Design and synthesis of 2′-Deoxy-2′-[(1,2,3)Triazol-1-Yl]uridines using click chemistry approach

Article abstract of DOI:10.1080/15257770.2014.1003652

A series of novel nucleosides bearing a 1,2,3-triazole moiety at the 2′-position of the sugar moiety has been synthesized starting from 2′-azidouridine and using the copper (I)-catalyzed Huisgen-Sharpless-Meldal 1,3-dipolar cycloaddition reaction. The reactions proceeded in overall yield of 52-82% and gave almost exclusively the 1,4-disubstituted 1,2,3-triazoles. The 2′-azidouridine was synthesized from uridine in two steps, and reacted with a variety of differently substituted alkynes to give the desired 2′-triazole-substituted uridine derivatives.

Full text of DOI:10.1080/15257770.2014.1003652

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Design and Synthesis of 2′-Deoxy-2′-
[(1,2,3)Triazol-1-Yl]Uridines Using Click
Chemistry Approach
Surender Kumara
a Department of Chemistry, University College, Kurukshetra
University, Kurukshetra, Haryana, India
Published online: 15 Apr 2015.
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To cite this article: Surender Kumar (2015) Design and Synthesis of 2′-Deoxy-2′-[(1,2,3)Triazol-1-
Yl]Uridines Using Click Chemistry Approach, Nucleosides, Nucleotides and Nucleic Acids, 34:5,
371-378, DOI: 10.1080/15257770.2014.1003652
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Nucleosides, Nucleotides and Nucleic Acids, 34:371–378, 2015
Copyright ꢀC Taylor and Francis Group, LLC
ISSN: 1525-7770 print / 1532-2335 online
DOI: 10.1080/15257770.2014.1003652
DESIGN AND SYNTHESIS OF
2ꢀ-DEOXY-2ꢀ-[(1,2,3)TRIAZOL-1-YL]URIDINES USING
CLICK CHEMISTRY APPROACH
Surender Kumar
Department of Chemistry, University College, Kurukshetra University, Kurukshetra,
Haryana, India
A series of novel nucleosides bearing a 1,2,3-triazole moiety at the 2ꢁ-position of the sugar
2
moiety has been synthesized starting from 2ꢁ-azidouridine and using the copper (I)-catalyzed
Huisgen–Sharpless–Meldal 1,3-dipolar cycloaddition reaction. The reactions proceeded in over-
all yield of 52–82% and gave almost exclusively the 1,4-disubstituted 1,2,3-triazoles. The 2ꢁ-
azidouridine was synthesized from uridine in two steps, and reacted with a variety of differently
substituted alkynes to give the desired 2ꢁ-triazole-substituted uridine derivatives.
Keywords Nucleosides; 2ꢁ-azidouridine; 1,2,3-triazole; click chemistry
INTRODUCTION
Chemically modified nucleosides and oligonucleotides have attracted a
lot of interest in scientific community due to their potential use in chemi-
cal biology, nanotechnology, material science, bio-analysis, and in medicinal
chemistry as therapeutic agents targeting several diseases caused by viruses
such as human immunodeficiency virus, hepatitis B virus, and hepatitis C
virus. The nucleoside structure has been the object of numerous chemical
modifications in order to find new therapeutic entities. In recent years, there
has been remarkable interest in the synthesis of nucleosides with modifica-
tions of nucleobase, sugar moiety, and phosphate backbone. Some of the
novel analogs proved valuable for treating cancer.[1–5] The triazole core is a
structural feature of many drugs. Recent studies have revealed that triazole
containing nucleosides have a broad spectrum of pharmacological activ-
ities such as antiviral[6] (including inhibition of reverse transcriptase[7]),
anti-microbial[8], anti-proliferative,[9] and antitumor properties.[10–12] In
particular 1,2,3-triazolyl-linked uridine derivatives[13] (1) have shown good
Received 4 August 2014; accepted 20 December 2014.
