Differential O-3/O-4 selectivity in the glycosylation of N-dimethylmaleoyl-protected hexosamine acceptors: Effect of a conformationally armed (superarmed) glycosyl donor

Article abstract of DOI:10.1016/j.carres.2013.08.002

An assessment of the relative O-3/O-4 reactivities of both α- and β-methyl glycosides of N-dimethylmaleoyl (DMM) glucosamine and allosamine acceptors protected at O-6 with a benzyl group using a d-glucopyranosyl conformationally armed donor (superarmed donor) counterpart is presented. The glycosylation of glucosamine derivatives followed the trends already observed for disarmed donors. On the other hand, the glycosylation of allosamine derivatives gave exclusively substitution on the equatorial O-4, in spite that with a disarmed donor the point of substitution is exclusively on the more hindered, electronically-preferred O-3.

Full text of DOI:10.1016/j.carres.2013.08.002

Carbohydrate Research 380 (2013) 167–173
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Differential O-3/O-4 selectivity in the glycosylation of N-dim-
ethylmaleoyl-protected hexosamine acceptors: effect of a conform-
ationally armed (superarmed) glycosyl donor
F. Della Felice a, Edmundo A. Rúveda a, Carlos A. Stortz b, María I. Colombo a,
⇑
a Instituto de Química Rosario (CONICET-UNR), Facultad de Ciencias Bioquímicas y Farmacéuticas, Suipacha 531, 2000 Rosario, Argentina
b Departamento de Química Orgánica-CIHIDECAR, Facultad de Ciencias Exactas y Naturales, UBA, Ciudad Universitaria, Pab. 2, 1428 Buenos Aires, Argentina
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 23 May 2013
Received in revised form 23 July 2013
Accepted 3 August 2013
Available online 12 August 2013
An assessment of the relative O-3/O-4 reactivities of both
ethylmaleoyl (DMM) glucosamine and allosamine acceptors protected at O-6 with a benzyl group using
a- and b-methyl glycosides of N-dim-
a
D
-glucopyranosyl conformationally armed donor (superarmed donor) counterpart is presented. The gly-
cosylation of glucosamine derivatives followed the trends already observed for disarmed donors. On the
other hand, the glycosylation of allosamine derivatives gave exclusively substitution on the equatorial O-
4, in spite that with a disarmed donor the point of substitution is exclusively on the more hindered, elec-
tronically-preferred O-3.
Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction
It has actually been shown that there are donors glycosylating
faster than the armed ones, and others glycosylating at a slower
In the last years, the demands for reliable and easy synthetic
approaches for oligosaccharides have expanded,1 as their
fundamental roles in biological processes were discovered. The
mechanism of the glycosylation reaction has thus regained atten-
tion,2,3 as the regio- and stereochemistry of the reaction define
the final products, and their outcome, complicated to predicted
and liable to subtle changes in the reaction medium, was at-
tempted to be rationalized.2–10 In this way, Vasella and co-work-
ers5,6 have shown the relevance of the acceptor hydrogen bonds
in determining the regiochemistry of a glycosylation reaction of
two secondary hydroxyl groups. This has been confirmed by
experimental and theoretical calculations made on the charged
reaction intermediates.7,8 Fraser-Reid and co-workers have
shown that the nature of the donor has an ultimate influence
on the regioselectivity, introducing the concept of reciprocal
donor–acceptor selectivity9 by which ‘armed’ donors (i.e., those
protected with electron-donating groups) react faster and in a
different way (dependent on the acceptor) than ‘disarmed’
donors (i.e., those protected with electron-withdrawing groups).
rate than the disarmed ones, leading to the concept of super-
armed and superdisarmed donors.11
Hexosamines are present in most of the glycoconjugates of
natural origin; they are especially important in mammals.12,13
Thus, the synthesis of relevant oligosaccharides, as those related
to Lex and peptidoglycan requires the manipulation of 6-O-
protected, N-protected glucosamine 3,4-diols which should be
specifically glycosylated. As disarmed donors tended to give
exclusive 1?4 glycosylation and armed donors gave predominat-
ing 3-linked disaccharides,14 sequential double-glycosylation of
the acceptor diols (with no protection–deprotection scheme)
were issued for the synthesis of Lex-related oligosaccharides.14,15
In any case, further work showed the influence of the anomeric
configuration and protecting groups at O-6 of the N-dim-
ethylmaleoyl (DMM) glucosamine acceptors on the regioselective
outcome of the reaction.16 From these reports it is obvious that
no single reason for this typical regioselectivity holds under all
glycosylation conditions. Besides electronic reasons, steric issues
were used to explain exclusive glycosylations at O-4 with bulky
donors.17,18
In a previous work,16 we have assessed the regioselectivity of
the isomeric
a- and b- 6-O-benzylated N-dimethylmaleoyl
(DMM) protected diols 1 and 2 when reacting with the disarmed
donors 3 and 4.
⇑
Corresponding author. Tel./fax: +54 341 4370477.
E-mail address: colombo@iquir-conicet.gov.ar (M.I. Colombo).
0008-6215/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.carres.2013.08.002

168
F. Della Felice et al. / Carbohydrate Research 380 (2013) 167–173
OBn
OBn
O
OC(NH)CCl3
O
OAc
AcO
O
HO
OBz
HO
HO
X
X
O
O
O
OH
Y
AcO
N
Y
OBz
N
AcO
O
O
CCl3
O
OBz
OBz
NH
5
X=OMe; Y=H
X=H; Y=OMe
1
2
X=H; Y=OMe
X=OMe; Y=H
3
4
6
the equivalent glucosamine derivatives.21 The superarmed donor
7 was synthesized as described by Bols and co-workers.20
A marked difference in regioselectivity was found for the reaction
with the furanosyl donor 3: the -anomer 1 gave rise to the 1?3
a
linked disaccharide preferentially (3.2:1), whereas the b-anomer 2
gave rise to the 1?4 disaccharide preferentially (2.9:1). The same
reaction carried out with the less reactive donor 4 gave no regiose-
lectivity for 1, and complete O-4 selectivity for 2.16 When the allos-
amine derivatives 5 and 6 were allowed to react with the donor 4
complete O-3 selectivity was encountered,8 in spite of the steric
hindrance of this axial oxygen. DFT calculations strongly support
this behavior from an electronic standpoint.8 In continuation of
these studies on the subtle factors acting on the regioselectivity of
glycosylation of DMM-protected hexosamine acceptors, we have
tried the reactions using the conformationally armed donor 7.
