Cu(I)-catalyzed formation of D-mannofuranosyl 1,4-disubstituted 1,2,3-triazolecarbohybrids

Article abstract of DOI:10.3987/COM-04-10246

2,3:5,6-Di-O-isopropylidene-D-mannofuranose has been exploited as a platform for the synthesis of new 1,2,3-triazolecarbohybrids. Placement of an azide group at C-1 (and C-6) of the carbohydrate allows for reaction with various alkynes in the presence of

Full text of DOI:10.3987/COM-04-10246

HETEROCYCLES, Vol. 65, No. 5, 2005
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HETEROCYCLES, Vol. 65, No. 5, 2005, pp. 1035 - 1049
Received, 8th October, 2004, Accepted, 2nd March, 2005, Published online, 3rd March, 2005
Cu(I)-CATALYZED FORMATION OF D-MANNOFURANOSYL 1,4-
DISUBSTITUTED 1,2,3-TRIAZOLECARBOHYBRIDS
Penny L. Miner, Timothy R. Wagner, and Peter Norris*
Department of Chemistry, Youngstown State University, 1 University Plaza,
Youngstown, OH 44555, U.S.A.; pnorris@ysu.edu
Abstract – 2,3:5,6-Di-O-isopropylidene-D-mannofuranose has been exploited as a
platform for the synthesis of new 1,2,3-triazolecarbohybrids. Placement of an
azide group at C-1 (and C-6) of the carbohydrate allows for reaction with various
alkynes in the presence of a Cu(I) catalyst to generate 1,4-disubstituted triazoles
regiospecifically. The use of sugar-derived alkynes leads to 1,2,3-triazole-linked
di- and trisaccharide carbohybrid analogs with retention of the β-D-manno
configuration.
INTRODUCTION
The Huisgen 1,3-dipolar cycloaddition reaction1 between an azide and an acetylene has often been used to
introduce the aromatic 1,2,3-triazole group onto saccharide frameworks with a view to the formation of
potential nucleoside analogs.2 Although this chemistry is exceedingly easy to carry out in practice, usually
by simply heating the two reactants in a suitable solvent, a major drawback is the formation of mixtures of
regioisomeric (1,4-disubstituted and 1,5-disubstituted) triazoles when unsymmetrical alkynes are
employed.3,4 Additionally, the use of electron-deficient alkynes works well, however unactivated alkynes
often require very long reaction times for completion.
Recently the 1,2,3-triazole system has been the subject of intense study following the realization that the
heterocycle is capable of being a useful linker for the conjugation of biologically active groups. Indeed,
Sharpless and coworkers5 have defined the cycloaddition route to 1,2,3-triazoles as a near perfect reaction
in terms of such factors as atom economy and the large driving force inherent in the formation of an
aromatic ring. Considering the robust nature of the resultant triazole ring, Sharpless has suggested the
system as a key component of his “Click Chemistry” paradigm for potential drug discovery.5
The problem of regiocontrol in the reaction between azides and unsymmetrical acetylenes has been

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HETEROCYCLES, Vol. 65, No. 5, 2005
addressed in a number of key reports and has lead to reliable syntheses of either the 1,4-disubstituted isomer
or its 1,5-disubstituted relative. Meldal has used Cu(I) salts to produce the 1,4-isomer exclusively6 and
Fokin and Sharpless have reported an azide-alkyne “ligation” process that gives the 1,4-isomer when a
CuSO4/sodium ascorbate mixture is used to generate the Cu(I) catalyst in situ.7 This chemistry, which may
be carried out in water as the solvent, has recently been applied to the synthesis of triazole-linked
glycopeptides.8 Also, a useful organic-soluble catalyst, (PPh3)3•CuBr, has been developed by
Santoyo-Gonzalez and coworkers9 that allows for homogenous catalysis in the synthesis of various
1,4-triazole-linked neoglycoconjugates.
The “Click Chemistry” concept requires suitable building blocks on which to introduce functionality5 and
the azidodeoxy sugars represent a potentially vast source of furanose and pyranose core structures for such
manipulation. Since the literature contains many hundreds of such compounds, which most often serve as
precursors to aminodeoxy sugars, we are interested in exploiting these platforms in order to build spatially
well-defined chiral structures by using chemistry such as the newly developed methods for regioselective
1,2,3-triazole formation.6-9 We chose 1-azido-1-deoxy-2,3:5,6-di-O-isopropylidene-β-D-mannofuranose (3,
Scheme 1) as a platform for several reasons. Firstly, to the best of our knowledge, there are no examples of
furanosyl azides being employed in metal-mediated 1,2,3-triazole synthesis. Secondly, all of the
functionality in 3 is above the plane of the furanose ring, which makes the compound quite strained
compared to the corresponding α-anomers; any epimerization at C-1 during triazole formation may provide
useful mechanistic information about the organometallic-mediated formation of 1,2,3-triazoles. Lastly, the
isopropylidene protecting groups should be stable to the required chemistry (Cu-acetylides) and the
5,6-acetal should be hydrolyzed selectively thus opening up O-5 and O-6 for further manipulation.
RESULTS AND DISCUSSION
Synthesis of azide (3) (Scheme 1) begins with 2,3:5,6-di-O-isopropylidene-α-D-mannofuranose (1), which
is the product of thermodynamic acetalization of D-mannose with acetone and sulfuric acid. Diacetonide
1
(1) crystallizes as the α-anomer and its H NMR spectrum reveals a narrow doublet at 5.38 ppm, which
corresponds to H-1 of the furanose ring coupling with the OH proton. The lack of any coupling with H-2 is
consistent for α-anomers in this system due to the ~90o torsional angle between H-1 and H-2.
O
O
O
O
O
O
triphosgene
NaN3
O
O
O
O
O
O
N3
H
O
O
O
THF, pyridine, 0oC
DMF, 100 o
C
H
OH
Cl
H
H
1
2
3
Scheme 1.
To introduce an azide group at C-1 of the mannofuranose skeleton we employed our glycosyl chloride
synthesis,10 which uses solid triphosgene as the chlorine source. Thus, chloride (2) (Scheme 1) was

