Carboxymethylglycoside lactones (CMGLs): structural variations on the carbohydrate moiety

Article abstract of DOI:10.1016/j.tetasy.2007.09.007

New glucose and galactose based bicyclic lactones, with variations in the anomeric configuration, the protecting groups (acetyl or benzyl) and the furanosyl or pyranosyl rings were synthesized from allyl glycosides and used for the preparation of a series

Full text of DOI:10.1016/j.tetasy.2007.09.007

Available online at www.sciencedirect.com
Tetrahedron: Asymmetry 18 (2007) 2201–2210
Carboxymethylglycoside lactones (CMGLs): structural
variations on the carbohydrate moiety
´
Arkadiusz Listkowski, Pisethnaline Ing, Rouba Cheaib, Stephane Chambert,
Alain Doutheau and Yves Queneau*
Institut de Chimie et de Biochimie Mole´culaires et Supramole´culaires, CNRS, UMR 5246, universite´ de Lyon,
universite´ Lyon 1, INSA-Lyon, CPE-Lyon, Laboratoire de Chimie Organique, Institut National des Sciences Applique´es de Lyon,
ˆ
Bat. Jules Verne, 20 Avenue Albert Einstein, Villeurbanne F-69621, France
Received 17 July 2007; accepted 7 September 2007
Abstract—New glucose and galactose based bicyclic lactones, with variations in the anomeric configuration, the protecting groups (acetyl
or benzyl) and the furanosyl or pyranosyl rings were synthesized from allyl glycosides and used for the preparation of a series of new
glycosylated alkyne amides.
ꢀ 2007 Elsevier Ltd. All rights reserved.
1. Introduction
lipids (Scheme 1).20 However, the method is limited to
targets having the a-gluco configuration, that of lactone 1
arising from isomaltulose, whereas other conjugate ana-
logues would be desired. It was therefore interesting to
evaluate the possibility to enlarge the structural spectrum
of the CMGLs. Herein we report the preparation of new
carboxymethyl glycoside lactones, which differ in the sugar
backbone, in the configuration at the anomeric centre and
also in the nature of the protecting groups. The new
lactones were obtained from the corresponding allyl glyco-
sides after oxidation to the carboxymethyl glycosides.
Their reactivity with respect to nucleophilic opening was
illustrated by the reaction with propargyl amine, chosen
for the wide spectrum of further possible transformations
of the alkyne function.
The well known biological importance of carbohydrates,
especially their high affinity for several pharmacologically
important receptors, has led to an increased interest in
the synthesis of glycoconjugates1,2 and their analogues,
such as those based on the use of sugar amino acids
(SAAs).3 Amongst other synthons, carboxymethyl glyco-
sides have proven to be valuable tools for the synthesis
of such adducts, mostly due to the ability of the carboxylic
acid group to efficiently connect the sugar moiety to an-
other entity by amide or ester linkages. Thus, this family
of compounds has been used as building blocks for the syn-
thesis of glycoconjugate libraries for broad spectrum
screening,4–6 in combinatorial approaches to find selective
inhibitors of enzymes7,8 or for the synthesis of potentially
biologically active glycoclusters.9 Their properties have
also been used in the solid-phase synthesis of oligosaccha-
rides10 or for the preparation of glycolipids11 and glycoden-
drimers.12–17
2. Results and discussion
2.1. Synthesis of acetylated glycolactones
Recently we have reported, that 3,4,6-tri-O-acetyl-a-D-
glucopyranoside-2-O-lactone 1 (a-CMGL),18,19 which is
readily prepared from isomaltulose, reacted with amines
and alcohols via selective opening of the lactone ring,
giving an access to pseudodisaccharides and pseudogluco-
Glucose and galactose were transformed into their allyl
2,3,4,6-tetra-O-acetyl glycosides 2, 3, 7 and 8 following
the literature procedure.21 Both anomers were separated
by chromatography at this stage (Scheme 2). Oxidation
of the double bond with ruthenium trichloride led to per-
acetylated carboxymethyl derivatives,5 which were subse-
quently deprotected with triethylamine in methanol and
water to give 4, 5, 9 and 10. These acids were then dissolved
*
Corresponding author. E-mail: yves.queneau@insa-lyon.fr
0957-4166/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2007.09.007

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A. Listkowski et al. / Tetrahedron: Asymmetry 18 (2007) 2201–2210
OH
OAc
OAc
O
HO
HO
O
O
O
AcO
AcO
AcO
AcO
i.
ii.
HO
O
O
HO
OH
O
O
OH
OH
O
Nu
O
1
isomaltulose
HO
Scheme 1. Opening of the lactone ring with nucleophilic reagents. Reagents and conditions: (i) H2O2, H+, then Ac2O, pyridine; (ii) NuH (1.1 equiv),
CH2Cl2, DMAP (cat), rt.
OAc
OH
OAc
R2
R2
R2
ii., iii.
iv.
O
O
O
R1
AcO
R1
HO
R1
AcO
O
O
AcO
HO
O
O
O
-HNEt
+
3
O
O
i.
2 R1=OAc, R2=H
3 R1=H, R2=OAc
4 R1=OH, R2=H
5 R1=H, R2=OH
1 R1=OAc, R2=H
6 R1=H, R2=OAc
Glucose or Galactose
i.
OAc
R2
+
-HNEt
O
3
OAc
OH
R2
R2
O
O
O
ii., iii.
iv.
R1
AcO
O
O
R1
R1
HO
O
O
AcO
O
AcO
HO
O
7 R1=OAc, R2=H
8 R1=H, R2=OAc
9 R1=OH, R2=H
10 R1=H, R2=OH
11 R1=OAc, R2=H
12 R1=H, R2=OAc
Scheme 2. Reagents and conditions: (i) (a) allyl alcohol, BF3ÆEt2O, reflux; (b) Ac2O, pyridine; (ii) RuCl3, NaIO4, CH2Cl2/CH3CN/H2O, 2 h, rt; (iii) TEA/
MeOH/H2O, 6h; (iv) Ac2O, pyridine.
in a 1:1 mixture of pyridine and acetic anhydride to give the
expected lactones 1, 6, 11 and 12 in 21–76% yield. An alter-
native, straightforward process, is the direct oxidation of
allyl glycosides by ozonolysis, followed by reaction with
NaClO2 and subsequent lactonization under acetylation
conditions without intermediate purification, to furnish
the same lactones, as mixtures of anomers (difficult to sep-
arate at this stage) in 38–58% overall yields (Scheme 3).
on adducts when compared to the acetylated ones, which
are sensitive to both basic and acidic conditions. To pre-
pare the benzylated lactone, we had to obtain the proper
allyl glycosides having the 2-OH function free. In the case
of the b-anomers, we used the orthoester strategy22 to
obtain allyl-3,4,6-tri-O-benzyl-b-D-glucopyranoside 1723
and allyl-3,4,6-tri-O-benzyl-b-D-galactopyranoside 1823
(Scheme 4). These compounds were transformed into the
expected lactones 19 and 20 via ozonolysis, oxidation of
the resulting aldehydes with NaClO2 and, finally, lactoniza-
tion under acetylation conditions in 50% and 43% overall
yield, respectively. The intermediate products were not
isolated.
OH
OH
R2
R2
1, 11
6, 12
O
i.
iii.
OH
O
O
R1
HO
R1
HO
ii.
HO
HO
O
O
For the synthesis of a-anomers (Scheme 5), we used the de-
O-alkylation strategy mediated by triisobutylaluminium
R1=OH, R2=H or
R1=H, R2=OH
(TIBAL) developed by Sinay et al., which has been shown
¨
Scheme 3. Reagents and conditions: (i) O3, MeOH, then DMS; (ii)
NaClO2, KH2PO4, H2O, 0 ꢁC, then rt; (iii) Ac2O, pyridine.
to selectively deprotect the 2-position of a-glucosides or
galactosides.24 Thus, after treatment of allyl-2,3,4,6-tetra-
O-benzyl-a-D-glucopyranoside 21 with 5 equiv of TIBAL,
the expected product 23 was isolated in 59% yield. The
same method applied to allyl-2,3,4,6-tetra-O-benzyl-a-D-
galactopyranoside 22, provided exclusively 24 in 56% yield.
