Glucosamine- and galactosamine- based monosaccharides with highly fluorinated motifs

Article abstract of DOI:10.1016/j.jfluchem.2016.09.002

Synthesis of modified monosaccharides, derivatives of glucose and galactose, having a highly fluorinated chain, as a library of synthetic building blocks for hyaluronic acid (HA) modified subunits has been developed. “Click” chemistry has been employed as a strategy for the synthesis of these molecules. 1,2,3-triazole ring derivatives were obtained with good to excellent yields.

Full text of DOI:10.1016/j.jfluchem.2016.09.002

Journal of Fluorine Chemistry 191 (2016) 1–13
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Glucosamine- and galactosamine- based monosaccharides with highly
fluorinated motifs
*
Joanna Tomaszewska, Karolina Kowalska, Katarzyna Koroniak-Szejn
ꢀ
Faculty of Chemistry, Adam Mickiewicz University, ul. Umultowska 89b, 60-614 Poznan, Poland
A R T I C L E I N F O
A B S T R A C T
Article history:
Synthesis of modified monosaccharides, derivatives of glucose and galactose, having a highly fluorinated
chain, as a library of synthetic building blocks for hyaluronic acid (HA) modified subunits has been
developed. “Click” chemistry has been employed as a strategy for the synthesis of these molecules. 1,2,3-
triazole ring derivatives were obtained with good to excellent yields.
Received 3 May 2016
Received in revised form 30 August 2016
Accepted 2 September 2016
Available online 4 September 2016
ã 2016 Elsevier B.V. All rights reserved.
Keywords:
“Click”
Chemistry
Hyaluronic acid
Glucosamine hydrochloride
Galactosamine hydrochloride
Fluorinated azides
1. Introduction
Hyaluronan as a therapeutic can act on cancer cells. HA interacts
with cell surface receptors CD44 and RHAMM and regulates
Synthetically available carbohydrates are of urgent interest for
the development of carbohydrate-based drugs, new drug delivery
systems as well as new enzymes inhibitors. In the literature there
are described several natural polymers which were successfully
used in drug delivery application like: chitosan, dextran, cellulose,
alginic acid or collagen [1–3]. One of the polysaccharides of great
interest is hyaluronic acid (1) (HA) and its derivatives. First isolated
from the bovine vitreous body [4], HA is a high molecular weight,
natural, linear polysaccharide that consist of the repeating
proliferation, migration and cell adhesion. High molecular weight
HA can inhibit proliferation and migration of tumor cells or retard
cell migration and metastasis [7,8]. According to the literature, high
concentrations of hyaluronan occur in the tumor cells. It‘s caused
by the HA receptors (CD44 and RHAMM) which are overexpressed
by most malignant tumor cells. It makes HA an important molecule
for cancer targeted drug delivery systems since it could be
recognized by the specific target tissue. As highlighted previously,
HA is a polymer which consist of disaccharides. The various of
chemical groups provides appropriate sites to which drugs could
be conjugated e.g. the N-acetylglucosamine hydroxyl, the reducing
end, carboxylate in glucuronic acid or the acetyl groups (after
enzymatic removal). Such diversity of bonds in hyaluronic acid that
are biodegradable and hydrolysable makes the combination of this
biologically active molecule with potential drug delivery system
more promising [1,9–11].
As an example for HA-drug conjugate Paclitaxel, used to treat
cancers, can be distinguished. These two molecules, combined
together, form a prodrug where HA is a backbone for paclitaxel. By
this combination poor aqueous solubility of paclitaxel is overcome.
Additionally, HA-Paclitaxel is targeted directly to the cells where
HA receptors CD44 are overexpressed [12,13]. Another HA-
conjugates were synthesised e.g. HA with 5-fluorouracil and HA-
disaccharide subunit composed from 1 to 3 linked
b-2-acet-
amido-2-deoxy- -glucose- -glucuronic acid (Fig. 1).
D
b
-(1 !4)-
D
Moreover, it’s properties like biodegradability, biocompatibility
and viscoelasticity make HA a promising drug carrier [5,6].
Naturally occurring molecules are frequently used as starting
materials for drugs and drug delivery systems. The advantage of
synthetic approach is the possibility of changing its properties to
make them more selective, more effective or both. Thereby, an
emphasis on the synthesis of hyaluronic acid subunits and their
further use for the construction of certain complex structures is
made which can potentially act as drugs or drugs delivery
platforms in a modern medicine.
* Corresponding author.
E-mail address: katarzyna.koroniak@amu.edu.pl (K. Koroniak-Szejn).
http://dx.doi.org/10.1016/j.jfluchem.2016.09.002
0022-1139/ã 2016 Elsevier B.V. All rights reserved.

2
J. Tomaszewska et al. / Journal of Fluorine Chemistry 191 (2016) 1–13
NaN3, HMPA
85 °C, 4.5h
OH
CF3(CF)x(CH2)yN3
x= 5 or 6 y= 1 or 2
CF3(CF)x(CH2)yOTs
HOOC
HO
x= 5 or 6 y= 1 or 2
O
O
HO
O
O
NaN3, HMPA
OH
NHAc
H(CF)xCH2OTs
H(CF)xCH2N3
x= 4 or 10
n
85 or 120 °C, 4.5h
x= 4 or 10
1
Aliquat336
Fig. 1. Hyaluronic Acid.
CF3(CF2)x(CH2)yI
x= 5-7,9
CF3(CF2)x(CH2)yN3
Et2O/H2O
80 °C, 18h
x= 5-7,9
y= 1-3
Camphotecin 20-(S). Both compounds shows antitumor activity
and are used successfully as an anticancer agent [5,14,15].
On the other hand, growing interest of fluorine and fluorinated
products has encouraged the researches for the search of novel and
improved methodologies for preparation of new compounds
having fluorinated motifs. The long chain of fluorinated fragment
attached to the parent molecule improved its lipophilicity, and also
quite often its stability. In many cases the incorporation of fluorine
to molecules depends on unique properties of this element. We can
replace a hydrogen atoms by fluorine because a small size of
fluorine atom could not change steric size of molecule and the CꢀꢀF
bond is stronger than CꢀꢀH bond [16,17].
y= 1-3
Scheme 1. Preparation of fluorinated azides [30–41].
HF2C(F2C)x
Br
O
HCF2(CF2)xCH2OH
x= 3 or 9
NaOH, THF,
RT
x= 3 or 9
It is worth to mention that some glycosides with perfluoroalkyl
chains were tested by Hatanaka et al. [18,19] as a substrate for
oligosaccharide biosynthesis. The results of the study showed that
the presence of fluorine atoms in saccharide did not cause of
toxicity and did not have any damaging effects on the cells.
Hatanaka showed that fluorous-tagged saccharide could be used
via biosynthetic method. Additionally, higher fluorine content is
responsible that the glycosides are more hydrophobic. This results
indicate interesting possibilities of application fluorine-containing
carbohydrates. [18,19]. However, they decided to investigate
cytotoxicity and cellular uptake of some perfluorocarboxylic acid
with various chain length from C(6) to C(10). The research suggest
that cytotoxicity increased with increasing of perfluoroalkyl chain
length. Besides, long-chained acids have stronger affinity to the cell
membrane than short-chained acids which in cells were much less.
In this case the reason may be high fluorine content [20].
Miethchen [21] mentioned in his work that neutral and non toxic
head groups of perfluoroalkylated carbohydrates can represent
binding sites for bio-receptors, what is very important information
for biomedical uses of fluorinated saccharides. Carbohydrate-
based fluorocompounds indicate interesting possibilities of
applications e.g. surfactants or liquid crystals [22].
Br
CF3(CF2)x(CH2)yOH
F3C(F2C) x
O
NaO H, THF,
RT
x= 5 or 6
y= 1 or 2
x= 5 or 6
y= 1 or 2
Scheme 2. Preparation of fluorinated propargyl ethers [21,43].
derivatives. It is documented that introduction into the molecule
1,2,3-triazole ring can mimic peptide bond which is naturally
occurring bond in our body [25,26]. Undoubtedly, click chemistry
impact on drug discovery in recent years has increased due to the
mild reaction conditions, chemoselectivity and good or excellent
reaction yields [27]. The “click” chemistry has become an efficient
tools for different modifications and bioconjugations. This reaction
are widely used in polysaccharides [28,29].
There are many contributions describing the access to highly
fluorinated azides [30–41] as well as fluorinated propargyl ethers
[42,43], nevertheless their synthetic preparation sometimes might
be challenging. The synthesis of such species is relatively well
documented, however especially fluorinated azides, with per-
fluorinated or highly fluorinated groups, are sometimes tricky to be
prepared. This is due to the presence of fluorine in reacting
molecule, what causes significant change in reactivity and other
properties. In general fluorinated alkyl azides were obtained from
tosylates or iodides in SN2 reaction with sodium azide according to
known or slightly modified procedures [30–41]. Various azides
with different linkers –CH2– between an azido moiety and
fluoroalkylated chain were prepared via known or slightly
modified methodologies (Scheme 1).
A fluorinated propargyl ethers have been obtained from
corresponding fluorinated alcohols and propargyl bromide
(Scheme 2) [42,43].
In this paper we would like to report our studies on preparation
of a library of modified monosaccharides as potential HA subunits
using as a parent compound 1-O-propargyl modified glucosamine
reacting with highly fluorinated azides. The second series of
molecules are “click” products of glucosamine and galactosamine
derived azides with highly fluorinated propargyl ethers.
The starting tetraacetylated saccharides are well known and
2. Results and discussion
Combination of these two previously mentioned features gives
us a rise to develop a synthetic pathway of monosaccharides as
building blocks for HA modified subunits having highly fluorinated
chain attached to the parent carbohydrate with 8, 13, 15, 17 or
21 fluorine atoms. Our concept was to develop the synthetic
method for the synthesis of model monosaccharides and in the
next step use it for the synthesis of hyaluronic acid subunits. One of
the common modification approach is a strategy using copper
catalyzed 1,3 dipolar cycloaddition reaction known as “click”
chemistry introduced by Sharpless [23] or Meldal [24]. To do this, a
modification of a monosaccharide (building block for HA subunit)
is required and next appropriate fluorinated azide (with 13, 15, 17,
21 fluorine atoms) (Scheme 1) or propargyl ether (with 8, 13, 15,
21 fluorine atoms) (Scheme 2) could be attached to the molecule
via “click” strategy (Scheme 3). In this paper we would like to
present our results on synthesis of such new modified units based
on glucosamine hydrochloride and galactosamine hydrochloride
can be prepared from d-glucosamine hydrochloride or
amine hydrochloride in few steps [44,45]. Preparative
D-galactos-