HETEROCYCLES, Vol. 65, No. 5, 2005
1037
produced on a 20 g scale in 87% yield. The 1H NMR spectrum of 2 shows a singlet for H-1 at 6.08 ppm thus
identifying the chloride as the α-anomer. Finally, stereospecific SN2 displacement of chloride with sodium
azide gave compound (3) as a waxy solid.11 That 3 is the β-anomer follows from its 1H NMR spectrum in
which the signal at 4.40 ppm for H-1 is split by H-2 (J = 3.7 Hz). The anomeric identity of the azide is
supported by the crystal structure of one of the derived 1,2,3-triazoles formed herein.
In order to introduce a second azide group onto the D-mannose backbone we decided to deprotect and then
activate at O-6. Firstly, selective hydrolysis of the 5,6-O-isopropylidene group using AcOH-water was
successful with monoacetal (4) (Scheme 2) being isolated in 84% yield.12 Activation at O-6 proved
problematic with the labile tosylate (5) decomposing upon silica gel chromatography; the best yield
achieved for clean 5 was 30%. Subsequent conversion to the bis(azide) (6) was uneventful and 6 was
isolated in 89% yield after chromatography.
O
O
HO
HO
TsO
HO
N3
AcOH, H2O (1:1)
50oC
p-MePhSO2Cl
NaN3
HO
O
O
N3
O
O
O
O
O
O
N3
N3
N3
O
O
O
O
pyridine, 0oC
DMF, 100 o
C
3
4
5
6
Scheme 2.
With azides (3) and (6) in hand we began to explore uncatalyzed Huisgen dipolar cycloaddition reactions
with various acetylenes. Thus, monoazide (3) reacts with diethyl acetylenedicarboxylate (DEAD) to give
the 1,2,3-triazole (7) as a crystalline solid (Equation 1) in 90% yield. The 1H NMR spectrum of triazole (7)
shows a doublet at 6.29 ppm with a coupling constant of 4.7 Hz, which identifies 7 as being the beta anomer.
Retention of the β-D-manno stereochemistry would be expected as there is no likelihood of anomeric
interconversion during a concerted Huisgen dipolar cycloaddition. In similar fashion bis(azide) (6) reacts
with two equivalents of DEAD to afford the bis(triazole) (8) (Equation 2). The proton for H-1 of the
mannofuranosyl ring in 8 appears as a doublet at 6.42 ppm and the corresponding signal for H-1 in triazole
(7) appears at 6.29 ppm. The fact that the coupling constants for these signals are so similar (4.8 and 4.7 Hz
respectively) suggests that the second triazole ring in bis(triazole) (8) does not distort the mannofuranose
ring compared with compound (7).
CO2Et
N
EtO2C
O
O
O
O
EtO2C
CO2Et
O
O
O
O
O
N3
N
N
O
PhMe, 110oC
7
3
Equation 1.

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HETEROCYCLES, Vol. 65, No. 5, 2005
EtO2C
CO2Et
N3
EtO2C
CO2Et
N
N
N
N
HO
(2 equiv.)
CO2Et
CO2Et
O
O
N3
N
O
N
O
HO
O
O
PhMe, 110oC
6
8
Equation 2.
Since DEAD is symmetrical it can only give one triazole upon cycloaddition however conventional (i.e.
uncatalyzed) reaction of azide (3) with terminal acetylenes (Scheme 3) gave mixtures of 1,4- and 1,5-
disubstituted isomers (9) in which the 1,4-isomer predominates.1 When the organic-soluble catalyst
(PPh3)3•CuBr9 was employed reaction of azide (3) with phenyl acetylene, ethyl propiolate, and propargyl
alcohol in toluene gave only one triazole product (10-12 respectively, Scheme 3) in good yield. In each case
triazoles (10) through (12) matched the major isomer formed in the uncatalyzed reactions.
R
R
N
H
O
O
O
O
O
O
N
N
H
R
H
R
O
O
O
O
O
O
N3
N
N
N
O
O
O
.
PhMe, 110oC
(Ph3P)3 CuBr
DBU
PhMe, 110oC
10 R = Ph
9
3
11 R = CO2Et
12 R = CH2OH
Scheme 3.
Encouraged by the efficiency of the Cu(I)-catalyzed triazole formation, and the fact that the
β-mannofuranosyl configuration is retained, we turned our attention to the synthesis of several
triazole-linked disaccharide and trisaccharide analogs. The term carbohybrid has been coined to describe
compounds in which portions of oligosaccharides are replaced by non-carbohydrate groups,13 and within
that potentially vast family we refer to 1,2,3-triazole-linked sugars as glycazoles.
The required sugar-derived alkyne partners were prepared by alkylation of several readily available
carbohydrate platforms with propargyl bromide. Thus, 1,2:5,6-di-O-isopropylidene-D-glucofuranose,
2,3:5,6-di-O-isopropylidene-D-mannofuranose, 1,2:3,4-di-O-isopropylidene-D-galactopyranose, and 1,2-
O-isopropylidene-D-xylofuranose where alkylated to give alkynes (13)-(16) respectively in the yields
shown in Table 1. With suitable alkynes in hand we treated each with mannofuranosyl azide (3) in the
presence of (PPh3)3•CuBr and DBU to generate the glycazoles (17)-(20) shown in Table 1. In each case
1
only the 1,4-disubstituted triazole was formed and analysis of H NMR spectra of the crude reaction
mixtures did not give any evidence for the formation of the 1,5-disubstituted isomers during these reactions.
In each case the anomeric proton on the mannofuranosyl ring in compounds (17-20) appears around 6.0
ppm as doublets with J ~ 3.3 Hz again proving that the β configuration of the azide precursor (i.e. 3) had

HETEROCYCLES, Vol. 65, No. 5, 2005
1039
been retained during the formation of the 1,2,3-triazole products. Each of the signals for the proton attached
at C-5 of the triazole rings in 17-20 appears as a singlet at 7.8-7.9 ppm, which indicates that they are the
same regioisomer in each case. Further evidence for these regioisomeric assignments is provided by the
X-Ray crystal structure of compound (17), which clearly shows it to be the 1,4-disubstituted triazole
(Figure 1, Tables 2 and 3).
Table 1. Monosaccharide-derived alkynes used in this work and yields for resultant triazole carbohybrids.
%Yield
Addition product with 3
Alkyne precursor
%Yield
O
O
O
O
N
N
O
O
O
O
O
O
N
62
73
O
O
O
H
O
O O
O
13
17
O
O
N
O
O
N
N
O
O
O
O
O
O
69
70
O
H
O
O
O
O
O
14
18
O
O
O
N
N
O
O
O
O
O
O
N
O
O
O
O
O
67
72
H
O
O
O
O
15
19
O
O
O
O
O
O
O
O
O
O
O
O
N
N
N
H
73
57
O
N
N
O
N
O
O
O
H
O
16
20
O
O
In conclusion, we have applied recently reported methods for regiocontrolled synthesis of disubstituted
1,2,3-triazoles to the formation of a variety of novel carbohybrids (glycazoles) derived from the
β-D-mannofuranosyl skeleton. The β-D-manno configuration is retained in each case. We are presently
applying these methods to the regioselective synthesis of both furanosyl and pyranosyl substrates with a
view to creating compounds with glycomimetic potential.