Within the superarmed donors,11 compounds like 7 owe their high
donating activity to the presence of bulky alkylsilyl groups which
force the reagent to adopt a skew boat conformation (probably
3S1) with axial or pseudoaxial silyloxy groups;19,20 this conforma-
tion stabilizes markedly the intermediate oxacarbenium ion and
thus, increases the rate of the glycosylation reaction20 and gener-
ates a marked b-stereoselectivity in the products.19
With these acceptors and donor in hand, we performed a num-
ber of coupling experiments. Glycosylations were carried out using
the known methodologies of a thioglycoside as donor, activated by
the addition of NIS and triflic acid at low temperatures. In our
hands, the use of triflic acid gave variable yields. However, with
TMSOTf a satisfactory reproducibility was obtained. The crude
reaction mixtures were analyzed by TLC and 1H NMR spectroscopy
to establish the isomeric ratios. The results were confirmed by iso-
lation of the disaccharides or derivatives by column chromatogra-
phy, as explained for each coupling experiment. The type of linkage
(1?3 or 1?4) was established in the 1H NMR spectra by looking at
the presence or absence of the signals corresponding to H(O)-3 and
H(O)-4, and in the corresponding correlated HMBC spectra by
observing the presence of H-10–C-4/C-10–H-4 or H-10–C-3/C-10–H-
3 correlations. The disaccharides were characterized after remov-
ing the bulky alkylsilyl groups and then acetylating all the free hy-
droxyl groups. The results of the four coupling reactions are shown
in Table 1.
The reaction of donor 7 with the acceptor 5 gave exclusively the
4-linked disaccharide 8, with a 54% yield. Some unreacted acceptor
was found, but no other coupling product was detected by TLC or
1H NMR. The determination of the anomeric configuration of disac-
charide 8 could only be determined after removing the silyl pro-
tecting groups, with further acetylation. The removal of the silyl
groups was first attempted by using tetrabutylammonium fluoride
(TBAF) in THF solution. However, when this reaction was carried
out and followed by acetylation of the free hydroxyl groups, the
spectra of the product showed characteristics indicating that prod-
uct 10 was not obtained, but instead, the unexpected product 12
OTBDMS
OBn
O
TBDMSO
TBDMSO
STol
3S1
TBDMS = tBuMe2Si; Tol = p-tolyl
7
2. Results and discussion
was generated. The 13C NMR and HMBC spectra confirmed the
DMM-protected glucosamine acceptors 1 and 2, were synthe-
sized as described earlier,16 whereas the allosamine acceptors (5
and 6) were obtained by reductive opening of the 4,6-O-benzyli-
dene acetals8 generated from inverting the C-3 configuration of
3
0
0
structure proposed for 12 and further, the JH1 ,H2 coupling con-
stant (8.0 Hz) established the b-anomeric configuration of the
disaccharide.
BnO
AcO
BnO
O
O
O
X
AcO
OAc
AcO
DMMN
Y
BnO
TBDMSO
TBDMSO
BnO
O
O
O
X
10
11
: X=OMe, Y=H
: X=H, Y=OMe
OTBDMS
Y
HO
DMMN
BnO
BnO
O
O
AcO
AcO
O
X
8
9
: X=OMe, Y=H
: X=H, Y=OMe
Y
OAc
O
N
O
OAc
12
13
: X=OMe, Y=H
: X=H, Y=OMe

F. Della Felice et al. / Carbohydrate Research 380 (2013) 167–173
169
Table 1
of reaction, determined that the product ratio was 2:1 favoring the
3-linked disaccharide (Table 1). Both disaccharides were fully char-
acterized by their NMR spectra. Deprotection (removal of the silyl
groups) with TBAF in EtOAc followed by acetylation, yielded the
Ratiosa and yields of 3- and 4-linked disaccharides obtained after reaction of donor 7
and different acceptors, and comparison with the use of other donors
Acceptor
Ratio 1?3/1?4
With donor 7
Yield (%)
Ratio 1?3/1?4
With donor 3 With donor 4
corresponding acetylated disaccharides 14b and 15b, for which
3
the b-configuration was established (3JH1 ,H2 8.1 Hz and JH1 ,H2
0
0
0
0
1 (GlcN,
2 (GlcN, b)
5 (AllN, b)
6 (AllN,
a
)
2:1
1:2.4
0:1
65
61
54
57
3.2:1b
1:2.9b
—
1:1b
0:1b
1:0c
1:0c
7.9 Hz, respectively).
Coupling of 7 with acceptor 2 yielded a mixture of disaccharides
16a and 17a, not separable by column chromatography. Integra-
tion of the 1H NMR signals of the crude reaction mixture indicated
that the 4-linked disaccharide was prevalent, in a 2.4:1 ratio. The
mixture could anyway be separated after acetylation by column
chromatography to yield 16b and 17b. Removal of the silyl groups
with TBAF in EtOAc, followed by acetylation, could only be possible
with 17b, yielding the corresponding acetylated disaccharide 17c,
a)
0:1
—
a
b
c
Ratios were determined by 1H NMR spectroscopy.
From Ref.
From Ref.
16
.
8
.
The formation of product 12 can be explained by rationalizing that
the basic fluoride ion increases the nucleophilicity of O-3 allowing
the attack to one of the carbonyl groups of DMM protecting group,
followed by ring expansion and acetylation as shown in Scheme 1.
Changing the reaction conditions (i.e., using ethyl acetate as sol-
vent, and adding acetic acid to reduce the basicity of the reagent)
made possible to obtain a mixture of 10 (28%) and 12 (11%). By
analysis of the 1H NMR spectra of 10, the anomeric configuration
for which the b-configuration was again established (3JH1 ,H2
0
0
7.9 Hz). Unfortunately, due to poor yields when obtaining disac-
charide 16b, removal of the silyl groups was not possible. Even
so, according to the b-stereoselectivity previously described on
all other disaccharides and taking into account that this selectivity
is expected when using glucosyl superarmed donors,19 it can be as-
sumed that a b-stereochemistry was also obtained in 16b.
was established as b (3JH1 ,H2 7.8 Hz).
0
0
OBn
O
BnO
R1O
R1O
BnO
BnO
R1O
R1O
BnO
O
O
O
O
R2O
O
O
X
O
X
X
R2O
BnO
R1O
R1O
O
OR1
OR1
R2O
Y
DMMN
DMMN
Y
Y
NDMM
R1O
8: X=OMe, Y=H, R1=TBDMS,R2=H
15a: X=H, Y=OMe, R1=TBDMS,R2=H
15b: X=H, Y=OMe, R1=R2=Ac
14a: X=H, Y=OMe, R1=TBDMS,R2=H
1
2
1
2
9
: X=H, Y=OMe, R =TBDMS,R =H
14b
16a
: X=H, Y=OMe, R =R =Ac
1
2
1
2
: X=OMe, Y=H, R =R =Ac
17a: X=OMe, Y=H, R1=TBDMS, R2=H
10
: X=OMe, Y=H, R =TBDMS,R =H
1
2
16b: X=OMe, Y=H,R1=TBDMS,R2=Ac
: X=OMe, Y=H, R =TBDMS, R =Ac
17b
17c: X=OMe, Y=H, R1=R2=Ac
All these results indicate that the behavior of the superarmed donor
7 in reaction with the anomeric allosamine acceptors 5 and 6 is
completely different to that observed in the reactions with the dis-
armed donor 4. The superarmed donor gave regiospecifically 4-
linked disaccharides with either allosamine acceptor, whereas the
disarmed donor gave exclusively the 3-linked disaccharides.8 In
spite that with both donors (different leaving groups and activation
conditions) the mechanism of the glycosylation reaction could be
different, it seems probably at first sight that the axial O-3, even
activated by a strong hydrogen bond,8 is too hindered to react with
the bulky superarmed donor 7. In this regard, Moitessier and co-
workers recently observed that an armed donor preferentially gly-
cosylated the more accessible hydroxyl group, whereas the reaction
with a disarmed donor occurred on the most reactive hydroxyl
group of a given acceptor.22 Alternatively, if the ring expansion
The coupling reaction of 7 and 6 also yielded exclusively the 4-
linked disaccharide 9 (Table 1), as confirmed by NMR spectroscopy.
