A simple procedure for connecting two carbohydrate moieties by click chemistry techniques

Article abstract of DOI:10.1002/ejoc.200600814

We describe a procedure to link two saccharides by click chemistry techniques. This methodology allows the generation of new molecules in which two carbohydrates are connected through a triazole ring. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.

Full text of DOI:10.1002/ejoc.200600814

FULL PAPER
DOI: 10.1002/ejoc.200600814
A Simple Procedure for Connecting Two Carbohydrate Moieties by Click
Chemistry Techniques
Sébastien G. Gouin,[a] Laurent Bultel,[a] Céline Falentin,[a] and José Kovensky*[a]
Keywords: Carbohydrates / Dipolar cycloaddition / Click chemistry
We describe a procedure to link two saccharides by click
chemistry techniques. This methodology allows the genera-
tion of new molecules in which two carbohydrates are con-
nected through a triazole ring.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2007)
cent success in the synthesis of glycoconjugates[10,13] by
“click chemistry” inspired us to envisage this approach to
constructing our molecules, and here we describe a fast pro-
cedure to connect saccharides through triazole rings
(Scheme 1).
Introduction
Carbohydrate–protein interactions have been extensively
investigated. Oligosaccharides serve to mediate a host of
biological events, including cell–cell recognition, adhesion,
and modulation of signal transduction pathways.[1] Many
proteins and lipids are glycosylated and this affects the
functions of the proteins to which they are attached.
In the area of multivalency, the development of multi-
valent carbohydrates of varying size as effectors of bio-
logical processes through clustering of receptors has been a
topic of interest. Generally, carbohydrates involved in the
binding are connected together through linkers.[2]
The Huisgen 1,3-dipolar cycloaddition between azides
and alkynes to afford triazoles is probably the most power-
ful “click” reaction for such linkages.[3] Interest in this reac-
tion became clear after the recent discovery of the advan-
tages of CuI as catalyst, reported independently by
Sharpless's[4] and Meldal's[5] groups. This reac-
tion in part owes its usefulness to its high compatibility
with functional groups (alcohols, carboxylic acids, amines)
in different solvent systems, including water. In the field of
carbohydrate chemistry, click chemistry has been used for
the synthesis of glycoconjugates[6,7] and carbohydrate
macrocycles[8] in which a sugar possessing an azido func-
tion is grafted onto a saccharide,[9] a peptide,[10] or a poly-
meric chain.[11] This methodology has also been employed
for the synthesis of glycosidase inhibitors.[12]
Scheme 1.
Results and Discussion
To demonstrate the broad compatibility of our tech-
nique, we have synthesized four azidoalkyl-saccharides
(Scheme 2). Azides have been introduced at different posi-
tions (C-2, C-5, C-6) in carbohydrate derivatives in their
pyranose or furanose forms, in the presence of a range of
protecting groups commonly used in oligosaccharide syn-
thesis.
Compounds 1 and 2 were obtained as described pre-
viously,[14,15] while the azido derivative 3 was prepared by
standard acetylation (pyridine/acetic anhydride, 96% yield)
of the 3-OH precursor, easily obtained in five steps from
glucosamine, as previously reported.[16]
Azide 4 was synthesized as shown in Scheme 3. Regiose-
lective reductive opening of the 4,6-benzylidene acetal
5[17,18] with TFA/TES gave the known alcohol 6,[19] which
was converted into 7 by treatment with an excess of levul-
inic anhydride.[20] First attempts to remove the benzyl group
were conducted with Pd–C in methanol under positive hy-
drogen pressure. Unfortunately, though, compound 8 was
We are currently involved in a research program dealing
with the construction of new probes for studying multival-
ency in carbohydrate–protein interactions. In this context,
it was necessary to develop a general method to connect
carbohydrates bearing a variety of protecting groups. Re-
[a] Laboratoire des Glucides UMR 6219, Université de Picardie
Jules Verne,
33 rue Saint-Leu, 80039 Amiens, France
Fax: +33-3-22-82-75-68
E-mail: jose.kovensky@u-picardie.fr
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Connecting Carbohydrate Moieties by Click Chemistry Techniques
FULL PAPER
Scheme 4.
Scheme 2.
try 2) or 1 h in acetonitrile, although the reactions did not
go to completion. To overcome the instability of CuI, it was
unstable under these conditions and migration of the Lev generated by in situ reduction of CuII salts (copper sulfate)
group from O-5 to O-6 occurred. The same approach in with the aid of sodium ascorbate,[25] but no reaction had
THF, however, allowed us to isolate 8 in quantitative yield. been observed in sec-butanol or in anhydrous DMF after 3
After conversion of the hydroxy group into the iodide 9 by and 2 h, respectively (Entries 4 and 6). Fortunately, though,
treatment with PPh3/I2/Im,[21] the synthesis of 4 was we observed dramatic increases in the reaction rates when
achieved by addition of LiN3 in DMF.
water was added to the sec-butanol or DMF (Entries 5 and
Conversely, four different alkynyl saccharides were se- 7), and only the expected triazole 14 was formed (71% and
lected: the mannoside 10,[22] the galactoside 11, the gluco- 88% yields, respectively, after flash chromatography). These
side 12,[23] and the lactoside 13 (Scheme 4), all easily ob- results demonstrate the high sensitivity of the reaction to
tained from the corresponding peracetylated sugars by the experimental conditions and corroborate precedent re-
treatment with but-3-yn-1-ol in the presence of boron triflu- ports on the positive effect of water.[26]
oride etherate.[23]
As previously observed, the catalyzed Huisgen reaction
The first attempted cycloadditions between saccharides 4 was found to be highly regioselective, yielding 1,4-disubsti-
and 10 are summarized in Table 1 and Scheme 5. Nitrogen tuted 1,2,3-triazole-containing carbohydrates.[5] In each cy-
donors including bases such as DIPEA and some solvents cloadduct, the olefinic proton associated with the 1,2,3-tri-
such as acetonitrile have been reported to improve results in azole moiety was identified as a singlet between δ = 7.25
CuI-catalyzed alkyne–azide coupling by helping to prevent and 7.65 ppm, while allylic methylene resonances were ob-
degradation of CuI by disproportionation or oxidation.[24] served around δ = 3 ppm. 13C NMR analysis of the com-
In our hands, these experimental conditions were inappro- pounds were also carried out: the large ∆ (δC4–δC5) values
priate, no reaction having occurred after 2 h in THF with a for the different triazoles, ranging from 20.4 to 22.5 ppm,
catalytic amount of CuI (Entry 1). In the presence of an corroborated the 1,4-disubstituted structure, since much
excess of CuI (Entry 3), however, the expected compound smaller values would be expected for 1,5-disubstituted re-
14 was obtained in moderate yield after 4 h in THF (En- gioisomers.[27]
Scheme 3.
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S. G. Gouin, L. Bultel, C. Falentin, J. Kovensky
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Table 1. Evaluation of different conditions for the cycloaddition.
