Synthesis and Photophysical Studies on N1-(2′-O,4′-C-Methyleneribofurano-nucleoside-3′-yl)-C4-(coumarin-7-oxymethyl)-1,2,3-triazoles

Article abstract of DOI:10.1016/j.carres.2018.09.007

A series of eight N¹-(2′-O,4′-C-methylene-β-D-ribofuranonucleoside-3′-yl)-C⁴-(coumarin-7-oxymethyl)-1,2,3-triazoles have been synthesized by Cu(I)-catalyzed azide-alkyne cycloaddition reaction of 3′-azido-3′-deoxy-2′-O,4′-C-methylene

Full text of DOI:10.1016/j.carres.2018.09.007

Accepted Manuscript
1
Synthesis and Photophysical Studies on N -(2′-O,4′-C-methyleneribofurano-
4
nucleoside-3′-yl)-C -(coumarin-7-oxymethyl)-1,2,3-triazoles
Smriti Srivastava, Vipin K. Maikhuri, Rajesh Kumar, Kapil Bohra, Harbansh Singla,
Jyotirmoy Maity, Ashok K. Prasad
PII:
S0008-6215(18)30493-2
10.1016/j.carres.2018.09.007
CAR 7610
DOI:
Reference:
To appear in: Carbohydrate Research
Received Date: 25 August 2018
Revised Date: 27 September 2018
Accepted Date: 27 September 2018
Please cite this article as: S. Srivastava, V.K. Maikhuri, R. Kumar, K. Bohra, H. Singla, J. Maity, A.K.
1
Prasad, Synthesis and Photophysical Studies on N -(2′-O,4′-C-methyleneribofurano-nucleoside-3′-
4
yl)-C -(coumarin-7-oxymethyl)-1,2,3-triazoles, Carbohydrate Research (2018), doi: https://
doi.org/10.1016/j.carres.2018.09.007.
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Graphical abstract

ACCEPTED MANUSCRIPT
1
Synthesis and Photophysical Studies on N -(2'-O,4'-C-methyleneribofurano-
4
nucleoside-3'-yl)-C -(coumarin-7-oxymethyl)-1,2,3-triazoles
a
a
a
b
a
Smriti Srivastava, Vipin K. Maikhuri, Rajesh Kumar, Kapil Bohra, Harbansh Singla,
a
a
Jyotirmoy Maity and Ashok K. Prasad
a
Bioorganic Laboratory, Department of Chemistry, University of Delhi, Delhi-110 007
Department of Chemistry, DDU College, University of Delhi, Dwarka, Sect. 3, Delhi-110 078
b
Abstract
A series of eight N -(2'-O,4'-C-methylene-β-
1
4
D
-ribofuranonucleoside-3'-yl)-C -(coumarin-7-
oxymethyl)-1,2,3-triazoles have been synthesized by Cu(I)-catalyzed azide-alkyne cycloaddition
reaction of 3'-azido-3'-deoxy-2'-O,4'-C-methyleneuridine and 3'-azido-3'-deoxy-2'-O,4'-C-
methylene-5-methyluridine with 7-propargyloxy coumarins in 82-88% yields. The synthesized
coumarintriazolyl-bicyclonucleoside conjugates possess an extra bridge between 2'-O and 4'-C in
the nucleoside moiety, which facilitates its pre-organization into N-type sugar puckering. This was
1
confirmed by X-ray crystal structure studies on one of the conjugates, i.e. on N -(3'-deoxy-2'-O,4'-
4
C-methylene-5-methyluridin-3'-yl)-C -(4-phenylcoumarin-7-oxymethyl)-1,2,3-triazole. Photophy-
sical studies carried out on the synthesized compounds demonstrate that they possess useful level
of fluorescence with Stokes shift of approximately 70 nm.
1
. Introduction
1
Modified nucleosides have shown their importance in the field of bio-medical science as
2
,3
2a
4,5
6
antibacterial, antifungal, antiviral
and anticancer agents. Efficient and facile synthetic
methodologies have been developed for synthesis of triazole-linked modified nucleosides in
7
,8
view of their unique biological and photophysical profiles. For the synthesis of substituted
triazoles Huisgen has pioneered azide-alkyne 1,3-dipolar cycloaddition reactions under thermal
condition. The Cu(I)-catalyzed version of the Huisgen [3+2] cycloaddition reaction between a
9
terminal alkyne and an azide regioselectively produces 1,4-disubstituted 1,2,3-triazoles. This
reaction has been used to introduce fluorescent moiety on less fluorescent or non-fluorescent
1
0,11
nucleosides among other class of molecules via a triazole linker.
The bicyclonucleosides, in particular 2'-O,4'-C-methyleneribonucleosides (LNA monomers)
have attracted the spotlight of nucleoside chemists worldwide due to their N-type sugar ring