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HETEROCYCLES, Vol. 65, No. 5, 2005
Figure 1. ORTEP representation of 17 at the 50% probability level.
Table 2. Crystal data and structure refinement for 17.
Empirical formula
Formula weight
Temperature
C27H41N3O11
583.63
100(2) K
Wavelength
0.71073 Å
Crystal system
Space group
Unit cell dimensions
Monoclinic
P 21 (No. 4)
a = 10.0048(13) Å α = 90o.
b = 10.3781(13) Å β = 107.051(2)o.
c = 14.6612(19) Å γ = 90o.
1455.4(3) Å3, 2
1.332 g/cm3
Volume, Z
Density (calculated)
Absorption coefficient
F(000)
0.103 mm-1
624
Crystal size
Theta range for data collection
Limiting indices
Reflections collected
Independent reflections
Refinement method
Data / restraints / parameters
Goodness-of-fit on F2
Final R indices [I>2σ(I)]
R indices (all data)
0.407 x 0.275 x 0.154 mm
1.45 to 28.33o.
-13<=h<=13, -13<=k<=13, -19<=l<=19
15527
7134 [R(int) = 0.0212]
Full-matrix least-squares on F2
7134 / 1 / 426
1.078
R1 = 0.0425, wR2 = 0.1088
R1 = 0.0436, wR2 = 0.1098
0.6(5)
Absolute structure parameter
Largest diff. peak and hole
0.374 and -0.256 e.Å-3

HETEROCYCLES, Vol. 65, No. 5, 2005
1041
Table 3. Selected bond lengths (Å) and angles (o) for 17.
C(6)-C(7)
1.535(2)
1.548(2)
C(9)-O(5)-C(6)
O(5)-C(6)-C(7)
C(6)-C(7)-C(8)
C(9)-C(8)-C(7)
O(5)-C(9)-C(8)
N(1)-C(9)-C(8)
O(5)-C(9)-N(1)
N(2)-N(1)-C(9)
N(3)-N(2)-N(1)
C(13)-N(1)-N(2)
N(1)-C(13)-C(14)
N(2)-N(3)-C(14)
N(3)-C(14)-C(15)
C(13)-C(14)-C(15)
O(8)-C(15)-C(14)
O(8)-C(16)-C(17)
C(19)-C(16)-C(17)
O(9)-C(18)-C(17)
O(9)-C(19)-C(16)
102.99(11)
104.86(11)
103.88(12)
102.30(12)
105.14(12)
116.49(12)
109.66(11)
116.63(12)
107.08(12)
110.95(12)
104.12(13)
109.17(12)
121.51(13)
129.81(14)
107.48(12)
111.29(12)
100.96(12)
107.35(13)
104.20(12)
C(7)-C(8)
C(8)-C(9)
1.529(2)
O(5)-C(6)
O(5)-C(9)
N(1)-C(9)
1.4398(17)
1.4283(17)
1.4421(19)
1.3515(19)
1.372(2)
N(1)-C(13)
C(13)-C(14)
N(3)-C(14)
N(1)-N(2)
N(2)-N(3)
C(14)-C(15)
O(8)-C(15)
O(8)-C(16)
C(16)-C(17)
C(17)-C(18)
C(16)-C(19)
O(9)-C(18)
O(9)-C(19)
1.361(2)
1.3540(18)
1.3033(19)
1.493(2)
1.4320(18)
1.4244(17)
1.533(2)
1.543(2)
1.530(2)
1.406(2)
1.4329(19)
EXPERIMENTAL
General: Reaction progress was monitored by TLC with UV light detection or the TLC plate was treated

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HETEROCYCLES, Vol. 65, No. 5, 2005
with a 5% sulfuric acid/ethanol solution to burn the reaction material to provide indication of the
carbohydrate product. Flash chromatography was performed on 32-63 µm, 60-Å silica gel. All products are
homogeneous by TLC. A Bruker Esquire-HP 1100 mass spectrometer was used for low-resolution MS and
a Micromass LCT was used for high resolution. A Varian Gemini 2000 NMR system was employed for
measurement of ¹H and ¹³C NMR spectra at 400 MHz and 100 MHz respectively, using CDCl3 or DMSO-d6
as solvents. X-Ray diffraction data was collected on a Bruker SMART APEX 4K CCD Single Crystal
Diffractometer at 100 K; Mo (Kα) radiation. The structure was solved using the SMART, SAINT, SADABS,
SHELXL, and SHELXP software.14 Melting points were recorded on a MelTemp apparatus and are
uncorrected. Optical rotations were recorded on a Perkin Elmer model 343 automatic polarimeter.
2,3:5,6-Di-O-isopropylidene-α-D-mannofuranose (1).
In a flame-dried 2000 mL Erlenmeyer flask equipped with a drying tube and magnetic stir bar, D-mannose
(20.0 g, 107.4 mmol) was dissolved in acetone (750 mL) at rt. Concentrated H2SO4 (14 mL) was added in 2
mL portions every five minutes and the reaction was allowed to stir for 12 h when TLC (EtOAc) showed
consumption of starting material. The reaction was neutralized with Na2CO3 and filtered. Charcoal (5 g)
and Na2CO3 (10 g) were added to the filtrate and the mixture was refluxed for 1 h. The reaction was cooled,
filtered, and evaporated and the remaining solid was recrystallized from methanol to afford 18.8 g of 1
(67%). mp = 119-121 ˚C. 1H NMR (CDCl3): δ 1.32 (s, 3H, -CH3), 1.37 (s, 3H, -CH3), 1.45 (s, 3H, -CH3),
1.46 (s, 3H, -CH3), 2.77 (d, 1H, -OH, J = 2.6 Hz), 4.06 (m, 2H, H-6, H-6’), 4.18 (dd, 1H, H-4, J = 3.7, 7.3
Hz), 4.40 (m, 1H, H-5), 4.61 (d, 1H, H-2, J = 5.9 Hz), 4.81 (dd, 1H, H-3, J = 3.7, 5.9 Hz), 5.38 (d, 1H, H-1,
J = 2.2 Hz). This data match that of a commercially available sample of 1.
2,3:5,6-Di-O-isopropylidene-α-D-mannofuranosyl chloride (2).
In a 500 mL flame-dried round bottom flask fitted with a septum and magnetic stir bar,
2,3:5,6-di-O-isopropylidene-α-D-mannofuranose (1) (24.0 g, 92.2 mmol) was dissolved in THF (250 mL).
Triphosgene (10.9 g, 36.9 mmol) was added and the flask placed in an ice bath. Pyridine (4.8 mL) was
added dropwise (CAUTION – CO2 gas evolved), and the mixture was allowed to stir for 4 h when TLC
(3:1 hexane: EtOAc, product Rf = 0.58) showed consumption of the starting material. The mixture was
filtered and the precipitate washed with THF. The filtrate was reduced to produce 22.85 g of 3 as a yellow
syrup (87%), which was used without further purification. 1H NMR (CDCl3): δ 1.35 (s, 3H, -CH3), 1.41 (s,
3H, -CH3), 1.48 (s, 6H, 2 x -CH3), 4.00 (dd, 1H, H-6, J = 4.4, 8.8 Hz), 4.08 (dd, 1H, H-6’, J = 6.2, 8.8 Hz),
4.19 (dd, 1H, H-4, J = 3.7, 7.9 Hz), 4.42 (ddd, 1H, H-5, J = 4.4, 6.2, 10.6 Hz), 4.87 (dd, 1H, H-3, J = 3.7, 5.9
Hz), 4.93 (d, 1H, H-2, J = 5.9 Hz), 6.08 (s, 1H, H-1). This data match that reported previously for
compound (2).10
1-Azido-1-deoxy-2,3:5,6-di-O-isopropylidene-β-D-mannofuranose (3).
In a 500 mL round bottom two neck flask equipped with a thermometer adapter and magnetic stir bar,