Entry
Equiv. of
alkyne
Equiv. of
DIPEA
Na ascorbate
Catalyst
Solvent
Time / h
% Yield
1
2
3
4
5
6
7
1
1.2
1
1
1
1
1
3
4
3
–
–
–
–
–
–
–
0.2 equiv. CuI
0.2 equiv. CuI
2.0 equiv. CuI
0.2 equiv. CuSO4
0.2 equiv. CuSO4
0.2 equiv. CuSO4
0.2 equiv. CuSO4
THF
THF
CH3CN
sBu
sBu/H2O
DMF
2
4
1
3
1.1
2
no reaction
55
49
no reaction
71
no reaction
88
0.4 equiv.
0.4 equiv.
0.4 equiv.
0.4 equiv.
DMF/H2O
1.5
Scheme 5.
Removal of the protecting groups from 14 with a cata- in the presence of base, probably due to the sensitivity of
lytic quantity of sodium methoxide in methanol gave the acetates to the alkaline medium. The reaction was therefore
compound 15 in 87% yield. The triazole ring was not affec- conducted in the absence of base and under vacuum, by a
ted by the basic conditions and no degradation occurred.
method previously described.[29,30] Compound 23 was iso-
The best experimental conditions (Table 1, Entry 7) lated in 55% yield. In spite of the moderate yield obtained,
found were applied to couplings of azido sugars 1–4 with this reaction is particularly interesting as the starting mate-
alkynyl derivatives 10–13, and the results are summarized rial can be recycled. The general procedure for the click
in Table 2.
reaction was employed and product 24 was isolated in 72%
All the reactions had gone to completion within 5 h at yield.
room temperature, with use of equimolar ratios of azide
and alkyne and catalytic quantities of copper sulfate. Yields
ranged from 70 to 100% after flash chromatography
(Table 2). Different cycloaddition trials on compound 4
showed similar yields independently of the α,β stereochem-
istry of the alkynyl saccharide employed (Entries 1, 2, 3).
The reaction time with alkynyl lactoside 13 was slightly
higher because of its lower solubility in the DMF/water
mixture (Entry 4). Notably, compound 4 (Entry 6) contains
a thiophenyl group, which can be activated for further gly-
cosylation. Under our conditions, the intermolecular 1,3-
dipolar cycloadditions tolerated the presence of a variety of
protecting groups (i.e., acetate or levulinate esters, benzyl
ethers, benzylidene or isopropylidene acetals). Azide groups
linked to secondary carbons atoms, on the other hand, pro-
vided the corresponding oligosaccharide analogues in very
good to excellent yields (Entries 6 and 7).
In order to modulate the distance between the monosac-
charides, we connected the azido group through a spacer
(Scheme 6). Alkylation of 8 with the azide derivative 22,
freshly prepared as described previously,[28] was problematic Scheme 6.
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Table 2. Structures of the cycloadducts obtained and experimental conditions.
Conclusion
Experimental Section
In summary, we have developed a procedure for the con-
nection of saccharides by click chemistry techniques. This
approach shows that different sugars bearing azide substit-
uents on C-2, C-5, or C-6 can be used as building blocks.
The reactions tolerate the presence of a range of protecting
groups commonly used in carbohydrate chemistry. More-
over, they can be conducted at room temperature, with
equimolar ratios of reagents, and products are obtained in
high yields. The high solubilities of the protected sugars in
DMF allowed us to add 30% water to the mixtures, which
greatly accelerated the cycloaddition reactions. Further-
more, we have also demonstrated the possibility of varying
the distances between triazole-linked saccharides units,
through the use of spacers to attach the azido group.
General: All purchased materials were used without further purifi-
cation. Dichloromethane was distilled from calcium hydride, tetra-
hydrofuran over sodium and benzophenone. Analytical thin-layer
chromatography (TLC) was carried out on Merck D.C.-Alufolien
(Kieselgel 60 F254). Flash chromatography was performed on Ged-
uran Si 60 (0.040–0.060 mm pore size) with distilled solvents. 1H,
13C nuclear magnetic resonance (NMR) spectra were recorded on
a Bruker AC 300 spectrometer, and chemical shifts are reported in
parts per million relative to tetramethylsilane or a residual solvent
(CHCl3) peak (1H: δ = 7.26 ppm, 13C: δ = 77.2 ppm). Assignments
of 1H and 13C were assisted by 2D 1H COSY and 2D 1H–13C
CORR experiments. High resolution mass spectra HRMS were ob-
tained by Electrospray Ionization (ESI) with a Micromass–Waters
Q-TOF Ultima Global instrument. Optical rotations were mea-
sured on a Perkin–Elmer 343 machine at 20 °C in a 1-cm cell in the
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S. G. Gouin, L. Bultel, C. Falentin, J. Kovensky
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stated solvent. [α]D values are given in 10–1 degcm2 g–1 (concentra-
tion c given as g/100 mL).
The reaction mixture was cooled and satd. NaHCO3 (160 mL) was
added. After the mixture had been stirred for 5 min, I2 (16.5 g,
65 mmol) was added and after an additional 10 min excess iodine
Phenyl 3-Acetyl-2-azido-2-deoxy-4,6-O-benzylidene-1-thio-α-D-gluco-
was removed by addition of
a sodium thiosulfate solution
pyranoside (3): The known phenyl 2-azido-4,6-O-benzylidene-2-de-
oxy-1-thio-α--glucopyranoside[16] (1.49 g, 3.9 mmol) was dis-
solved in a mixture of acetic anhydride (20 mL) and pyridine
(25 mL) and the mixture was stirred at room temp. for 18 h. The
solvent was removed under reduced pressure and the residue was
purified by flash chromatography (cyclohexane/EtOAc, 9:1) to af-
ford 3 as a white solid (1.6 g, 96%). [α]2D0 = +145 (c = 1, CH2Cl2).
1H NMR (300 MHz, CDCl3): δ = 7.44 (m, 10 H, arom. H), 5.65
(100 mL). The organic layer was diluted with toluene, separated,
washed with water, dried with Na2SO4, and filtered, and the solvent
was removed under reduced pressure. The residue was purified by
flash chromatography (cyclohexane/EtOAc, 3:1) to afford 9 as a
colorless oil (2.89 g, 67%). [α]2D0 = +73 (c = 0.3, CH2Cl2). 1H NMR
(300 MHz, CDCl3): δ = 5.47 (dd, J2,3 = J3,4 = 9.5 Hz, 1 H, 3-H),
4.94 (d, J1,2 = 3.6 Hz, 1 H, 1-H), 4.88 (dd, J4,5 = 9.5 Hz, 1 H, 4-
H), 4.82 (dd, 1 H, 2-H), 3.77 (m, 1 H, 5-H), 3.46 (s, 3 H, CH3O),
(d, J1,2 = 6.0 Hz, 1 H, 1-H), 5.54 (s, 1 H, PhCH), 5.53 (dd, J2,3
=
3.60 (dd, J5,6a = 2.4, J6a,6b = 10.9 Hz, 1 H, 6a-H), 3.60 (dd, J5,6b
=
J3,4 = 10.0 Hz, 1 H, 3-H), 4.51 (ddd, J4,5 = 10.0, J5,6a = 5.0, J5,6b
= 10.0 Hz, 1 H, 5-H), 4.26 (dd, J6a,6b = 10.0 Hz, 1 H, 6a-H), 4.07
(dd, 1 H, 2-H), 3.80 (dd, 1 H, 6b-H), 3.70 (dd, 1 H, 4-H), 2.18 (s,
3 H, CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 169.9 (CO),
137.2, 134.2, 133.1, 128.6, 126.6 (arom. C), 102.1 (PhCH), 88.2 (C-
1), 80.0 (C-4), 70.9 (C-3), 68.8 (C-6), 64.3 (C-5), 62.7 (C-2), 21.3
(CH3) ppm. HRMS: m/z: found 450.1114; C21H21O5N3NaS re-
quires 450.1100 [M + Na]+.