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conformation, which make them RNA mimic. When incorporated into an oligonucleotide,
conformational restriction of LNA monomers provides a preorganized backbone of the
oligonucleotide and increase base stacking interactions, leading to an energetically favorable
1
2
13
duplex formation. Coumarin-nucleoside conjugates have been synthesized by Kosiova, et al.
1
4
15
and Seela, et al. for the determination of their fluorescent properties. Olomolo, et al.
synthesized coumarin triazolyl-conjugated nucleosides and evaluated their potential against dual
action HIV I protease and non-nucleoside reverse trancriptase. Coumarins and their derivatives
have shown sufficient fluorescence in the visible light range to be used in laser dyes and organic
light-emitting diodes. Intense fluorescent triazol-linked sugar coumarin derivatives were
16
synthesized by Rajaganesh et al., whereas fluorescent coumarin-triazolylglycosides were
1
7
18
synthesized by Nyuchev et al. for their application in surface imaging. He, et al. synthesized
3,4-bis-triazolocoumarin-sugar conjugates and studied their quenching specificity with silver (I) in
1
9
aqueous media and Xue, et al. synthesized triazolyl bidentate glycoligands and performed optical
studies with them. The current developments in the field of bicyclic-nucleosides as well as in
triazole-linked fluorescent nucleoside conjugates encouraged us to synthesize coumarintriazolyl-
1
4
bicyclonucleosides, viz. N -(2'-O,4'-C-methyleneribofuranosyl-nucleoside-3'-yl)-C -(coumarin-7-
oxymethyl)-1,2,3-triazoles and evaluate their photo-physical properties.
2
.
Results and Discussion
The retrosynthetic analysis of the desired coumarintriazolyl-bicyclonucleoside conjugate
revealed that Cu(I)-catalyzed Huisgen [3+2] cycloaddition reaction between 3'-
azidobicyclonucleoside and 7-propargyloxycoumarin should lead to the desired compound
(
Scheme 1). Two 3-azidobicyclonucleosides, i.e. 3'-azido-3'-deoxy-2'-O,4'-C-methyleneuridine
5a) and 3'-azido-3'-deoxy-2'-O,4'-C-methylene-5-methyluridine (5b) were synthesized by
(
Vorbrüggen coupling of uracil and thymine, respectively, with the common glycosyl donor 3-
azido-3-deoxy-1,2-O-diacetyl-5-O-methanesulfonyl-4-C-methanesulfonyloxymethyl-α-
ribofuranose (3), which in turn was synthesized from the commercially available diacetone-
glucose through intermediate compounds 1 and 2 following literature procedure in an overall
D
-
D
-
2
0,21,22
yields of 15-20% (Scheme 2).

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Scheme 1: Retrosynthetic analysis of coumarintriazolyl-bicyclonucleoside conjugates.
Scheme 2: Synthesis of 3'-azido-3'-deoxy-2'-O,4'-C-methylene-β- -ribofuranosyl pyrimidines.
D
The other key precursor, 7-propargyloxycoumarin (6), 4-methyl-7-propargyloxycoumarin (7), 6-
chloro-4-methyl-7-propargyloxycoumarin (8) and 4-phenyl-7-propargyloxycoumarin (9) were
synthesized by propargylation of 7-hydroxycoumarin, 7-hydroxy-4-methylcoumarin, 6-chloro-7-
hydroxy-4-methylcoumarin and 7-hydroxy-4-phenylcoumarin, respectively using propargyl
23,24
bromide in acetone in the presence of potassium carbonate in 80-85% yields.
Each of the two
3-azidobicyclonucleoside, 5a and 5b were subjected to Cu(I)-catalyzed azide-alkyne
cycloaddition reaction with 7-propargyloxycoumarins 6-9 in the presence of CuSO
4
2
.5H O-
1
sodium ascorbate as a coupling reagent in mixture of THF:tert-BuOH:H O (1:1:1) to afford N -
2
4
1
(
3'-deoxy-2'-O,4'-C-methyleneuridin-3'-yl)-C -(coumarin-7-oxymethyl)-1,2,3-triazole (10), N -(3'-
4
deoxy-2'-O,4'-C-methyleneuridin-3'-yl)-C -(4-methylcoumarin-7-oxymethyl)-1,2,3-triazole (11),
1
4
N -(3'-deoxy-2'-O,4'-C-methyleneuridin-3'-yl)-C -(6-chloro-4-methylcoumarin-7-oxymethyl)-
1
4
1
,2,3-triazole (12), N -(3'-deoxy-2'-O,4'-C-methyleneuridin-3'-yl)-C -(4-phenylcoumarin-7-