This result confirms the previous observations, showing
2.2. Synthesis of benzylated glycolactones
The benzylated analogues of CMGLs were then prepared.
Such compounds would allow easier further manipulations

A. Listkowski et al. / Tetrahedron: Asymmetry 18 (2007) 2201–2210
2203
OAc
OBn
OBn
OAc
R2
R2
R2
R2
v., vi., vii.
ii., iii., iv.
i.
O
O
O
O
R1
AcO
R1
BnO
R1
BnO
R1
AcO
O
O
AcO
OH
O
O
Br
O
O
O
13 R1=OAc, R2=H
14 R1=H, R2=OAc
15 R1=OAc, R2=H
16 R1=H, R2=OAc
17 R1=OBn, R2=H
18 R1=H, R2=OBn
19 R1=OBn, R2=H
20 R1=H, R2=OBn
Scheme 4. Reagents and conditions: (i) allyl alcohol, 2,6-lutidine (2 equiv), Bu4NBr (1.2 equiv), 4 h; (ii) MeONa/MeOH; (iii) NaH (1.25 equiv/OH), BnBr
(1.25 equiv/OH), DMF; (iv) allyl alcohol, BF3ÆOEt2; (v) O3, MeOH, then DMS; (vi) NaClO2, KH2PO4, H2O, 0 ꢁC, then rt; (vii) Ac2O, pyridine.
OBn
OBn
OBn
R2
R2
R2
O
O
ii., iii.
iv.
O
i.
R1
BnO
R1
BnO
R1
BnO
O
BnO
OH
O
O
O
O
21 R1=OBn, R2=H
22 R1=H, R2=OBn
23 R1=OBn, R2=H
24 R1=H, R2=OBn
25 R1=OBn, R2=H
26 R1=H, R2=OBn
Scheme 5. Reagents and conditions: (i) TIBAL (5 equiv), toluene, 50 ꢁC, overnight; (ii) O3, MeOH, then DMS; (iii) NaClO2, KH2PO4, H2O, 0 ꢁC, then rt;
(iv) Ac2O, pyridine.
that a benzyloxy group at the C-3 position in galactose
derivatives is not sensitive to debenzylation under such
conditions, in spite of its proper cis-orientation in respect
to the alkoxy group at position C-2 and C-4.25,26 Lactones
25 and 26 were then prepared from the allyl glycosides fol-
lowing the previously mentioned oxidation–acetylation se-
quence in 52% and 36% yield.
sulfonic acid at reflux with azeotropic removal of water
resulted in the expected product, although in a slower
and less effective manner according to TLC. None of these
conditions allowed us to obtain the b-lactone from 29. This
might be due to the observed lower stability of these benzy-
lated lactones as compared to the acetylated ones, or, in
this case, to a less favourable cycle strain in a 6–5 trans sys-
tem. Indeed, all benzylated CMGLs, 30 in particular, had
to be stored under a neutral atmosphere at low tempera-
ture, in order to prevent their spontaneous opening by a
trace amount of water, especially when the compound is
not a solid.
A lactone having a furanosyl ring was also prepared in this
benzylated lactone series. Reaction of 1,2-O-isopropylid-
ene-3,5,6-tri-O-benzyl-a-D-glucofuranose 27 with allyl
alcohol (used also as solvent) containing BF3 etherate as
catalyst led to allyl glucofuranosides 28 and 29 in 59%
and 27% yield, respectively, easily separated from each
other by chromatography (Scheme 6). The typical proce-
dure was applied to allyl glycoside 28 and afforded lactone
30 in 24% yield. An alternative method, based on heating in
toluene in the presence of a catalytic amount of p-toluene-
2.3. GMGLs opening reactions
Having in hand this series of lactones, we used them for
preparing new carbohydrate containing propargyl amides.
These products can indeed be easily anchored to other
BnO
BnO
BnO
BnO
OBn
O
OBn
O
ii.
iii., iv
BnO
BnO
O
O
OBn
O
O
OH
i.
28
30
O
O
BnO
BnO
O
O
OBn
O
27
ii.
iii., iv
OH
29
Scheme 6. Reagents and conditions: (i) BF3ÆEt2O (0.03 equiv), allyl alcohol, reflux, 1.5 h; (ii) O3, MeOH, then DMS; (iii) NaClO2, KH2PO4, H2O, 0 ꢁC,
then rt; (iv) Ac2O, pyridine.

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A. Listkowski et al. / Tetrahedron: Asymmetry 18 (2007) 2201–2210
OAc
OAc
R1
R1
O
O
R2
AcO
R2
AcO
i.
O
O
HO
O
O
N
H
O
1 R1=H, R2=OAc
31 R1=H, R2=OAc
32 R1=OAc, R2=H
6 R1=OAc, R2=H
OAc
OBn
OBn
AcO
AcO
BnO
O
O
O
O
O
O
BnO
O
O
O
BnO
BnO
HO
33
HO
HO
N
N
N
H
H
H
34
35
OBn
OBn
BnO
BnO
BnO
BnO
OBn
O
O
BnO
BnO
O
O
O
O
HO
HO
NH
O
O
O
OH
38
N
N
H
H
36
37
Scheme 7. Reagents and conditions: (i) propargyl amine (1.0 equiv, or 1.5 equiv), CH2Cl2, rt, 10 h.
OH
OH
O
O
O
HO
HO
HO
HO
ii.
i.
O
O
32
NH
HO
HO
O
O
N
H
N
H
N
O
N
O
N
N
40
39
HO
OH
Scheme 8. Reagents and conditions: (i) MeONa/MeOH (1 M); (ii) 50-azido-50-deoxyuridine (1 equiv), CuI (catalytic amount), Et3N (catalytic amount),
CH3CN:H2O, rt, 24 h.
compounds possessing an azido moiety using Huisgen
cycloaddition (‘click’ chemistry).27 Thus the glucose and
galactose based lactones 1 and 6 were treated with 1 equiv
of propargyl amine in anhydrous CH2Cl2 to give the
expected amides 31 and 32, which were isolated by column
chromatography in 94% and 84% yield, respectively
(Scheme 7). The same sequence provided acetylated
b-galactose lactone 33 and the perbenzylated lactones
34–38 in 54–94% yield. An illustration of the interest of
such alkynyl synthons is given with the formation of
triazole 40 by reaction of the deacetylated amide 39
with 50-azido-50-deoxyuridine28 (Scheme 8) under Cu(I)
catalysis in CH3CN–H2O (1:1).
sugar backbone, were obtained by the oxidation of 1-O-al-
lyl sugars and subsequent formation of the lactone ring.
The benzylated carboxymethyl lactones proved to be more
sensitive to opening by water, therefore necessitating
strictly anhydrous storage conditions. All new lactones
exhibited similar reactivities towards nucleophilic species
as the parent a-gluco CMGL, as illustrated by the prepara-
tion of a series of propargyl amides. One of the latter could
be used, as an example, in a Huisgen cycloaddition with
azidodeoxyuridine, en route towards potential analogues
of nucleotide sugars.