8.4 Hz, 1 H, 6b-H), 2.72 (m, 2 H, CH3COCH2CH2), 2.49 (m, 2 H,
CH3COCH2CH2), 2.17 (s, 3 H, CH3Lev), 2.06, 2.02 (2ϫs, 3 H
each, 2ϫCH3CO) ppm. 13C NMR (75 MHz CDCl3): δ = 206.2
(CH3CO), 171.6, 170.1 (CO), 96.8(C-1), 72.5, 71.1 (C-2, C-4), 69.4
(C-3), 68.9 (C-5), 55.8 (CH3O), 38.9 (CH3COCH2CH2), 30.8
(CH3Lev), 27.1 (CH3COCH2CH2), 20.8 (CH3CO), 3.9 (C-6) ppm.
HRMS: m/z: found 509.0294; C16H23INaO9 requires 509.0285 [M
+ Na]+.
Methyl 2,3-Di-O-acetyl-6-O-benzyl-4-O-levulinyl-α-D-glucopyrano-
Methyl 2,3-Di-O-acetyl-6-azido-6-deoxy-4-O-levulinyl-α-D-glucopy-
side (7): Levulinic anhydride (1.8 g, 8.41 mmol) in dichloromethane
(5 mL), Et3N (2.36 mL, 16.8 mmol), and DMAP (25 mg,
0.20 mmol) were added under argon to a solution of compound 6
(1.55 g, 4.21 mmol) in dry dichloromethane (20 mL), and the mix-
ture was stirred for 16 h at room temp. The solvent was removed
under reduced pressure and the residue was purified by flash
chromatography (cyclohexane/EtOAc, 7:3 to 13:7) to afford 7 as a
colorless oil (1.91 g, 97%). [α]2D0 = +118 (c = 0.2, CH2Cl2). 1H
NMR (300 MHz, CDCl3): δ = 7.30 (m, 5 H, arom. H), 5.49 (dd,
J2,3 = 10.0, J3,4 = 9.5 Hz, 1 H, 3-H), 5.15 (dd, J4,5 = 10.0 Hz, 1 H,
4-H), 4.93 (d, J1,2 = 3.6 Hz, 1 H, 1-H), 4.91 (dd, 1 H, 2-H), 4.54
(s, 2 H, CH2Ph), 3.94 (m, 1 H, 5-H), 3.56 (m, 2 H, 6-a, 6b-H), 3.42
(s, 3 H, CH3O), 2.67 (t, J = 6.3 Hz, 2 H, CH3COCH2CH2), 2.40
(t, J = 6.3 Hz, 2 H, CH3COCH2CH2), 2.15 (s, 3 H, CH3Lev), 2.07,
2.04 (2ϫs, 3 H each, 2ϫCH3CO) ppm. 13C NMR (75 MHz,
CDCl3): δ = 206.1 (CH3COCH2), 171.8, 170.7 (CH3CO), 170.6
(COCH2CH2), 138.2, 128.7, 128.3, 128.1 (arom. C), 97.1 (C-1), 74.0
(PhCH2), 71.4 (C-2), 70.4 (C-3), 69.6 (C-4), 68.8 (C-5, -6), 55.8
(CH3O), 38.1 (CH3COCH2CH2), 29.1 (CH3Lev), 28.2
(CH3COCH2CH2), 21.1 (CH3CO) ppm. HRMS: m/z: found
489.1715; C23H30NaO10 requires 489.1737 [M + Na]+.
ranoside (4): A mixture of compound 9 (150 mg, 0.3 mmol) and
LiN3 (20% in water, 377 µL, 1.5 mmol) in dry DMF (5 mL) was
stirred under argon at 50 °C until total consumption of starting
material. EtOAc (20 mL) was added and the organic layer was
washed with water (20 mL). The aqueous layer was extracted three
times with EtOAc (3ϫ10 mL). The organic layers were combined,
dried with Na2SO4, and filtered, and the solvent was removed un-
der reduced pressure to afford 4 (90 mg, 75%). [α]2D0 = +107 (c =
0.2, CH2Cl2). 1H NMR (300 MHz, CDCl3): δ = 5.56 (dd, J2,3
=
10, J3,4 = 9.6 Hz, 1 H, 3-H), 5.09 (dd, J4,5 = 9.5 Hz, 1 H, 4-H),
5.04 (d, J1,2 = 3.7 Hz, 1 H, 1-H), 4.94 (dd, 1 H, 2-H), 4.02 (dt, J5,6a
= J5,6b = 5.0 Hz, 1 H, 5-H), 3.52 (s, 3 H, CH3O), 3.44 (d, 2 H,
6a-, 6b-H), 2.80 (m, 2 H, CH3COCH2CH2), 2.54 (m, 2 H,
CH3COCH2CH2), 2.24 (s, 3 H, CH3Lev), 2.15, 2.12 (2ϫs, 3 H
each, 2ϫCH3CO) ppm. 13C NMR (75 MHz, CDCl3): δ = 206.4
(CH3CO), 171.7, 170.3, 170.2, (CO), 96.7(C-1), 70.9 (C-2), 69.7,
69.5 (C-3, -4), 68.7 (C-5), 55.6 (CH3O), 50.9 (C-6), 38.9
(CH3COCH2CH2), 30.8 (CH3Lev), 27.8 (CH3COCH2CH2), 20.8
(CH3CO) ppm. HRMS: m/z: found 424.1346; C16H23N3NaO9 re-
quires 424.1332 [M + Na]+.
But-3-ynyl 2,3,4,6-Tetra-O-acetyl-α-D-galactopyranoside (11): This
Methyl 2,3-Di-O-acetyl-4-O-levulinyl-α-D-glucopyranoside (8): A
compound was obtained by the procedure described in ref.[22]. The
pure α anomer was separated from the α/β mixture by flash
chromatography (dichloromethane/EtOAc, 98:2, 20% yield). [α]2D0
mixture of compound 7 (200 mg, 0.429 mmol) and Pd/C (10%,
20 mg) in THF (6 mL) was stirred for 40 min at room temp. under
a positive pressure of hydrogen. The mixture was filtered through
celite, and the solvent was removed under reduced pressure to give
7 as a colorless oil (161 mg, quant). [α]2D0 = +94 (c = 0.2, CH2Cl2).