J. Tomaszewska et al. / Journal of Fluorine Chemistry 191 (2016) 1–13
3
Scheme 3. Synthesized monosaccharides with highly fluorinated motifs.
methodologies leading to insertion of azidoacetylo moiety on
glucosamine or galactosamine hydrochloride are already known in
literature, however it is worth to note that the synthesis of 1,3,4,6-
conditions with the use of CuSO4 and sodium ascorbate (NaASC)
and led us to the library of desired products 9-12, 15–18 with very
good yields (Table 1). In each case we had also performed the
reaction with non-fluorinated reagent 3 and 20 yielding non-
fluorinated triazole derivatives 8 and 14 in order to compare the
reaction scope.
tetra-O-acetyl-N-azidoacetylo-
ra-O-acetyl-N-azidoacetylo- -galactosamine (13) leads in our case
selectively to pure anomer . In the literature there are different
D-glucosamine (2) and 1,3,4,6-tet-
D
b
contributions describing mostly the synthesis of these sugars as
mixtures of anomers (typically 1:1) [46–49], only in few cases
Next, the second set of compounds 26-31 was prepared in the
reactions of monosaccharide with propargyl moiety 19 and non-
fluorinated azide 20 or highly fluorinated azides 21-25. The
starting saccharide 19 was prepared from 1,3,4-tetra-O-acetylo-2-
exclusively anomers
b [50,51]. Our synthesis of pure b anomer is
relatively simple and straitghforwad and uses tetraacetylated
glucosamine and galactosamine hydrochlorides as well as azido-
acetic acid as starting materials and DCC as coupling reagent
(Scheme 4).
The first group of modified monosaccharides we have used as a
parent compound are different azides – derivatives glucosamine 2
and galactosamine hydrochlorides 13. The “click” reactions of
monosaccharides with azido group and highly fluorinated
propargyl ethers (4-7) were performed under standard Sharpless
deoxy-3-trichloroacetamido-b-D-glucopyranoside with propargyl
alcohol and boron trifluoroetherate according to known procedure
[52]. These reactions, however, were performed under Meldal
conditions with the use of CuI as a catalyst (Table 2). Nevertheless,
the reactionyields are much lower compared to the “click” reaction
between azidosugar and fluorinated propargyl ether described
above (Table 1). Reactions performed under Sharpless conditions
were also successful and yielded desired products, however
workup and purification was troublesome and product isolation
was very difficult, sometimes not possible.
In sugar chemistry in multistage reactions it‘s necessary to use
corresponding protecting groups. For all prepared in this paper
acetylated compounds with 1,2,3-triazole ring and partially
fluorinated alkyl chains it‘s possible the deprotection reaction of
the acetates protecting groups. In this reaction using solution of
sodium methoxide in MeOH the reaction yields are quite good.
Below, we would like to present our results on deprotection
reaction for some selected acetylated compounds 8, 12, 14, 18, 26,
27 (Table 3).
3. Conclusions
Herein we have presented the synthesis of a library of modified
monosaccharides with 1,2,3-triazole ring having highly fluorinated
aliphatic chain. All compounds were prepared via “click” reaction
with good yields. Two different “click” reaction methodologies has
been used: Sharpless or Meldal conditions.
Scheme 4. Insertion of azidoacetylo moiety on peracetylated glucosamine or
peracetylated galactosamine hydrochloride yielding
b products 2 and 13.

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J. Tomaszewska et al. / Journal of Fluorine Chemistry 191 (2016) 1–13
Table 1
“Click” reaction of azidosaccharides 2, 13 with propargyl ethers 3-7a.
L.P
1.
Starting material
Propargyl ether
Product
Reaction Yield%
91
2
2
2
2
2
3
4
5
6
7
8
2.
3.
4.
5.
6.
87
91
88
93
99
9
10
11
12
13
3
14

J. Tomaszewska et al. / Journal of Fluorine Chemistry 191 (2016) 1–13
5
Table 1 (Continued)
L.P
7.
Starting material
Propargyl ether
Product
Reaction Yield%
80
13
13
13
13
4
15
16
17
18
8.
76
89
99
5
6
7
9.
10.
a
Reactions conditions: CuSO4, NaASC, tBuOH/H2O, rt.
4. Experimental section
AJS ESI source. Optical rotations of sugars were measured with
JASCO P-2000 at 20 ꢁ 0.05 ꢂC, D values were determined at 589 nm
All chemicals were reagent grade and used as purchased
without further purification. Anhydrous DCM was prepared by pre-
drying with anhydrous CaCl2 followed by distillation over CaH2
under argon atmosphere. Thin-layer chromatography (TLC) was
carried out on silica gel plates (Silica gel 60, F254, Merck) with
detection by UV light or with stain solution (Cerium Molybdate
Stain and Potassium Permanganate). Purification was performed
with column chromatography using normal-phase silica gel (Silica
gel 60, 70–230 mesh, Fluka). 1H, 13C, 19F NMR were recorded with a
Varian VNMR-S 400 MHz, VARIAN Mercury 300 MHz or Bruker
Avance 600 MHz, Bruker ASCEND 600 (600 MHz). Chemical shifts
in MeCN, DCM or DMSO as a solvent. [a]D values are given in
degrees. Melting points were measured with MEL-TEMP1
apparatus.
4.1. Propargyl-3,4,6-tri-O-acetyl-2-deoxy-2-trichloracetamido-
b-D-
glucopyranoside 19
BF3xOEt2 (19.3 mL,152.52 mmol) and propargyl alcohol (9.6 mL,
162.40 mmol) were added to a stirring solution of 1,3,4,6-tetra-O-
acetyl-2-deoxy-2-trichloroacetamido-b-D-glucopyranoside
(5.00 g, 10.15 mmol) in anhydrous DCM (20 mL), under an argon
atmosphere, at room temperature. The reaction mixture was
stirred for 48 h. It was subsequently diluted with EtOAc (100 mL)
and washed with sat. NaHCO3 (2 ꢃ100 mL). The organic phase was
dried over Na2SO4 and concentrated to dryness. The crude product
was purified by column chromatography (Hex:EtOAc 2:1, v/v) and
afforded 19 as a white solid; yield 2.85 g (56%); mp 139–143 ꢂC;
are reported as d values (ppm). NMR spectra were calibrated using
an internal reference: TMS (1H), CDCl3 (13C) and CFCl3 (19F). Spectra
were recorded in deuterated solvents CDCl3 (7.26 ppm (1H) or
77.0 ppm (13C)), CD3CN (1.93 (1H) or 118.2 (13C)) and (CD3)2SO
(2.49 ppm (1H) or 39.5 ppm (13C)). Multiplicities of signals are
described as follows: s = singlet, d = doublet, dd = doublet of
doublets, ddd = doublet of doublet of doublets, t = triplet, td =
triplet of doublets, tt = triplet of triplets, m = multiplet. Coupling
constants (J) are given in hertz (Hz). Mass spectra (ESI) were
carried out with TripleTOF1 5600 + System, AB SCIEX and Agilent
1200 LC system with Agilent Q-TOF 6540 spectrometer with DUAL
[
a
]D = ꢀ10.06 (c 1.05, MeCN); 1H NMR (403 MHz, CDCl3):
d 6.82 (d,
1H, J = 9.0 Hz, NH), 5.38 (dd, 1H, J = 9.3 Hz, J = 10.7 Hz, H-3), 5.14 (t,
1H, J = 9.6 Hz, H-4), 4.91 (d,1H, J = 8.4 Hz, H-1), 4.40 (d, 2H, J = 2.4 Hz,
CH2ꢀꢀCRC), 4.31 (dd, 1H, J = 4.7 Hz, J = 12.4 Hz, H-6a), 4.17 (dd, 1H,
J = 2.4 Hz, J = 12.4 Hz, H-6b), 4.07-3.99 (m, 1H, H-2), 3.77 (ddd, 1H,

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J. Tomaszewska et al. / Journal of Fluorine Chemistry 191 (2016) 1–13
Table 2
“Click” reaction of monosaccharides with propargyl moiety 19 with non-fluorinated azide 20 and fluorinated azides 21-25a.
L.P
1.
Starting material
Azide
Product
Reaction Yield%
76
19
20
26
2.
91
19
21
27
3.
56
19
22
28
4.
56
19
23
29