HETEROCYCLES, Vol. 65, No. 5, 2005
1043
2,3:5,6-di-O-isopropylidene-α-D-mannofuranosyl chloride (2, 22.85 g, 82.2 mmol) and NaN3 (26.7 g,
410.8 mmol) were heated at 80 ˚C in DMF (250 mL) for 12 h when TLC (3:1 hexane : EtOAc, product Rf =
0.32) showed consumption of the starting material. The reaction was diluted with water (100 mL) and then
extracted with CH2Cl2 (3 x 20 mL). The organic phase was washed with water (20 mL) and then dried using
MgSO4. Evaporation of the solvent gave a waxy homogenous solid identified as 3 (22.5 g, 96%). 1H NMR
(CDCl3): δ 1.36 (s, 3H, -CH3), 1.38 (s, 3H, -CH3), 1.44 (s, 3H, -CH3), 1.55 (s, 3H, -CH3), 3.59 (dd, 1H, H-4,
J = 3.7, 7.7 Hz), 4.11 (m, 2H, H-6, H-6’), 4.40 (d, 1H, H-1, J = 3.7 Hz), 4.45 (m, 1H, H-5), 4.67 (dd, 1H,
H-2, J = 3.7, 5.9 Hz), 4.77 (dd, 1H, H-3, J = 3.3, 5.9 Hz). 13C NMR (CDCl3): δ 25.6, 26.3, 26.4, 28.2, 67.9,
74.0, 79.6, 80.6, 82.2, 90.1, 110.3, 114.6. This data are consistent with an authentic sample of 3 prepared by
a different route.11
1-Azido-1-deoxy-2,3-O-isopropylidene-β-D-mannofuranose (4).
In a 500 mL two neck round bottom flask equipped with a thermometer adapter and magnetic stir bar, azide
(3) (6.0 g, 21.0 mmol) was dissolved in 1:1 glacial acetic acid and water (300 mL). The reaction was heated
to 50 ˚C for 3 h after which time TLC (EtOAc, product Rf = 0.34) showed complete disappearance of 3. The
residue after evaporation in vacuo was evaporated with toluene (2 x 100 mL) to afford 4 as a clear syrup in
84% yield (4.32 g). 1H NMR (DMSO-d6): δ 1.37 (s, 3H, -CH3), 1.56 (s, 3H, -CH3), 3.67 (dd, 1H, H-4, J =
4.0, 8.4 Hz), 3.75 (dd, 1H, H-6, J = 5.5, 11.4 Hz), 3.90 (dd, 1H, H-6’, J = 3.3, 11.7 Hz), 4.10 (m, 1H, H-5),
4.46 (d, 1H, H-1, J = 3.7 Hz), 4.69 (dd, 1H, H-2, J = 3.7, 6.2 Hz), 4.84 (dd, 1H, H-3, J = 4.0, 6.2 Hz). 13C
NMR (DMSO-d6): δ 26.0, 26.8, 65.2, 70.0, 78.8, 81.0, 82.0, 89.6, 103.2.
1-Azido-1-deoxy-2,3-O-isopropylidene-6-O-p-toluenesulfonyl-β-D-mannofuranose (5).
In a 100 mL round bottom flask equipped with a magnetic stir bar and septum 1-azido-1-deoxy-2,3-O-
isopropylidene-β-D-mannofuranose (4) (3.25 g, 13.4 mmol) was dissolved in pyridine (60 mL).
p-Toluenesulfonyl chloride (3.06 g, 16.0 mmol) was added and the temperature lowered to 0 ºC. The
mixture was stirred for 12 h when TLC (ethyl acetate) showed the disappearance of the starting material.
Water (12 mL) was mixed with the reaction for 10 min, the mixture was poured over ice and then extracted
with methylene chloride (3 x 10 mL). The combined organic layers were washed with water (10 mL). The
organic layer was dried over MgSO4, evaporated, and purified by elution from a column of silica gel (1:1
1
hexane: ethyl acetate) to afford an unstable white solid in 30% yield. H NMR (CDCl3): δ 1.34 (s, 3H,
-CH3), 1.50 (s, 3H, -CH3), 2.45 (s, 3H, -PhCH3), 2.64 (d, 1H, -OH, J = 5.5 Hz), 3.58 (dd, 1H, H-4, J = 4.0,
8.1 Hz), 4.17 (m, 2H, H-6, H-6’), 4.34 (m, 2H, H-1, H-5), 4.66 (dd, 1H, H-2, J = 3.7, 5.9 Hz), 4.81 (dd, 1H,
H-3, J = 4.0, 6.2 Hz), 7.35 (d, 2H, Ar-H), 7.81 (d, 2H, Ar-H). 13C NMR (CDCl3): δ 22.9, 25.7, 26.4, 68.7,
72.7, 77.9, 80.6, 82.0, 90.2, 114.8, 129.1 (double intensity), 131.0 (double intensity), 133.4, 146.1.
APCI-MS (m/z) calcd: 399.41, found: 391.3 (M–N2+H2O).
1,6-Diazido-1,6-dideoxy-2,3-O-isopropylidene-β-D-mannofuranose (6).
In a 50 mL two neck round bottom flask equipped with a magnetic stir bar and thermometer adapter,