As occurred for 8, attempts of removal of the silyl groups with
TBAF in THF resulted (after acetylation) in the anomalous product
13, produced by attack of O-3 to one of the DMM carbonyl group.
In this case, the reaction in EtOAc did not result in the expected
generation of the desilylated disaccharide 11. However, the b-ste-
reochemistry of the disaccharide was again established by deter-
3
0
0
mining the JH1 ,H2 coupling constant in 13 (7.9 Hz).
The coupling reaction of 7 and 1 yielded a mixture of 1?3 and
1?4 disaccharides (14a and 15a, respectively) in a total yield of
65%, together with some unreacted material. The mixture of disac-
charides was separated by column chromatography. Both the rela-
tive yield of each isolated disaccharide and integration of
characteristic signals of the 1H NMR spectrum of the crude mixture
BnO
RO
BnO
RO
BnO
RO
BnO
RO
O
N
O
O
O
OMe
O
OMe
OH
OMe
O
OMe
O
N
NH
O
O
O
O
N
H
O
H O
F
O
O
F
Ac2O
Pyr
8
12
Scheme 1.

170
F. Della Felice et al. / Carbohydrate Research 380 (2013) 167–173
2H, H-30, H-4), 3.67–3.60 (m, 2H, H-20, H-6b), 3.61–3.50 (m, 2H,
H-60), 3.49 (s, 3H, OCH3), 3.32 (br s, 1H, OH), 1.87 (s, 6H, CCH3 ꢂ 2),
0.86 (2s, 18H, C(CH3)3 ꢂ 2), 0.84 (s, 9H, C(CH3)3), 0.08 (s, 3H, Si-
CH3), 0.05 (s, 3H, Si-CH3), 0.04 (s, 3H, Si-CH3), 0.03 (s, 3H, Si-CH3),
0.02 (s, 3H, Si-CH3), ꢀ0.01 (s, 3H, Si-CH3); 13C NMR d: 171.91
(CO ꢂ 2), 138.56 (C-Ar), 138.13 (C-Ar0), 136.99 (C ꢂ 2), 128.29,
127.44, 127.42 (C-Ar ꢂ 5, C-Ar0 ꢂ 5), 102.80 (C-10), 97.09 (C-1),
78.25 (C-50), 78.04 (C-4), 76.26 (C-30), 76.20 (C-20) 73.38 (CH2Ph),
73.13 (CH2Ph0), 72.58 (C-5), 70.99 (C-40), 70.79 (C-60), 69.81 (C-6,
C-3), 56.71 (OCH3), 55.38 (C-2), 25.84 (C(CH3)3 ꢂ 3), 17.91 (Si-
CMe3 ꢂ 3), 8.72 (CCH3 ꢂ 2), ꢀ4.20, ꢀ4.28, ꢀ4.37, ꢀ4.42, ꢀ4.58,
ꢀ4.94 (Si-CH3 ꢂ 6); ESI-HMRS: calcd for [C51H83NO12Si3 – H]ꢀ:
984.51503. Found, m/z: 984.51322. Unreacted acceptor 5 (28%).
observed during the deprotection (Scheme 1) occurs during the gly-
cosylation reaction, it may well explain the regioselectivity ob-
served.
In clear contrast with the results observed with the anomeric
allosamine acceptors 5 and 6, the reaction of the superarmed donor
7 with the glucosamine derivatives 1 and 2, showed the same
trends as those observed previously in reactions with the disarmed
donor 3,16 even though, as mentioned above, the glycosylations
could occur through different mechanisms with both donors.
3. Experimental
Melting points were determined on an Electrothermal 9100
apparatus and are uncorrected. The 1H and 13C NMR spectra were
recorded on a Bruker Avance 300 spectrometer for CDCl3 solutions
with Me4Si as internal standard. Proton and carbon peaks assign-
ments were performed with the aid of 2D NMR techniques (COSY,
HSQC and HMBC). High resolution mass spectrometry (HRMS-ESI)
was performed in a Bruker microTOF-Q II apparatus. Optical rota-
tions were measured with a Jasco DIP-1000 polarimeter. Column
chromatography was performed on silica gel 60 H, slurry packed,
run under low pressure of nitrogen and employing increasing
amounts of EtOAc in hexane as solvent. Analytical TLC was carried
out using Kieselgel Merck GF254 with a thickness 0.20 mm. The
homogeneity of all compounds prior to the high resolution mass
spectral determination was carefully verified by TLC. Reactions
were routinely run under a dry nitrogen atmosphere with mag-
netic stirring. All chemicals were used as purchased or purified
according to standard procedures. The glycosyl acceptors 1, 2, 5
and 6, and the donor 7 were synthesized and purified as described
earlier.8,15,19 Their chemical and spectral characterization matched
those found in the literature.8,15,19
3.1.2. Methyl 6-O-benzyl-2,3,4-tri-O-(tert-butyldimethylsilyl)-b-
D-glucopyranosyl-(1?4)-6-O-benzyl-2-deoxy-2-
dimethylmaleimido-a-D-allopyranoside (9)
57%; as a foam: Rf 0.59 (7:3 hexane:EtOAc). 1H NMR d: 7.36–
7.28 (m, 10H, ArH, ArH0), 5.21 (br d, 1H, JOH,H-3 1.4 Hz, OH), 4.92
(d, 1H, J1 ,2 6.0 Hz, H-10), 4.73 (br s, 1H, H-1), 4.71 (d, 1H, J
10.1 Hz, CH2Ph), 4.56–4.48 (m, 4H, CH2Ph, CH2Ph0, H-3), 4.45–
4.36 (m, 1H, H-5), 4.30 (dd, 1H, J 3.6; 2.4 Hz, H-2), 4.00 (ddd, 1H,
J 1.2; 6.8; 7.3 Hz, H-50), 3.93–3.83 (m, 1H, H-40), 3.88–3.78 (m,
2H, H-4, H-6a), 3.76–3.71 (m, 3H, H-20, H-3, H-6b), 3.63 (d, with
appearance of s, 1H, H-6a0), 3.60 (d, with appearance of s, 1H, H-
6b0), 3.33 (s, 3H, OCH3), 1.95 (s, 6H, CCH3 ꢂ 2), 0.91 (s, 9H, C(CH3)3),
0.87 (s, 9H, C(CH3)3), 0.85 (s, 9H, C(CH3)3), 0.11 (s, 3H, Si-CH3), 0.10
(s, 6H, Si-CH3 ꢂ 2), 0.06 (s, 3H, Si-CH3), 0.04 (s, 3H, Si-CH3), 0.02 (s,
3H, Si-CH3); 13C NMR d: 172.37 (CO ꢂ 2), 138.56 (C-Ar), 137.49
(C-Ar0, C ꢂ 2), 128.25, 128.19, 127.40, 127.31 (C-Ar ꢂ 5, C-Ar0 ꢂ 5),
102.28 (C-10), 98.47 (C-1), 80.02 (C-50), 79.39 (C-40), 77.19 (C-20),
75.12 (C-4), 73.26 (CH2Ph), 73.10 (CH2Ph0), 71.34 (C-60), 70.97
(C-30), 69.48 (C-3), 68.94 (C-6), 66.16 (C-5), 55.86 (OCH3), 54.88
(C-2), 25.93 (C(CH3)3), 25.88 (C(CH3)3 ꢂ 2), 17.92 (Si-CMe3 ꢂ 3),
8.90 (CCH3 ꢂ 2), –3.70, ꢀ3.90, ꢀ4.45, ꢀ4.75, ꢀ4.77 (Si-CH3 ꢂ 6);
ESI-HMRS: calcd for [C51H83NO12Si3 + K]+: 1024.48547. Found:
m/z: 1024.48113. Unreacted acceptor 6 (24%).