J. Tomaszewska et al. / Journal of Fluorine Chemistry 191 (2016) 1–13
7
Table 2 (Continued)
L.P
5.
Starting material
Azide
Product
Reaction Yield%
34
19
24
30
6.
38
19
Reaction conditions: CuI, Et3N, MeCN/H2O, rt.
25
31
a
J = 2.4 Hz, J = 4.7 Hz, J = 9.9 Hz, H-5), 2.46 (t, 1H, J = 2.4 Hz, RCH),
by DCC (2.15 g, 10.44 mmol) and 2-azidoacetic acid (2.11 g,
20.88 mmol). The reaction mixture was allowed to warm up to
room temperature and stirred overnight. After finishing the
precipitate was filtered and the solvents were evaporated. Product
was purified by column chromatography (Hex:EtOAc 1:1, v/v) or
crystallization EtOAc/CCl3/Hex gave 13 as white solid; yield 1.4 g
2.11 (s, 3H, OAc), 2.05 (s, 3H, OAc), 2.04 (s, 3H, OAc); 13C NMR
(101 MHz, CDCl3):
d 170.9, 170.6, 169.2, 162.0, 97.9, 92.2, 78.1, 75.7,
72.2, 71.5, 68.2, 61.8, 56.1, 55.6, 20.7, 20.6, 20.5; MS (ESI) m/z [M
+Na]+ calcd for C17H20Cl3NNaO9: 510.0102; found: 510.0094.
4.2. 1,3,4,6-Tetra-O-acetyl-N-azidoacetylo-
b
-D-glucosamine 2
(63%); mp 120–124 ꢂC; [
(403 MHz, CDCl3): 6.52 (d, 1H, J = 9.4 Hz, NH), 5.84 (d, 1H,
a
]D = +17.04 (c 1.06, DCM); 1H NMR
d
A solution of 2-deoxy-2-amino-1,3,4,6-tetra-O-acetyl-
b
-
D
-glu-
J = 8.8 Hz, H-1), 5.41 (d, 1H, J = 2.9 Hz, H-3), 5.26 (dd, 1H, J = 3.3 Hz,
J = 11.3 Hz, H-4), 4.41–4.33 (m, 1H, H-2), 4.21–4.07 (m, 3H, H-6a, H-
6b, H-5), 3.93 (s, 2H, CH2N3), 2.18 (s, 3H, OAc), 2.14 (s, 3H, OAc), 2.06
copyranosyl hydrochloride (2 g, 5.22 mmol) in anhydrous DCM
(40 mL) was cooled to 0 ꢂC. Next Et3N (1.06 mL) was added followed
by DCC (3.82 g, 18.56 mmol) and 2-azidoacetic acid (3.75 g,
37.1 mmol). The reaction mixture was allowed to warm up to
room temperature and stirred overnight. After finishing the
precipitate was filtered and the solvents were evaporated. Product
was purified by column chromatography (Hex:EtOAc 1:1, v/v) or
crystallization EtOAc/CCl3/Hex gave 2 as white solid; yield 1.79 g
(s, 3H, OAc), 2.03 (s, 3H, OAc); 13C NMR (75 MHz, CDCl3):
d 170.5,
170.4, 170.1, 169.4, 167.3, 92.5, 71.8, 69.9, 66.3, 61.3, 52.6, 50.0, 33.7,
20.8, 20.6, 20.6; MS (ESI) m/z [M+Na]+ calcd for C16H22N4NaO10
:
453.1234; found: 453.1232.
4.4. General procedure for the click reaction of sugar azides: N-
azidoacetylo-b-D-glucopyranoside 2 and N-azidoacetylo-b-D-
galactopyranoside 13
(82%); mp 113–117 ꢂC; [
(403 MHz, CDCl3): 6.65 (d, 1H, J = 9.4 Hz, NH), 5.81 (d, 1H,
a
]D = +16.14 (c 1.02, DCM); 1H NMR
d
J = 8.7 Hz, H-1), 5.30 (dd, 1H, J = 9.3 Hz, J = 10.5 Hz, H-3), 5.14 (t, 1H,
J = 9.6 Hz, H-4), 4.29 (dd, 1H, J = 2.8 Hz, J = 10.6 Hz, H-6a), 4.28-4.22
(m, 1H, H-2), 4.14 (dd, 1H, J = 2.3 Hz, J = 12.5 Hz, H-6b), 3.92 (s, 2H,
CH2N3), 3.88 (ddd, 1H, J = 2.3 Hz, J = 4.7 Hz, J = 10.0 Hz, H-5), 2.12 (s,
1,3,4,6-Tetra-O-acetyl-N-azidoacetylo-
(1 equiv) or 1,3,4,6-tetra-O-acetyl-N-azidoacetylo-D-galactos-
amine (13) (1 equiv) and octyne (3) (1.5 equiv) or corresponding
propargyl ether (4-7) (1.5 equiv) were dissolved in the mixture of t-
BuOH/H2O (1:1, v/v, 7 mL for 1 mmol of sugar). To the reaction
mixture 1 M aq. solution of NaASC (0.1 equiv) and 1 M aq. solution
b
-
D
-glucosamine
(2)
3H, OAc), 2.10 (s, 3H, OAc), 2.06 (s, 3H, OAc), 2.05 (s, 3H, OAc); 13
C
NMR (101 MHz, CDCl3): d 171.0, 170.6, 169.3, 169.3, 167.1, 92.1, 72.8,
72.1, 67.8, 61.6, 53.0, 52.5, 20.8, 20.7, 20.6, 20.5; MS (ESI) m/z [M
+Na]+ calcd for C16H22N4NaO10: 453.1234; found: 453.1234.
of CuSO4 5H2O (0.1 equiv) were added and stirred at room
ꢄ
temperature for 24 h. The mixture was dissolved in H2O (2–4 mL)
and extracted with Et2O (3 ꢃ 4 mL). Organic phases were combined
and washed with 1N HCl (4 mL) and dried over Na2SO4. Solvent was
evaporated. The crude product was purified by column chroma-
tography (Hex:EtOAc 1:1, v/v) to afford desired products
8,9,10,11,12,14,15,16,17,18.
4.3. 1,3,4,6-Tetra-O-acetyl-N-azidoacetylo-D-galactosamine 13
A solution of 2-deoxy-2-amino-1,3,4,6-tetra-O-acetyl-
b-D-gal-
actopyranosyl hydrochloride (2 g, 5.22 mmol) in anhydrous DCM
(40 mL) was cooled to 0 ꢂC. Next Et3N (1.06 mL) was added followed

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J. Tomaszewska et al. / Journal of Fluorine Chemistry 191 (2016) 1–13
Table 3
The deprotection reactions for selected acetylated sugars after “click” reaction 8, 12, 14, 18, 26, 27a.
L.P
1.
Starting material
Product
Reaction Yield%
79
8
32
2.
70
12
33
3.
70
14
34
4.
82
18
35
5.
61
26
36
6.
85
27
Reaction conditions: DCM:MeOH (3:7, v/v), NaOMe 25 wt.% in MeOH, rt.
37
a