1H NMR (300 MHz, CDCl3): δ = 5.55 (dd, J2,3 = J3,4 = 9.8 Hz, 1
H, 3-H), 5.03 (dd, J4,5 9.8 Hz, 1 H, 4-H), 4.96 (d, J1,2 = 3.6 Hz, 1
H, 1-H), 4.86 (dd, 1 H, 2-H), 3.78–3.62 (m, 3 H, 5-, 6a-, 6b-H),
3.40 (s, 3 H, CH3O), 2.74 (m, 2 H, CH3COCH2CH2), 2.50 (m, 2
H, CH3COCH2CH2), 2.17 (s, 3 H, CH3Lev), 2.07, 2.04 (2ϫs, 3 H
each, CH3CO) ppm. 13C NMR (75 MHz, CDCl3): δ = 172.9, 170.6
(CO), 97.2 (C-1), 71.5 (C-2), 70.1, 69.9, 69.8 (C-3, -4, -5), 61.3 (C-
6), 55.8 (CH3O), 38.1 (CH3COCH2CH2), 30.0 (CH3Lev), 28.2
(CH3COCH2CH2), 21.1 (CH3CO) ppm. HRMS: m/z: found
399.1256; C16H24NaO10 requires 399.1267 [M + Na]+.
1
= +130 (c = 0.1, CH2Cl2). H NMR (300 MHz, CDCl3): δ = 5.43
(brd, J3,4 = 3.0 Hz, J4,5 Ͻ 1 Hz, 1 H, 4-H), 5.33 (dd, J2,3 = 11.0 Hz,
1 H, 3-H), 5.15 (d, J1,2 = 4.0 Hz, 1 H, 1-H), 5.09 (dd, 1 H, 2-H),
4.28 (t, J5,6a = J5,6b = 7.0 Hz, 1 H, 5-H), 4.09–4.04 (m, 2 H, 6a-,
6b-H), 3.75 (dt, J = 7, J = 10 Hz, 1 H, OCHHCH2), 3.60 (dt, J =
7, J = 10 Hz, 1 H, OCHHCH2), 2.47 (dt, J = 3, J = 7 Hz, 2 H,
OCH2CH2), 2.11, 2.05, 2.02, 1.97 (4ϫs, 3 H each, 4ϫCH3CO),
1.95 (m, 1 H, CCH) ppm. 13C NMR (75 MHz, CDCl3): δ = 170.5,
170.3, 170.0 (CO), 96.3 (C-1), 80.8 (CH2CCH), 69.8 (CH2CCH),
68.2 (C-2, -4), 67.6 (C-3), 66.7 (OCH2CH2CCH), 66.6 (C-5), 61.8
(C-6), 20.9, 20.7 (CH3CO), 19.8 (OCH2CH2) ppm. HRMS: m/z:
found 423.1282; C18H24NaO10 requires 423.1267 [M + Na]+.
Methyl 2,3-Di-O-acetyl-6-O-iodo-4-O-levulinyl-α-
(9): A solution of compound 8 (3.3 g, 8.8 mmol), PPh3 (6.9 g,
26 mmol), imidazole (2.38 g, 35 mmol), and I2 (5.57 g, 21.9 mmol) The pure β product was isolated by flash chromatography (cyclo-
in anhydrous toluene (160 mL) was stirred at room temp. for 6 h.
hexane/EtOAc, 2:3 to 1:1, 43% yield). [α]2D0 = –9 (c = 0.4, CH2Cl2).
D-glucopyranoside
But-3-ynyl 2,3,4,6,2Ј,3Ј,6Ј-Hepta-O-acetyl-β-
D-lactopyranoside (13):
This compound was obtained by the procedure described in ref.[22]
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Connecting Carbohydrate Moieties by Click Chemistry Techniques
1H NMR (300 MHz, CDCl3): δ = 5.31 (brd, J3Ј,4Ј = 3 Hz, J4Ј,5Ј
1 Hz, 1 H, 4Ј-H), 5.13 (dd, J2,3 = J3,4 = 9.0 Hz, 1 H, 3-H), 5.06
(dd, J1Ј,2Ј = J2Ј,3Ј = 8.0 Hz, 1 H, 2Ј-H), 4.90 (dd, 1 H, 3Ј-H), 4.85
(dd, J1,2 = 8 Hz, 1 H, 2-H), 4.50 (d, 1 H, 1-H), 4.50 (m, 2 H, 1Ј-,
6a-H), 4.09–4.03 (m, 4 H, 6b-, 5Ј-, 6Јa- 6Јb-H), 3.88–3.75 (m, 2 H,
5Ј-H, OCHHCH2), 3.74 (dd, 1 H, J4,5 = 9 Hz, 4-H), 3.63–3.59 (m,
FULL PAPER
Ͻ
anosid-6-yl)-1H-1,2,3-triazole (16): Flash chromatography (EtOAc/
cyclohexane, 4:1 to EtOAc). [α]2D0 = +110 (c = 0.2, CH2Cl2). 1H
NMR (300 MHz, CDCl3): δ = 7.50 (s, 1 H, CHN), 5.44 (dd, J2,3
=
J3,4 = 10.0 Hz, 1 H, 3-H), 5.43 (brd, J3Ј,4Ј = 3.0, J4,5 Ͻ 1 Hz, 1 H,
4Ј-H), 5.26 (dd, J2Ј,3Ј = 11, J3Ј,4Ј = 3.0 Hz, 1 H, 3Ј-H), 5.09 (d, J1Ј,2Ј
= 4.0 Hz, 1 H, 1Ј-H), 5.08 (dd, J1Ј,2Ј = 4.0 Hz, 1 H, 2Ј-H), 4.79 (m,
2 H, 5-H, OCHHCH2), 2.42 (dt, 2 H, J = 3.0, J = 7.0 Hz, 3 H, 1-, 2-, 4-H), 4.59 (dd, J5,6a = 2.2, J6a,6b = 14.3 Hz, 1 H, 6a-
OCH2CH2), 2.11, 2.08 (ϫ2), 2.02, 2.01(ϫ2), 1.92 (7ϫs, 3 H each, H), 4.25 (dd, J5,6b = 8.3 Hz, 1 H, 6b-H), 4.20–3.90 (m, 5 H, 5-,
7ϫCH3CO), 1.92 (m, 1 H, CCH) ppm. 13C NMR (75 MHz, 5Ј-, 6Јa-, 6Јb-, OCHHCH2), 3.75 (dt, J = 7.0, J = 10.0 Hz, 1 H,
CDCl3): δ = 170.7, 170.5, 170.4, 170.1, 170.0, 169.4 (CO), 101.4 OCHHCH2), 3.08 (s, 3 H, CH3O), 3.02 (t, J = 7.0 Hz, 2 H,
(C-1Ј), 101.0 (C-1), 80.9 (CCH), 76.6 (C-4), 73.0 (C-3), 71.9 (C-2), OCH2CH2), 2.73 (m, 2 H, CH3COCH2CH2), 2.50 (m, 2 H,
71.4 (C-3Ј), 71.0 (C-5Ј), 69.9 (CH2CCH), 69.5 (C-2Ј), 68.3 CH3COCH2CH2), 2.14 (s, 3 H, CH3Lev), 2.09 (ϫ 2), 1.99, 1.95
(OCH2CH2CCH), 67.0 (C-4Ј), 62.3, 61.2 (C-6, -6Ј), 21.1, 21.1, 21.0,
20.9 (CH3CO), 20.2 (OCH2CH2) ppm. HRMS: m/z: found
711.2089; C30H40NaO18 requires 711.2112 [M + Na]+.