Address correspondence to Surender Kumar, Department of Chemistry, University College, Kuruk-
shetra University, Kurukshetra 136119, Haryana, India. E-mail: skjchem@yahoo.com
371

372
S. Kumar
FIGURE 1 Structure of various 1,2,3-triazole substituted nucelosides.
antifungal activity against human and plant pathogens. Zhou et al.[14] have re-
ported the synthesis of 1,2,3-triazole functionalized thymidines (2–4) which
were found to be antiviral agents. Mahony et al.[15] have reported 2-triazolyl-
2-deoxyadenosines (5) as t-RNA synthetase inhibitor. Encouraged by these
findings, we decided to synthesize a number of novel modified nucleosides
(6, Figure 1) bearing a triazole ring in 2ꢁ-position in search of new therapeu-
tic agents.
RESULTS AND DISCUSSION
Click-reaction of azide with alkyne is the most efficient way to prepare
di-substituted 1,2,3-triazoles. For several decades this reaction suffered from
a lack of selectivity, yielding a mixture of 1,4- and 1,5-di-substituted 1,2,3-
triazoles. The Cu-catalyzed Huisgen–Sharpless–Meldal click reaction has
emerged as a key reaction for synthesizing selectively 1,4-di-substituted tria-
zoles under simple reaction conditions.
Propargyl ethers of phenols[13] (7–12) were prepared by the reaction
of phenols with propargyl bromide and potassium carbonate in anhydrous
dimethylformamide (DMF) at room temperature with an overall 65–80%
yield. The 2ꢁ-Deoxy-2ꢁ-azidouridine (14) was synthesized by treating uridine

Nucleosides Synthesis Using Click Chemistry Approach
373
SCHEME 1 Synthesis of propargyl ethers of phenols and their derivatives.
with (C6H5O)2CO, NaN3, and 15-crown-5-ether in anhydrous DMF with 65%
yield (Scheme 1). Propargyl ethers of phenols were then treated with 2ꢁ-
azidouridine (14) in the presence of sodium ascorbate and copper sulphate
in t-butanol/water (1:1) to give exclusively 1,4-disubstituted1,2,3-triazoles
(Scheme 2). The desired nucleosides were purified by column chromatog-
raphy and structures of all target nucleosides (15–22) were confirmed by
SCHEME 2 Synthesis of 1,2,3-triazole-conjugated uridines.

374
S. Kumar
1H NMR, 13C NMR, 2D (COSY and HETCOR), and high-resolution mass
spectra. We are further expanding the scope of the click reaction to struc-
turally diverse alkynes. We are also currently synthesizing DMT derivatives of
the desired triazolylnucleosides, and then phosphoramidite building blocks
would be synthesized to study the hybridizing properties.
CONCLUSIONS
We have synthesized eight novel 1,4-disubstituted-1,2,3-triazole conju-
gated uridines starting from uridine with an overall 52–82% yield using
Cu(I)-catalyzed Huisgen–Sharpless–Meldal 1,3-dipolar cycloaddition reac-
tion. Bromonucleoside (22) can be interesting for further derivatization
and synthesis of other derivatives from 22 via Suzuki cross-coupling reaction
are going on. The antiviral and antibacterial activity of novel synthesized
nucleosides is still under progress.
Experimental
General. Reactions were performed under an atmosphere of nitrogen
when anhydrous solvents were used. Column chromatography was carried
out on glass columns using silica gel 60 (0.040–0.063 mm). NMR spectra
1
were recorded at 400 MHz for H NMR, 100 MHz for 13C NMR. The δ
1
values are in ppm relative to tetramethylsilane as internal standard for H
and 13C NMR. Assignments of NMR spectra are based on 2D (COSY and
HETCOR) spectra and follow standard carbohydrate and nucleoside style;
i.e. the carbon atom next to a nucleobase is assigned C-1ꢁ. ESI mass spectra
were recorded in positive-ion mode.