0
0
3.1. General procedure for the glycosylation and acetylation
reactions
A suspension of the corresponding acceptor (1 or 2) (1 equiv),
donor 7 (1.3 equiv) and activated 3 Å molecular sieves (740 mg/
mmol donor) in anhydrous CH2Cl2 (5.0 mL) was stirred at room
temperature. After 30 min, the mixture was cooled to ꢀ60 °C, NIS
(1 equiv) and then TMSOTf (0.15 equiv) were added and the stir-
ring continued for 55 min, when the solution turned red. The mix-
ture was then neutralized by addition of Et3N and filtered through
a silica gel pad with copious washings with EtOAc. The filtrate was
washed with satd aq Na2SO3, brine, dried (Na2SO4), evaporated and
the residue was chromatographed to yield the corresponding
disaccharides. The glycosylation of acceptors 5 or 6 was performed
under the same reaction conditions except that 0.53 equiv of TfOH
was used instead of TMSOTf, and the temperature was ꢀ50 °C. The
acetylations were carried out under standard conditions: pyridine,
DMAP, Ac2O, room temperature, overnight.
3.1.3. Methyl 6-O-benzyl-2,3,4-tri-O-(tert-butyldimethylsilyl)-b-
D-glucopyranosyl-(1?3)-6-O-benzyl-2-deoxy-2-
dimethylmaleimido- -glucopyranoside (14a) and methyl 6-
a-D
O-benzyl-2,3,4-tri-O-(tert-butyldimethylsilyl)-b-
D-
glucopyranosyl-(1?4)-6-O-benzyl-2-deoxy-2-
dimethylmaleimido-
3.1.3.1. Disaccharide 14a.
a-D-glucopyranoside (15a)
43%; as a foam: ½a D31
ꢁ
+49.9 (c 0.54,
CHCl3); Rf 0.61 (7:3 hexane:EtOAc). 1H NMR d: 7.40–7.21 (m, 10H,
ArH, ArH0), 5.12 (dd, 1H, J3,4 8.6 Hz, J3,2 11.1 Hz, H-3), 5.08 (s, 1H,
OH), 4.91 (d, 1H, J1 ,2 5.2 Hz, H-10), 4.69 (d, 1H, J1,2 3.6 Hz, H-1),
4.65 (d, 1H, J 12.4 Hz, CH2Ph), 4.61 (d, 1H, J 12.4 Hz, CH2Ph), 4.54
(d, 1H, J 11.9 Hz, CH2Ph0), 4.51 (d, 1H, J 11.9 Hz, CH2Ph0), 4.14 (dd,
1H, H-2), 4.13–4.08 (m, 1H, H-50), 3.88–3.79 (m, 3H, H-40, H-5, H-
6a), 3.74 (dd, 1H, J 5.9; 10.8 Hz, H-6b), 3.68 (br s, 1H, H-30), 3.66–
3.59 (m, 2H, H-60), 3.57 (br d, 1H, H-20), 3.50, (ddd, 1H, J4,5
9.1 Hz, H-4), 3.28 (s, 3H, OCH3), 1.92 (br s, 6H, CCH3 ꢂ 2), 0.88 (s,
9H, C(CH3)3), 0.86 (s, 9H, C(CH3)3), 0.78 (s, 9H, C(CH3)3), 0.04 (s,
6H, Si-CH3 ꢂ 2), 0.03 (s, 6H, Si-CH3 ꢂ 2), 0.00 (s, 3H, Si-CH3),
ꢀ0.11 (s, 3H, Si-CH3); 13C NMR d: 172.71, 171.47 (CO ꢂ 2), 138.60
(C-Ar), 138.27 (C), 138.11 (C-Ar0), 136.14 (C), 128.25, 127.69,
127.52, 127.47, 127.34 (C-Ar ꢂ 5, C-Ar0 ꢂ 5), 100.37 (C-10), 98.45
(C-1), 78.80 (C-30), 78.75 (C-50), 76.82 (C-20), 75.82 (C-3), 73.45
(CH2Ph), 73.29 (CH2Ph0), 71.22 (C-5), 71.04 (C-40), 70.78 (C-60),
70.01 (C-4), 69.70 (C-6), 55.01 (C-2, OCH3), 25.85 (C(CH3)3), 25.81
(C(CH3)3), 25.63 (C(CH3)3), 17.85 (Si-CMe3 ꢂ 2), 17.70 (Si-CMe3),
8.74 (CCH3 ꢂ 2), ꢀ3.78, ꢀ4.48, ꢀ4,58, ꢀ4.68, ꢀ4.73, ꢀ4.97 (Si-
CH3 ꢂ 6). ESI-HMRS: calcd for [C51H83NO12Si3 + Na]+: 1008.51153.
Found: m/z: 1008.50806.