(ϫ2), 1.93 (6ϫs, 3 H each, 6ϫCH3CO) ppm. 13C NMR (75 MHz,
CDCl3): δ = 206.7 (CH3CO), 171.8, 170.5, 170.3, 170.1 (CO), 144.3
(NC=CH), 123.3 (NC=CH), 97.5 (C-1Ј), 96.6 (C-1), 96.2 (C-1Ј),
70.8 (C-2), 70.0 (C-4), 69.4 (C-3), 68.1 (C-2Ј, -4Ј), 66.4 (C-5Ј), 67.5
(C-3Ј), 67.4 (OCH2CH2), 66.4 (C-5), 62.1 (C-6Ј), 55.7 (CH3O), 50.8
( C - 6 ) , 3 8 . 2 ( C H 3 C O C H 2 C H 2 ) , 2 9 . 9 ( C H 3 L e v ) , 28 . 3
(CH3COCH2CH2), 26.5 (OCH2CH2), 21.0 (CH3CO) ppm. HRMS:
m/z: found 824.2682; C34H47N3NaO19 requires 824.2701
[M + Na]+.
General Procedure for the Huisgen Cycloadditions: Compounds 14–
21 and 24 were synthesized by this procedure. Alkynyl-saccharide
(0.13 mmol) and azido-saccharide (0.13 mmol) were dissolved in a
DMF/H2O mixture (4+1.3 mL). Copper sulfate (0.2 or 0.4 equiv.)
and sodium ascorbate (0.4 or 0.8 equiv.) were added and the mix-
ture was stirred at room temp. until TLC indicated the disappear-
ance of the starting materials. The mixture was poured into H2O/
satd. NH4Cl solution (1:1, 20 mL) and the product was extracted
four times with EtOAc. The organic layer was dried with Na2SO4
and filtered, and the solvent was removed under reduced pressure.
The residue was purified by flash chromatography.
1-(2Ј,3Ј,4Ј,6Ј-Tetra-O-acetyl-β-
2ЈЈ,3ЈЈ-di-O-acetyl-6ЈЈ-deoxy-4ЈЈ-O-levulinyl-α-
D
-glucopyranosyloxyethyl)-4-(methyl
-glucopyranosid-6-
D
yl)-1H-1,2,3-triazole (17): Flash chromatography (EtOAc/cyclohex-
ane, 4:1 to EtOAc). [α]2D0 = +32 (c = 0.3, CH2Cl2). 1H NMR
(300 MHz, CDCl3): δ = 7.49 (s, 1 H, CHN), 5.45 (dd, J2,3 = J3,4
=
9.0 Hz, 1 H, 3-H), 5.13 (dd, J2Ј,3Ј = J3Ј,4Ј = 10.0 Hz, 1 H, 3Ј-H),
5.13 (dd, J3Ј,4Ј = J4Ј,5Ј = 10.0 Hz, 1 H, 4Ј-H), 5.12–4.79 (m, 4 H,
1-, 2-, 2Ј-, 4-H), 4.59 (dd, J5,6a = 2.2, J6a,6b = 14.2 Hz, 1 H, 6a-H),
4.50 (d, J1Ј,2Ј = 8.0 Hz, 1 H, 1Ј-H), 4.35–4.00 (m, 5 H, 5-, 6b-,
6Јa-, 6Јb-H, OCHHCH2), 3.75 (m, 2 H, 5Ј-H, OCHHCH2), 3.10
(s, 3 H, CH3O), 2.93 (t, 2 H, J = 7.0 Hz, OCH2CH2), 2.75 (m, 2
H, CH3COCH2CH2), 2.50 (m, 2 H, CH3COCH2CH2), 2.15 (s, 3
H, CH3Lev), 2.09, 2.05, 2.03, 1.98, 1.96, 1.95 (6 ϫs, 3 H each,
6 ϫ CH3CO) ppm. 13C NMR (75 MHz, CDCl3): δ = 206.7
(CH3CO), 171.9, 170.7, 170.2, 169.5, 169.4 (CO), 144.4 (NC=CH),
123.8 (NC=CH), 100.9 (C-1Ј), 96.6 (C-1), 72.8 (C-3Ј), 71.9 (C-5Ј),
71.3 (C-2Ј), 70.8 (C-2), 70.0 (C-4), 69.5 (C-3), 69.0 (OCH2CH2),
68.5 (C-4Ј), 68.0 (C-5), 61.2 (C-6Ј), 55.5 (CH3O), 50.5 (C-6), 37.9
(CH3COCH2CH2), 29.7 (CH3Lev), 28.0 (CH3COCH2CH2), 26.5
(OCH2CH2), 20.8 (CH3CO) ppm. HRMS: m/z: found 824.2695;
C34H47N3NaO19 requires 824.2701 [M + Na]+.