J. Tomaszewska et al. / Journal of Fluorine Chemistry 191 (2016) 1–13
9
4.4.1. 1-(1,3,4,6-Tetra-O-acetyl-2-azidoacetamido-2-deoxy-
b
-D-
4.4.4. 1-(1,3,4,6-Tetra-O-acetyl-2-azidoacetamido-2-deoxy-b-D-
glucopyranosyl)-4-hexyl-1H-1,2,3-triazole 8
glucopyranosyl)-4-(2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-
1,3,4,6-Tetra-O-acetyl-2-azidoacetamido-2-deoxy-
b
-
D
-gluco-
pentadecafluoroheptylmethoxy)methyl-1H-1,2,3-triazole 11
1,3,4,6-Tetra-O-acetyl-2-azidoacetamido-2-deoxy- -gluco-
pyranoside (2) (0.091 g, 0.212 mmol) and 1-octyne (3) (0.035 g,
0.318 mmol) gave 8 as a white solid; yield 0.094 g (82%); mp 172–
b-D
pyranoside (2) (0.108 g, 0.269 mmol) and 3-((1-perfluoroheptyl)
methoxy)prop-1-yne (6) (0.177 g, 0.404 mmol) gave 11 as a white
solid; yield 0.179 g (88%); mp 192–195 ꢂC; [a]D = +9.97 (c 0.85,
175 ꢂC; [a]D = +12.98 (c 1.02, DCM); 1H NMR (403 MHz, CDCl3):
d
7.41 (s, 1H, triazole-H), 6.79 (d, 1H, J = 8.9 Hz, NH), 5.89 (d, 1H,
J = 8.7 Hz, H-1), 5.35 (dd, 1H, J = 9.4 Hz, J = 10.4 Hz, H-3), 5.09 (t, 1H,
J = 9.6 Hz, H-4), 4.96 (d, 2H, J = 3.7 Hz, CH2triazole), 4.28 (dd, 1H,
J = 4.6 Hz, J = 12.5 Hz, H-6a), 4.14–4.04 (m, 2H, H-6b, H-2), 3.86 (ddd,
1H, J = 2.2 Hz, J = 4.5 Hz, J = 10.0 Hz, H-5), 2.71 (t, 2H, J = 7.6 Hz,
triazoleCH2), 2.08 (s, 3H, OAc), 2.07 (s, 3H, OAc), 2.03 (s, 3H, OAc),
1.97 (s, 3H, OAc), 1.71-1.61 (m, 2H, triazole-CH2CH2), 1.40–1.24 (m,
6H, (CH2)3), 0.88 (t, 3H, J = 6.9 Hz, CH3); 13C NMR (101 MHz, CDCl3):
MeCN); 1H NMR (600 MHz, CD3CN):
d 7.80 (s, 1H, triazole-H), 6.79
(d, 1H, J = 9.2 Hz, NH), 5.84 (d, 1H, J = 8.8 Hz, H-1), 5.29 (dd, 1H,
J = 9.4 Hz, J = 10.7 Hz, H-3), 5.01 (dd, 1H, J = 9.4 Hz, J = 10.4 Hz, H-4),
4.99 (s, 2H, CH2triazole), 4.75 (s, 2H, triazoleCH2O), 4.20 (dd, 1H,
J = 4.6 Hz, J = 12.5 Hz, H-6a), 4.13 (t, 2H, J = 14.4 Hz, H-6b, H-2), 4.07–
4.02 (m, 2H, OCH2(CF2)6CF3), 3.92 (ddd, 1H, J = 2.4 Hz, J = 4.8 Hz,
J = 10.1 Hz, H-5), 2.04 (s, 3H, OAc), 2.00 (s, 3H, OAc),1.98 (s, 3H, OAc),
d
170.6, 170.5, 169.3, 169.1, 165.9, 149.1, 122.1, 91.7, 72.6, 71.8, 67.9,
1.95 (s, 3H, OAc); 13C NMR (101 MHz, CD3CN):
d 171.1, 171.0, 170.4,
61.6, 53.8, 53.0, 31.5, 29.2, 28.9, 25.6, 22.5, 20.8, 20.7, 20.5, 14.0; MS
169.9, 166.9, 144.0, 126.2, 120.0-107.7, 92.4, 73.2, 72.5, 69.0, 67.2,
(ESI) m/z [M+H]+ calcd for C24H37N4O10
: 541.2509; found:
65.8, 62.5, 53.8, 52.9, 20.9, 20.79, 20.78, 20.75; 19F NMR (379 MHz,
541.2503; m/z [M+Na]+ calcd for C24H36N4NaO10: 563.2330; found:
CD3CN):
d
ꢀ80.33, ꢀ118.92, ꢀ121.31, ꢀ121.98, ꢀ122.55, ꢀ125.40;
563.2299.
MS (ESI) m/z [M+H]+ calcd for C27H28F15N4O11: 869.1515; found:
869.1512; m/z [M+Na]+ calcd for C27H27F15N4NaO11: 891.1335;
found: 891.1333.
4.4.2. 1-(1,3,4,6-Tetra-O-acetyl-2-azidoacetamido-2-deoxy-b-D-
glucopyranosyl)-4-(2,2,3,3,4,4,5,5-octafluorobutylmethoxy)methyl-
1H-1,2,3-triazole 9
4.4.5. 1-(1,3,4,6-Tetra-O-acetyl-2-azidoacetamido-2-deoxy-
glucopyranosyl)-4-(2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10-
eicosafluorononylmethoxy)methyl-1H-1,2,3-triazole 12
b-D-
1,3,4,6-Tetra-O-acetyl-2-azidoacetamido-2-deoxy-b-D-gluco-
pyranoside (2) (0.170 g, 0.395 mmol) and 3-((1-octafluorobutyl)
methoxy)prop-1-yne (4) (0.160 g, 0.593 mmol) gave 9 as a white
1,3,4,6-Tetra-O-acetyl-2-azidoacetamido-2-deoxy-b-D-gluco-
solid; yield 0.241 g (87%); mp 164–166 ꢂC; [
a
]D = +12.84 (c 0.99,
pyranoside (2) (0.150 g, 0.349 mmol) and 3-((1-eicosafluorode-
canyl)methoxy)prop-1-yne (7) (0.299 g, 0.524 mmol) gave 12 as a
MeCN); 1H NMR (400 MHz, CDCl3):
d 7.76 (s, 1H, triazole-H), 6.94
(d, 1H, J = 9.1 Hz, NH), 6.07 (tt, 1H, J = 5.5 Hz, J = 51.9 Hz, HCF2), 5.89
(d, 1H, J = 8.7 Hz, H-1), 5.35 (dd, 1H, J = 9.4 Hz, J = 10.4 Hz, H-3), 5.11
(dd, 1H, J = 9.4 Hz, J = 10.4 Hz, H-4), 5.04 (d, 2H, J = 5.3 Hz,
triazoleCH2O), 4.82 (s, 2H, CH2triazole), 4.28 (dd, 1H, J = 4.6 Hz,
J = 12.5 Hz, H-6a), 4.24-4.14 (m, 1H, H-2), 4.15–4.03 (m, 3H, H-6b,