0
0
3.1.1. Methyl 6-O-benzyl-2,3,4-tri-O-(tert-butyldimethylsilyl)-b-
D-glucopyranosyl-(1?4)-6-O-benzyl-2-deoxy-2-
dimethylmaleimido-b-
D
-allopyranoside (8)
ꢀ29.3 (c 1.52, CHCl3); Rf 0.67 (1:1 hex-
54%; as a foam: ½a D20
ꢁ
ane:EtOAc). 1H NMR d: 7.37–7.33 (m, 5H, ArH), 7.30–7.26 (m, 5H,
ArH0), 5.69 (d, 1H, J1,2 8.8 Hz, H-1), 4.82 (d, 1H, J1 ,2 4.3 Hz, H-10),
4.66 (d, 1H, J 12.4 Hz, CH2Ph), 4.57 (d, 1H, J 12.4 Hz, CH2Ph), 4.46
(br s, 2H, CH2Ph0), 4.33 (m, 1H, H-3), 4.10 (ddd, J5,6b 4.8 Hz, 1H,
H-5), 3.95 (ddd, 1H, H-2), 3.92–3.82 (m, 2H, H-50, H-6a), 3.77 (dd,
0
0
with appearance of t, J4 ,3 –J4 ,5 2.8 Hz, 1H, H-40), 3.73–3.68 (m,
0
0
0
0
We thank an anonymous reviewer for the suggestion that the ring expansion
could occur during the glycosylation reaction.

F. Della Felice et al. / Carbohydrate Research 380 (2013) 167–173
171
3.1.3.2. Disaccharide 15a.
24%; as a foam: ½a D31
ꢁ
+72.7 (c 0.43,
(CH2Ph), 73.08 (CH2Ph0), 71.35 (C-60), 71.31 (C-3), 70.66 (C-30),
68.20 (C-6), 56.62 (OCH3), 54.65 (C-2), 25.90 (C(CH3)3), 25.84
(C(CH3)3), 25.74 (C(CH3)3), 20.77 (COCH3), 17.92 (Si-CMe3), 17.89
(Si-CMe3), 17.81 (Si-CMe3), 8.77 (CCH3 ꢂ 2), ꢀ3.81, ꢀ3.89, ꢀ4.62,
ꢀ4.66, ꢀ4.92, ꢀ5.04 (Si-CH3 ꢂ 6); ESI-HMRS: calcd for [C53H85-
NO13Si3 + Na]+: 1050.52209. Found: m/z: 1050.51686. Unreacted
acceptor 2 (10%).
CHCl3); Rf 0,66 (7:3 hexane:EtOAc). 1H NMR d: 7.35–7.31 (m, 5H,
ArH), 7.28–7.23 (m, 5H, ArH0), 4.99 (dd, 1H, J3,2 11.3 Hz, J3,4
8.7 Hz, H-3), 4.83 (d, 1H, J1 ,2 6.0 Hz, H-10), 4.69 (d, 1H, J1,2 3.6 Hz,
H-1), 4.68 (d, 1H, J 12.4 Hz, CH2Ph), 4.53 (d, 1H, J 12.4 Hz, CH2Ph),
4.49 (d, 1H, J 11.9 Hz, CH2Ph0), 4.44 (d, 1H, J 11.9 Hz, CH2Ph0), 4.35
(br s, 1H, OH), 4.10 (dd, 1H, H-2), 4.04 (ddd, 1H, J 1.0; 6.9 (ꢂ2) Hz,
H-50), 3.89–3.83 (m, 2H, H-40, H-5), 3.79–3.71 (m, 3H, H-30, H-6),
3.67–3.60 (m, 2H, H-20, H-4), 3.59 (br s, 1H, H-6a0), 3.57 (br s, 1H,
H-6b0), 3.31 (s, 3H, OCH3), 1.94 (s, 6H, CCH3 ꢂ 2), 0.91 (s, 9H,
C(CH3)3), 0.88 (s, 9H, C(CH3)3), 0.83 (s, 9H, C(CH3)3), 0.10 (2s, 6H,
Si-CH3 ꢂ 2), 0.07 (s, 3H, Si-CH3), 0.04 (s, 3H, Si-CH3), 0.02 (s, 3H,
Si-CH3), ꢀ0.01 (s, 3H, Si-CH3); 13C NMR d: 171.97 (CO ꢂ 2),
138.34 (C-Ar), 138.09 (C-Ar0), 136.98 (C ꢂ 2), 128.27, 128.21,
127.62, 127.44, 127.37, 127.30 (C-Ar ꢂ 5, C-Ar0 ꢂ 5), 101.75 (C-10),
98.63 (C-1), 80.09 (C-50), 79.32 (C-4), 78.81 (C-30), 77.30 (C-20),
73.40 (CH2Ph), 73.28 (CH2Ph0), 70.86, 70.83 (C-4, C-60), 69.84 (C-
5), 68.33 (C-6), 65.16 (C-3), 56.17 (C-2), 55.48 (OCH3), 25.89
(C(CH3)3), 25.80 (C(CH3)3), 25.77 (C(CH3)3), 17.87 (Si-CMe3 ꢂ 3),
8.76 (CCH3 ꢂ 2), ꢀ3.63, ꢀ4.03, ꢀ4.41, ꢀ4.55, ꢀ4,87, ꢀ4,95 (Si-
CH3 ꢂ 6); ESI-HMRS: calcd for [C51H83NO12Si3 + Na]+: 1008.51153.
Found: m/z: 1008.50648. Unreacted acceptor 1 (24%).
0
0
3.2. Reactions for deprotection of the tert-butyldimethylsilyl
groups
3.2.1. Attempt of deprotecting disaccharide 8
Tetrabutylammonium fluoride (TBAF, 1 M solution in THF,
240
l
L, 0.24 mmol) was added dropwise to a solution of
8
(17.2 mg, 17.44
lmol) in THF (1.0 mL) in an ice-water bath, and
the mixture was allowed to reach room temperature during
1 h. After 16 h (TLC) the solvent was evaporated and the residue
was acetylated and chromatographed yielding compound 12
(5.3 mg, 38%) as a foam: Rf 0.22 (1:1 hexane:EtOAc). 1H NMR d:
7.42–7.33 (m, 5H, ArH0), 7.32–7.27 (m, 5H, ArH), 5.63 (dd, 1H,
J3,2–J3,4 3.0 Hz, H-3), 5.12–5.04 (m, 2H, H-30, H-40), 4.90 (dd, 1H,
J2 ,1 8.0 Hz, J2 ,3 9.7 Hz, H-20), 4.78 (d, 1H, J1,2 8.3 Hz, H-1), 4.69
(d, 1H, J 12.1, CH2Ph), 4.56 (d, 1H, CH2Ph), 4.53 (d, 1H, J 12.1,
CH2Ph0), 4.51 (d, 1H, H-10), 4.46 (d, 1H, J 12.1, CH2Ph0), 4.03–
3.88 (m, 3H, H-2, H-4, H-5), 3.71 (dd, 1H, J6a,6b 10.7 Hz, J6a,5
1.0 Hz, H-6a), 3.66 (dd, 1H, J6b,5 3.6 Hz, H-6b), 3.54 (br s, 3H,
H-50, H-60), 3.49 (s, 3H, OCH3), 2.07 (s, 3H, COCH3), 1.99 (br s,
3H, C(N)CCH3), 1.97 (s, 3H, COCH3), 1.93 (s, 3H, COCH3), 1.92
(br s, 3H, C(O)CCH3), 1.86 (s, 3H, COCH3); 13C NMR d: 170.31,
169.90, 169.45, 169.19 (CO ꢂ 4), 167.87 (C(O)CMe), 154.89
(C(N)O), 145.83 (C(N)CMe), 138.17 (C-Ar0), 138.01 (C-Ar), 132.86
(C(O)CMe), 128.50, 128.27, 127.78, 127.49 (C-Ar ꢂ 5, C-Ar0 ꢂ 5),
101.16 (C-1), 100.86 (C-10), 73.74 (CH2Ph), 73.62 (CH2Ph0), 73.53
(C-4), 73.07 (C-5), 73.00 (C-30, C-50), 71.53 (C-20), 71.05 (C-3),
69.12 (C-40), 68.62 (C-60), 68.47 (C-6), 60.48 (C-2), 56.64 (OCH3),
20.87 (COCH3), 20.63 (COCH3 ꢂ 3), 10.00 (C(N)CCH3), 9.09
(C(O)CCH3); ESI-HMRS: calcd for [C41H49NO16 + H]+: 812.31241.