Synthesis of 2ꢁ-Deoxy-2ꢁ-azidouridine (14). Diphenyl carbonate (4.82 g,
22.54 mmol) was dissolved in anhydrous DMF (10 mL). uridine (5.0 g,
20.49 mmol) and NaHCO3 (86 mg, 1.02 mmol) were added. The suspen-
sion was heated to 100◦C, for 4 hours. The suspension was cooled to room
temperature and diethyl ether (50 mL) was added and stirred for 30 min
at room temperature. The light brown suspension was filtrated and the
solid was washed with diethyl ether (2 × 30 mL) and dried under vacuum
overnight. The crude nucleoside[16] (13, 5.21 g, 20.49 mmol), NaN3 (5.33 g,
81.97 mmol), and 15-crown-5-ether (0.63 g, 2.86 mmol) were dissolved in
anhydrous DMF (20 mL). The suspension was heated to 150◦C for 20 min,
the suspension changed from colorless to dark brown. Benzoic acid (2.75 g,
22.54 mmol) was added and the suspension was heated to 150◦C for 2 hours
and then cooled to room temperature. The reaction mixture was diluted
with H2O (30 mL) and extracted with CHCl3 (2 × 30 mL). The chloroform
layer was extracted with H2O (30 mL). The water phase was evaporated
to dryness affording a yellow foam. The resulting residue was purified by

Nucleosides Synthesis Using Click Chemistry Approach
375
column chromatography (0–12% CH3OH in CH2Cl2) to afford 14 (3.58 g,
65%) as a white foam, and the data were found correct.[17]
Synthesis of 2ꢁ-Deoxy-2ꢁ-[4-(phenoxymethyl)-1H-1,2,3-triazol-1-yl]uridi-
ne (15, 52%). To a stirred mixture of azide 14 (350 mg, 1.30 mmol) and
7 (214 mg, 1.62 mmol) in t-BuOH/H2O (7 mL, 1:1 v/v) was added sodium
ascorbate (32 mg, 0.16 mmol) and CuSO4.5H2O (20 mg, 0.08 mmol). The
mixture was stirred at room temperature for 10 hours. The mixture was con-
centrated under reduced pressure and the residue was purified by silica gel
column chromatography (0–6% CH3OH in CH2Cl2) to give desired product
(15) (272 mg, 52%) as a foam: Rf 0.50 (CH3OH: CH2Cl2, 1:9 v/v)); 1H NMR
(400 MHz, DMSO) δ 11.37 (br s, 1H, NH), 8.25 (s, 1H, H-5ꢁꢁ), 8.02 (d, 1H,
J = 7.6 Hz, H-6), 7.30 (t, 2H, J = 8.0 Hz, Ph), 7.04 (d, 2H, J = 8.8 Hz, Ph),
6.95 (t, 1H, J = 7.2 Hz, Ph), 6.48 (d, 1H, J = 6.0 Hz, H-1ꢁ), 5.90 (d, 1H, J =
5.2 Hz, 3ꢁ-OH), 5.71 (d, 1H, J = 7.6 Hz, H-5), 5.44 (t, 1H, J = 5.6 Hz, H-2ꢁ),
5.29 (t, 1H, J = 5.2 Hz, 5ꢁ-OH), 5.14 (s, 2H, CH2), 4.44 (q, 1H, J = 5.2 Hz,
H-3ꢁ), 4.12 (m, 1H, H-4ꢁ), 3.77-3.74 (m, 1H, H-5ꢁ), 3.66-3.63 (m, 1H, H-5ꢁ);
13C NMR (100 MHz, CDCl3) δ 162.9 (C-4), 150.3 (C-2), 158.1 (Ph), 142.3
(C-4ꢁꢁ), 140.0 (C-6), 129.5 (Ph), 125.5 (C-5ꢁꢁ), 120.8, 114.6 (Ph), 102.3 (C-5),
85.8 (C-4ꢁ), 85.7 (C-1ꢁ), 69.2 (C-3ꢁ), 64.8 (C-2ꢁ), 60.9 (CH2), 60.4 (C-5ꢁ); ESI
MS m/z (424.1215 [M + Na]+, C18H19N5O6−Na+ calcd. 424.1228).
The compounds 16–22 were synthesized using the same procedure as
compound 15 and were obtained as foam.