OCH2(CF2)3CF2H), 3.89 (ddd, 1H, J = 2.2 Hz, J = 4.6 Hz, J = 10.0 Hz, H-
5), 2.09 (s, 3H, OAc), 2.08 (s, 3H, OAc), 2.04 (s, 3H, OAc), 1.98 (s, 3H,
white solid; yield 0.325 g (93%); mp 197–199 ꢂC; [
a
]D = +9.01 (c
1.02, MeCN); 1H NMR (600 MHz, CD3CN):
d 7.80 (s, 1H, triazole-H),
6.80 (d, 1H, J = 9.2 Hz, NH), 6.47 (tt, 1H, J = 51.0 Hz, J = 5.1 Hz, HCF2),
5.84 (d, 1H, J = 8.8 Hz, H-1), 5.29 (dd, 1H, J = 9.4 Hz, J = 10.7 Hz, H-3),
5.01 (dd, 1H, J = 9.4 Hz, J = 10.4 Hz, H-4), 4.98 (s, 2H, CH2triazole),
4.75 (s, 2H, triazoleCH2O), 4.20 (dd, 1H, J = 4.8 Hz, J = 12.5 Hz, H-6a),
4.12 (t, 2H, J = 14.3 Hz, H-6b, H-2), 4.07-4.01 (m, 2H,
OCH2(CF2)9CF2H), 3.91 (ddd, 1H, J = 2.4 Hz, J = 4.8 Hz, J = 10.1 Hz,
H-5), 2.05 (s, 3H, OAc), 2.00 (s, 3H, OAc), 1.98 (s, 3H, OAc), 1.95 (s,
OAc); 13C NMR (101 MHz, CDCl3):
144.3, 124.5, 118.4-104.5, 91.9, 72.7, 72.1, 68.0, 67.0, 65.5, 61.6, 53.7,
d 171.0, 170.7, 169.4, 169.3, 165.5,
53.1, 20.8, 20.7, 20.5, 20.5; 19F NMR (377 MHz, CDCl3):
d
ꢀ119.79,
3H, OAc); 13C NMR (151 MHz, CD3CN):
168.5, 145.7, 127.7, 118.7-108.2, 94.0, 74.9, 74.1, 70.7, 60.9, 67.5, 64.1,
55.5, 54.6, 22.5, 22.4, 22.4, 22.3; 19F NMR (282 MHz, CD3CN):
d 172.7, 172.5, 171.9, 171.5,
ꢀ125.52, ꢀ130.21, ꢀ137.30; MS (ESI) m/z [M+H]+ calcd for
C
24H29F8N4O11: 701.1705; found: 701.1702; m/z [M+Na]+ calcd
d
for C24H28F8N4NaO11: 723.1525; found: 723.1523.
ꢀ118.97, ꢀ121.09, ꢀ121.33, ꢀ122.58, ꢀ128.74, ꢀ137.66, ꢀ137.82; MS
(ESI) m/z [M+Na]+ calcd for C30H28F15N4NaO11: 1023.1333; found:
1023.1334.
4.4.3. 1-(1,3,4,6-Tetra-O-acetyl-2-azidoacetamido-2-deoxy-
b-D-
glucopyranosyl)-4-(3,3,4,4,5,5,6,6,7,7,8,8,8-
tridecafluorohexylethoxy)methyl-1H-1,2,3-triazole 10
4.4.6. 1-(1,3,4,6-Tetra-O-acetyl-2-azidoacetamido-2-deoxy-
b-D-
1,3,4,6-Tetra-O-acetyl-2-azidoacetamido-2-deoxy-b-D-gluco-
galactopyranosyl)-4-hexyl-1H-1,2,3-triazole 14
pyranoside (2) (0.120 g, 0.279 mmol) and 3-((2-perfluorohexyl)
ethoxy)prop-1-yne (5) (0.168 g, 0.419 mmol) gave 10 as a white
solid; yield 0.212 g (91%); mp 159–164 ꢂC; [a]D = +10.48 (c 1.05,
1,3,4,6-Tetra-O-acetyl-2-azidoacetamido-2-deoxy-b-D-galacto-
pyranoside (13) (0.055 g, 0.128 mmol) and octyne (3) (0.021 g,
0.192 mmol) gave 14 as a white solid; yield 0.068 g (99%); mp 169–
MeCN); 1H NMR (400 MHz, CDCl3):
d
7.69 (s, 1H, triazole-H), 6.62
172 ꢂC; [a]D = +13.95 (c 1.04, DCM); 1H NMR (403 MHz, CDCl3):
d
(d, 1H, J = 9.0 Hz, NH), 5.88 (d, 1H, J = 8.7 Hz, H-1), 5.32 (dd, 1H,
J = 9.4 Hz, J = 10.4 Hz, H-3), 5.12 (t, 1H, J = 9.6 Hz, H-4), 5.02 (d, 2H,
J = 3.3 Hz, triazoleCH2O), 4.70 (s, 2H, CH2triazole), 4.29 (dd, 1H,
J = 4.6 Hz, J = 12.5 Hz, H-6a), 4.18–4.09 (m, 2H, H-6b, H-2), 3.87 (t,
2H, J = 6.7 Hz, OCH2CH2), 2.45 (m, 2H, CH2(CF2)5CF3), 2.10 (s, 6H,
OAc), 2.05 (s, 3H, OAc), 2.00 (s, 3H, OAc); 13C NMR (101 MHz,
7.47 (s, 1H, triazole-H), 7.21 (d, 1H, J = 8.7 Hz, NH), 5.92 (d, 1H,
J = 8.8 Hz, H-1), 5.37 (d, 1H, J = 3.4 Hz, H-3), 5.33 (dd, 1H, J = 3.4 Hz,
J = 11.1 Hz, H-4), 4.97 (s, 2H, CH2-triazole), 4.35-4.23 (m, 1H, H-2),
4.17–4.06 (m, 3H, H-6a, H-6b, H-5), 2.70 (t, 2H, J = 7.6 Hz,
triazoleCH2), 2.15 (s, 3H, OAc), 2.06 (s, 3H, OAc), 2.03 (s, 3H,
OAc),1.93 (s, 3H, OAc),1.70–1.60 (m, 2H, triazoleCH2CH2), 1.40-1.24
(m, 6H, (CH2)3), 0.89 (t, 3H, J = 6.9 Hz, CH3); 13C NMR (101 MHz,
CDCl3):
d 171.0, 170.7, 169.4, 169.3, 165.7, 145.2, 124.1, 121.7-105.1,
91.8, 72.6, 72.1, 68.1, 64.4, 62.6, 61.7, 53.5, 53.1, 31.3, 20.8, 20.7, 20.5,
CDCl3):
d 170.3, 170.3, 170.1, 169.3, 166.1, 149.0, 122.1, 92.2, 71.6,
20.5; 19F NMR (377 MHz, CDCl3):
d
ꢀ80.87, ꢀ113.47, ꢀ121.95,
69.7, 66.4, 61.3, 52.1, 50.3, 33.9, 31.5, 29.2, 28.9, 25.5, 22.5, 20.8,
ꢀ122.94, ꢀ123.73, ꢀ126.21; MS (ESI) m/z [M+H]+ calcd for
20.6, 20.5, 14.0; MS (ESI) m/z [M+H]+ calcd for C24H37N4O10
541.2509; found: 541.2500; m/z [M+Na]+ calcd for C24H36N4NaO10
563.2329; found: 563.2297.
:
:
C
27H30F13N4O11: 833.1703; found: 833.1699; m/z [M+Na]+ calcd
for C27H29F13N4NaO11: 855.1523; found: 855.1519.