Found: m/z: 812.31103.
0
0
0
0
3.1.4. Methyl 6-O-benzyl-2,3,4-tri-O-(tert-butyldimethylsilyl)-b-
D
-glucopyranosyl-(1?3)-4-O-acetyl-6-O-benzyl-2-deoxy-2-
dimethylmaleimido-b- -glucopyranoside (16b) and methyl
6-O-benzyl-2,3,4-tri-O-(tert-butyldimethylsilyl)-b-
glucopyranosyl-(1?4)-3-O-acetyl-6-O-benzyl-2-deoxy-2-
dimethylmaleimido-b- -glucopyranoside (17b)
3.1.4.1. Disaccharide 16b.
D
D
-
D
4% (from 2), as a foam: Rf 0.53 (7:3
1
hexane:EtOAc). H NMR d: 7.37–7.27 (m, 10H, ArH, ArH0), 4.90–
4.85 (m, 2H, H-3, H-4), 4.75 (d, 1H, J1,2 8.33 Hz, H-1), 4.56 (t, 4H,
CH2Ph, CH2Ph0), 4.41, (d, 1H, J1 ,2 6.2 Hz, H-10), 4.07 (dd, 1H, J2,3
10.4 Hz, H-2), 3.82 (br d, 1H, J 3.1 Hz, H-40), 3.79–3.74 (m, 1H, H-
50), 3.73–3.69 (m, 1H, H-5), 3.68–3.64 (m, 1H, H-6a0), 3.63–3.60
(m, 1H, H-30), 3.60–3.56 (m, 3H, H-6b0, H-6), 3.40 (s, 3H, OCH3),
3.35 (d, 1H, H-20), 1.92 (2s, 9H, COCH3, CCH3 ꢂ 2), 0.85 (s, 9H,
C(CH3)3), 0.82 (s, 9H, C(CH3)3), 0.79 (s, 9H, C(CH3)3), 0.06 (s, 3H,
Si-CH3), 0.03 (s, 3H, Si-CH3), 0.02 (s, 6H, (Si-CH3) ꢂ 2), ꢀ0.03 (2s,
6H, (Si-CH3) ꢂ 2); 13C NMR d: 169.58 (CO ꢂ 3), 138.36, 138.10 (C-
Ar, C-Ar0), 137.33 (C ꢂ 2), 128.33, 128.26, 127.76, 127.64, 127.57,
127.50 (C-Ar ꢂ 5, C-Ar0 ꢂ 5), 100.00 (C-10), 99.30 (C-1), 80.70 (C-
50), 78.67 (C-30), 78.10 (C-20), 73.72 (C-5), 73.51 (CH2Ph), 73.16
(CH2Ph0), 71.31 (C-60), 70.74 (C-4, C-40), 70.42 (C-3), 69.54 (C-6),
56.52 (OCH3), 55.63 (C-2), 25.90 (C(CH3)3), 25.80 (C(CH3)3 ꢂ 2),
21.10 (COCH3), 17.89 (Si-CMe3 ꢂ 2), 17.83 (Si-CMe3), 8.90 (CCH3 -
ꢂ 2), ꢀ3.89, ꢀ4.13, ꢀ4.64, ꢀ4.84, ꢀ4,88, ꢀ4.98 (Si-CH3 ꢂ 6). ESI-
HMRS: calcd for [C53H85NO13Si3 + Na]+: 1050.52209. Found: m/z:
1050.51737.
0
0
3.2.2. Methyl 2,3,4-tri-O-acetyl-6-O-benzyl-b-
D-glucopyranosyl-
(1?4)-3-O-acetyl-6-O-benzyl-2-deoxy-2-dimethylmaleimido-b-
D-allopyranoside (10)
Tetrabutylammonium fluoride (TBAF, 1 M solution in THF,
240
l
L, 0.24 mmol) was added dropwise to a solution of
mol) in EtOAc (2.0 mL) with AcOH (9.6
8
L,
(25.1 mg, 24.4
l
l
0.17 mmol) at ꢀ20 °C, and the mixture was allowed to reach room
temperature during 1 h. After 16 h (TLC) the solvent was evapo-
rated and the residue was acetylated and chromatographed yield-
ing compound 10 (5.7 mg, 28%) as a foam and the anomalous
compound 12 (2.3 mg, 11%).