2ꢁ-Deoxy-2ꢁ-[4-(4-chlorophenoxymethyl)-1H-1,2,3-triazol-1-yl]uridine
(16, 64%). Rf 0.45 (CH3OH: CH2Cl2, 1:9 v/v); 1H NMR (400 MHz, DMSO)
δ 11.38 (br s, 1H, NH), 8.27 (s, 1H, H-5ꢁꢁ), 8.02 (d, 1H, J = 8.0 Hz, H-6),
7.34 (d, 2H, J = 8.8 Hz, Ph), 7.08 (d, 2H, J = 8.8 Hz, Ph), 6.48 (d, 1H, J
= 6.0 Hz, H-1ꢁ), 5.92 (d, 1H, J = 5.6 Hz, 3ꢁ-OH), 5.72 (d, 1H, J = 8.0 Hz,
H-5), 5.46 (t, 1H, J = 6.0 Hz, H-2ꢁ), 5.31 (t, 1H, J = 5.2 Hz, 5ꢁ-OH), 5.15
(s, 2H, CH2), 4.44 (q, 1H, J = 5.6 Hz, H-3ꢁ), 4.13 (br s, 1H, H-4ꢁ), 3.78-3.74
(m, 1H, H-5ꢁ), 3.67-3.62 (m, 1H, H-5ꢁ); 13C NMR (100 MHz, CDCl3) δ 162.9
(C-4), 156.9 (Ph), 150.3 (C-2), 142.0 (C-4ꢁꢁ), 140.0 (C-6), 129.2 (Ph), 125.7
(C-5ꢁꢁ), 124.5, 116.4 (Ph), 102.3 (C-5), 85.8 (C-4ꢁ), 85.7 (C-1ꢁ),69.2 (C-3ꢁ),
64.8 (C-2ꢁ), 61.3 (CH2), 60.4 (C-5ꢁ); ESI MS m/z (458.0847 [M + Na]+,
C18H18ClN5O6−Na+ calcd. 458.0838).
2ꢁ-Deoxy-2ꢁ-[4-(2-chlorophenoxymethyl)-1H-1,2,3-triazol-1-yl]uridine
(17, 53%). Rf 0.70 (CH3OH: CH2Cl2, 3:17 v/v); 1H NMR (400 MHz, DMSO)
δ 11.39 (s, 1H, NH), 8.28 (s, 1H, H-5ꢁꢁ), 8.03 (d, 1H, J = 8.0 Hz, H-6), 7.43
(dd, 1H, J = 4.0, 8.0 Hz, Ph), 7.38 (dd, 1H, J = 4.0, 8.0 Hz, Ph), 7.35-7.30
(m, 1H, Ph), 7.0-6.96 (m, 1H, Ph), 6.50 (d, 1H, J = 8.0 Hz, H-1ꢁ), 5.93
(d, 1H, J = 4.0 Hz, 3ꢁ-OH), 5.73 (dd, 1H, J = 4.0, 8.0 Hz, H-5), 5.46 (t,
1H, J = 4.0 Hz, H-2ꢁ), 5.31 (br s, 1H, 5ꢁ-OH), 5.26 (s, 2H, CH2), 4.45 (q,
1H, J = 4.0 Hz, H-3ꢁ), 4.14-4.12 (m, 1H, H-4ꢁ), 3.78-3.75 (m, 1H, H-5ꢁ),
3.67-3.64 (m, 1H, H-5ꢁ); 13C NMR (100 MHz, DMSO) δ 162.9 (C-4), 153.4
(Ph), 150.3 (C-2), 141.9 (C-4ꢁꢁ), 140.1 (C-6), 130.0, 128.3 (Ph), 125.8 (C-5ꢁꢁ),

376
S. Kumar
121.8, 121.4, 114.4 (Ph), 102.3 (C-5), 85.8 (C-4ꢁ), 85.7 (C-1ꢁ), 69.2 (C-3ꢁ),
64.8 (C-2ꢁ), 61.9 (CH2), 60.4 (C-5ꢁ); ESI MS m/z (458.0845 [M + Na]+,
C18H18ClN5O6−Na+ calcd. 458.0838).
