3), 4.17 (m, 1H, H-40), 4.24 (m, 1H,
H-2), 4.53–4.63 (m, 6H, H-1, CHPh,), 4.65 (d, 1H,
Jgem = 10.9 Hz, CHPh), 4.74 (d, 1H, Jgem = 12.0 Hz,
CHPh), 4.80 (br s, 1H, OH), 4.91 (d, 1H, CHPh,
4.15. Methyl 2,4-di-O-benzyl-3-O-(3,5-di-O-benzyl-3-C-
vinyl-a-L-xylofuranosyl)-a-L-rhamnopyranoside (16)
A 1.0 M soln of lithium tri-sec-butylborohydride (L-
Selectride) in THF (0.4 mL) was added slowly under
nitrogen to a soln of the ulose 15 (0.20 g, 0.29 mmol)
in 2.5 mL of THF at ꢀ40 ꢁC. After 1 h, satd aq NaH-
CO3 soln (10 mL) was added and the mixture was
extracted with CH2Cl2 (3 · 10 mL). The combined
organic extracts were dried and solvent was removed
in vacuo. The residue was purified by column chroma-
tography (1:0!8:2 hexane–EtOAc) to give 16 as a col-
ourless oil (0.16 g, 80%); Rf 0.24 (8:2 hexane–EtOAc);
[a]D ꢀ63.0 (c 1.0, CHCl3); IR: m 3491, no peaks near
Jgem = 10.7 Hz),
5.28
(d,
1H,
Ja,b = 11.1 Hz,
CHa@CHbHc), 5.41 (d, 1H, J1 ;2 ¼ 0:9 Hz, H-10), 5.48
(d, 1H, Ja,c = 17.7 Hz, CHa@CHbHc), 6.29 (dd, 1H,
Ja,b, Ja,c, CHa@CHbHc), 7.24–7.40 (m, 20H, Ph); 13C
NMR (100 MHz, CDCl3): d 18.2 (C-6), 54.9 (OCH3),
67.5 (C-5), 68.0 (CH2Ph), 68.9 (C-50), 73.4 (CH2Ph),
74.0 (CH2Ph), 74.0 (CH2Ph), 75.7 (CH2Ph), 78.6, 78.9
(C-2, C-20), 80.4 (2C, C-3, C-4), 84.2 (C-30), 85.9 (C-
40), 99.3 (C-1), 112.0 (C-10), 117.4 (HC@CH2), 127.5,
127.6, 127.7, 127.8, 128 (3C), 128.5 (3C), 128.7, 137.5
(C-Ar), 137.7 (HC@CH2), 138.6, 138.6, 138.9, 139.0
(C-Ar); HRESIMS: found m/z 714.3637 [M+NH4]+;
calcd for C42H52O9N 714.3637.
0
0
1750 cmꢀ1 1H NMR (400 MHz, CDCl3): d 1.36 (d,
;
3H, J5,6 = 9.5 Hz, H-6), 3.30 (s, 3H, OCH3), 3.59 (t,
1H, J3,4 = J4,5 = 9.5 Hz, H-4), 3.66–3.79 (m, 1H, H-5),
3.75 (dd, 1H, J4 ;5 a ¼ 7:4 Hz, J5 a;5 b ¼ 11:2 Hz, H-50a),
0
0
0
0
3.84 (dd, 1H, J4,5b = 2.4 Hz, J5 a;5 b, H-50b), 3.95–3.99
(m, 1H, H-2), 4.16 (dd, 1H, J2,3 = 3.2 Hz, H-3), 4.25
0
0
4.14. Methyl 2,4-di-O-benzyl-3-O-(3,5-di-O-benzyl-3-C-
vinyl-a-L-erythro-pentofuranosyl-2-ulose)-a-L-rhamno-
pyranoside (15)
(d, 1H, J1 ;2 ¼ 4:4 Hz, H-20), 4.34 (dd, 1H, H-40),
0
0
4.37–4.78 (m, 9H, H-1, CHPh), 4.81 (br s, 1H, OH),
0
0
,
Dess–Martin periodinane (0.25 g, 0.59 mmol) was
added to stirred soln of the alcohol 14 (0.21 g,
0.30 mmol) in dry CH2Cl2 (10 mL) at 20 ꢁC. After
2 h, the reaction mixture was poured into stirred satd
aq NaHCO3 soln (10 mL) containing Na2S2O3 (1.0 g,
6.3 mmol), and extracted with CH2Cl2 (2 · 15 mL).
The combined organic extracts were dried and the sol-
vent was removed in vacuo. The residue was purified by
column chromatography (9:1!8:2 petroleum ether–
EtOAc) to give 15 as an oil (0.18 g, 86%); Rf 0.34;
[a]D +4.0 (c 1.0; CHCl3); IR: m 1730 (C@O), no peaks
5.32–5.42 (m, 2H, CHa@CHbHc), 5.48 (d, 1H, J1 ;2
H-10), 6.09 (dd, 1H, Ha, Ja,b = 10.9 Hz, Ja,c = 18.1 Hz,
CHa@CHbHc), 7.24–7.37 (m, 20H, Ph); 13C NMR
(100 MHz, CDCl3): d 18.3 (C-6), 55.0 (OCH3), 65.8
(CHPh), 68.0 (C-5), 68.9 (CHPh), 73.5 (2C, CHPh),
75.6 (CHPh), 76.0 (C-20), 78.7 (C-2), 79.6 (C-3), 80.7
(C-4), 83.7 (C-40), 87.3 (C-30), 99.1 (C-1), 103.7 (C-10),
118.0 (HC@CH2), 126.7, 127.7, 127.8, 127.9 (2C),
128.0, 128.1, 128.5, 128.6 (2C), 128.7 (C-Ar), 133.3
(HC@CH2), 138.3, 138.6, 138.7, 139.1 (C-Ar); HRE-
SIMS: found m/z 714.3635 [M+NH4]+; calcd for
C42H52O9N 714.3637.
1
near 3400 cmꢀ1; H NMR (400 MHz, CDCl3): d 1.34

220
M. T. de Oliveira et al. / Carbohydrate Research 343 (2008) 211–220
8. Jones, N. A.; Nepogodiev, S. A.; MacDonald, C. J.;
Acknowledgements
Hughes, D. L.; Field, R. A. J. Org. Chem. 2005, 70, 8556–
8559.
9. Timmer, M. S. M.; Stocker, B. L.; Seeberger, P. H. J. Org.
Chem. 2006, 71, 8294–8297.
10. Mukaiyama, T.; Hashimoto, Y.; Shoda, S. Chem. Lett.
1983, 935–938.
This work is supported by the BBSRC, the EPSRC and
the Weston Foundation. We are indebted to the EPSRC
Mass Spectrometry Service Centre, Swansea for invalu-
able support. M.T.O. is grateful to the Programme
Alban, the European Union Programme of High Level
Scholarships for Latin America, Scholarship No.
E04D033454BR.
`
11. Gelin, M.; Ferrieres, V.; Plusquellec, D. Eur. J. Org.
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Supplementary data
15. Lee, Y. J.; Lee, K.; Jung, E. H.; Jeon, H. B.; Kim, K. S.
Org. Lett. 2005, 7, 3263–3266.
16. Gadikota, R. R.; Callam, C. S.; Lowary, T. L. Org. Lett.
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Complete crystallographic data for the structural analy-
sis of compounds 3 and 10 have been deposited with the
Cambridge Crystallographic Data Centre, CCDC Nos.
658522 and 658523, respectively. Copies of this informa-
tion may be obtained free of charge from Cambridge
Crystallographic Data Centre, (e-mail: deposit@ccdc.
`
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