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HETEROCYCLES, Vol. 65, No. 5, 2005
tosylate (5) (0.50 g, 1.3 mmol) and NaN3 (0.41 g, 6.3 mmol) in DMF (15 mL) were heated at 100 ºC for 12
h when TLC (2:1 hexane: EtOAc) showed no starting material. The reaction was poured over water (25
mL) and the mixture was extracted with CH2Cl2 (3 x 15 mL), which was then back extracted with water (10
1
mL). After drying over MgSO4 removal of solvent gave 6 as a yellow syrup in 89% yield. H NMR
(CDCl3): δ 1.36 (s, 3H, -CH3), 1.56 (s, 3H, -CH3), 2.52 (d, 1H, -OH, J = 5.1 Hz), 3.48 (dd, 1H, H-6, J = 5.9,
12.8 Hz), 3.64 (m, 2H, H-4, H-6’), 4.18 (m, 1H, H-5), 4.48 (d, 1H, H-1, J = 3.7 Hz), 4.70 (dd, 1H, H-2, J =
3.7, 6.2 Hz), 4.84 (dd, 1H, H-3, J = 4.0, 6.2 Hz). 13C NMR (CDCl3): δ 25.8, 26.5, 55.2, 70.1, 79.1, 80.8, 82.1,
90.2, 114.9. APCI-MS (m/z) calcd: 270.11, found: 243.1 (M-N2,+H). HRMS (M+Na) calcd: 293.0974,
found: 293.0962.
1-(2,3:5,6-Di-O-isopropylidene-β-D-mannofuranosyl)-1H-[1,2,3]triazol-4,5-dicarboxylic acid diethyl
ester (7).
Azide (3) (210 mg, 0.74 mmol) and diethyl acetylenedicarboxylate (126 mg, 0.74 mmol) were refluxed in
toluene (5 mL) overnight. Removal of solvent and purication by flash chromatography (3:1 hexane:
EtOAc) gave triazole (7) as a colorless solid (190 mg, 90%). mp = 122-124 ˚C, recrystallized from ethanol.
1H NMR (CDCl3): δ 1.27 (s, 3H, -CH3), 1.29 (s, 3H, -CH3), 1.39 (m, 9H, -CH3, 2 x -OCH2CH3), 1.47 (s, 3H,
-CH3), 4.00 (dd, 1H, H-4, J = 4.0, 8.1 Hz), 4.17 (m, 2H, H-6, H-6’), 4.41 (m, 4H, -OCH2CH3), 4.65 (m, 1H,
H-5), 4.94 (dd, 1H, H-3, J = 4.0, 5.9 Hz), 5.08 (dd, 1H, H-2, J = 4.4, 6.2 Hz), 6.29 (d, 1H, H-1, J = 4.7 Hz).
13C NMR (CDCl3): δ 15.1, 15.4, 25.7, 26.1, 26.3, 28.2, 62.9, 64.0, 67.7, 73.7, 77.9, 80.5, 81.8, 91.7, 110.5,
115.8, 131.9, 140.1, 159.7, 160.9. APCI-MS (m/z) calcd: 455.19, found: 456.1 (M+H). HRMS (M+Na)
calcd: 478.1801, found: 478.1826. Anal. Calcd for C20H29N3O9: C, 52.74; H, 6.42; N, 9.23. Found: C,
52.91; H, 6.46; N, 9.24.
1-(2,3-O-Isopropylidene-β-D-mannofuranosyl)-1,6-di(1H-[1,2,3]triazol-4,5-dicarboxylic acid diethyl
esters) (8).
Refluxing azide (6) (270 mg, 1.0 mmol) with DEAD (340 mg, 2.0 mmol) in toluene (5 mL) overnight gave,
after chromatography (3:1 hexane: EtOAc), bis(triazole) (8) as a colorless syrup (458 mg, 75%). 1H NMR
(CDCl3): δ 1.15 (s, 3H, -CH3), 1.24 (s, 3H, -CH3), 1.38 (m, 12H, 4 x -OCH2CH3), 3.11 (d, 1H, -OH, J = 5.5
Hz), 3.93 (dd, 1H, H-4, J = 4.8, 8.8 Hz), 4.42 (m, 10H, H-6, H-6’, 4 x -OCH2CH3), 4.70 (m, 1H, H-5), 4.95
(m, 1H, H-3), 5.10 (dd, 1H, H-2, J = 4.8, 5.9 Hz), 6.42 (d, 1H, H-1, J = 4.8 Hz). 13C NMR (CDCl3): δ 15.1
(double intensity), 15.4 (double intensity), 25.7, 26.0, 53.4, 62.9, 63.0, 64.1, 64.3, 69.1, 80.6, 81.3, 81.9,
91.9, 116.0, 131.8, 133.5, 140.30, 140.31, 159.6, 159.9, 160.9 (double intensity). APCI-MS (m/z) calcd:
610.57, found: 611.3 (M+H). HRMS (M+Na) calcd: 633.2132, found: 633.2146.
Cu(I)-catalyzed 1,2,3-triazole synthesis.
Azide (3) (0.5 g, 1.75 mmol), either phenyl acetylene, ethyl propiolate, or propargyl alcohol (1 equivalent),
(PPh3)3•CuBr9 (0.2 equivalent), and DBU (3 equivalents) were refluxed in toluene for 16 h. After
chromatography (3:1 hexane : EtOAc) the triazoles were isolated as colorless syrups.