4. Experimental
4.1. General
3. Conclusion
A series of new carboxymethyl-D-glycoside-2-O-lactones,
including variations on the protecting groups and on the
All chemicals were purchased from Aldrich. Organic
solutions were dried over anhydrous sodium sulfate. The

A. Listkowski et al. / Tetrahedron: Asymmetry 18 (2007) 2201–2210
2205
reactions were monitored by thin-layer chromatography on
Silica Gel 60 F254 (Merck); detection was carried out by
charring with a 5% H2SO4 solution in ethanol. Silica gel
(Kieselgel 60, 70–230 mesh ASTM, Merck) was used for
flash chromatography. NMR spectra were recorded with
a Bruker ALS300, DRX300 or DRX500 spectrometer in
CDCl3. The signal of the residual protonated solvent was
taken as reference. Chemical shift (d) and coupling con-
stants (J) are reported in ppm and Hz, respectively. The
13C aromatic resonances occurring at the typical d values
were omitted for simplicity. Optical rotations were mea-
sured with a Perkin–Elmer 241 polarimeter for solutions
in CHCl3 at room temperature. Elemental analyses were
performed by ‘Service Central de Microanalyses du CNRS’
69360 Solaize (France).
and 4.65 (dd, 1H, H-2)), 4.52 (d, 1H, H-7B), 4.47–4.42
(m, 1H, H-5), 4.15–4.09 (m, 2H, H-6A and H-6B), 2.15,
2.06, 2.055 (3 · s, 3 · 3H, 3 · CH3); 13C NMR (75 MHz)
d 170.8, 170.5, 170.2, (3 · C@O from acetyl), 164.2
(C@O), 91.5 (C-1), 76.4 (C-2), 71.9 (C-3), 70.5 (C-5), 67.3
(C-4), 64.9 (C-7), 61.7 (C-6), 21.1, 20.9, 20.8 (3 · CH3).
Anal. Calcd for C14H18O10: C, 48.56; H, 5.24. Found: C,
48.64; H, 5.49.
4.6. Carboxymethyl-3,4,6-tri-O-acetyl-b-D-glucopyranoside-
2-O-lactone 11
White amorphous solid, 21% (pentane/AcOEt; 3:2);
½aꢀD ¼ þ93 (c 1, CH2Cl2); HRMS (ESI) m/z calcd for
C14H18O10Na (M+H)+ 347.0978, found 347.0979; 1H
NMR (300 MHz) d 5.30 (dd, 1H, J3,4 = 9.1 Hz, J2,3
=
4.2. General procedure for preparation of carboxymethyl-
2,3,4,6-tetra-O-acetyl-D-glycosides 4, 5, 9 and 10
10.2 Hz, H-3), 5.05 (dd, 1H, J3,4 = 9.1 Hz, J4,5 = 10.2 Hz,
H-4), 4.75 (d, 1H, J1,2 = 7.9 Hz, H-1), 4.50 (AB system,
2H, da 4.52 db 4.69, JA,B = 17.4 Hz, H-7), 4.30 (dd, 1H,
J1,2 = 7.9 Hz, J2,3 = 10.2 Hz, H-2), 4.21 (dd, 1H,
J5,6B = 4.7 Hz, J6A,6B = 12.5 Hz, H-6B), 4.12 (dd, 1H,
J5,6B = 2.3 Hz, J6A,6B = 12.5 Hz, H-6B), 3.91 (ddd, 1H,
J5,6A = 2.3 Hz, J5,6B = 4.7 Hz, J4,5 = 10.2 Hz, H-5), 2.09,
2.09, 2.05 (3 · s, 3 · 3H, 3 · CH3); 13C NMR (75 MHz) d
170.6, 169.9, 169.6, 164.9 (4 · C@O), 95.0 (C-1), 76.5,
73.8, 71.2,68.2 (C-2, C-3, C-4, C-5), 64.5 (C-7), 61.6 (C-
6), 20.8, 20.7, 20.6 (3 · CH3). Anal. Calcd for C14H18O10:
C, 48.56; H, 5.24. Found: C, 48.46; H, 5.41.
Allyl-2,3,4,6-tetra-O-acetyl-D-glycoside (0.1 g, 0.26 mmol)
was dissolved in CH2Cl2/CH3CN/H2O 2:2:3 (1.2 mL).
Then NaIO4 (0.420 g, 1.98 mmol) was added followed by
RuCl3 (1.2 mg, 0.005 mmol) and the reaction mixture was
stirred vigorously for 2 h at rt. The mixture was diluted
with water and extracted twice with CH2Cl2. The combined
organic layers were dried, concentrated and purified on col-
umn chromatography (AcOEt/MeOH; 7:3), to give the
expected carboxymethyl-2,3,4,6-tetra-O-acetyl-D-glycoside
4 (86%), 5 (95%), 9 (88%) and 10 (50%), identified by com-
parison of the NMR spectra with the literature
data.9,11,13,18
4.7. Carboxymethyl-3,4,6-tri-O-acetyl-b-D-galactopyrano-
side-2-O-lactone 12
4.3. General procedure for preparation of peracetylated
lactones
White amorphous solid, 76% (pentane/AcOEt; 3:2 then
2:1); ½aꢀD ¼ þ85 (c 1, CH2Cl2); HRMS (ESI) m/z calcd
for C14H18O10Na (M+Na)+ 369.0798, found 369.0797;
1H NMR (500 MHz) d 5.46 (dd, 1H, J4,5 = 1.9 Hz,
J3,4 = 3.5 Hz, H-4), 5.16 (dd, 1H, J2,3 = 10.5 Hz, H-3),
4.77 (d, 1H, J1,2 = 7.6 Hz, H-1), 4.70 (d, 1H,
JA,B = 17.7 Hz, H-7A), 4.48–4.50 (m, 2H, 4.54 (d, 1H, H-
7B), 4.53 (dd, 1H, H-2)), 4.20–4.16 (m, 2H, H-6A and H-
6B), 4.13–4.09 (m, 1H, H-5), 2.14 (s, 3H, CH3), 2.04 (s,
6H, 2 · CH3); 13C NMR (75 MHz) d 170.3 (double inten-
sity), 169.7, 165.2 (4 · C@O), 95.5 (C-1), 74.6 (C-2), 72.8
(C-5), 69.5 (C-3), 66.8 (C-4), 64.5 (C-7), 61.0 (C-6), 20.6,
20.5, 20.4 (3 · CH3). Anal. Calcd for C14H18O10: C,
48.56; H, 5.24. Found: C, 48.64; H, 5.49.
The
carboxymethyl-2,3,4,6-tetra-O-acetyl-D-glycoside
(0.355 g, 0.874 mmol) was dissolved in MeOH/Et3N/H2O
8:1:1 (6 mL) and after 6 h, it was coevaporated with water
to its half volume about 3 times, until no triethylamine
remained. Then it was concentrated to dryness, to give
the proper carboxymethyl-D-glycoside, which was dis-
solved in pyridine (12 mL). Acetic anhydride (7 mL) was
added at 0 ꢁC, and the reaction was stirred at rt for 24 h.
The solvents were then evaporated under a diminished
pressure and the oily residue was purified using column
chromatography.
4.4. Carboxymethyl-3,4,6-tri-O-acetyl-a-D-glucopyranoside-
2-O-lactone 1
4.8. General procedure for selective 2-O-debenzylation using
TIBAL
White solid, 41% (pentane/AcOEt; 3:2). All characteristics
have been published previously.18
Allyl 2,3,4,6-tetra-O-benzyl-a-D-pyranoside (6.0 g, 10.3
mmol) was dissolved in dry toluene (27 mL) and tri-
isobutylaluminium (TIBAL, 51.5 mmol) as a 1.5 M toluene
solution was added. The reaction mixture was stirred at
50 ꢁC under a nitrogen atmosphere for 48 h, then cooled
to 0 ꢁC before the dropwise addition of 1 M HCl. The mix-
ture was then portioned between water and ethyl acetate.
The aqueous phase was extracted with ethyl acetate and
the combined organic layers were dried, concentrated and
purified on column chromatography.