1-(2Ј,3Ј,4Ј,6Ј-Tetra-O-acetyl-α-
(methyl 2ЈЈ,3ЈЈ-di-O-acetyl-6ЈЈ-deoxy-4ЈЈ-O-levulinyl-α-
D
-mannopyranosyloxyethyl)-4-
-glucopyr-
D
anosid-6-yl)-1H-1,2,3-triazole (14): Flash chromatography (EtOAc/
cyclohexane, 4:1 to EtOAc). [α]2D0 = +80 (c = 0.4, CH2Cl2). 1H
NMR (300 MHz, CDCl3): δ = 7.55 (s, 1 H, CHN), 5.46 (dd, J2,3
=
J3,4 = 10.0 Hz, 1 H, 3-H), 5.27–5.15 (m, 5 H, 2Ј-, 3Ј-, 4Ј-H), 4.89
(d, J1Ј,2Ј = 3.0 Hz, 1 H, 1Ј-H), 4.86–4.79 (m, 3 H, 1-, 2-, 4-H), 4.59
(brd, J5,6a Ͻ 1, J6a,6b = 13.9 Hz, 1 H, 6a-H), 4.50–3.90 (m, 5 H,
5-, 6b-, 6Јa-, 6Јb-H, OCHHCH2), 3.80–3.73 (m, 2 H, 5Ј-H,
OCHHCH2), 3.09 (s, 3 H, CH3O), 3.05–3.01 (m, 2 H, OCH2CH2),
2.75 (m, 2 H, CH3COCH2CH2), 2.52 (m, 2 H, CH3COCH2CH2),
2.15 (s, 3 H, CH3Lev), 2.14, 2.12, 2.06, 2.02, 2.01, 1.97 (6ϫs, 3 H
each, 6ϫCH3CO) ppm. 13C NMR (75 MHz, CDCl3): δ = 206.7
(CH3CO), 171.9, 170.8, 170.2, 169.7 (CO), 144.2 (NC=CH), 123.8
(NC=CH), 97.5 (C-1Ј), 96.6 (C-1), 70.8 (C-2), 70.2 (C-4), 69.6,
69.5, 66.1 (C-2Ј, -3Ј, -4Ј), 69.1 (C-5Ј), 68.8 (C-5), 68.1 (C-3Ј), 67.0
(OCH2CH2), 62.4 (C-6Ј), 55.3 (CH3O), 50.6 (C-6), 37.9
(CH3COCH2CH2), 29.7 (CH3Lev), 28.0 (CH3COCH2CH2), 26.2
(OCH2CH2), 20.9 (CH3CO) ppm. HRMS: m/z: found 824.2686;
C34H47N3NaO19 requires 824.2701 [M + Na]+.
1-(2Ј,3Ј,4Ј,6Ј,2ЈЈ,3ЈЈ,6ЈЈ-Hepta-O-acetyl-β-
D-lactopyranosyloxy-
ethyl)-4-(methyl 2ЈЈЈ,3ЈЈЈ-di-O-acetyl-6ЈЈ-deoxy-4ЈЈ-O-levulinyl-α-
D-
glucopyranosid-6-yl)-1H-1,2,3-triazole (18): Flash chromatography
(EtOAc/cyclohexane, 4:1 to EtOAc). [α]2D0 = +13 (c = 0.3, CH2Cl2).
1H NMR (300 MHz, CDCl3): δ = 7.49 (s, 1 H, CHN), 5.43 (dd,
J2,3 = J3,4 = 9.0 Hz, 1 H, 3-H), 5.30 (brd, 1 H, J3ЈЈ,4ЈЈ = 3.0, J4ЈЈ,5ЈЈ
Ͻ 1 Hz, 4ЈЈ-H), 5.13 (dd, J2Ј,3Ј = J3Ј,4Ј = 9.0 Hz, 1 H, 3Ј-H), 5.06
(dd, J1ЈЈ,2ЈЈ = J2ЈЈ,3ЈЈ = 8.0 Hz, 1 H, 2ЈЈ-H), 4.90–4.78 (m, 5 H, 1-,
2-, 2Ј-, 3ЈЈ-, 4-H), 4.59 (dd, J5,6a = 2.3, J6a,6b = 14.3 Hz, 1 H, 6a-
H), 4.44 (m, 3 H, 1Ј-, 1ЈЈ-, 6Јa-H), 4.25 (dd, J5,6b = 8.4 Hz, 1 H,
6b-H), 4.20–4.00 (m, 5 H, 5-, 6Јb-, 6ЈЈa-, 6ЈЈb-H, OCHHCH2), 3.80
(m, 1 H, 5ЈЈ-H), 3.74 (m, 2 H, 4Ј-H, OCHHCH2), 3.52 (m, 1 H,
5Ј-H), 3.07 (s, 3 H, CH3O), 2.91 (t, J = 7.0 Hz, 2 H, OCH2CH2),
2.72 (m, 2 H, CH3COCH2CH2), 2.50 (m, 2 H, CH3COCH2CH2),
2.14 (s, 3 H, CH3Lev), 2.10, 2.08, 2.01 (ϫ2), 1.98, 1.97 (ϫ2), 1.93,
1.91 (9 ϫ s, 3 H each, 9 ϫ CH3CO) ppm. 13C NMR (75 MHz,
CDCl3): δ = 206.7 (CH3CO), 172, 170.7, 170.5, 170.4, 170.0, 169.5
(CO), 144.8 (NC=CH), 124.0 (NC=CH), 101.4 (C-1ЈЈ), 101.0 (C-
1Ј), 96.9 (C-1), 76.7 (C-4Ј), 72.7 (C-3Ј, -5Ј), 71.6 (C-2Ј), 71.0, 70.8,
70.7, 70.0 (C-2, -4, -3ЈЈ, -5ЈЈ), 69.5 (C-3), 69.2 (C-2ЈЈ), 69.1
(OCH2CH2), 68.9 (C-5), 67.0 (C-4ЈЈ), 62.3, 61.2 (C-6Ј, -6ЈЈ), 55.7
1-(α-D-Mannopyranosyloxyethyl)-4-(methyl 6ЈЈ-deoxy-α-D-glucopyr-
anosid-6-yl)-1H-1,2,3-triazole (15): Flash chromatography (EtOAc/
cyclohexane, 4:1 to EtOAc). [α]2D0 = +59 (c = 0.1, D2O). H NMR
1
(300 MHz, CD3OD): δ = 7.26 (s, 1 H, CHN), 4.28 (dd, J5,6a = 7.7,
J6a,6b = 14.2 Hz, 1 H, 6a-H), 4.19 (d, J1Ј,2Ј = 2.0 Hz, 1 H, 1Ј-H),
4.10 (d, J1,2 = 4.0 Hz, 1 H, 1-H), 3.98 (dd, 1 H, J5,6b = 8.0 Hz, 6b-
H), 3.42–3.36 (m, 1 H, OCHHCH2), 3.30–2.50 (m, 11 H, 2-, 3-,
4-, 5-, 2Ј-, 3Ј-, 4Ј-, 5Ј-, 6Јa-, 6Јb-H, OCHHCH2), 2.60 (s, 3 H,
CH3O), 2.43 (m, 2 H, OCH2CH2) ppm. 13C NMR (75 MHz,
CD3OD): δ = 146.0 (NC=CH), 125.5 (NC=CH), 101.6 (C-1Ј),
101.2 (C-1), 74.9, 74.8, 73.3, 72.8, 72.5, 72.0, 71.6, 68.5 (C-2, -3,
-4, -5, -2Ј, -3Ј, -4Ј, -5Ј), 67.4 (OCH2CH2), 62.9 (C-6Ј), 55.3 (CH3O),
52.3 (C-6), 27.0 (OCH2CH2) ppm. HRMS: m/z: found 474.1704;
C17H29N3NaO11 requires 474.1700 [M + Na]+.