2ꢁ-Deoxy-2ꢁ-[4-(4-methylphenoxymethyl)-1H-1,2,3-triazol-1-yl]uridine
(18, 67%). Rf 0.55 (CH3OH: CH2Cl2, 1:9 v/v); 1H NMR (400 MHz, DMSO)
δ 11.37 (br s, 1H, NH), 8.23 (s, 1H, H-5ꢁꢁ), 8.02 (d, 1H, J = 7.6 Hz, H-6),
7.09 (d, 2H, J = 8.0 Hz, Ph), 6.93 (d, 2H, J = 8.0 Hz, Ph), 6.48 (d, 1H, J
= 5.6 Hz, H-1ꢁ), 5.90 (d, 1H, J = 5.2 Hz, 3ꢁ-OH), 5.71 (d, 1H, J = 7.6 Hz,
H-5), 5.44 (t, 1H, J = 5.6 Hz, H-2ꢁ), 5.29 (t, 1H, J = 4.8 Hz, 5ꢁ-OH), 5.09 (s,
2H, CH2), 4.44 (q, 1H, J = 4.4 Hz, H-3ꢁ), 4.13 (br s, 1H, H-4ꢁ), 3.77-3.74 (m,
1H, H-5ꢁ), 3.66-3.63 (m, 1H, H-5ꢁ), 2.23 (s, 3H, CH3); 13C NMR (100 MHz,
DMSO) δ 162.8 (C-4), 156.0 (Ph), 150.3 (C-2), 142.4 (C-4ꢁꢁ), 140.0 (C-6),
129.8, 129.4 (Ph), 125.4 (C-5ꢁꢁ), 114.4 (Ph), 102.3 (C-5), 85.8 (C-4ꢁ), 85.7
(C-1ꢁ), 69.2 (C-3ꢁ), 64.8 (C-2ꢁ), 60.9 (CH2), 60.4 (C-5ꢁ), 20.0 (CH3); ESI MS
m/z (438.1387 [M + Na]+, C19H21N5O6−Na+ calcd. 438.1384).
2ꢁ-Deoxy-2ꢁ-[4-(4-methoxyphenoxymethyl)-1H-1,2,3-triazol-1-yl]uridine
(19, 63%). Rf 0.50 (CH3OH: CH2Cl2, 1:9 v/v); 1H NMR (400 MHz, DMSO)
δ 11.39 (br s, 1H, NH), 8.23 (s, 1H, H-5ꢁꢁ), 8.02 (d, 1H, J = 8.0 Hz, H-6),
6.98 (d, 2H, J = 8.8 Hz, Ph), 6.86 (d, 2H, J = 8.8 Hz, Ph), 6.49 (d, 1H, J =
6.0 Hz, H-1ꢁ), 5.92 (d, 1H, J = 5.6 Hz, 3ꢁ-OH), 5.72 (d, 1H, J = 8.0 Hz, H-5),
5.44 (t, 1H, J = 6.0 Hz, H-2ꢁ), 5.31 (br s, 1H, 5ꢁ-OH), 5.07 (s, 2H, CH2),
4.44 (q, 1H, J = 4.8 Hz, H-3ꢁ), 4.13 (br s, 1H, H-4ꢁ), 3.78-3.74 (m, 1H, H-5ꢁ),
3.70 (s, 3H, OCH3), 3.66-3.63 (m, 1H, H-5ꢁ); 13C NMR (100 MHz, CDCl3) δ
162.9 (C-4), 153.6, 152.1 (Ph), 150.4 (C-2), 142.6 (C-4ꢁꢁ), 140.1 (C-6), 125.4
(C-5ꢁꢁ), 115.6, 114.6 (Ph), 102.4 (C-5), 85.8 (C-4ꢁ), 85.7 (C-1ꢁ), 69.2 (C-3ꢁ),
64.8 (C-2ꢁ), 61.5 (CH2), 60.4 (C-5ꢁ), 55.3 (OCH3); ESI MS m/z (454.1355
[M + Na]+, C19H21N5O7−Na+ calcd. 454.1334).