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1045
1-(2,3:5,6-Di-O-isopropylidene-β-D-mannofuranosyl)-4-phenyl-1H-[1,2,3]triazole (10). 67% yield. 1H
NMR (CDCl3): δ 1.36 (s, 3H, -CH3), 1.41 (s, 3H, -CH3), 1.48 (s, 3H, -CH3), 1.61 (s, 3H, -CH3), 3.80 (dd, 1H,
H-4, J = 3.7, 7.7 Hz), 4.11 (dd, 1H, H-6, J = 4.4, 9.2 Hz), 4.15 (dd, 1H, H-6’, J = 6.2, 9.2 Hz), 4.53 (ddd, 1H,
H-5, J = 4.0, 6.2, 10.3 Hz), 4.92 (dd, 1H, H-2, J = 3.7, 5.9 Hz), 4.98 (dd, 1H, H-3, J = 3.7, 5.9 Hz), 6.14 (d,
1H, H-1, J = 3.7 Hz), 7.32 (m, 5H, Ar-H), 8.08 (s, 1H, triazole-H). 13C NMR (CDCl3): δ 25.2, 26.4, 26.7,
28.2, 67.9, 73.8, 80.2, 80.3, 80.8, 89.9, 110.5, 114.7, 121.4, 126.7 (double intensity), 129.2 (double
intensity), 129.8, 131.5, 148.2. APCI-MS (m/z) calcd: 387.43, found: 388.3 (M+H). HRMS (M+Na) calcd:
410.1692, found: 410.1703.
1-(2,3:5,6-Di-O-isopropylidene-β-D-mannofuranosyl)-1H-[1,2,3]triazol-4-carboxylic acid ethyl ester
1
(11). 81% yield. H NMR (CDCl3): δ 1.38 (s, 3H, -CH3), 1.45 (m, 6H, -CH3, -OCH2CH3), 1.50 (s, 3H,
-CH3), 1.60 (s, 3H, -CH3), 3.80 (dd, 1H, H-4, J = 3.8, 7.8 Hz), 4.06 (dd, 1H, H-6, J = 4.2, 9.0 Hz), 4.14 (dd,
1H, H-6’, J = 6.2, 9.2 Hz), 4.47 (m, 3H, H-5, -OCH2CH3), 4.92 (dd, 1H, H-2, J = 3.6, 5.9 Hz), 4.98 (dd, 1H,
H-3, J = 5.9, 3.7 Hz), 6.17 (d, 1H, H-1, J = 3.6 Hz), 8.35 (s, 1H, triazole-H). 13C NMR (CDCl3): δ 15.5, 25.2,
26.3, 26.6, 28.1, 62.4, 67.7, 73.7, 80.2, 80.4, 80.8, 89.8, 110.5, 114.8, 129.3, 140.7, 161.5. APCI-MS (m/z)
calcd: 383.39, found: 384.2 (M+H). HRMS (M+Na) calcd: 406.1590, found: 406.1614.
1-(2,3:5,6-Di-O-isopropylidene-β-D-mannofuranosyl)-1H-[1,2,3]triazol-4-ylmethanol (12). 57% yield.
1H NMR (CDCl3): δ 1.35 (s, 3H, -CH3), 1.40 (s, 3H, -CH3), 1.47 (s, 3H, -CH3), 1.58 (s, 3H, -CH3), 2.46 (s,
1H, -OH), 3.77 (dd, 1H, H-4, J = 3.7, 7.7 Hz), 4.06 (dd, 1H, H-6, J = 4.0, 8.8 Hz), 4.12 (dd, 1H, H-6’, J = 5.9,
8.8 Hz), 4.49 (ddd, 1H, H-5, J = 4.0, 5.9, 7.7 Hz), 4.82 (d, 2H, -CH2OH, J = 4.4 Hz), 4.88 (dd, 1H, H-2, J =
3.7, 6.2 Hz), 4.96 (dd, 1H, H-3, J = 4.0, 6.2 Hz), 6.10 (d, 1H, H-1, J = 3.7 Hz), 7.87 (s, 1H, triazole-H). 13C
NMR (CDCl3): δ 25.2, 26.3, 26.7, 28.1, 57.2, 67.7, 73.7, 80.1, 80.2, 80.7, 89.7, 110.5, 114.7, 123.7, 148.5.
APCI-MS (m/z) calcd: 341.36, found: 342.1 (M+H). HRMS (M+Na) calcd: 364.1485, found: 364.1463.
Synthesis of sugar-derived alkynes.
1,2:5,6-Di-O-isopropylidene-D-glucofuranose, 2,3:5,6-di-O-isopropylidene-D-mannofuranose, 1,2:3,4-di-
O-isopropylidene-D-galactopyranose, or 1,2-O-isopropylidene-D-xylofuranose (1.15 g), KOH (1.5 g, 26.5
mmol) and propargyl bromide (3.1 g, 26.5 mmol) in MeCN (10 mL) were stirred at rt for 24 h. The mixtures
were evaporated in vacuo and partitioned between CH2Cl2 (25 mL) and water (25 mL). The aqueous phase
was extracted with CH2Cl2 (3 x 20 mL) then the combined organic layers were dried over MgSO4, reduced,
and purified by chromatography (3:1 hexane : EtOAc) to give the alkynes as colorless syrups.
1,2:5,6-Di-O-isopropylidene-3-O-(prop-2-ynyloxy)-D-glucofuranose (13). 62% yield. 1H NMR
(CDCl3): δ 1.30 (s, 3H, -CH3), 1.34 (s, 3H, -CH3), 1.41 (s, 3H, -CH3), 1.49 (s, 3H, -CH3), 2.52 (t, 1H,
-OCH2CCH, J = 2.4 Hz), 3.98 (dd, 1H, H-4, J = 5.4, 8.6 Hz), 4.11 (m, 3H, H-5, H-6, H-6’), 4.26 (m, 3H,
H-3, -OCH2CCH), 4.62 (d, 1H, H-2, J = 3.7 Hz), 5.87 (d, 1H, H-1, J = 3.7 Hz). 13C NMR (CDCl3): δ 26.6,
27.5, 28.0 (double intensity), 59.2, 68.3, 73.6, 76.1, 80.3, 82.1, 82.6, 83.9, 106.2, 110.0, 112.9. APCI-MS
(m/z) calcd: 298.3, found: 299.3 (M+H). HRMS (M+Na) calcd: 321.1314, found: 321.1311.