4.5. Carboxymethyl-3,4,6-tri-O-acetyl-a-D-galactopyrano-
side-2-O-lactone 6
White amorphous solid, 52% (pentane/AcOEt; 3:2);
½aꢀD ¼ þ113 (c 0.9, CH2Cl2); MS (ESI) m/z = 346.09
[C15H18O11 (M+H)+]; 1H NMR (300 MHz) d 5.48 (dd,
1H, J3,4 = 3.3 Hz, J4,5 = 1.2 Hz, H-4), 5.43 (dd, 1H,
J2,3 = 9.9 Hz, H-3), 5.39 (d, 1H, J1,2 = 3.0 Hz, H-1),
4.71–4.61 (m, 2H, 4.67 (d, 1H, J7A,7B = 18.0 Hz, H-7A)

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A. Listkowski et al. / Tetrahedron: Asymmetry 18 (2007) 2201–2210
4.9. Allyl 3,4,6-tri-O-benzyl-a-D-glucopyranoside 23
137.9 (3 · C quat.), 133.7 (–CH@CH2), 117.7 (–CH@CH2),
100.4 (C-1), 83.9 (C-3), 77.9 (C-4), 76.1 (double intensity,
C-2 and C-5), 73.4, 72.6, 71.7 (3 · CH2), 71.2 (C-6), 69.2
(C-7). Other characteristics have been published else-
where.31 From the same reaction allyl-3,5,6-tri-O-benzyl-
b-D-glucofuranoside 29 was isolated as a minor, more po-
White amorphous solid, 55% (pentane/AcOEt; 6:1 then
5:1); 1H NMR (300 MHz) d 7.50–7.10 (m, 15H), 6.05–
5.85 (m, 1H, –CH@CH2), 5.36–5.28 (m, 1H, –CH@CH2),
5.26–5.20 (m, 1H, CH@CH2), 4.98 (d, 1H, J1,2 = 3.4 Hz,
H-1), 4.96 (d, 1H, JA,B = 11.2 Hz, from benzyl), 4.91–
4.82 (m, 2H, 4.88 (d, 1H, JA,B = 11.2 Hz), 4.86 (d, 1H,
JA,B = 10.7 Hz) from benzyl), 4.67 (d, 1H, JA,B = 12.2 Hz,
from benzyl), 4.57–4.50 (m, 2H, 4.53 (d, 1H,
JA,B = 12.2 Hz), 4.52 (d, 1H, JA,B = 10.7 Hz) from benzyl),
4.24 (dddd, 1H, J7A,9A = 1.5 Hz, J7A,9B = 1.5 Hz,
J7A,8 = 5.3 Hz, J7A,7B = 12.8 Hz, H-7A), 4.07 (dddd, 1H,
J7B,9A = 1.3 Hz, J7B,9B = 1.3 Hz, J7B,8 = 6.2 Hz, H-7B),
3.88–3.64 (m, 6H, H-2, H-3, H-4, H-5, H-6A, H-6B),
2.11 (br s, 1H, OH); 13C NMR (75 MHz) d 138.6, 138.1,
137.8 (3 · C quat.), 133.5 (–CH@CH2), 117.9 (–CH@CH2),
97.5 (C-1), 83.3, 77.3 and 72.9, 70.5 (C-2, C-3, C-4 and C-
5), 75.3, 76.9, 73.4 (3 · CH2), 68.4, 68.3 (C-6 and C-7).
Other characteristics have been published elsewhere.29
1
lar product (0.52 g, 27%). H NMR (300 MHz) d 7.30–
7.10 (m, 15H), 5.95–5.80 (m, 1H, –CH@CH2), 5.35–5.20
(m, 1H, –CH@CH2), 5.20–5.17 (m, 1H, –CH@CH2), 4.92
(br s, 1H, H-1), 4.73 (d, 1H, JA,B = 11.4 Hz, from benzyl),
4.64–4.44 (m, 5H, from benzyls), 4.38 (dd, 1H,
J3,4 = 5.0 Hz, J4,5 = 8.7 Hz, H-4), 4.26–4.14 (m, 2H, H-2
and H-7A), 4.06 (ddd, 1H, J5,6A = 2.1 Hz, J5,6B = 5.4 Hz,
H-5), 4.00–3.90 (m, 2H, H-3 and H-7B), 3.87 (dd, 1H,
J6A,6B = 10.7 Hz, H-6A), 3.70 (dd, 1H, H-6B), 2.07 (br d,
1H, J2,OH = 3.0 Hz, OH); 13C NMR (75 MHz) d 138.8,
138.6, 138.0 (3 · C quat.), 134.2 (–CH@CH2), 117.0
(–CH@CH2), 107.8 (C-1), 82.9 (C-3), 79.9 (C-4), 78.4 (C-
2), 76.6 (C-5), 73.3, 72.5, 71.9 (3 · CH2), 70.8 (C-6), 68.8
(C-7). Other characteristics have been published elsewhere.32
4.10. Allyl 3,4,6-tri-O-benzyl-a-D-galactopyranoside 24
4.12. General procedure for the preparation of perbenzylated
lactones
White amorphous solid, 62% (pentane/AcOEt; 5:1); 1H
NMR (500 MHz) d 7.50–7.20 (m, 15H), 6.00–5.85 (m,
1H, –CH@CH2), 5.14–5.08 (m, 1H, –CH@CH2), 4.92 (d,
1H, J1,2 = 3.8 Hz, H-1), 4.83 (d, 1H, JA,B = 11.6 Hz, from
benzyl), 4.67 (d, 1H, JA,B = 11.8 Hz, from benzyl), 4.63 (d,
1H, JA,B = 11.8 Hz, from benzyl), 4.49 (d, 1H,
JA,B = 11.6 Hz, from benzyl), 4.43 (d, 1H, JA,B = 11.8 Hz,
from benzyl), 4.36 (d, 1H, JA,B = 11.8 Hz, from benzyl),
4.15–4.85 (m, 2H, H-7A and H-2), 3.99–3.93 (m, 1H,
The starting allyl glycoside (4.1 mmol) was dissolved in
MeOH (50 mL), cooled to ꢁ78 ꢁC and ozone was bubbled
through a reaction mixture until TLC indicated a lack of
starting material (about 20 min). Excess ozone was re-
moved by passing O2 through the solution, then dimethyl
sulfide (3.0 mL) was added and the mixture was stirred at
rt overnight. Solvents were evaporated under reduced pres-
sure and the oily residue was dissolved in MeOH (100 mL),
cooled to about 0 ꢁC and NaClO2 (3.0 g, 33.2 mmol) in
10% KH2PO4 water solution (36 mL) was added dropwise.
The reaction mixture was stirred at rt. overnight, then pH
was decreased to about 5 with glacial acetic acid and sol-
vents were removed under vacuum. The residue was sus-
pended in pyridine and acetic anhydride (120 mL, 1:1
mixture) and stirred at rt overnight. Then it was concen-
trated and extracted with water and ethyl acetate. Organic
layer was dried, concentrated and purified on column chro-
matography to give the expected product.
J7B;CH@CH ¼ 6:3 Hz, J7A,7B = 13.0 Hz, H-7B), 3.93–3.91
2
(m, 1H, H-4), 3.90–3.86 (m, 1H, H-5), 3.65 (dd,
J3,4 = 2.8 Hz, J2,3 = 10.1 Hz, H-3), 3.56–3.46 (m, 2H,
H-6A and H-6B), 2.16 (br s, 1H, OH); 13C NMR
(125 MHz) d 138.5, 138.2, 137.9 (3 · C quat.), 133.7
(–CH@CH2), 117.8 (–CH@CH2), 97.7 (C-1), 79.6 (C-3),
74.6 (CH2), 73.9 (C-4), 73.5, 72.4 (2 · CH2), 69.7 (C-5),
69.0 (C-2), 68.8 (C-6), 68.5 (C-7). Other characteristics
have been published elsewhere.30,31
4.11. Allyl 3,5,6-tri-O-benzyl-a-D-glucofuranoside 28
1,2-Isopropylidene-3,5,6-tri-O-benzyl-a-D-glucofuranose
(1.95 g, 3.97 mmol) was dissolved in dry allyl alcohol
(35 mL) containing BF3 etherate (0.015 mL, 0.12 mmol)
and the reaction mixture was stirred at reflux for 1.5 h. It
was then cooled to the room temperature and the solvents
were evaporated. The oily residue was purified chromato-
graphically (pentane/ethyl acetate 6:1 then 4:1) to give 28
(1.15 g, 59%) as a major, less polar product.