2ꢁ-Deoxy-2ꢁ-[4-(3-nitophenoxymethyl)-1H-1,2,3-triazol-1-yl]uridine (20,
1
82%). Rf 0.55 (CH3OH: CH2Cl2, 1:9 v/v); H NMR (400 MHz, DMSO) δ
11.39 (br s, 1H, NH), 8.31 (s, 1H, H-5ꢁꢁ), 8.02 (d, 1H, J = 8.0 Hz, H-6), 7.89
(s, 1H, Ph), 7.84 (d, 1H, J = 7.6 Hz, Ph), 7.60 (t, 1H, J = 8.0 Hz, Ph), 7.53
(d, 1H, J = 8.4 Hz, Ph), 6.49 (d, 1H, J = 5.6 Hz, H-1ꢁ), 5.93 (d, 1H, J =
5.2 Hz, 3ꢁ-OH), 5.72 (d, 1H, J = 8.0 Hz, H-5), 5.46 (t, 1H, J = 6.0 Hz, H-2ꢁ),
5.32 (br s, 3H, CH2, 5ꢁ-OH), 4.45 (q, 1H, J = 5.2 Hz, H-3ꢁ), 4.13-4.10 (m, 1H,
H-4ꢁ), 3.78-3.75 (m, 1H, H-5ꢁ), 3.66-3.64 (m, 1H, H-5ꢁ); 13C NMR (100 MHz,
CDCl3) δ 162.9 (C-4), 158.6 (Ph), 150.4 (C-2), 148.7 (Ph), 141.6 (C-4ꢁꢁ),
140.1 (C-6), 130.7 (Ph), 126.0 (C-5ꢁꢁ), 122.1, 115.8, 109.1 (Ph), 102.3 (C-5),
85.8 (C-4ꢁ), 85.7 (C-1ꢁ), 69.2 (C-3ꢁ), 64.9 (C-2ꢁ), 61.7 (CH2), 60.4 (C-5ꢁ); ESI
MS m/z (469.1073 [M + Na]+, C18H18N6O8−Na+ calcd. 469.1079).
2ꢁ-Deoxy-2ꢁ-[4-(phenyl)-1H-1,2,3-triazol-1-yl]uridine (21, 68%). Rf 0.60
1
(CH3OH: CH2Cl2, 1:9 v/v); H NMR (300 MHz, DMSO) δ 11.40 (br s,
1H, NH), 8.61(s, 1H, H-5ꢁꢁ), 8.04 (d, 1H, J = 7.8 Hz, H-6), 7.88 (d, 2H, J =
7.2 Hz, Ph), 7.46 (t, 2H, J = 7.2 Hz, Ph), 7.35 (d, 1H, J = 7.2 Hz, Ph), 6.54 (d,
1H, J = 5.4 Hz, H-1ꢁ), 5.94 (br s, 1H, 3ꢁ-OH), 5.72 (d, 1H, J = 7.8 Hz, H-5),

Nucleosides Synthesis Using Click Chemistry Approach
377
5.45 (br s, 1H, H-2ꢁ), 5.31 (br s, 1H, 5ꢁ-OH), 4.49 (br s, 1H, H-3ꢁ), 4.17 (br s,
1H, H-4ꢁ), 3.80-3.66 (m, 2H, H-5ꢁ); 13C NMR (75 MHz, DMSO) δ 163.4 (C-4),
150.8 (C-4ꢁꢁ), 146.5 (C-2), 140.6 (C-6), 131.0, 129.4 (Ph), 128.4 (C-5ꢁꢁ), 125.6,
122.8 (Ph), 102.8 (C-5), 86.4 (C-4ꢁ, C-1ꢁ), 69.8 (C-3ꢁ), 65.6 (C-2ꢁ), 60.9 (C-5ꢁ);
ESI MS m/z (394.1133 [M + Na]+, C17H17N5O5−Na+ calcd. 394.1127).
2ꢁ-Deoxy-2ꢁ-[4-(4-bromophenyl)-1H-1,2,3-triazol-1-yl]uridine (22, 70%).
1
Rf 0.65 (CH3OH: CH2Cl2, 1:9 v/v); H NMR (300 MHz, DMSO) δ 11.40
(br s, 1H, NH), 8.68 (s, 1H, H-5ꢁꢁ), 8.03 (d, 1H, J = 8.1 Hz, H-6), 7.85 (d,
2H, J = 8.1 Hz, Ph), 7.66 (d, 2H, J = 8.1 Hz, Ph), 6.52 (d, 1H, J = 5.4 Hz,
H-1ꢁ), 5.91 (d, 1H, J = 3.6 Hz, 3ꢁ-OH), 5.72 (d, 1H, J = 8.1 Hz, H-5), 5.45
(br s, 1H, H-2ꢁ), 5.31 (br s, 1H, 5ꢁ-OH), 4.47 (br s, 1H, H-3ꢁ), 4.16 (br s, 1H,
H-4ꢁ), 3.80-3.65 (m, 2H, H-5ꢁ); 13C NMR (75 MHz, DMSO) δ 163.4 (C-4),
150.9 (C-4ꢁꢁ), 145.5 (C-2), 140.6 (C-6), 132.3 (Ph), 130.3 (C-5ꢁꢁ), 127.6, 123.2,
121.3 (Ph), 102.8 (C-5), 86.4 (C-4ꢁ, C-1ꢁ), 69.8 (C-3ꢁ), 65.6 (C-2ꢁ), 60.9 (C-5ꢁ);
ESI MS m/z (449.0345 [M + Na]+, C17H16BrN5O5−Na+ calcd. 449.0335).