10
J. Tomaszewska et al. / Journal of Fluorine Chemistry 191 (2016) 1–13
4.4.7. 1-(1,3,4,6-Tetra-O-acetyl-2-azidoacetamido-2-deoxy-
b
-D-
eicosafluorodecanyl)methoxy)prop-1-yne
(7)
(0.128 g,
galactopyranosyl)-4-(2,2,3,3,4,4,5,5-octafluorobutylmethoxy)
methyl-1H-1,2,3-triazole 15
0.225 mmol) gave 18 as a white solid; yield 0.150 mg (99%); mp
192–196 ꢂC; [a]D = +23.49 (c 1.05, DMSO); 1H NMR (403 MHz,
1,3,4,6-Tetra-O-acetyl-2-azidoacetamido-2-deoxy-
b-D
-galac-
DMSO-d6): d 8.64 (d,1H, J = 9.3 Hz, NH), 8.08 (s,1H, triazole-H), 7.22
topyranoside (13) (0.060 g, 0.15 mmol) and 3-((1-octafluorobutyl)
methoxy)prop-1-yne (4) (0.060 g, 0.225 mmol) gave 15 as a
(tt, 1H, J = 5.2 Hz, J = 50.1 Hz, HCF2), 5.71 (d, 1H, J = 8.8 Hz, H-1), 5.28
(d, 1H, J = 2.7, H-3), 5.13 (dd, 1H, J = 3.4 Hz, J = 11.3 Hz, H-4), 4.09 (s,
2H, triazoleCH2O), 4.82 (s, 2H, CH2triazole), 4.32-4.18 (m, 2H, H-6a,
H-6b), 4.18-4.10 (m, 1H, H-2), 4.09-3.97 (m, 2H, H-5,
CH2(CF2)9CF2H), 2.10 (s, 3H, OAc), 2.02 (s, 3H, OAc), 1.99 (s, 3H,
white solid; yield 0.084 g (80%); mp 174–178 ꢂC; [
a
]D = +5.93
(c 1.01, DCM); 1H NMR (403 MHz, CDCl3):
d 7.73 (s, 1H, triazole-H),
6.73 (d, 1H, J = 9.1 Hz, NH), 6.04 (tt, 1H, J = 5.5 Hz, J = 51.9 Hz, CF2H),
5.89 (d, 1H, J = 8.7 Hz, H-1), 5.37 (d, 1H, J = 3.3 Hz, H-3), 5.29 (dd, 1H,
J = 3.4 Hz, J = 11.2 Hz, H-4), 5.01 (s, 2H, CH2triazole), 4.80 (s, 2H,
triazoleCH2O), 4.34-4.25 (m, 1H, H-2), 4.17-4.02 (m, 5H, H-6a,
H-6b, H-5, CH2(CF2)3CF2H), 2.16 (s, 3H, OAc), 2.08 (s, 3H, OAc), 2.03
OAc), 1.91 (s, 3H, OAc); 13C NMR (101 MHz, DMSO-d6):
d 169.9,
169.88,169.5,168.9,166.1, 142.3,104.7-118.5,125.9, 92.2, 70.8, 69.9,
66.4, 65.8, 61.3, 51.7, 48.5, 40.4, 20.49, 20.45, 20.3; 19F NMR
(282 MHz, CDCl3):
d
ꢀ120.08, ꢀ122.31, ꢀ123.78, ꢀ129.76, ꢀ137.38,
(s, 3H, OAc), 1.95 (s, 3H, OAc); 13C NMR (151 MHz, CDCl3);
d
170.6,
ꢀ137.56; MS (ESI) m/z [M + H]+ calcd for C30H29F20N4O11
:
170.5, 170.2, 169.5, 165.7, 144.3, 124.5, 117.5-105.6, 92.3, 71.7,
1001.1513; found: 1001.1513; m/z [M+Na]+ calcd for
69.8, 67.0, 66.5, 65.5, 61.4, 53.2, 50.5, 33.9, 25.6, 24.9, 20.8; 19F NMR
C30H28F15N4NaO11: 1023.1333; found: 1023.1333.
(379 MHz, CDCl3):
d
ꢀ120.30, ꢀ126.02, ꢀ130.76, ꢀ137.83; MS
(ESI) m/z [M+H]+ calcd for C24H29F8N4O11: 701.1705; found:
4.5. General procedure for the click reaction of sugar with propargyl
moiety
701.1705.
4.4.8. 1-(1,3,4,6-Tetra-O-acetyl-2-azidoacetamido-2-deoxy-
b
-D-
Propargyl-3,4,6-tri-O-acetyl-2-deoxy-2-trichloroacetamido-
galactopyranosyl)-4-(3,3,4,4,5,5,6,6,7,7,8,8,8-
b-D-glucopyranoside (19) (1 equiv) and azidohexadecane (20)
tridecafluorohexylethoxy)methyl-1H-1,2,3-triazole 16
(1.3 equiv) or corresponding fluorinated azide (21-25) (1.3 equiv)
were dissolved in the mixture of MeCN (1.33 mL for 1 mmol of
sugar) and H2O (2.67 mL for 1 mmol of sugar). To the reaction
mixture Et3N (1.3 equiv) and CuI (0.1 equiv) were added and stirred
at room temperature for 24 h. The mixture was dissolved in H2O
(3 mL) and extracted with Et2O (3 ꢃ 3 mL). The combined organic
layers were washed with brine (3 ꢃ 3 mL) and dried over Na2SO4.
Solvent was evaporated. The crude product was purified by
column chromatography (Hex:EtOAc 1:1, v/v) to afford
26,27,28,29,30,31.
1,3,4,6-Tetra-O-acetyl-2-azidoacetamido-2-deoxy-b-D-galacto-
pyranoside (13) (0.060 g, 0.15 mmol) and 3-((2-perfluorohexyl)
ethoxy)prop-1-yne (5) (0.090 g, 0.225 mmol) gave 16 as a white
solid; yield 0.095 g (76%); mp 175–178 ꢂC; [a]D = ꢀ31.80 (c 1.02,
MeCN); 1H NMR (403 MHz, CDCl3):
d 7.68 (s, 1H, triazole-H), 6.66
(d, 1H, J = 8.6 Hz, NH), 5.88 (d, 1H, J = 6.4 Hz, H-1), 5.37 (d, 1H,
J = 3.2 Hz, H-3), 5.28 (dd, 1H, J = 3.4 Hz, J = 11.2 Hz, H-4), 4.99 (s, 2H,
triazoleCH2O), 4.67 (s, 2H, CH2triazole), 4.32-4.24 (m, 1H, H-2),
4.18-4.06 (m, 3H, H-6a, H-6b, H-5), 3.85 (t, 2H, J = 6.6 Hz,
OCH2CH2(CF2)5CF3), 2.90-2.34 (m, 2H, CH2(CF2)5CF3), 2.16 (s, 3H,
OAc), 2.08 (s, 3H, OAc), 2.03 (s, 3H, OAc), 1.95 (s, 3H, OAc); 13C NMR
4.5.1. 1-((3,4,6-Tri-O-acetyl-2-deoxy-2-trichloroacetamido-
glucopyranosyl)methoxy)-4-hexadecyl-1H-1,2,3-triazole 26
Propargyl-3,4,6-tri-O-acetyl-2-deoxy-2-trichloroacetamido-
-glucopyranoside (19) (0.115 g, 0.235 mmol) and azidohexade-
b-D-
(101 MHz, CDCl3):
d 170.5, 170.4, 170.2, 169.5, 165.8, 145.3, 124.1,
121.1-102.5, 92.3, 71.7, 69.8, 66.5, 64.4, 62.6, 61.3, 53.2, 50.5, 31.4,
20.8, 20.6, 20.5; 19F NMR (379 MHz, CDCl3):
d
ꢀ81.29, ꢀ113.92,
b-D
ꢀ122.41, ꢀ123.39, ꢀ124.19, ꢀ126.66; MS (ESI) m/z [M+H]+ calcd for
cane (20) (0.082 g, 0.306 mmol) gave 26 as a white solid; yield
C
C
27H30F13N4O11: 833.1703; found: 833.1700; m/z [M+Na]+ calcd for
27H29F13N4NaO11: 855.1523; found: 855.1516.
0.135 g (76%); mp 128–130 ꢂC; [a]D = ꢀ5.34 (c 1.02, DCM); 1H NMR
(403 MHz, CDCl3):
d 7.51 (s, 1H, triazole-H), 7.03 (d, 1H, J = 9.0 Hz,
NH), 5.30 (dd, 1H, J = 9.4 Hz, J = 10.7 Hz, H-3), 5.15 (t, 1H, J = 9.6 Hz,
H-4), 4.97 (d, 1H, J = 8.4 Hz, H-1), 4.94 (d, 1H, J = 13.1 Hz,
OCHatriazole), 4.83 (d, 1H, J = 13.1 Hz, OCHb-triazole), 4.37-4.24
(m, 3H, H-6b, triazoleCH2) 4.18 (dd, 1H, J = 2.3 Hz, J = 12.3 Hz, H-6a),
4.12-4.04 (m, 1H, H-2), 3.79 (ddd, 1H, J = 2.3 Hz, J = 4.7 Hz, J = 9.9 Hz,
H-5), 2.12 (s, 3H, OAc), 2.05 (s, 3H, OAc), 2.02 (s, 3H, OAc) 1.91-1.77
(m, 2H, CH2), 1.36-1.28 (m, 6H, (CH2)3), 1.25 (s, 20H, (CH2)10), 0.88
4.4.9. 1-(1,3,4,6-Tetra-O-acetyl-2-azidoacetamido-2-deoxy-
galactopyranosyl)-4-(2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-
pentadecafluorooctylmethoxy)methyl-1H-1,2,3-triazole 17
b-D-
1,3,4,6-Tetra-O-acetyl-2-azidoacetamido-2-deoxy-b-D-galacto-
pyranoside (13) (0.040 g, 0.10 mmol) and 3-((1-perfluoroheptyl)
methoxy)prop-1-yne (6) (0.065 g, 0.15 mmol) gave 17 as a white
solid; yield 0.077 g (89%); mp 184–188 ꢂC; [
a
]D = +45.06 (c 0.82,
(t, 3H, J = 6.8 Hz, CH3); 13C NMR (101 MHz, CDCl3):
d 170.9, 170.7,
DCM); 1H NMR (300 MHz, CDCl3):
d 7.72 (s, 1H, triazole-H), 6.51 (d,
169.3, 162.0, 144.2, 122.6, 99.9, 92.3, 72.1, 71.9, 68.1, 62.7, 61.9, 55.7,
50.4, 31.9, 30.3, 29.7, 29.65, 29.62, 29.5, 29.4, 29.3, 29.0, 26.5, 22.7,
20.8, 20.6, 20.5, 14.1; MS (ESI) m/z [M+H]+ calcd for C33H54Cl3N4O9:
755.2956; found: 755.2946; m/z [M+Na]+ calcd for
1H, J = 8.6 Hz, NH), 5.87 (d, 1H, J = 8.8 Hz, H-1), 5.37 (d, 1H, J = 3.3 Hz,
H-3), 5.27 (dd, 1H, J = 3.3 Hz, J = 11.3 Hz, H-4), 5.00 (s, 2H,
triazoleCH2O), 4.82 (s, 2H, CH2triazole), 4.34-4.22 (m, 1H, H-2),
4.15-4.01 (m, 3H, H-6a, H-6b, H-5), 2.16 (s, 3H, OAc), 2.08 (s, 3H,
OAc), 2.04 (s, 3H, OAc),1.96 (s, 3H, OAc); 13C NMR (101 MHz, CDCl3):
C33H53Cl3N4NaO9: 777.2776; found: 777.2762.
d
170.6, 170.4, 170.2, 169.5, 165.7, 144.3, 124.4, 119.0-107.0, 92.3,
71.7, 69.8, 67.2, 66.5, 65.6, 61.3, 53.2, 50.5, 33.9, 25.6, 24.9, 20.6; 19
F
4.5.2. 1-((3,4,6-Tri-O-acetyl-2-deoxy-2-trichloroacetamido-
b-D-
glucopyranosyl)methoxy)-4-(1,1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10-
henicosafluorododecyl)-1H-1,2,3-triazole 27
NMR (282 MHz, CDCl3):
d
ꢀ81.25, ꢀ120.10, ꢀ122.56, ꢀ123.26,
ꢀ123.77, ꢀ126.63; MS (ESI) m/z [M+H]+ calcd for C27H28F15N4O11
:
869.1515;
found:
869.1518;
m/z
[M+Na]+
calcd
for
Propargyl-3,4,6-tri-O-acetyl-2-deoxy-2-trichloroacetamido-
b-D-glucopyranoside (19) (0.046 g, 0.095 mmol) and 1-azido-
C27H27F15N4NaO11: 891.1335; found: 891.1335.
3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,12,12,12-henicosafluorododo-
decane (21) (0.073 g, 0.124 mmol) gave 27 as a white solid; yield
0.092 g (91%); mp 177–180 ꢂC; [a]D = ꢀ6.57 (c 0.84, DCM); 1H NMR
4.4.10. 1-(1,3,4,6-Tetra-O-acetyl-2-azidoacetamido-2-deoxy-
galactopyranosyl)-4-(2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10-
eicosafluorononylmethoxy)methyl-1H-1,2,3-triazole 18
b-D-
(300 MHz, CDCl3):
d 7.59 (s, 1H, triazole-H), 6.84 (d, 1H, J = 8.9 Hz,
NH), 5.27 (dd, 1H, J = 9.4 Hz, J = 10.7 Hz, H-3), 5.16 (t, 1H, J = 9.6 Hz,
H-4), 4.97 (d, 1H, J = 13.1 Hz, OCHatriazole) 4.90 (d, 1H, J = 8.3 Hz, H-
1,3,4,6-Tetra-O-acetyl-2-azidoacetamido-2-deoxy-
pyranoside (13) (0.060 g, 0.15 mmol) and
b
-
D
-galacto-
3-((1-