4.13. Carboxymethyl-3,4,6-tri-O-benzyl-b-D-glucopyrano-
side-2-O-lactone 19
Pale yellow oil, 50% (pentane/acetone/toluene; 5:1:1 then
4.5:1:1); ½aꢀD ¼ ꢁ21 (c 1, CH2Cl2); HRMS (ECI) m/z calcd
for C29H31O7 (M+H)+ 491.2070, found 491.2070; 1H
NMR (300 MHz) d 7.40–7.10 (m, 15H), 5.03 (d, 1H,
JA,B = 11.2 Hz, from benzyl), 4.84 (d, 1H, JA,B = 10.7 Hz,
from benzyl), 4.81–4.93 (d, 1H, JA,B = 11.2 Hz, from benz-
yl), 4.63–4.47 (m, 3H, 4.59 (d, 1H, JA,B = 12.2 Hz), 4.51 (d,
1H, JA,B = 12.2 Hz), 4.50 (d, 1H, JA,B = 10.7 Hz) 3times
from benzyls), 4.43 (d, 1H, J7A,7B = 17.0 Hz, H-7A),
4.35–4.24 (m, 2H), 4.33 (d, 1H, J1,2 = 7.7 Hz, H-1), 4.28
(d, 1H, H-7B), 3.75–3.43 (m, 6H, H-2, H-3, H-4, H-5, H-
6A and H-6B); 13C NMR (75 MHz) d 171.2 (C@O),
138.7, 138.0, 137.9 (3 times C quat.), 103.2 (C-1), 84.5,
76.9, 75.2 and 74.6 (C-2, C-3, C-4, C-5), 75.1, 75.0 and
73.4 (3 · CH2), 68.7 (C-6), 65.6 (C-7). Anal. Calcd for
1H NMR (300 MHz) d 7.40–7.20 (m, 15H), 5.99–5.82 (m,
1H, –CH@CH2), 5.30–5.14 (m, 3H, –CH@CH2 and 5.16
(d, 1H, J1,2 = 4.5 Hz, H-1)), 4.78 (d, 1H, JA,B = 11.4 Hz,
from benzyl), 4.69 (d, 1H, JA,B = 11.7 Hz, from benzyl),
4.62–4.48 (m, 4H, from benzyl), 4.38–4.20 (m, 3H, H-2,
H-4 and H7A), 4.12–3.98 (m, 3H, H-3, H-5 and H-7B),
3.85 (dd, 1H, J5,6A = 2.0 Hz, J6A,6B = 10.7 Hz, H-6A),
3.68 (dd, 1H, J5,6B = 5.9 Hz, H-6B), 2.93 (d, 1H,
J2,OH = 5.4 Hz, OH); 13C NMR (75 MHz) d 138.9, 138.6,

A. Listkowski et al. / Tetrahedron: Asymmetry 18 (2007) 2201–2210
2207
C29H30O7Æ1.8H2O: C, 66.60; H, 6.49. Found: C, 66.69; H,
6.24.
(C-3), 77.0 (C-2), 74.7 (CH2), 73.7 (C-4), 73.4, 72.8
(2 · CH2), 72.3 (C-5), 67.8 (C-6), 64.1 (C-7). Anal. Calcd
for C29H30O72/3H2O: C, 69.31; H, 6.28. Found: C, 69.09;
H, 6.26.
4.14. Carboxymethyl-3,4,6-tri-O-benzyl-b-D-galactopyrano-
side-2-O-lactone 20
4.17. Carboxymethyl-3,5,6-tri-O-benzyl-a-D-glucofurano-
side-2-O-lactone 30
White solid, 43% (pentane/AcOEt, 5:1 then 4:1);
½aꢀD ¼ þ51 (c 0.2, CH2Cl2); HRMS (ESI) m/z calcd for
C29H30O7Na (M+Na)+ 513.1889, found 513.1888; 1H
NMR (500 MHz) d 7.50–7.20 (m, 15H), 4.94 (d, 1H,
JA,B = 11.2 Hz, from benzyl), 4.85 (d, 1H, JA,B = 12.0 Hz,
from benzyl), 4.79–4.69 (m, 2H, H-2 and 1H from benzyl),
4.65 (d, 1H, J7A,7B = 17.2 Hz, H-7), 4.61 (d, 1H,
J1,2 = 7.9 Hz, H-1), 4.58 (d, 1H, JA,B = 11.2 Hz, from
benzyl), 4.51–4.41 (m, 3H), 4.43 (d, 1H, JA,B = 11.2 Hz,
from benzyl), 4.46 (d, 1H, H-7) and 4.49 (d, 1H,
JA,B = 11.2 Hz, from benzyl), 4.99–4.96 (m, 1H, H-4),
3.77–3.71 (m, 1H, H-5), 3.69 (dd, 1H, J3,4 = 3.2 Hz,
J2,3 = 10.1 Hz, H-3), 3.67–3.63 (m, 2H, H-6A and H-6B);
13C NMR (125 MHz) d 166.6 (C@O), 137.9, 137.45,
137.40 (3 · C quat.), 95.7 (C-1), 78.6 (C-3), 77.7 (C-2),
75.2 (C-5), 75.1 (CH2), 73.7 (C-4), 73.5, 73.0 (2 · CH2),
67.8 (C-6), 64.2 (C-7). Anal. Calcd for C29H30O7Æ2H2O:
C, 66.15; H, 6.51. Found: C, 66.58; H, 6.08.
Pale yellow oil, 24% (pentane/acetone/toluene; 7:1:1 then
5:1:1); ½aꢀD ¼ þ19 (c 0.7, CH2Cl2); HRMS (ESI) m/z calcd
for C29H31O7 (M+H)+ 491.2070, found 491.2068; 1H
NMR (300 MHz) d 7.40–7.20 (m, 15H), 5.61 (d, 1H,
J1,2 = 4.0 Hz, H-1), 4.82–4.74 (m, 2H, 4.78 (dd, 1H,
J2,3 = 1.4 Hz, H-2) and 4.77 (d, 1H, JA,B = 11.7 Hz, from
benzyl), 4.62–4.44 (m, 5 · H from benzyls)), 4.43–4.33
(m, 2H), 4.40 (dd, 1H, J3,4 = 3.7 Hz, J4,5 = 8.6 Hz, H-4)
and 4.37 (d, 1H, J7A,7B = 17.3 Hz, H-7A), 4.26 (dd, 1H,
H-3), 4.18 (d, H-7B), 3.98 (ddd, 1H, J5,6A = 2.3 Hz,
J5,6B = 4.9 Hz, H-5), 3.87 (dd, 1H, J6A,6B = 10.7 Hz, H-
6A), 3.69 (dd, 1H, H-6B); 13C NMR (75 MHz) d 165.4
(C@O), 138.3, 138.2, 136.8 (3 · C quat.), 95.8 (C-1), 81.9
(C-3), 80.2 (C-2), 79.7 (C-4), 75.8 (C-5), 73.3, 72.7, 72.2
(3 · CH2), 69.9 (C-6), 58.3 (C-7). Anal. Calcd for
C29H30O7ÆH2O: C, 68.49; H, 6.34. Found: C, 68.53; H,
6.06.
4.15. Carboxymethyl-3,4,6-tri-O-benzyl-a-D-glucopyrano-
side-2-O-lactone 25
4.18. General procedure for the reaction of the lactones with
propargyl amine
White crystals (ether), 56% (pentane/acetone/toluene
8:1:1); mp = 103–104 ꢁC; ½aꢀD ¼ þ88 (c 0.8, CH2Cl2);
HRMS (ESI) m/z calcd for C29H31O7 (M+H)+ 491.2070,
found 491.2070; 1H NMR (300 MHz) d 7.40–7.10 (m,
15H), 5.27 (d, 1H, J1,2 = 3.1 Hz, H-1), 4.93 (d, 1H,
JA,B = 10.9 Hz, from benzyl), 4.84 (d, 1H, JA,B = 10.8 Hz,
from benzyl), 4.78 (d, 1H, JA,B = 10.9 Hz, from benzyl),
4.63–4.42 (m, 6H, 3 · H from benzyl and 4.58 (d, 1H,
J7A,7B = 17.9 Hz, H-7A), 4.46 (d, 1H, H-7B), 4.45 (dd,
1H, J2,3 = 9.1 Hz, H-2)), 4.06–3.98 (m, 2H, H-5 and 4.02
(dd, 1H, J3,4 = 8.9 Hz, H-3)), 3.77–3.56 (m, 3H, H-4, H-
6A, H-6B); 13C NMR (75 MHz) d 164.5 (C@O), 137.7,
137.6, 137.5 (3 · C quat.), 91.7 (C-1), 81.7 (C-3), 79.6 (C-
2), 76.0 (C-4), 75.6, 75.2, 73.5 (3 · CH2), 72.7 (C-5), 67.8
(C-6), 64.5 (C-7). Anal. Calcd for C29H30O7Æ1/3H2O: C,
70.15; H, 6.22. Found: C, 70.20; H, 6.07.