3.1.4.2. Disaccharide 17b.
14% (from 2), as a foam: ½a D32
ꢁ
+10.9
(c 0.42, CHCl3); Rf 0.48 (7:3 hexane:EtOAc). 1H NMR d: 7.37–7.26
(m, 10H, ArH, ArH0), 5.51 (dd, 1H, J3,2 10.8 Hz, J3,4 8.9 Hz, H-3),
3.2.2.1. Disaccharide 10.
Rf 0.40 (1:1 hexane:AcOEt). 1H NMR
d: 7.39–7.34 (m, 5H, ArH0), 7.33–7.29 (m, 5H, ArH), 5.57 (dd, 1H, H-
5.10 (d, 1H, J1,2 8.6 Hz, H-1), 4.73 (d, 1H, J1 ,2 6.4 Hz, H-10), 4.64
(d, 1H, J 12.1 Hz, CH2Ph), 4.56 (d, 1H, J 12.1 Hz, CH2Ph), 4.52 (d,
1H, J 11.9 Hz, CH2Ph0), 4.49 (d, 1H, J 11.9 Hz, CH2Ph0), 4.02 (dd,
1H, H-2), 3.97–3.88 (m, 2H, H-4, H-50), 3.88–3.83 (m, 2H, H-30, H-
6a), 3.72–3.67 (m, 2H, H-40, H-6b), 3.66–3.63 (m, 1H, H-5), 3.62–
3.53 (m, 2H, H-60), 3.47 (br d, 1H, H-20), 3.42 (s, 3H, OCH3), 1.94
(s, 6H, CCH3 ꢂ 2), 1.87 (s, 3H, COCH3), 0.89 (s, 9H, C(CH3)3), 0.85
(s, 9H, C(CH3)3), 0.84 (s, 9H, C(CH3)3), 0.08 (s, 6H, Si-CH3 ꢂ 2),
0.06 (s, 3H, Si-CH3), 0.03 (s, 3H, Si-CH3), 0.01 (s, 3H, Si-CH3),
ꢀ0.02 (s, 3H, Si-CH3); 13C NMR d: 171.55, 170.41 (CO ꢂ 3),
138.36, 138.24 (C-Ar, C-Ar0), 128.30, 128.25, 127.57, 127.52,
127.37 (C-Ar ꢂ 5, C-Ar0 ꢂ 5), 100.79 (C-10), 98.92 (C-1), 80.67 (C-
50), 78.67 (C-40), 77.85 (C-20), 75.17 (C-5), 73.54 (C-4), 73.24
3), 5.55 (d, 1H, J1,2 8.6 Hz, H-1), 5.10–5.04 (m, 2H, H-30, H-40), 4.88
0
0
(dd, 1H, J2 ,1 7.8 Hz, J2 ,3 9.8 Hz, H-20), 4.69 (d, 1H, J 12.1 Hz, CH2-
Ph0), 4.55 (d, 1H, CH2Ph0), 4.52 (d, 1H, CH2Ph), 4.50 (d, 1H, H-10),
4.46 (d, 1H, J 11.9 Hz, CH2Ph), 4.01 (dd, 1H, J2,3 2.5 Hz, H-2), 3.98
(br s, 2H, H-4, H-5), 3.71 (d, 1H, J6a,6b 10.8 Hz, H-6a), 3.66 (dd,
1H, J6b,5 2.7 Hz, H-6b), 3.56–3.47 (m, 3H, H-50, H-6), 3.46 (s, 3H,
OCH3), 1.99 (s, 3H, COCH3), 1.97 (s, 3H, COCH3), 1.93 (s, 3H, COCH3),
1.90 (br s, 6H, CCH3 ꢂ 2), 1.87 (s, 3H, COCH3); 13C NMR d: 171.63,
170.61, 170.32, 169.42, 169.16 (CO ꢂ 6), 138.10, 138.01 (C-Ar ꢂ 2,
C ꢂ 2), 128.51, 128.31, 127.88, 127.79, 127.55 (C-Ar ꢂ 5, C-Ar0 ꢂ 5),
100.85 (C-10), 97.48 (C-1), 73.73 (C-4, CH2Ph0), 73.59 (CH2Ph), 73.21
(C-5), 73.10 (C-50), 72.98 (C-40), 71.44 (C-20), 70.98 (C-3), 68.95
(C-30), 68.37 (C-6, C-60), 56.76 (OCH3), 54.42 (C-2), 20.80 (COCH3),
0
0
0
0

172
F. Della Felice et al. / Carbohydrate Research 380 (2013) 167–173
20.62 (COCH3 ꢂ 3), 8.77 (CCH3 ꢂ 2); ESI-HMRS: calcd for [C41H49-
NO16 + Na]+: 834.29436. Found: m/z: 834.29312.
1H, J6 b,5 4.4 Hz, H-6b0), 3.40–3.33 (m, 1H, H-50), 3.29 (s, 3H,
OCH3), 1.97 (s, 3H, COCH3), 1.93 (s, 6H, CCH3 ꢂ 2), 1.92 (s, 3H,
COCH3), 1.89 (s, 3H, COCH3), 1.86 (s, 3H, COCH3); 13C NMR d:
171.16, 170.46, 169.40, 169.18, 168.66 (CO ꢂ 6), 137.48 (C-Ar, C-
Ar0), 137.14 (C ꢂ 2), 128.72, 128.39, 128.27, 127.81 (C-Ar ꢂ 5, C-
Ar0 ꢂ 5), 99.76 (C-10), 98.67 (C-1), 76.10 (C-4), 73.77 (CH2Ph),
73.48 (CH2Ph0), 73.26 (C-30), 72.61 (C-50), 71.93 (C-20), 69.85 (C-
5), 69.19 (C-40), 68.63 (C-60), 67.24 (C-6), 66.92 (C-3), 55.29
(OCH3), 53.63 (C-2), 20.86 (COCH3), 20.66 (COCH3 ꢂ 2), 20.61
(COCH3), 8.84 (CCH3 ꢂ 2); ESI-HMRS: calcd for [C41H49NO16 + K]+:
850.26829. Found: m/z: 850.27111.
0
0
3.2.3. Attempt of deprotecting disaccharide 9
The reaction for compound 9 (86.9 mg, 88.1
out as described for compound 8 in THF solution, yielding com-
lmol) was carried
pound 13 (1.4 mg, 1.72 lmol) as a foam: Rf 0.75 (1:1 hex-
1
ane:EtOAc). H NMR d: 7.41–7.26 (m, 10H, ArH, ArH0), 5.64
(unresolved dd, 1H, J3,4–J3,2 3.3 Hz, H-3), 5.11–5.00 (m, 2H, H-30,
H-50), 4.88 (dd, 1H, J2 ,1 7.9 Hz, J2 ,3 9.4 Hz, H-20), 4.77 (d, 1H,
J1,2 4.2 Hz, H-1), 4.72 (d, 1H, J 12.0 Hz, CH2Ph), 4.53 (d, 1H, J
11.9 Hz, CH2Ph0), 4.52 (d, 1H, J 12.0 Hz, CH2Ph), 4.50 (d, 1H, H-
10), 4.49 (d, 1H, J 11.9 Hz, CH2Ph0), 4.18–4.12 (m, 2H, H-2, H-5),
3.96 (dd, 1H, J4,5 10.1 Hz, H-4), 3.74–3.64 (m, 2H, H-6), 3.58–
3.48 (m, 3H, H-40, H-60), 3.38 (s, 3H, OCH3), 2.10 (s, 3H, COCH3),
2.04 (d, 3H, J 1,2 Hz, C(N)CCH3), 1.97 (s, 3H, COCH3), 1.94 (d,
3H, J 1.2 Hz, C(O)CCH3), 1.93 (s, 3H, COCH3), 1.88 (s, 3H, COCH3);
13C NMR d: 170.82, 170.32, 169.50, 169.05 (CO ꢂ 4), 167.74
(C(O)CMe), 154.20 (C(N)O), 146.27 (C(N)CMe), 138.07 (C-Ar0),
137.93 (C-Ar), 132.83 (C(O)CMe), 128.60, 128.27, 127.97,
127.93, 127.71, 127.49 (C-Ar ꢂ 5, C-Ar0 ꢂ 5), 100.66 (C-10), 98.60
(C-1), 73.80 (CH2Ph), 73.51 (CH2Ph0), 73.14 (C-40), 72.98 (C-30),
72.61 (C-4), 71.57 (C-20), 70.06 (C-3), 69.36 (C-50), 68.92 (C-60),
68.28 (C-6), 65.52 (C-5), 58.30 (C-2), 55.80 (OCH3), 21.25
(COCH3), 20.62 (COCH3 ꢂ 3), 10.19 (C(N)CCH3), 9.12 (C(O)CCH3);
ESI-HMRS: calcd for [C41H49NO16 + Na]+: 834.29436. Found: m/z:
834.29352.