J. Tomaszewska et al. / Journal of Fluorine Chemistry 191 (2016) 1–13
11
1), 4.84 (d, 1H, J = 12.9 Hz, OCHbtriazole), 4.66 (t, 2H, J = 7.4 Hz,
triazoleCH2), 4.31 (dd, 1H, J = 4.7 Hz, J = 12.3 Hz, H-6a), 4.19 (dd, 1H,
J = 2.3 Hz, J = 12.3 Hz, H-6b), 4.09-3.98 (m, 1H, H-2), 3.77 (ddd, 1H,
J = 2.4 Hz, J = 4.5 Hz, J = 9.8 Hz, H-5), 2.91-2.71 (m, 2H,
CH2(CF2)9CF3), 2.12 (s, 3H, OAc), 2.05 (s, 3H, OAc), 2.03 (s, 3H,
2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-pentadecafluorooctyl (24) (0.150 g,
0.353 mmol) gave 30 as a white solid; yield 0.086 g (34%); mp
140–143 ꢂC; [
CDCl3):
a
]D = ꢀ40.24 (c 1.01, MeCN); 1H NMR (403 MHz,
d
7.71 (s, 1H, triazole-H), 6.91 (d, 1H, J = 8.8 Hz, NH), 5.29
(dd, 1H, J = 9.4 Hz, J = 10.7 Hz, H-3), 5.16 (t, 1H, J = 9.7 Hz, H-4), 5.11-
4.96 (m, 3H, OCHatriazole, CH2(CF2)6CF3), 4.92 (d, 1H, J = 8.4 Hz, H-
1), 4.87 (d, 1H, J = 13.2 Hz, OCHbtriazole), 4.30 (dd, 1H, J = 4.7 Hz,
J = 12.4 Hz, H-6a), 4.19 (dd,1H, J = 2.3 Hz, J = 12.4 Hz, H-6b), 4.11-4.02
(m, 1H, H-2), 3.78 (ddd, 1H, J = 2.4 Hz, J = 4.7 Hz, J = 9.9 Hz, H-5), 2.11
(s, 3H, OAc), 2.06 (s, 3H, OAc), 2.04 (s, 3H, OAc); 13C NMR (101 MHz,
OAc); 13C NMR (151 MHz, CDCl3):
d
170.9, 170.7, 169.3, 162.0, 144.8,
123.3, 117.5-107.7, 100.1, 92.2, 72.3, 71.6, 68.0, 62.8, 61.8, 55.9, 42.4,
31.8, 20.8, 20.6, 20.5; 19F NMR (282 MHz, CDCl3):
d
ꢀ81.22,
ꢀ114.63, ꢀ122.26, ꢀ123.20, ꢀ123.91, ꢀ126.60; MS (ESI) m/z [M
+H]+ calcd for C29H25Cl3F21N4O9: 1077.0352; found: 1077.0309;
m/z [M+Na]+ calcd for C29H24Cl3F21N4NaO9: 1099.0124; found:
1099.0124.
CDCl3):
d 171.7, 170.7, 169.3, 162.1, 145.6, 124.6, 118.5-106.9, 100.2,
92.2, 72.2, 71.7, 68.2, 62.7, 61.8, 55.8, 49.3, 20.8, 20.6, 20.5; 19F NMR
(282 MHz, CDCl3):
d
ꢀ81.22, ꢀ117.31, ꢀ122.13, ꢀ122.47, ꢀ123.27,
4.5.3. 1-((3,4,6-O-acetyl-2-deoxy-2-trichloroacetamido-
b
-D-
ꢀ123.41, ꢀ126.61; MS (ESI) m/z [M+H]+ calcd for C25H23Cl3F15N4O9:
glucopiranosyl)methoxy)-4-(2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9-
913.0291; found:
913.0245; m/z
[M+Na]+ calcd
for
eicosafluorododecyl)-1H-1,2,3-triazole 28
C25H22Cl3F15N4NaO9: 935.0111; found: 935.0088.
Propargyl-3,4,6-tri-O-acetyl-2-deoxy-2-trichloroacetamido-
b-D-glucopyranoside (19) (0.097 g, 0.198 mmol) and 1-azido-
4.5.6. 1-((3,4,6-O-acetyl-2-deoxy-2-trichloroacetamido-
glucopiranosyle)methoxy)-4-(3,3,4,4,5,5,6,6,7,7,8,8,8-
tridecafluorooctyl)-1H-1,2,3-triazole 31
b-D-
2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11-eicosafluoroundecane (22)
(0.143 g, 0.257 mmol) gave 28 as a white solid; yield 0.117 g (56%);
mp 158–164 ꢂC; [
CDCl3):
a
]D = ꢀ9.17 (c 1.02, DCM); 1H NMR (403 MHz,
Propargyl-3,4,6-tri-O-acetyl-2-deoxy-2-trichloroacetamido-
-glucopyranoside (19) (0.080 g, 0.164 mmol) and 1-azido-
3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl (25) (0.083 g,
d
7.71 (s, 1H, triazole-H), 6.85 (d, 1H, J = 8.8 Hz, NH), 6.06 (t,
b-D
1H, J = 5.0 Hz, J = 51.9 Hz, CF2H), 5.28 (dd, 1H, J = 9.3 Hz, J = 10.7 Hz,
H-3), 5.14 (t, 1H, J = 9.6 Hz, H-4), 5.09-4.96 (m, 3H, OCHatriazole,
CH2(CF2)9CF2H), 4.91 (d, 1H, J = 8.3 Hz, H-1), 4.87 (d, 1H, J = 13.1 Hz,
OCHbtriazole), 4.30 (dd, 1H, J = 4.7 Hz, J = 12.4 Hz, H-6a), 4.19 (dd,
1H, J = 2.3 Hz, J = 12.4 Hz, H-6b), 4.10-4.02 (m, 1H, H-2), 3.77 (ddd,
1H, J = 2.4 Hz, J = 4.7 Hz, J = 9.9 Hz, H-5), 2.11 (s, 3H, OAc), 2.05 (s, 3H,
0.213 mmol) gave 31 as a white solid; yield 0.055 g (38%); mp
157–161 ꢂC; [
CDCl3);
a
]D = ꢀ43.87 (c 1.00, MeCN); 1H NMR (403 MHz,
d
7.61 (s, 1H, triazole-H), 6.95 (d, 1H, J = 8.8 Hz, NH), 5.30
(dd, 1H, J = 9.4 Hz, J = 10.7 Hz, H-3), 5.15 (t, 1H, J = 9.6 Hz, H-4), 4.96
(d, 1H, J = 13.4 Hz, OCHatriazole), 4.92 (d, 1H, J = 8.3 Hz, H-1), 4.84
(d, 1H, J = 13.0 Hz, OCHbtriazole), 4.66 (t, 2H, J = 7.4 Hz, triazole-
CH2), 4.30 (dd, 1H, J = 4.7 Hz, J = 12.4 Hz, H-6a), 4.19 (dd, 1H,
J = 2.3 Hz, J = 12.3 Hz, H-6b), 4.07-3.99 (m, 1H, H-2), 3.77 (ddd, 1H,
J = 2.4 Hz, J = 4.7 Hz, J = 9.9 Hz, H-5), 2.89-2.74 (m, 2H,
CH2(CF2)5CF3), 2.11 (s, 3H, OAc), 2.05 (s, 3H, OAc), 2.03 (s, 3H,
OAc), 2.03 (s, 3H, OAc); 13C NMR (75 MHz, CDCl3):
169.3, 162.1, 145.5, 124.5, 117.9-103.1, 100.2, 92.1, 72.2, 71.6, 68.0,
62.7, 61.7, 55.8, 49.3, 20.7, 20.6, 20.5; 19F NMR (379 MHz, CDCl3):
d 171.0 170.7,
d
ꢀ17.27, ꢀ122.33, ꢀ123.39, ꢀ123.77, ꢀ129.71, ꢀ137.39, ꢀ137.52; MS
(ESI) m/z [M+H]+ calcd for C28H24Cl3F20N4O9: 1045.0289; found:
1045.0247; m/z [M+Na]+ calcd for C28H23Cl3F20N4NaO9: 1067.0109;
found: 1067.0076.
OAc); 13C NMR (101 MHz, CDCl3):
123.3, 121.5-107.2, 100.0, 92.2, 72.2, 71.6, 68.1, 62.8, 61.8, 55.8, 42.3,
d 170.9, 170.7, 169.3, 162.0, 144.7,
31.7, 20.7, 20.6, 20.5; 19F NMR (379 MHz, CDCl3):
d
ꢀ80.27, ꢀ113.67,
4.5.4. 1-((3,4,6-O-acetyl-2-deoxy-2-trichloroacetamido-b-D-
glucopiranosyle)methoxy)-4-(4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,11-
heptadecafluoroundecyl)-1H-1,2,3-triazole 29
ꢀ121.41, ꢀ122.36, ꢀ122.98, ꢀ125.66; MS (ESI) m/z [M+H]+ calcd for
C
25H25Cl3F13N4O9: 877.0479; found: 877.0462; m/z [M+Na]+ calcd
for C25H24Cl3F13N4NaO9: 899.0299; found: 899.0252.
Propargyl-3,4,6-tri-O-acetyl-2-deoxy-2-trichloroacetamido-
b-D-glucopyranoside (19) (0.299 g, 0.612 mmol) and 1-azido-
4.6. General procedure for the deprotection reaction of acetyl groups in
monosaccharides
4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,11-heptadecafluoroundecane (23)
(0.400 g, 0.795 mmol) gave 29 as a white solid; yield 0.341 g
(56%); mp 161–165 ꢂC; [a]D = ꢀ6.36 (c 1.03, DCM); 1H NMR
To a solution of sugars 8, 12, 14, 18, 26, 27 (1 eqiuv) in DCM/
MeOH (3:7, v/v, 4.7 mL for 1 mmol of sugar) was added 25% sodium
methoxide solution (5 equiv) at room temperature. The reaction
mixture was stirred overnight and MeOH (3.2 mL for 1 mmol of
sugar) was added. Neutralization was achieved with addition of
Dowex 50WX8 (50–100 mesh, H+-form). The ion exchange resin
was filtered and the filtrate was concentrated in vacuo. The crude
product was purified by column chromatography (DCM:MeOH 5:1,
v/v) to afford desired products 32, 33, 34, 35, 36, 37.
(403 MHz, CDCl3):
d 7.55 (s, 1H, triazole-H), 6.87 (d, 1H,
J = 8.8 Hz, NH), 5.83 (d, 1H, J = 8.7 Hz, H-1), 5.27 (dd, 1H,
J = 9.4 Hz, J = 10.7 Hz, H-3), 5.16 (t, 1H, J = 9.6 Hz, H-4), 4.97 (d, 1H,
J = 13.1 Hz, OCHatriazole), 4.92 (d, 1H, J = 8.4 Hz, H-1), 4.84 (d, 1H,
J = 13.0 Hz, OCHbtriazole), 4.44 (td, 2H, J = 2.9 Hz, J = 6.8 Hz, triazo-
leCH2), 4.31 (dd, 1H, J = 4.7 Hz, J = 12.4 Hz, H-6a), 4.19 (dd, 2H,
J = 2.4 Hz, J = 12.3 Hz, H-6b), 4.09-4.01 (m, 1H, H-2), 3.77 (ddd, 1H,
J = 2.4 Hz, J = 4.7 Hz, J = 9.9 Hz, H-5), 2.30-2.19 (m, 2H, CH2CH2CH2),
2.19-2.08 (m, 2H, CH2(CF2)7CF3), 2.11 (s, 3H, OAc), 2.05 (s, 3H, OAc),
2.03 (s, 3H, OAc); 13C NMR (101 MHz, CDCl3):
d 170.9, 170.6, 169.3,
4.6.1. 1-(2-Azidoacetamido-2-deoxy-
1H-1,2,3-triazole 32
b
-
D
-glucopyranosyl)-4-hexyl-
-glu-
161.9, 144.7, 122.7, 120.7-109.4, 100.1, 91.2, 72.2, 71.6, 68.0, 62.8,
61.8, 55.8, 49.2, 28.1, 21.6, 20.7, 20.6, 20.5; 19F NMR (379 MHz,
1-(1,3,4,6-Tetra-O-acetyl-2-azidoacetamido-2-deoxy-b-D
CDCl3);
d
ꢀ81.24, ꢀ114.54, ꢀ122.17, ꢀ122.40, ꢀ123.21, ꢀ123.76,
ꢀ126.62; MS (ESI) m/z [M+H]+ calcd for C28H27Cl3F17N4O9:
copyranosyl)-4-hexyl-1H-1,2,3-triazole (8) (0.057 g, 0.106 mmol)
and 25% CH3ONa in MeOH (0.029 g, 0.530 mmol) gave 32 as a white
991.0572; found:
991.0544;
m/z
[M+Na]+
calcd
for
solid; yield 0.031 g (79%); 1H NMR (403 MHz, DMSO–d6);
d 8.24 (d,
C28H26Cl3F17N4NaO9: 1013.0392; found: 1013.0370.
1H, J = 7.9 Hz, NH), 7.75 (s, 1H, triazole-H), 5.75 (app s, 1H, H-1),
5.12-4.83 (m, 4H, H-3, H-4, CH2triazole), 3.95 (ddd, 1H, J = 3.2 Hz,
J = 7.5 Hz, J = 12.0 Hz, H-5), 3.62-3.27 (m, 3H, H-6a, H-6b, OH), 3.18-
3.05 (m, 1H, H-2), 2.60 (t, 2H, J = 7.6 Hz, triazoleCH2), 1.62-1.53 (m,
2H, triazole-CH2CH2), 1.34-1.22 (m, 6H, (CH2)3), 0.86 (t, 3H,
4.5.5. 1-((3,4,6-O-acetyl-2-deoxy-2-trichloroacetamido-
glucopiranosyle)methoxy)-4-(2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-
pentadecafluorooctyl)-1H-1,2,3-triazole 30
Propargyl-3,4,6-tri-O-acetyl-2-deoxy-2-trichloroacetamido-
b-D-glucopyranoside (19) (0.133 g, 0.272 mmol) and 1-azido-
b-D-
J = 6.9 Hz, CH3); 13C NMR (101 MHz, DMSO–d6):
d 165.6, 146.5,