The starting lactone (0.51 mmol, 0.177 g for peracetylated
lactones, 0.250 g for perbenzylated lactones) was dissolved
in anhydrous CH2C2 (2 mL) followed by the addition of
propargyl amine (0.035 mL, 0.51 mmol for peracetylated
lactones, 0.052 mL, 0.767 mmol for perbenzylated lac-
tones) and the reaction mixture was stirred overnight under
a nitrogen atmosphere at rt. It was then concentrated and
the product was isolated by column chromatography.
4.19. (N-Propargylcarbamoyl)methyl-3,4,6-tri-O-acetyl-a-
D-glucopyranoside 31
Pale yellow oil, 94% (CH2Cl2/MeOH; 450:15). All charac-
teristics have been published previously.19
4.16. Carboxymethyl-3,4,6-tri-O-benzyl-a-D-galactopyrano-
side-2-O-lactone 26
4.20. (N-Propargylcarbamoyl)methyl-3,4,6-tri-O-acetyl-a-
D-galactopyranoside 32
White amorphous solid, 36%, (pentane/acetone/toluene
8:1:1), ½aꢀD ¼ þ71 (c 0.8, CH2Cl2); HRMS (ESI) m/z calcd
for C29H31O7 (M+H)+ 491.2070, found 491.2071; 1H
NMR (300 MHz) d 7.4–7.2 (m, 15H), 5.27 (d, 1H,
J1,2 = 3.0 Hz, H-1), 4.89 (d, 1H, JA,B = 11.4 Hz, from
benzyl), 4.80 (dd, 1H, J2,3 = 9.2 Hz, H-2), 4.74 (d, 1H,
JA,B = 11.9 Hz, from benzyl), 4.71 (d, 1H, JA,B = 11.9 Hz,
from benzyl), 4.57 (d, 1H, JA,B = 11.4 Hz, from benzyl),
4.53–4.33 (m, 4H, AB systems from benzyl and H-7),
4.15 (ddd, 1H, J5,6A = 6.2 Hz, J5,6B = 6.6 Hz, H-5), 4.00
(dd, 1H, J4,5 = 1.7 Hz, H-4), 3.92 (dd, 1H, J3,4 = 2.8 Hz,
H-3), 3.65–3.50 (m, 2H), 3.59 (dd, 1H, J6A,6B = 10.9 Hz,
H-6A), 3.56 (dd, 1H, H-6B); 13C NMR (75 MHz) d 164.9
(C@O), 137.8, 137.6, 137.4 (3 · C quat.), 91.5 (C-1), 77.7
White amorphous solid, 84% (CH2Cl2/MeOH; 400:15);
½aꢀD ¼ þ122 (c 0.6, CH2Cl2); HRMS (ESI) m/z calcd for
1
C17H23O10NNa (M+Na)+ 424.1220, found 424.1213; H
NMR (300 MHz) d 7.78 (t, 1H, JNH;CH ¼ 5:4 Hz, NH),
2
5.34 (dd, 1H, J4,5 = 1.1 Hz, J3,4 = 3.4 Hz, H-4), 5.13 (dd,
1H, J2,3 = 10.5 Hz, H-3), 4.94 (d, 1H, J1,2 = 3.8 Hz, H-1),
4.21 (d, 1H, J7A,7B = 16.0 Hz, H-7A), 4.18–4.11 (m, 1H,
H-5), 4.09–3.97 (m, 6H, H-2, H-6A, H-6B, H-7B, and
2 · NH–CH2–), 3.89 (d, 1H, J2,OH = 5.8 Hz, OH), 2.23 (t,
1H, JCH ꢁCCH ¼ 4:3 Hz, CCH), 2.08, 1.994, 1.990 (3 · s,
2
3 · 3H, 3 · CH3); NMR (75 MHz) d 170.9, 170.5, 170.1,
169.2 (4 · C@O), 99.6 (C-1), 79.1 (CCH), 71.6 (CCH),
70.3 (C-3), 67.8 (C-4), 67.3 (C-7 or C-6) 67.1, 66.5 (C-2
and C-5), 61.6 (C-6 or C-7), 28.5 5 (NH–CH2–), 20.8,

2208
A. Listkowski et al. / Tetrahedron: Asymmetry 18 (2007) 2201–2210
20.6, 20.5 (3 · CH3). Anal. Calcd for C17H23O10N: C,
J3,4 = 2.6 Hz, J2,3 = 9.8 Hz, H-3) and OH), 2.06 (t, 1H,
50.87; H, 5.78; N, 3.49. Found: C, 50.95; H, 5.89; N, 3.23.
JCH –CCH ¼ 2:5 Hz, CCH); 13C NMR (75 MHz) d 169.5
2
(C@O), 138.1, 137.6, 137.5 (3 · C quat.), 103.5 (C-1),
81.9 (C-3), 79.1 (CCH), 74.5 (CH2), 73.7, 73.5 (CH2),
72.1 (double intensity, CH2 and C-2 or C-4 or C-5), 71.4
(CCH), 70.5, 68.7 (C-7), 68.1 (C-6), 28.5 (NH–CH2–).
Anal. Calcd for C32H35O7NÆ1/2H2O: C, 68.19; H, 6.62;
N, 2.49. Found: C, 68.57; H, 6.27; N, 2.46.
4.21. (N-Propargylcarbamoyl)methyl-3,4,6-tri-O-acetyl-b-D-
galactopyranoside 33
Pale yellow oil, 83% (CH2Cl2/MeOH; 30:1); ½aꢀD ¼ ꢁ2 (c
0.6, CH2Cl2); HRMS (ESI) m/z calcd for C17H23O10NNa
(M+Na)+ 424.1220, found 424.1219; 1H NMR
(300 MHz) d 7.45 (br t, 1H, JNH;CH ¼ 5:1 Hz, NH), 5.35
4.24. (N-Propargylcarbamoyl)methyl-3,4,6-tri-O-benzyl-a-
D-glucopyranoside 36
2
(br dd, 1H, J4,5 = 2.8 Hz, J3,4 = 3.1 Hz, H-4), 4.90 (dd,
1H, J2,3 = 10.2 Hz, H-3), 4.40 (d, 1H, J1,2 = 7.7 Hz, H-1),
4.34 (d, 1H, J7A,7B = 16.0 Hz, H-7A), 4.22–4 (d, 1H, H-
7B), 4.14–4.02 (m, 4H, H-6A, and 2 · NH–CH2–), 3.95–
3.88 (m, 1H, H-5), 3.84 (dd, 1H, H-2), 3.50 (br s, 1H,
Colorless oil, 54% (pentane/acetone/toluene; 4:1:1 then
pentane/AcOEt; 1:1); ½aꢀD ¼ þ88 (c 0.5, CH2Cl2); HRMS
(ESI) m/z calcd for C32H35O7NNa (M+Na)+ 568.2311,
found 568.2309; 1H NMR (300 MHz) d 7.70 (t, 1H,
OH), 2.27 (t, 1H, JCH –CCH ¼ 2:5 Hz, CCH), 2.12, 2.032,
2
2.028 (3 · s, 3 · 3H, 3 · CH3); NMR (75 MHz) d 170.55,
170.48, 170.1, 169.3 (4 · C@O), 103.4 (C-1), 79.0 (CCH),
72.8 (C-3), 71.8 (CCH), 71.0 (C-5), 68.81 (C-7), 68.79 (C-
2), 67.0 (C-4), 61.4 (C-6), 28.6 (NH–CH2–), 20.7, 20.63,
20.57 (3 · CH3). Anal. Calcd for C17H23O10N: C, 50.87;
H, 5.78; N, 3.49. Found: C, 50.44; H, 5.74; N, 3.41.