1-(2Ј,3Ј,4Ј,6Ј-Tetra-O-acetyl-α-
D
-galactopyranosyloxyethyl)-4-
-glucopyr-
(methyl 2ЈЈ,3ЈЈ-di-O-acetyl-6ЈЈ-deoxy-4ЈЈ-O-levulinyl-α-
D
Eur. J. Org. Chem. 2007, 1160–1167
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1165

S. G. Gouin, L. Bultel, C. Falentin, J. Kovensky
FULL PAPER
(CH3O), 50.8 (C-6), 38.1 (CH3COCH2CH2), 29.7 (CH3Lev), 28.3 (OCH2CH2), 26.3 (CH3C), 20.8 (CH3CO) ppm. HRMS: m/z: found
(CH3COCH2CH2), 26.7 (OCH2CH2), 21.0 (CH3CO) ppm. HRMS:
m/z: found 1112.3516; C46H63N3NaO27 requires 1112.3547 [M +
Na]+.
848.3218; C41H51N3NaO15 requires 848.3218 [M + Na]+.
Methyl 2,3-Di-O-acetyl-6-O-azidopropyl-4-O-levulinyl-α-
D
-glucopy-
ranoside (23): 3-Azidopropan-1-ol (691 mg, 6.84 mmol, prepared
from 3-chloropropan-1-ol as in ref.[29]) and 2,6-di-tert-butyl-4-
methylpyridine (1.4 g, 6.84 mmol) were dissolved in dry dichloro-
methane (37 mL). Tf2O (1.135 mL, 6.84 mmol) was added at 0 °C
and the mixture was stirred at room temp. for 15 min. Water
(100 mL) was added and the product 22 was extracted with CH2Cl2
(2ϫ150 mL). The organic layer was dried with MgSO4 and con-
centrated to 310 mL (c = 22.5 m). Compound 8 (507 mg,
1.35 mmol), was added to the solution (60 mL) and the solvent was
removed on a rotavapor and under high vacuum. The procedure
was repeated three times. The residue was purified by flash
chromatography (cyclohexane/EtOAc, 3:1 to 1:1) to afford 23 as a
colorless oil (340 mg, 55%). [α]2D0 = +121 (c = 0.2, CH2Cl2). 1H
NMR (300 MHz, CDCl3): δ = 5.46 (dd, J2,3 = J3,4 = 10.0 Hz, 1 H,
3-H), 5.11 (dd, J4,5 = 9.6 Hz, 1 H, 4-H), 4.94 (d, J1,2 = 3.7 Hz, 1
H, 1-H), 4.86 (dd, 1 H, 2-H), 3.86 (m, 1 H, 5-H), 3.54–3.36 (m, 6
H, 6a-, 6b-H, CH2CH2O, CH2CH2N3), 3.40 (s, 3 H, CH3O), 2.69
(m, 2 H, CH3COCH2CH2), 2.48 (m, 2 H, CH3COCH2CH2), 2.15
(s, 3 H, CH3Lev), 2.04, 2.02 (2ϫs, 3 H each, CH3CO), 1.83 (m, 2
H, OCH2CH2CH2N3) ppm. 13C NMR (75 MHz, CDCl3): δ =
171.4, 170.4, 170.2 (CO), 96.9 (C-1), 71.0 (C-2), 70.1 (C-3), 69.0
(CH2), 68.9, 68.5, 68.4 (C-4, -5, CH2), 55.5 (CH3O), 48.4 (CH2N3),
37.8 (CH3COCH2CH2), 29.8 (CH3Lev), 29.2 (OCH2CH2CH2N3),
27.9 (CH3COCH2CH2), 20.8 (CH3CO) ppm. HRMS: m/z: found
482.1765; C19H29N3NaO10 requires 482.1751 [M + Na]+.
1-(2Ј,3Ј,4Ј,6Ј-Tetra-O-acetyl-α-
azido-1ЈЈ,2ЈЈ:3ЈЈ,4ЈЈ-di-O-isopropylidene-6-deoxy-α-
D
-mannopyranosyloxyethyl)-4-(6-
-galactopyrano-
D
sid-6-yl)-1H-1,2,3-triazole (19): Flash chromatography (EtOAc/cy-
1
clohexane, 4:1 to EtOAc). [α]2D0 = –3 (c = 0.3, CH2Cl2). H NMR
(300 MHz, CDCl3): δ = 7.63 (s, 1 H, CHN), 5.46 (d, J1,2 = 5.0 Hz,
1 H, 1-H), 5.25–5.16 (m, 3 H, 2Ј-, 3Ј-, 4Ј-H), 4.79 (s, 1 H, 1Ј-H),
4.59 (dd, J2,3 = 3.0, J3,4 = 8.0 Hz, 1 H, 3-H), 4.54 (dd, J5,6a = 4.0,
J6a,6b = 14.0 Hz, 1 H, 6a-H), 4.27 (dd, J5,6b = 8.0 Hz, 1 H, 6b-H),
4.27 (dd, 1 H, 2-H), 4.23–4.04 (m, 5 H, 4-, 5-, 6Јa-, 6Јb-H,
OCHHCH2), 4.00 (dt, J = 6.0, J = 10.0 Hz, 1 H, OCHHCH2), 3.80
(m, 1 H, 5Ј-H), 3.67 (dt, J = 6.0, J = 10.0 Hz, 1 H, OCHHCH2),
3.01 (t, J = 7.0 Hz, 2 H, OCH2CH2), 2.12, 2.05, 1.99, 1.94 (4ϫs,
3 H each, 4 ϫ CH3CO), 1.45, 1.33, 1.31, 1.23 (4 ϫ s, 3 H each,
4ϫCH3C) ppm. 13C NMR (75 MHz, CDCl3): δ = 170.7, 170.0,
169.9, 169.7 (CO), 143.9 (NC=CH), 123.2 (NC=CH), 97.5 (C-1Ј),
96.6 (C-1), 71.3 (C-5Ј), 70.8 (C-3), 70.4 (C-2), 69.6, 69.1, 66.1 (C-
4, -2Ј, -3Ј, -4Ј), 68.6 (C-5Ј), 67.3 (C-5), 67.2 (OCH2CH2), 62.4 (C-
6Ј), 50.5 (C-6), 28.0 (CH3COCH2CH2), 26.2 (OCH2CH2), 26.0,
25.9, 24.9, 24.5 (CH3C), 20.9, 20.7 (CH3CO) ppm. HRMS: m/z:
found 708.2618; C30H43N3NaO15 requires 708.2592 [M + Na]+.