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(Prop-2-ynyloxy) 2,3:5,6-di-O-isopropylidene-α-D-mannofuranoside (14). 69% yield. 1H NMR
(CDCl3): δ 1.33 (s, 3H, -CH3), 1.38 (s, 3H, -CH3), 1.46 (s, 3H, -CH3), 1.48 (s, 3H, -CH3), 2.44 (t, 1H,
HCCCH2, J = 2.4 Hz), 3.96 (dd, 1H, H-4, J = 3.6, 7.8 Hz), 4.06 (dd, 1H, H-6, J = 4.2, 8.7 Hz), 4.11 (dd, 1H,
H-6’, J = 6.2, 8.7 Hz), 4.19 (dd, 2H, -OCH2CCH, J = 2.3, 4.3 Hz), 4.41 (ddd, 1H, H-5, J = 4.3, 6.2, 7.8 Hz),
4.63 (d, 1H, H-2, J = 5.9 Hz), 4.79 (dd, 1H, H-3, J = 3.6, 5.9 Hz), 5.18 (s, 1H, H-1). 13C NMR (CDCl3): δ
25.7, 26.4, 27.1, 28.2, 55.3, 70.0, 74.1, 75.8, 78.8, 80.5, 81.7, 86.1, 105.9, 110.3, 113.7. APCI-MS (m/z)
calcd: 298.33, found: 299.2 (M+H). HRMS (M+Na) calcd: 321.1314, found: 321.1306.
1,2:3,4-Di-O-isopropylidene-6-O-(prop-2-ynyloxy)-D-galactopyranose (15). 67% yield. 1H NMR
(CDCl3): δ 1.33 (s, 3H, -CH3), 1.35 (s, 3H, -CH3), 1.46 (s, 3H, -CH3), 1.55 (s, 3H, -CH3), 2.44 (t, 1H,
HCCCH2, J = 2.4 Hz), 3.67 (dd, 1H, H-6, J = 7.1, 10.1 Hz), 3.78 (dd, 1H, H-6’, J = 5.2, 10.1 Hz), 4.00 (ddd,
1H, H-5, J = 1.9, 5.2, 7.1 Hz), 4.21 (d, 1H, -OCH2CCH, J = 2.4 Hz), 4.24 (d, 1H, -OCH2CCH, J = 2.4 Hz),
4.26 (dd, 1H, H-4, J = 1.8, 7.9 Hz), 4.32 (dd, 1H, H-2, J = 2.4, 5.1 Hz), 4.61 (dd, 1H, H-3, J = 2.4, 7.9 Hz),
5.55 (d, 1H, H-1, J = 5.1 Hz). 13C NMR (CDCl3): δ 25.7, 26.2, 27.2, 27.3, 59.7, 67.9, 69.8, 71.6, 71.8, 72.3,
75.8, 80.7, 97.4, 109.6, 110.3. APCI-MS (m/z) calcd: 298.33, found: 299.0 (M+H). HRMS (M+Na) calcd:
321.1314, found: 321.1290.
1,2-O-Isopropylidene-3,5-di-O-(prop-2-ynyloxy)-D-xylofuranose (16). 73% yield. 1H NMR (CDCl3): δ
1.32 (s, 3H, -CH3), 1.50 (s, 3H, -CH3), 2.47 (t, 1H, -CH2CCH, J = 2.6 Hz), 2.50 (t, 1H, -CH2CCH, J = 2.6
Hz), 3.72 (dd, 1H, H-5, J = 6.6, 10.0 Hz), 3.81 (dd, 1H, H-5’, J = 5.6, 10.0 Hz), 4.11 (d, 1H, H-3, J = 3.1 Hz),
4.19-4.25 (m, 4H, 2 x -OCH2CCH), 4.40 (m, 1H, H-4), 4.62 (d, 1H, H-2, J = 3.8 Hz), 5.92 (d, 1H, H-1, J =
3.8 Hz). 13C NMR (CDCl3): δ 27.6, 28.0, 58.9, 59.8, 68.4, 75.8, 76.2, 80.0, 80.2, 80.6, 82.6, 83.4, 106.1,
112.9. APCI-MS (m/z) calcd: 266.29, found: 267.2 (M+H). HRMS (M+Na) calcd: 289.1052, found:
289.1039.
1,4-Disubstituted triazole (17).
Mannofuranosyl azide (3) (0.25 g, 0.88 mmol), alkyne (13) (0.288 g, 0.96 mmol), (PPh3)3•CuBr (0.268 g,
0.29 mmol) and DBU (0.432 mL) were refluxed in toluene (15 mL) overnight. The reaction was
concentrated and purified by chromatography (2:1 hexane : EtOAc) to give 0.360 g (73%) of 17 as a
colorless solid. mp = 196-198 ˚C, recrystallized from ethanol. 1H NMR (CDCl3): δ 1.29 (s, 3H, -CH3), 1.33,
1.34 (2s, 6H total, 2 x -CH3), 1.39 (s, 6H, 2 x -CH3), 1.46, 1.48, 1.56 (3s, 9H total, 3 x -CH3), 3.76 (dd, 1H,
H-4man, J = 3.7, 8.1 Hz), 4.07 (m, 9H, H-6 and H-6’man, H-3, H-4, H-5, H-6, and H-6’glc, -OCH2CNCH-),
4.50 (ddd, 1H, H-5man, J = 4.0, 5.9, 8.1 Hz), 4.61 (d, 1H, H-2glc, J = 3.7 Hz), 4.87 (dd, 1H, H-2man, J = 3.6,
5.9 Hz), 4.96 (dd, 1H, H-3man, J = 3.7, 5.9 Hz), 5.88 (d, 1H, H-1glc, J = 3.7 Hz), 6.10 (d, 1H, H-1man, J = 3.6
Hz), 7.87 (s, 1H, triazole-H). 13C NMR (CDCl3): δ 25.2, 26.3, 26.7 (double intensity), 27.4, 28.1 (double
intensity), 28.3, 65.1, 68.0, 68.4, 73.7 (double intensity), 80.3, 80.35, 80.7, 82.2, 82.8, 83.6, 89.9, 106.3,
110.0, 100.7, 112.9, 114.8, 124.5, 145.2. APCI-MS (m/z) calcd: 583.27, found 584.3 (M+H). HRMS
(M+Na) calcd: 606.2639, found: 606.2645. [α]D = +55.6˚ (c 5.0, CH2Cl2). Anal. Calcd for C27H41N3O11: C,

HETEROCYCLES, Vol. 65, No. 5, 2005
1047
55.56; H, 7.08; N, 7.20. Found: C, 55.39; H, 7.38; N, 7.21.
1,4-Disubstituted triazole (18).
Mannofuranosyl azide (3) (0.774 g, 2.7 mmol), alkyne (14) (0.89 g, 3.0 mmol), (PPh3)3•CuBr (0.554 g, 0.59
mmol) and DBU (1.33 mL) were refluxed in toluene (15 mL) overnight. The reaction was reduced and the
residue purified by chromatography (2:1 hexane : EtOAc) to give 1.11 g (70%) of triazole (18) as a
colorless syrup. 1H NMR15 (CDCl3): δ 1.29, 1.33, 1.36, 1.37 (4s, 12H, 4 x -CH3), 1.44 (overlapping 3s, 9H,
3 x -CH3), 1.56 (s, 3H, -CH3), 3.74 (dd, 1H, H-4ringB, J = 3.7, 8.1 Hz), 3.96 (dd, 1H, H-4ringA, J = 3.7, 8.1 Hz),
4.06 (m, 6H, (H-6, H-6’)ringA, (H-6, H-6’)ringB, -OCH2CNCH-), 4.39 (ddd, 1H, H-5ringB, J = 4.4, 6.6, 8.1 Hz),
4.48 (m, 1H, H-5ringA, J = 4.0, 5.9, 7.7 Hz), 4.61-4.76 (m, 2H, (H-2ringB, H-3ringB), 4.86 (dd, 1H, H-2ringA, J =
3.7, 5.9 Hz), 4.94 (dd, 1H, H-3ringA, J = 3.7, 5.9 Hz), 5.08 (s, 1H, H-1ringB), 6.08 (dd, 1H, H-1ringA, J = 3.3 Hz),
7.82 (s, 1H, triazole-H). 13C NMR (CDCl3): δ 25.2, 25.7, 26.3, 26.4, 26.7, 27.1, 28.1, 28.2, 64.1, 65.9, 67.9,
68.1, 73.7, 80.3, 80.6 (double intensity), 80.7, 83.1, 83.3, 89.8, 106.6, 110.3, 113.6, 114.8, 124.4, 129.2,
132.8. APCI-MS (m/z) calcd: 583.27, found 584.3 (M+H). HRMS (M+Na) calcd: 606.2639, found:
606.2645. [α]D = +3.5˚ (c 5.0, CH2Cl2).
1,4-Disubstituted triazole (19).
Mannofuranosyl azide (3) (0.25 g, 0.88 mmol), alkyne (15) (0.288 g, 0.96 mmol), (PPh3)3•CuBr (0.268 g,
0.29 mmol) and DBU (0.432 mL) were refluxed overnight in toluene (15 mL). After evaporation of the
solvent and purification by chromatography (2:1 hexane : EtOAc) triazole (19) was isolated as a colorless
solid (0.37 g, 72%), which was recrystallized from methanol. mp = 142-144 ˚C. 1H NMR15 (CDCl3): δ 1.31
(s, 6H, 2 x -CH3), 1.32, 1.38, 1.41, 1.44, 1.50, 1.55 (6s, 18H total, 6 x -CH3), 3.63 to 4.94 (several m, 14H,
H-2 to H-6’man, H-2 to H-6’gal, -OCH2CNCH-), 5.52 (d, 1H, H-1gal, J = 4.8 Hz), 6.07 (d, 1H, H-1man, J = 3.3
Hz), 7.87 (s, 1H, triazole-H). 13C NMR (CDCl3): δ 25.3, 25.7, 26.2, 26.3, 26.7, 27.2, 27.3, 28.2, 65.8, 67.9,
67.9, 70.3, 71.6, 71.8, 72.3, 73.7, 80.3, 80.7, 89.8, 97.4, 109.6 (double intensity), 110.2, 110.6, 114.8, 124.5,
145.6. APCI-MS (m/z) calcd: 583.3, found 584.3 (M+H). HRMS (M+Na) calcd: 606.2639, found:
606.2627. [α]D = -18.1˚ (c 5.0, CH2Cl2). Anal. Calcd for C27H41N3O11: C, 55.56; H, 7.08; N, 7.20. Found: C,
55.70; H, 7.26; N, 7.22.
1,4-Disubstituted bis(triazole) (20).
Mannofuranosyl azide (3) (0.292 g, 1.0 mmol), bis(alkyne) (16) (0.150 g, 0.56 mmol), (PPh3)3•CuBr (0.157
g, 0.17 mmol) and DBU (0.51 mL) were refluxed overnight in toluene (15 mL). After evaporation and
purification of the residue by chromatography (2:1 hexane : EtOAc), bis(triazole) (20) was isolated as a
colorless syrup (0.489 g, 57%). 1H NMR15 (CDCl3): δ 1.30, 1.34, 1.35 (3s, 9H total, 3 x -CH3), 1.40, 1.47
(2s, 12H total, 4 x -CH3), 1.56, 1.57, 1.64 (3s, 9H total, 3 x -CH3), 3.73 to 4.96 (several m, 23H total, 2 x
H-2 to H-6’man, H-2 to H-5’xyl, 3 x -OCH2), 5.90 (d, 1H, H-1xyl, J = 3.7 Hz), 6.07 (d, 1H, H-1man, J = 3.3 Hz),
6.09 (d, 1H, H-1man, J = 3.7 Hz), 7.87 (s, 1H, triazole-H), 7.89 (s, 1H, triazole-H). 13C NMR (CDCl3): δ 24.1
(double intensity), 25.1 (double intensity), 25.5 (double intensity), 26.3, 26.8, 27.0 (double intensity), 63.6,