JNH;CH ¼ 5:4 Hz, NH), 7.30–7.05 (m, 15H), 4.84 (d, 1H,
2
JA,B = 11.3 Hz, from benzyl), 4.76–4.68 (m, 3H, 2 · H
from benzyls and H-1), 4.54 (d, 1H, JA,B = 12.0 Hz, from
benzyl), 4.58–4.47 (m, 3H, 3 · H from benzyls), 4.11 (d,
1H, J7A,7B = 16.2 Hz, from benzyl), 4.01–3.93 (m, 3H,
3.97 (d, 1H, H-7B) and 2 · NH–CH2–), 3.80–3.60 (m,
5H, H-2, H-3, H-4, H-5, H-6A), 3.57 (dd, 1H,
J5,6A = 1.7 Hz, J6A,6B = 10.5 Hz, H-6B); 3.25 (br s, 1H,
4.22. (N-Propargylcarbamoyl)methyl-3,4,6-tri-O-benzyl-b-
D-glucopyranoside 34
OH), 2.13 (t, 1H, JCH –CCH ¼ 2:5 Hz, CCH); 13C NMR
2
(75 MHz) d 169.6 (C@O), 138.4 (double intensity), 137.8,
(3 · C quat.), 99.6 (C-1), 82.1, 79.2 (CCH), 74.4, 75.2
(CH2), 74.8 (CH2), 73.5 (CH2), 71.7, 71.4 (CCH), 71.3,
68.0 (C-6), 67.3 (C-7), 28.5 (NH–CH2–). Anal. Calcd for
C32H35O7N: C, 70.44; H, 6.47. Found: C, 70.07; H, 6.35.
Pale yellow amorphous solid, 94% (CH2Cl2/MeOH;
300:12); ½aꢀD ¼ þ5 (c 0.3, CH2Cl2); HRMS (ESI) m/z calcd
for C32H35O7N (M+H+) 568.2311, found 568.2312; 7.46 (t,
1H, JNH;CH ¼ 5:2 Hz, NH), 7.30–7.10 (m, 15H), 4.85–4.69
2
(m, 3H, 4.82 (d, 1H, JA,B = 11.5 Hz), 4.76 (d, 1H,
JA,B = 11.5 Hz) and 4.72 (d, 1H, JA,B = 11.1 Hz) from
benzyls), 4.52 (d, 1H, JA,B = 12.1 Hz, from benzyl), 4.49–
4.39 (m, 2H, 4.46 (d, 1H, JA,B = 11.1 Hz), 4.43 (d, 1H,
JA,B = 12.1 Hz) from benzyls), 4. 4.24 (d, 1H,
J7A,7B = 16.0 Hz, H-7A), 4.18 (d, 1H, J1,2 = 7.4 Hz, H-1),
4.12 (d, 1H, H-7B), 4.04–3.87 (m, 2H, 2 · NH–CH2–),
3.66–3.32 (m, 7H, H-2, H-3, H-4, H-5, H-6A, H-6B and
4.25. (N-Propargylcarbamoyl)methyl-3,4,6-tri-O-benzyl-a-
D-galactopyranoside 37
Pale yellow oil, 64% (pentane/acetone/toluene; 4:1:1 then
pentane/AcOEt; 1:1); ½aꢀD ¼ þ84 (c 0.6, CH2Cl2); HRMS
(ESI) m/z calcd for C32H35O7N (M+H)+ 568.2311, found
1
568.2310; H NMR (300 MHz) d 7.75 (t, 1H, JNH;CH
¼
2
OH), 2.12 (t, 1H, JCH –CCH ¼ 2:5 Hz, CCH); 13C NMR
5:2 Hz, NH), 7.35–7.15 (m, 15H), 4.81 (d, 1H, J1,2
=
2
(75 MHz) d 169.6 (C@O), 138.3, 137.7, 137.6 (3 · C quat.),
103.2 (C-1), 84.4, 79.2 (CCH), 77.2, 75.2 (CH2), 75.0, 74.9
(CH2), 73.7, 73.5 (CH2), 71.5 (CCH), 68.9 (C-7), 68.2 (C-6),
28.5 (NH–CH2–). Anal. Calcd for C32H35O7N: C, 70.44;
H, 6.47; N, 2.57. Found: C, 70.03; H, 7.07; N, 2.59.
3.9 Hz, H-1), 4.78 (d, 1H, JA,B = 11.4 Hz, from benzyl),
4.69 (d, 1H, JA,B = 11.4 Hz, from benzyl), 4.53–4.47 (m,
2H), 4.49, (2 · d, 2 · JA,B = 11.4 Hz), 4.43 (d, 1H,
JA,B = 11.7 Hz, from benzyl), 4.37 (d, 1H, JA,B = 11.7 Hz,
from benzyl), 4.20–3.91 (m, 7H, H-7A, H-7B, both
HNCH2, H-4, H-5, and 4.18 (dd, 1H, J2,3 = 10.0 Hz, H-
2)), 3.73 (dd, 1H, J3,4 = 2.6 Hz, H-3), 3.60–3.45 (m, 2H,
4.23. (N-Propargylcarbamoyl)methyl-3,4,6-tri-O-benzyl-b-
D-galactopyranoside 35
H-6A and H-6B), 2.13 (t, 1H, JCH –CCH ¼ 2:6 Hz, CCH);
2
13C NMR (75 MHz) d 169.9 (C@O), 138.2, 137.6, 137.5,
(3 · C quat.), 99.8 (C-1), 79.2 (CCH), 78.8 (C-3), 74.6,
73.45 (2 · CH2), 73.2, (C-4), 72.0 (CH2), 71.3 (CCH),
70;1 (C-5), 68.3 (C-6), 68.0 (C-2), 67.4 (C-7), 28.5 (NH–
CH2–). Anal. Calcd for C32H35O7NÆ1/2H2O: C, 69.30; H,
6.54; N, 2.53. Found: C, 69.63; H, 6.28; N, 2.43.