2Ј,3Ј,4Ј,6Ј-Tetra-O-acetyl-β-
2ЈЈ-deoxy-4,6-O-benzylidene-1-thio-α-
D
-glucopyranosyloxyethyl)-4-(phenyl
-glucopyranosid-2-yl)-1H-
D
1,2,3-triazole (20): Flash chromatography (dichloromethane, then
EtOAc). [α]2D0 = +48 (c = 0.4, CH2Cl2). 1H NMR (300 MHz,
CDCl3): δ = 7.49 (s, 1 H, CHN), 7.44–7.22 (m, 10 H, arom. H),
5.95 (dd, J2,3 = J3,4 = 10.0 Hz, 1 H, 3-H), 5.77 (d, J1,2 = 5.0 Hz, 1
H, 1-H), 5.55 (s, 1 H, PhCH), 5.34 (dd, 1 H, 2-H), 5.17 (dd, J2Ј,3Ј
= J3Ј,4Ј = 10.0 Hz, 1 H, 3Ј-H), 5.08 (dd, J4Ј,5Ј = 10.0 Hz, 1 H, 4Ј-
H), 4.97 (dd, J1Ј,2Ј = 10.0 Hz, 1 H, 2Ј-H), 4.54–4.49 (m, 2 H, 1Ј-,
5-H), 4.30–4.27 (m, 2 H, 6a-, 6Јa-H), 4.02–3.98 (m, 2 H, 6Ј-H,
OCHHCH2), 3.88–3.85 (m, 3 H, 4-, 6-H, OCHHCH2), 3.72–3.69
(m, 1 H, 5Ј-H), 3.02 (t, J = 7 Hz, 2 H, OCH2CH2), 2.07, 2.05,
2.04 (ϫ2), 1.99, 1.97 (6ϫs, 3 H each, 6ϫCH3CO) ppm. 13C NMR
(75 MHz, CDCl3): δ = 170.5, 170.1, 169.7, 169.2, 169.1 (CO), 144.0
(NC=CH), 137.5, 134.0, 133.3, 128.9, 128.2, 126.0 (arom. C), 121.5
(NC=CH), 101.6 (PhCH), 100.5 (C-1Ј), 88.2 (C-1), 79.8 (C-4), 72.7
(C-3Ј), 71.7 (C-5Ј), 71.3 (C-2Ј), 70.9 (C-3), 69.0 (OCH2CH2), 68.6
(C-6), 68.2 (C-4Ј), 64.3 (C-5), 62.9 (C-2), 61.8 (C-6Ј), 26.3
(OCH2CH2), 20.4 (CH3CO) ppm. HRMS: m/z: found 850.2477;
C39H45N3NaO15S requires 850.2469 [M + Na]+.
1-(2Ј,3Ј,4Ј,6Ј-Tetra-O-acetyl-α-
(methyl 2ЈЈ,3ЈЈ-di-O-acetyl-6ЈЈ-O-levulinyl-α-
D
-mannopyranosyloxyethyl)-4-{3-
-glucopyranoside)-
D
propyl}-1H-1,2,3-triazole (24): Flash chromatography (EtOAc).
[α]2D0 = +56 (c = 0.3, CH2Cl2). H NMR (300 MHz, CDCl3): δ =
1
7.4 (brs, 1 H, CHN), 5.48 (dd, J2,3 = J3,4 = 10.0 Hz, 1 H, 3-H),
5.27–5.14 (m, 5 H, 4-, 2Ј-, 3Ј-, 4Ј-H), 4.95 (d, J1,2 = 3.6 Hz, 1 H,
H-1), 4.88 (dd, 1 H, 2-H), 4.82 (brs, J1Ј,2Ј Ͻ 1 Hz, 1 H, H-1Ј), 4.47
(m, 2 H, CH2), 4.24 (m, 1 H, 6aЈ-H), 4.09 (m, 2 H, 5Ј-, 6Јb-H),
3 . 9 0 – 3 . 4 0 ( m , 9 H , 5 - , 6 a - , 6 b - H , N C H 2 C H 2 C H 2 O,
NCH2CH2CH2O, OCH2CH2), 3.36 (s, 3 H, CH3O), 3.02 (m, 2 H,
OCH2CH2), 2.70 (m, 2 H, CH3COCH2CH2), 2.49 (m, 2 H,
CH3COCH2CH2), 2.15 (s, 3 H, CH3Lev), 2.14, 2.12, 2.09, 2.06,
2.03, 1.98 (6 ϫ s, 3H each, 6 ϫ CH3 CO), 1.91 (m, 2 H,
OCH2CH2CH2N) ppm. 13C NMR (75 MHz, CDCl3): δ = 171.6,
170.8, 170.2, 169.8 (CO), 144.0 (NC=CH), 122.6 (NC=CH), 97.6
(C-1Ј), 96.9 (C-1), 71.0 (C-2), 70.2 (C-3), 69.6, 69.2, 68.8, 68.5, 66.1
(C-4, -5, -2Ј, -3Ј, -4Ј, -5Ј, CH2), 67.9, 67.0 (2CH2), 62.5 (C-6Ј), 55.5
(CH3O), 37.8 (CH3COCH2CH2), 30.4 (NCH2CH2), 29.8
(CH3 Lev), 28.0 (CH3 COCH2CH2 ), 26.1 (NCCH2 ), 21.0
(CH3CO) ppm. HRMS: m/z: found 882.3087, C37H53N3NaO20 re-
quires 882.3120 [M + Na]+.
2Ј,3Ј,4Ј,6Ј-Tetra-O-acetyl-β-D-glucopyranosyloxyethyl)-4-(5-azido-5-
deoxy-1,2-O-isopropylidene-3,6-di-O-benzyl-β-L-idofuranosid-5-yl)-
1H-1,2,3-triazole (21): Flash chromatography (EtOAc). [α]2D0 = –24
1
(c = 0.2, CH2Cl2). H NMR (300 MHz, CDCl3): δ = 7.52 (s, 1 H,
CHN), 7.34–7.19 (m, 10 H, arom. H), 5.88 (d, J1,2 = 4.0 Hz, 1 H,
1-H), 5.18 (dd, J2Ј,3Ј = J3Ј,4Ј = 9.0 Hz, 1 H, 3Ј-H), 5.02 (dd, J4Ј,5Ј
=
Acknowledgments
9.0 Hz, 1 H, 4Ј-H), 4.99 (m, 2 H, 2Ј-, 5-H), 4.62 (dd, J3,4 = 4.0, J4,5
= 13.0 Hz, 1 H, 4-H), 4.59 (dd, J2,3 = 3.0 Hz, 1 H, 2-H), 4.56 (m,
2 H, 1Ј-H, PhCH), 4.39 (d, J = 12.1 Hz, 1 H, PhCH), 4.30–4.22 This work was carried out with the financial support of the Centre
(m, 3 H, 6Ј-H, 2 PhCH), 4.13–3.94 (m, 2 H, 6Ј-H, OCHCH2), 3.94 National de la Recherche Scientifique and the Ministère délégué à
(d, 1 H, 3-H), 3.90–3.60 (m, 4 H, OCHCH2, 5Ј-, 6a-, 6b-H), 3.01 l’Enseignement Supérieur et à la Recherche.
(t, J = 7.0 Hz, 2 H, OCH2CH2), 2.06, 2.02, 1.99, 1.97 (4ϫs, 3 H
each, 4ϫCH3CO) ppm. 13C NMR (75 MHz, CDCl3): δ = 170.8,
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Received: September 18, 2006
Published Online: January 10, 2007
Eur. J. Org. Chem. 2007, 1160–1167
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1167