FUNDING
Department of Science and Technology (DST) and University Grants
Commission (UGC), New Delhi are highly acknowledged for providing the
financial assistance for this project.
REFERENCES
1. Kukhanova, M.; Krayevsky, A.; Prusoff, W.; Cheng, Y. Design of anti-HIV compounds from nucleoside
to nucleoside 5-triphosphate analogs. Problems and perspectives. Curr. Pharm. Des. 2000, 6, 585–598.
2. Galmarini, C.; Mackey, J.; Dumontet, C. Nucleoside analogues and nucleobases in cancer treatment.
Lancet Oncol. 2002, 3, 415–424.
3. Iyer, R.; Padmanabhan, S.; Zhang, G.; Morrey, J.; Korba, B. Nucleotide analogs as novel anti-hepatitis
B virus agents. Curr. Opin. Pharmacol. 2005, 5, 520–528.
4. Tang, Y.B.; Peng, Z.G.; Liu, Z.Y.; Li, Y.P.; Jiang, J.D.; Li, Z.R. Some new acyclic nucleotide analogues
as antiviral prodrugs: Synthesis and bioactivities in vitro. Bioorg. Med. Chem. Lett. 2007, 17, 6350–6353.
5. Cihlar, T.; Ray, A.S. Nucleoside and nucleotide HIV reverse transcriptase inhibitors: 25 years after
zidovudine. Antiviral Res. 2010, 85, 39–58.
6. (a) Wan, J.; Xia, Y.; Liu, Y.; Wang, M.; Rocchi, P.; Yao, J.; Qu, F.; Neyts, J.; Iovanna, J.L.; Peng,
L. Discovery of novel arylethynyltriazole ribonucleosides with selective and effective antiviral and
anti-proliferative activity. J. Med. Chem., 2009, 52, 1144–1155. (b) Montague, A.; Roy, V.; Balzarini,
J.; Snoeck, R.; Andrei, G.; Agrofoglio, L.A. Synthesis of new C5-(1-substituted-1,2,3-triaole-4 or 5-yl)-
2-deoxyuridines and their antiviral evaluation. Eur. J. Med. Chem. 2011, 46, 778–786. (c) Ferreira,
M.D.L.G.; Pinheiro, L.C.S.; Filho, O.A.S.; Pec¸anha, M.D.S.; Sacramento, C.Q.; Machado, V.; Ferreira,
V.F.; Souza, T.M.L.; Boechat, N. Design, synthesis, and antiviral activity of new 1H-1,2,3-triazole
nucleoside ribavirin analogs. Med. Chem. Res. 2014, 23, 1501–1511.
7. Kirschberg, T.A.; Balakrishnan, M.; Huang, W.; Hluhanich, R.; Kutty, N.; Liclican, A.C.; McColl,
D.J.; Squires, N.H.; Lansdon, E.B. Triazole derivatives as non-nucleoside inhibitors of HIV-1 reverse
transcriptase – Structure–activity relationships and crystallographic analysis. Bioorg. Med. Chem. Lett.
2008, 18, 1131–1134.
8. Khalil, N.S.A.M. Efficient synthesis, structure and antimicrobial activity of some novel N- and S-β-D-
glucosides of 5-pyridin-3-yl-1,2,4-triazoles. Carbohydr. Res. 2006, 341, 2187–2199.

378
S. Kumar
9. Kumar, J.M.; Idris, M.M.; Srinivas, G.; Kumar, P.V.; Meghah, V.; Kavitha, M.; Reddy, C.R.; Mainkar,
P.S.; Pal, B.; Chandrasekar, S.; Nagesh, N. Phenyl 1,2,3-triazole-thymidine ligands stabilize G-
quadruplex DNA, inhibit DNA synthesis and potentially reduce tumor cell proliferation over 3ꢁ-azido
deoxythymidine. PLOS One 2013, 8, e70798.