Pale yellow oil, 85% (pentane/acetone/toluene; 4:1:1 then
pentane/AcOEt; 1:1); ½aꢀD ¼ þ3 (c 1, CH2Cl2); HRMS
(ESI) m/z calcd for C32H35O7NNa (M+Na)+ 568.2311,
found 568.2311; 1H NMR (300 MHz) d 7.48 (t, 1H,
JNH;CH ¼ 5:0 Hz, NH), 7.30–7.10 (m, 15H), 4.77 (d, 1H,
2
JA,B = 11.5 Hz, from benzyl), 4.63 (d, 1H, JA,B = 11.9 Hz,
from benzyl), 4.55–4.46 (m, 2H, 4.51 (d, 1H,
JA,B = 11.5 Hz), 4.77 (d, 1H, JA,B = 11.9 Hz) from benzyl),
4.37 (d, 1H, JA,B = 11.9 Hz, from benzyl), 4.34 (d, 1H,
JA,B = 11.9 Hz, from benzyl), 4.24–4.04 (m, 3H), 4.20 (d,
1H, JA,B = 16.2 Hz, H-7A), 4.16 (d, 1H, J1,2 = 7.9 Hz, H-
1), 4.09 (d, 1H, H-7B), 4.97–3.84 (m, 4H, H-2, 2 · NH–
CH2–, and H4 or H-5), 3.57–3.44 (m, 3H, H-6A, H-6B
and H-4 or H-5), 3.35–3.17 (m, 2H, 3.32 (dd, 1H,
4.26. (N-Propargylcarbamoyl)methyl-3,4,6-tri-O-benzyl-a-
D-glucofuranoside 38
Pale yellow oil, 85% (CH2Cl2/MeOH; 30:1); ½aꢀD ¼ þ10 (c
0.9, CH2Cl2); HRMS (ESI) m/z calcd for C32H35O7NNa
(M+Na)+ 568.2311, found 568.2315; 1H NMR
(300 MHz) d 7.30–7.10 (m, 16H, NH and aromatics),
5.00 (d, 1H, J1,2 = 4.3 Hz, H-1), 4.67 (d, 1H,

A. Listkowski et al. / Tetrahedron: Asymmetry 18 (2007) 2201–2210
2209
JA,B = 11.5 Hz, from benzyl), 4.57 (d, 1H, JA,B = 11.7 Hz,
from benzyl), 4.48 (br s, 2H, CH2 from benzyl), 4.47–4.39
(m, 2H), 4.44 (d, 1H, JA,B = 11.7 Hz), 4.42 (d, 1H,
2H, H-6A, H-3), 3.77 (m, 1H, H-5), 3.66 (dd, 1H,
J2,3 = 9.5 Hz, H-2), 3.49 (t, 1H, J3,4 = 9.4 Hz, H-4). 13C
NMR (125 MHz) d 175.8, 159.8, 150.7 (3C@O), 148.7
(Cq), 143.2 (CHCHCO), 127.2 (CHCN), 103.1
(CHCHCO), 100.9 (C-1), 93.4 (C-10), 82.7 (C-20), 74.7
(C-3), 74.2 (C-5), 74.0 (C-40), 73.1 (C-2), 71.7 (C-30), 71.5
(C-4), 67.0 (C-7), 62.5 (C-6), 52.3 (C-50), 35.2 (NHCH2).
Anal. Calcd for C20H28O12N6Æ2H2O: C, 41.38; H, 5.56;
N, 14.48. Found: C, 41.38; H, 5.35; N, 14.18.
JA,B = 11.5 Hz),
4.33
(dd,
1H,
J3,4 = 4.5 Hz,
J4,5 = 8.3 Hz, H-4), 4.22–4.10 (m, 4H), 4.22–4.17 (H-2),
4.17 (d, 1H, J7A,7B = 15.6 Hz, H-7A), 4.04 (d,1H, H-7B),
4.04 (dd, 1H, J2,3 = 2.5 Hz, H-3), 3.95–3.86 (m, 3H, H-5
and both HNCH2), 3.74 (dd, 1H, J5,6A = 2.2 Hz,
J6A,6B = 10.7 Hz, H-6A), 3.59 (dd, 1H, J5,6B = 5.5 Hz, H-
6B), 3.50 (br s, OH), 2.09 (t, 1H, JCH ꢁCCH ¼ 2:5 Hz,
2
CCH); 13C NMR (75 MHz) d 169.4 (C@O), 138.6, 138.3,
137.7, (3 · C quat.), 103.0 (C-1), 83.2 (C-3), 79.3 (CCH),
78.2 (C-4), 76.0 (C-5), 75.7 (C-2), 73.3, 72.4, 71.9
(3 · CH2), 71.5 (CCH), 70.5 (C-6), 68.4 (C-7), 28.5 (NH–
CH2–). Anal. Calcd for C32H35O7N: C, 70.44; H, 6.47;
N, 2.57. Found: C, 70.08; H, 6.09; N, 2.54.
References
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1. For recent reviews, see: (a) Galonic, D. P.; Gin, D. Y. Nature
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2. (a) Wessel, H. P. In Carbohydrates in Chemistry and Biology;
4.27. (N-Propargylcarbamoyl)methyl-a-D-glucopyranoside
39
Ernst, B., Hart, G. W., Sinay, P., Eds.; Wiley-CCH:
¨
Weinheim, Germany, 2000; Vol. 1, pp 565–585; (b) Wessel,
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Heidelberg, Germany, 2001; pp 2725–2752.
Amide 32 (1.061 g, 0.00264 mol) was dissolved in MeOH
(15 mL) and MeONa in MeOH (1 M) was added in a cat-
alytic amount. The reaction was stirred at room tempera-
ture. After 48 h, Dowex (H+) was added and the mixture
was stirred for 30 min. Then Dowex was separated by fil-
tration, the organic solvents were evaporated and the resi-
due was purified by column chromatography (CH2Cl2/
MeOH; 4:1) to give 0.663 g of the desired product as a
white foam in 91% yield. ½aꢀD ¼ þ188 (c 1, H2O); HRMS
(ESI) m/z calcd for C11H17O7N (M+Na)+ 298.0903, found
298.09054; 1H NMR (500 MHz, D2O) d 5.06 (d, 1H,
J1,2 = 3.6 Hz, H-1), 4.28 (AB system, 2H, d7A 4.36, d7B
3. (a) Gruner, S. A. W.; Locardi, E.; Lohof, E.; Kessler, H.
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4.21, JA,B = 15.6 Hz, H-7), 4.13 (d, 2H, JNH–CH ¼ 2:3 Hz,
2
NH–CH2), 3.93 (dd, 1H, J6A,5 = 2.2 Hz, J6A,6B = 12.2 Hz,
H-6A), 3.86 (t, 1H, J2,3 = J3,4 = 9.8 Hz, H-3), 3.84 (dd,
1H, J6B,5 = 12.2 Hz, H-6B), 3.76 (ddd, 1H, J4,5 = 9.8 Hz,
H-5), 3.69 (dd, 1H, H-2), 3.53 (t, 1H, H-4), 2.72 (t, 1H,
CH2CCH); 13C NMR (125 MHz) d 172.2 (C@O), 99.2
(C-1), 79.6 (CCH), 73.2 (C-4), 72.6 (C-5), 72.3 (CCH),
71.5 (C-2), 69.7 (C-3), 66.8 (C-7), 60.7 (C-6), 28.8
(NHCH2). Anal. Calcd for C11H17O7NÆ1/4H2O: C, 47.23;
H, 6.31; N, 5.01. Found: C, 47.06; H, 6.37; N, 4.84.
13. Binder, W. H.; Schmid, W. Monatsh. Chem. 1995, 126, 923–
931.
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Chem. 2003, 2462–2470.
4.28. N-Methyl[-4-[1-(50-deoxyuridin)-1,2,3-triazole]]car-
bamoylmethyl-a-D-glucopyranoside 40
15. Autar, R.; Khan, A. S.; Schad, M.; Hacker, J.; Liskamp, R.
M. J.; Pieters, R. J. ChemBioChem 2003, 4, 1317–1325.
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Amide 39 (0.604 g, 0.0022 mol) was dissolved in 11 mL
CH3CN/H2O (1:1), (0.59 g, 0.0022 mol) of azidouridine
were added, as well as a catalytic amount of CuI and of tri-
ethylamine (1 mL). After 24 h, the reaction was completed,
the solvents evaporated and the residue chromatographed
on a 10g C18 cartridge using a H2O/MeOH gradient
(9:1) to give 0.560 g of the product in 47% yield as a white
solid, ½aꢀD ¼ þ89 (c 1, H2O); HRMS (ESI) m/z calcd for
1
C20H28O12N6Na (M+Na)+ 567.1663, found 567.1666; H
NMR (CD3OD, 500 MHz) d 8.09 (s, 1H, CCHN), 7.53
(d, 1H, JNCHCHCO = 8.2 Hz, NCHCHCO), 5.90 (m, 2H,
CHCHCO, H-10), 5.03 (d, 1H, J1,2 = 3.6 Hz, H-1), 4.99
(m, 2H, H-50), 4.73 (s, 2H, NHCH2), 4.46–4.37 (m, 3H,
H-20, H-40, H-7A), 4.30 (t, 1H, J3 ;4 ¼ 6:0 Hz, H-30), 4.24
(d, 1H, J7A,7B = 16.1 Hz, H-7B), 4.00 (dd, 1H,
J6B,6A = 2.2 Hz, J6B,5 = 12.0 Hz, H-6B), 3.89–3.86 (m,
0
0

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