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HETEROCYCLES, Vol. 65, No. 5, 2005
64.6, 66.7 (double intensity), 67.8, 72.5 (double intensity), 79.0, 79.1 (triple intensity), 79.2, 79.5 (double
intensity), 82.0, 82.1, 88.6, 104.9 (double intensity), 109.4 (double intensity), 111.5, 113.6 (double
intensity), 123.3, 123.4, 143.7, 144.1. APCI-MS (m/z) calcd: 836.38, found 837.3 (M+H). HRMS (M+Na)
calcd: 859.3701, found: 859.3705. [α]D = +11˚ (c 5.0, CH2Cl2).
ACKNOWLEDGEMENTS
The Graduate School at Youngstown State University is acknowledged for funding through the PACER
initiative. The National Institutes of Health (R15 AI053112-01) and Research Corporation (CC5400) are
thanked for funding. Purchase of the CCD X-ray diffractometer at Youngstown State was supported
through funding from NSF-CCLI grant number 0087210 and the Ohio Board of Regents Action Fund, grant
number CAP-491.
REFERENCES AND NOTES
1. R. Huisgen, R. Knorr, L. Moebius, and G. Szeimies, Chem. Ber., 1965, 98, 4014.
2. A. San-Felix, R. Alvarez, S. Velazquez, E. De Clerq, J. Balzarini, and M. J. Camarasa, Nucleosides
Nucleotides, 1995, 14, 595.
3. P. Norris, D. Horton, and B. R. Levine, Heterocycles, 1996, 43, 2643.
4. X. Zhu and R. R. Schmidt, J. Org. Chem., 2004, 69, 1081.
5. H. C. Kolb, M. G. Finn, and K. B. Sharpless, Angew. Chem., Int. Ed., 2001, 40, 2004; see also H. C.
Kolb and K. B. Sharpless, Drug Discovery Today, 2003, 8, 1128.
6. C. W. Tornøe, C. Christensen, and M. Meldal, J. Org. Chem., 2002, 67, 3057.
7. V. V. Rostovtsev, L. G. Green, V. V. Fokin, and K. B. Sharpless, Angew. Chem., Int. Ed., 2002, 41,
2596.
8. B. H. M. Kuijpers, S. Groothuys, A. R. Keereweer, P. J. L. M. Quaedflieg, R. H. Blaauw, F. L. van
Delft, and F. P. J. T. Rutjes, Org. Lett., 2004, 6, 3123.
9. F. Pérez-Balderas, M. Ortega-Muñoz, J. Morales-Sanfrutos, F. Hernández-Mateo, F. G. Calvo-Flores,
J. A. Calvo-Asín, J. Isac-García, and F. Santoyo-González, Org. Lett., 2003, 5, 1951.
10. R. M. Cicchillo and P. Norris, Carbohydr. Res., 2000, 328, 431.
11. J. Bogusiak, Pol. J. Chem., 2000, 74, 503.
12. For a related selective deprotection see: G. W. J. Fleet, J. Estevez, J. Burton, R. Estevez, H. Ardron, M.
Wormald, R. Dwek, and R. Brown, Tetrahedron: Asymmetry, 1998, 9, 2137.
13. U. J. Nilsson, E. J.-L. Fournier, and O. Hindsgaul, Bioorg. Med. Chem., 1998, 6, 1563.
14. SMART, Software for the CCD Detector System, version 5.625; Bruker Analytical X-Ray Instruments,
Inc.: Madison, WI, 2001. SAINT-Plus, Data Processing Software for the CCD Detector System,
version 6.22; Bruker Analytical X-Ray Instruments, Inc.: Madison, WI, 2001. Sheldrick, G.M.
SADABS, Software for Area Detector Absorptions and Other Corrections, version 2.03; University of

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Gőttingen: Germany, 2001. Sheldrick, G.M. SHELXTL NT, Software Package for the Refinement of
Crystal Structures, version 6.10; University of Gőttingen: Germany, 2000.
15. The following designations are used to explain the 1H NMR spectra of 18-20. For triazole (18), ringA =
N-glycosidic mannofuranose ring, ringB = O-glycosidic mannofuranose ring. For triazole (19), man =
mannofuranose ring, gal = galactopyranose ring. For triazole (20), man = mannofuranose ring, xyl =
xylofuranose ring.