0
0
0
0
3.2.6. Methyl 2,3,4-tri-O-acetyl-6-O-benzyl-b-
D-glucopyranosyl-
(1?4)-3-O-acetyl-6-O-benzyl-2-deoxy-2-dimethylmaleimido-
a
-
D-glucopyranoside (17c)
The reaction for compound 16b (20.1 mg, 20.38 lmol) was car-
ried out as described for compound 8 in EtOAc and AcOH solution,
yielding compound 17c (8.0 mg, 50%) as a foam: Rf 0.52 (1:1 hex-
ane:EtOAc). 1H NMR d: 7.40–7.27 (m, 10H, Ar-H), 5.48 (dd, 1H,
J3,2 10.7 Hz, J3,4 9.0 Hz, H-3), 5.09 (d, 1H, J1,2 8.6 Hz, H-1), 5.07 (t,
1H, J4 ,3 –J4 ,5 9.5 Hz, H-40), 5.00 (t, 1H, J3 ,2 –J3 ,4 9.3 Hz, H-30), 4.81
0
0
0
0
0
0
0
0
(t, 1H, J2 ,1 –J2 ,3 8.6 Hz, H-20), 4.77, 4.51 (2 d, 1H each, J 12.1 Hz,
CH2Ph ꢂ 2), 4.48 (d, 1H, J 7.8 Hz, H-10), 4.46, 4.39 (2 d, 1H each, J
0
0
0
0
11.9 Hz, CH2Ph0 ꢂ 2), 3.99 (dd, 1H, H-2), 3.97 (t, 1H, J4,3 –J3,5
0
9.5 Hz, H-4), 3.81–3.70 (m, 2H, H-6), 3.59–3.55 (m, 1H, H-5), 3.54
(d, 1H, J 3.1 Hz, H-6a0), 3.48 (d, 1H, J 4.3 Hz, H-6b0), 3.43 (s, 3H,
OCH3), 3.41–3.35 (m, 1H, H-50), 1.97 (s, 3H, COCH3), 1.93 (s, 9H,
COCH3, CCH3 ꢂ 2), 1.88 (s, 3H, COCH3), 1.87 (s, 3H, COCH3); 13C
NMR d: 171.43, 170.40, 170.23, 169.40, 168.82 (CO ꢂ 6), 137.75,
137.42 (C-Ar, C-Ar0), 137.37–137.07 (C ꢂ 2), 128.61, 128.42,
128.09, 127.90, 127.81 (C-Ar ꢂ 5, C-Ar0 ꢂ 5), 99.87 (C-10), 99.14
(C-1), 75.32 (C-4), 74.59 (C-5), 73.68 (CH2Ph⁄), 73.35 (C-30, CH2-
3.2.4. Methyl 2,3,4-tri-O-acetyl-6-O-benzyl-b-
D-glucopyranosyl-
(1?3)-4-O-acetyl-6-O-benzyl-2-deoxy-2-dimethylmaleimido-
a-
D-glucopyranoside (14b)
The reaction for compound 14a (15.2 mg, 14.41 lmol) was car-
ried out as described for compound 8 in EtOAc and AcOH solution,
⁄
Ph0 ), 72.64 (C-50), 71.76 (C-20), 70.92 (C-3), 69.07 (C-40), 68.49
yielding compound 14b (4.4 mg, 35%) as a foam: Rf 0.37 (1:1 hex-
(C-60), 67.26 (C-6), 56.85 (OCH3), 54.65 (C-2), 20.61 (COCH3 ꢂ 3),
20.47 (COCH3), 8.78 (CCH3 ꢂ 2); ESI-HMRS: calcd for [C41H49-
NO16 + Na]+: 834.29436. Found: m/z: 834.29556. Unreacted disac-
charide 16b (7%).
1
ane:EtOAc). H NMR d: 7.42–7.29 (m, 10 H, ArH ꢂ 5 ArH0 ꢂ 5),
5.18–5.06 (m, 2H, H-3, H-40), 5.05–4.94 (m, 2H, H-30,H-4), 4.71
(dd, 1H, J2 ,1 –J2 ,.3 8.1 Hz, H-20), 4.62 (d, 1H, J1,2 3.8 Hz, H-1), 4.53
(br s, 2H, CH2Ph0), 4.48 (d, 1H, H-10), 4.47 (d, 1H, J 11.6 Hz, CH2Ph),
4.39 (d, 1H, J 11.6 Hz, CH2Ph), 4.23 (dd, 1H, J2,3 10.9 Hz, H-2), 4.00–
3.92 (m, 1H, H-5), 3.60–3.49 (m, 5H, H-50, H-60, H-6), 3.31 (s, 3H,
OCH3), 2.02 (br s, 3H, CCH3), 1.96 (br s, 3H, CCH3), 1.94 (s, 3H,
COCH3), 1.92 (s, 3H, COCH3), 1.83 (s, 3H, COCH3), 1.77 (s, 3H,
COCH3); 13C NMR d: 172.25, 172.14, 170.60, 169.68, 169.37,
168.84 (CO ꢂ 6), 138.83 (C), 137.88 (C-Ar), 137.40 (C-Ar0), 135.99
(C), 128.36, 128.33, 128.01, 127.80, 127.61 (C-Ar ꢂ 5, C-Ar0 ꢂ 5),
99.03 (C-10), 98.70 (C-1), 73.51 (CH2Ph0), 73.27 (C-3, CH2Ph),
73.03 (C-30), 72.55 (C-50), 71.85 (C-20), 69.70 (C-4), 69.30 (C-40),
68.99 (C-60), 68.89 (C-5), 68.47 (C-6), 55.32 (OCH3), 55.12 (C-2),
20.63 (COCH3 ꢂ 2), 20.57 (COCH3), 20.31 (COCH3), 8.82 (CCH3 ꢂ 2).
ESI-HMRS: calcd for [C41H49NO16 + Na]+: 834.29436. Found: m/z:
834.29399.
0
0
0
0
Acknowledgments
We thank Dr. Manuel González-Sierra for spectral determina-
tions and helpful discussions. Financial support from UNR, UBA,
and CONICET is also acknowledged. M.I.C., C.A.S., and E.A.R. are Re-
search Members of the National Research Council of Argentina
(CONICET).
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.carres.2013.
08.002.
3.2.5. Methyl 2,3,4-tri-O-acetyl-6-O-benzyl-b-
(1?4)-3-O-acetyl-6-O-benzyl-2-deoxy-2-dimethylmaleimido-
D-glucopyranosyl-
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