12
J. Tomaszewska et al. / Journal of Fluorine Chemistry 191 (2016) 1–13
123.3, 90.5, 72.1, 71.0, 70.5, 61.0, 54.6, 51.4, 31.1, 29.0, 28.3, 25.0,
22.1, 14.0; MS (ESI) m/z [M+H]+ calcd for C16H29N4O6: 373.2087;
found: 373.2080; m/z [M+Na]+ calcd for C16H28N4NaO6: 395.1907;
found: 395.1900.
0.200 mmol) gave 36 as a white solid; yield 0.015 g (61%); 1H
NMR (403 MHz, DMSO–d6); 8.33 (s, 1H, triazole-H), 8.14 (app s,
d
1H, J = 8.9 Hz, NH), 5.02-4.93 (br s,1H, OH), 4.88 (dd, 1H, H-3), 4.66
(dd,1H, H-4), 4.32 (app t,1H, H-6b), 4.17 (d,1H, J = 7.9 Hz, H-1), 3.71
(m, 1H, H-5), 3.52-3.14 (m, 5H, OH, triazole-CH2, OCHatriazole,
OCHbtriazole), 3.15-3.00 (m, 2H, H-6a, H-2), 1.83-1.74 (m, 2H,
triazoleCH2CH2), 1.23 (s, 26H, (CH2)13), 0.85 (t, 3H, J = 6.9 Hz, CH3);
4.6.2. 1-(2-Azidoacetamido-2-deoxy-b-D-glucopyranosyl)-4-
(2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10-eicosafluorononylmethoxy)
methyl-1H-1,2,3-triazole 33
13C NMR (101 MHz, DMSO–d6):
d 143.7,124.0,102.9, 79.2, 77.2, 70.1,
1-(1,3,4,6-Tetra-O-acetyl-2-azidoacetamido-2-deoxy-
copyranosyl)-4-(2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10-eicosafluoro-
nonylmethoxy)methyl-1H-1,2,3-triazole (12) (0.081 g,
b
-
D
-glu-
61.7, 61.2, 57.3, 49.3, 31.3, 29.7, 29.1, 29.2, 29.0, 28.9, 28.7, 28.4, 25.9,
22.1, 14.0; MS (ESI) m/z [M+H]+ calcd for C27H48Cl3N4O6: 629.2639;
found: 629.2641; m/z [M+Na]+ calcd for C27H47Cl3N4NaO6:
651.2459; found: 651.2457.
0.081 mmol) and 25% CH3ONa in MeOH (0.022 g, 0.405 mmol)
gave 33 as a white solid; yield 0.047 g (70%); 1H NMR (403 MHz,
DMSO–d6);
d
8.30 (d,1H, J = 8.9 Hz, NH), 8.11 (s,1H, triazole-H), 7.20
4.6.6. 1-((2-Deoxy-2-trichloroacetamido-b-D-glucopyranosyl)
(tt, 1H, J = 5.1 Hz, J = 51.0 Hz, HCF2), 5.75 (app s, 1H, H-1), 5.43-5.28
(dd, dd, 2H, H-3, H-4), 5.15 (s, 2H, triazoleCH2O), 4.75 (s, 2H,
CH2triazole), 4.30-4.07 (m, 3H, H-6a, H-6b, H-5), 3.12-3.38 (m, 4H,
methoxy)-4-(1,1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10-
henicosafluorododecyl)-1H-1,2,3-triazole 37
1-((3,4,6-Tri-O-acetyl-2-deoxy-2-trichloroacetamido-b-D-glu-
copyranosyl)methoxy)-4-(1,1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10-
henicosafluorododecyl)-1H-1,2,3-triazole (27) (0.118 g,
H-2, OH, CH2(CF2)9CF2H); 13C NMR (101 MHz, DMSO–d6):
d
165.4,
142.6, 126.1, 119.1-104.5, 99.5, 72.1, 70.5, 66.4-65.1, 64.8-64.1, 54.9,
48.6; 19F NMR (379 MHz, DMSO-d6):
d
ꢀ119.38, ꢀ122.33, ꢀ123.48,
0.110 mmol) and 25% CH3ONa in MeOH (0.030 g, 0.550 mmol)
ꢀ129.48, ꢀ138.95; MS (ESI) m/z [M+H]+ calcd for C22H21F20N4O7:
gave 37 as a white solid; yield 0.087 g (85%); 1H NMR (403 MHz,
833.1091;
found:
833.1078;
m/z
[M+Na]+
calcd
for
DMSO–d6); d 8.65 (d,1H, J = 8.5 Hz, NH), 8.07 (s,1H, triazole-H), 5.11
C
22H20F20N4NaO7: 855.0910; found: 855.0909.
(sbr, 1H, OH), 4.77 (d, 1H, J = 8.4 Hz, H-1), 4.68-4.56 (m, 3H, H-3, H-
4, triazoleCH2), 4.33 (dd, 1H, J = 2.5 Hz, J = 15.9 Hz, H-6a), 4.24 (dd,
1H, J = 2.4 Hz, J = 15.9 Hz, H-6b), 3.72 (m, 1H, H-5), 3.58-3.43 (m, 1H,
H-2), 3.34 (app s, 3H, OH, OCHatriazole, OCHbtriazole), 2.93-2.77
4.6.3. 1-(2-Azidoacetamido-2-deoxy-b-D-galactopyranosyl)-4-hexyl-
1H-1,2,3-triazole 34
1-(1,3,4,6-Tetra-O-acetyl-2-azidoacetamido-2-deoxy-
b-D
-gal-
(m, 2H, CH2(CF2)9CF3); 13C NMR (101 MHz, DMSO–d6):
d
161.3,
actopyranosyl)-4-hexyl-1H-1,2,3-triazole (14)
(0.058 g,
143.8, 124.4, 118.7-105.9, 99.7, 93.1, 77.1, 73.1, 70.8, 61.6, 61.0, 57.4,
0.107 mmol) and 25% CH3ONa in MeOH (0.029 g, 0.535 mmol)
48.6, 30.4; 19F NMR (379 MHz, DMSO-d6):
d
ꢀ82.20, ꢀ114.77,
gave 34 as a white solid; yield 0.028 g (70%); 1H NMR (403 MHz,
ꢀ123.99, ꢀ123.85, ꢀ127.35; MS (ESI) m/z [M+H]+ calcd for
DMSO–d6);
d
8.17 (d,1H, J = 8.5 Hz, NH), 7.76 (s,1H, triazole-H), 5.73
C
23H19Cl3F21N4O6: 951.0035; found: 951.0033; m/z [M+Na]+ calcd
(app s, 1H, H-1), 5.11-4.93 (m, 4H, H-3, H-4, CH2triazole), 4.75 (s,
1H, OH), 3.82-3.3.64 (m, 2H, H-6a, H-6b), 3.56-3.13 (m, 2H, H-2,
OH), 3.98 (ddd, 1H, J = 3.2 Hz, J = 7.5 Hz, J = 12.0 Hz, H-5), 2.63-2.54
(m, 2H, triazoleCH2), 1.61-1.53 (m, 2H, triazoleCH2CH2), 1.33-1.22
(m, 6H, (CH2)3), 0.86 (t, 3H, J = 6.9 Hz); 13C NMR (101 MHz, DMSO–
for C23H18Cl3F21N4NaO6: 972.9854; found: 972.9853.
Acknowledgments
This work was partially financed by Foundation for Polish
Science (grant: Homing Plus/2001-3/5) and Polish National Science
Centre (grant SONATA 4 - 2012/07/D/ST5/02303). The authors
thank Perlan Technologies Polska Sp. z o. o. for providing the HPLC/
Q-TOF Agilent 1260/6540 instrument.
d6):
d 165.7, 146.5, 122.8, 90.8, 70.5, 68.2, 67.3, 60.6, 51.5, 50.7, 31.1,
29.1, 28.4, 25.1, 22.1, 14.0; MS (ESI) m/z [M+H]+ calcd for
C
C
16H29N4O6: 373.2087; found: 373.2086; m/z [M+Na]+ calcd for
16H28N4NaO6: 395.1907; found: 395.1881.
4.6.4. 1-(2-Azidoacetamido-2-deoxy-b-D-galactopyranosyl)-4-
Appendix A. Supplementary data
(2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10-eicosafluorononylmethoxy)
methyl-1H-1,2,3-triazole 35
Supplementary data associated with this article can be
found, in the online version, at http://dx.doi.org/10.1016/j.
jfluchem.2016.09.002.
1-(1,3,4,6-Tetra-O-acetyl-2-azidoacetamido-2-deoxy-b-D-gal-
actopyranosyl)-4-(2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10-eicosafluoro-
nonylmethoxy)methyl-1H-1,2,3-triazole (18) (0.100 g, 0.100 mmol)
and 25% CH3ONa in MeOH (0.027 g, 0.500 mmol) gave 35 as a white
solid; yield 0.068 g (82%); 1H NMR (403 MHz, DMSO–d6);
d 8.21 (d,
References
1H, J = 8.5 Hz, NH), 8.10 (s, 1H, triazole-H), 7.22 (tt, 1H, J = 5.2 Hz,
J = 50.2 Hz, HCF2), 5.75 (app s, 1H, H-1), 5.19-5.09 (m, 4H, H-3, H-4,
triazoleCH2O), 4.85 (s, 2H, CH2triazole), 4.74-4.69 (dd, 1H, H-6a),
4.27-4.16 (app m, 1H, H-6b), 4.02 (ddd, 1H, J = 3.2 Hz, J = 7.5 Hz,
J = 12.0 Hz, H-5), 3.60-3.28 (m, 4H, H-2, OH, CH2(CF2)9CF2H); 13C
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d 165.5, 141.9, 125.6, 119.3-104.7, 90.8,
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