10. Yu, J.L.; Wu, Q.P.; Zhang, Q.S.; Liu, Y.H.; Li, Y.Z.; Zhou, Z.M. Synthesis and antitumor activity of
novel 2ꢁ,3ꢁ-dideoxy-2ꢁ,3ꢁ-diethane thionucleosides bearing 1,2,3-triazole residues. Bioorg. Med. Chem.
Lett. 2010, 20, 240–243.
11. (a) Amblard, F.; Cho, J.H.; Shinazi, R.F. Cu(I)-catalyzed Huisgen Azide-Alkyne 1,3-dipolar cycload-
dition reaction in nucleoside, nucleotide, and oligonucleotide chemistry. Chem. Rev. 2009, 109,
4207–4220. (b) Pradere, U.; Roy, V.; McBrayer, R.T.; Schinazi, R.F.; Agrofoglio, L.A. Preparation of
ribavirin analogues by copper- and ruthenium-catalyzed azide-alkyne 1,3-dipolar cycloaddition. Tetra-
hedron 2008, 64, 9044–9051. (c) Elakri, K.; Bougrin, K.; Balzarini, J.; Faraj, A.; Benhida, R. Efficient
synthesis and in vitro cytostatic activity of 4-substituted triazolyl-nucleosides. Bioorg. Med. Chem. Lett.
2007, 17, 6656–6659.
12. Seela, F.; Pujari, S.S.; Schafer, A.H. Hydrogelation and spontaneous fiber formation of 8-aza-7-
deazaadenine nucleoside “click” conjugates. Tetrahedron 2011, 67, 7418–7425.
13. (a) Alvarez, R.; Velazquez, S.; San-Felix, A.; Aquaro, S.; De Clercq, E.; Perno, C-F.; Karls-
son, A.; Balzarini, J.; Camarasa, M.J. 1,2,3-Triazole-[2,5-Bis-O-(tert-butyldimethylsilyl)-.beta.-D-
ribofuranosyl]-3ꢁ-spiro-5ꢁꢁ-(4ꢁꢁ-amino-1ꢁꢁ,2ꢁꢁ-oxathiole 2ꢁꢁ,2ꢁꢁ-dioxide) (TSAO) analogs: Synthesis and
anti-HIV-1 activity. J. Med. Chem. 1994, 37, 4185–4194. (b) Chaudhary, P.M.; Chavan, S.R.; Shirazi, F.;
Razdan, M.; Nimkar, P.; Maybhate, S.P.; Likhite, A.P.; Gonnade, R.; Hazara, B.G.; Deshpande, M.V.;
Deshpande, S.R. Exploration of click reaction for the synthesis of modified nucleosides as chitin
synthase inhibitors. Bioorg. Med. Chem. 2009, 17, 2433–2440.
14. Zhou, L.; Amer, A.; Korn, M.; Burda, R.; Balzarini, J.; De Clercq, E.; Kern, E.R.; Torrence, P.F.
Synthesis and antiviral activities of 1,2,3-triazole functionalized thymidines: 1,3-dipolar cycloaddition
for efficient regioselective diversity generation. Antivi. Chem. Chemother. 2005, 16, 375–383.
15. Mahony, G.O.; Svensson, S.; Sundgren, A.; Grotli, M. Synthesis of 2ꢁ-([1,2,3]triazol-1-yl)-2ꢁ-
deoxyadenosines. Nucleos. Nucleot. Nucl. 2008, 27, 449–459.
16. Hampton, A.; Nichol, A.W. Nucleosides V purine ribonucleoside 2ꢁ,3ꢁ-cyclic carbonates. Preparation
and use for the synthesis of 5ꢁ-monosubstituted nucleosides. Biochemistry 1966, 5, 2076–2082.
17. Kirschenheuter, G. P.; Zhai, Y.; Pieken, W.A. An improved synthesis of 2ꢁ-azido-2ꢁ-deoxyuridine.
Tetrahedron Lett. 1994, 35, 8517–8520.