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1
4
oxymethyl)-1,2,3-triazole (13), N -(3'-deoxy-2'-O,4'-C-methylene-5-methyluridin-3'-yl)-C -
1
(
coumarin-7-oxymethyl)-1,2,3-triazole (14), N -(3'-deoxy-2'-O,4'-C-methylene-5-methyluridin-
4
1
3
'-yl)-C -(4-methylcoumarin-7-oxymethyl)-1,2,3-triazole
(15),
N -(3'-deoxy-2'-O,4'-C-
4
methylene-5-methyluridin-3'-yl)-C -(6-chloro-4-methylcoumarin-7-oxymethyl)-1,2,3-triazole
1
4
(16)
and
N -(3'-deoxy-2'-O,4'-C-methylene-5-methyluridin-3'-yl)-C -(4-phenylcoumarin-7-
oxymethyl)-1,2,3-triazole (17) in 82-88% yields (Scheme 3).
Scheme 3: Synthesis of coumarintriazolyl-bicyclonucleoside conjugates 10-17.
The structures of all the synthesized compounds 1-17 were unambiguously established on the
1
13
basis of their spectral (IR, H-, C NMR and HRMS) data analysis. The structures of known
compounds 1-9 were further confirmed on the basis of comparison of their physical and spectral
2
0-24
data with those reported in the literature.
The synthetic procedure and experimental details of
'-O-acetyl-3'-azido-3'-deoxy-5'-O-methanesulfonyl-4'-C-methanesulfonyloxymethyl-uridine (4a),
'-azido-3'-deoxy-5'-O-methanesulfonyl-2'-O,4'-C-methyleneuridine, 3'-azido-5'-O-benzoyl-3'-
2
3
deoxy-2'-O,4'-C-methyleneuridine and 3'-azido-3'-deoxy-2'-O,4'-C-methyleneuridine (5a) are
22
reported in a patent only. Herein, we have provided their synthesis and characterization data in
the supporting information.

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1
The single crystal X-ray diffraction studies was performed on N -(3'-deoxy-2'-O,4'-C-methylene-
4
5
-methyluridin-3'-yl)-C -(4-phenylcoumarin-7-oxymethyl)-1,2,3-triazole (17), which revealed its
important structural features. The crystal structure of compound 17 showed that the nucleoside
moiety of the compound is locked in the N-type conformation due to the presence of 2'-O,4'-C-
methylene bridge (Figure 1). Further, we report herein the crystal structures of compounds 1 and
2
for the first time, which clearly reveal the opposite configuration of C-3 hydroxy group in
compound 1 with respect to the C-3 azido group in compound 2 (Scheme 2 and Figure 2). The
detailed crystallographic data of compounds 1, 2 and 17 were deposited in the Cambridge
Crystallographic Data Centre with CCDC nos. 1535099, 1535166 and 1547973, respectively
(Figure 2).
(a)
(b)
(c)
(d)
(e)
Figure 1: (a) Molecular structure of compound 17; (b) and (c) ORTEP diagram of compound 17
drawn in 50% thermal probability ellipsoids. Solvent molecules are omitted for clarity; (d)
Preferred N-type sugar ring puckering in compound 17; (e) Representative N-type sugar
puckering in nucleosides.

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OH
HO
HO
MsO
MsO
O
O
O
O
N3
O
O
1
2
(a)
(b)
(c)
(d)
Figure 2: (a) and (c) Molecular structures of compounds 1 and 2; (b) and (d) Mercury diagram of
compounds 1 and 2 drawn in 20% thermal probability ellipsoids showing inversion of
configuration at C-3 carbon on chemical conversion of compound 1 to 2.
1
Photophysical Studies: The photophysical properties of all the synthesized N -(3'-deoxy-2'-O,4'-C-
4
methylene-β-
D
-ribofuranosylnucleoside-3'-yl)-C -(coumarin-7-oxymethyl)-1,2,3-triazoles 10-17
and their precursors, i.e. azidosugars 5a-5b and propargyloxy coumarins 6-9 were determined in
-5
methanol at 10 M concentration. The absorbance spectra of six coumarintriazolyl-
bicyclonucleoside conjugates 10, 11, 14, 15, 16 and 17 have been shown in Figure 3a. The
fluorescence spectra of the two azidonucleoside precursors 5a-5b and four propargyloxycoumarin
derivatives 6-9 have been shown in Figure 3b and fluorescence spectra of all eight synthesized
coumarintriazolyl-bicyclonucleoside conjugates 10-17 have been shown in Figure 3c. All
coumarintriazolyl-bicyclonucleoside conjugates showed absorbance at approximately 320-330 nm
and emission at around 400 nm (Table 1). Fluorescence intensities of conjugates 10-17 have been
compared with the corresponding coumarin alkynes 6-9 and azides 5a-5b, and has been found
higher than both the precursors. All studied compounds have shown maximum fluorescence
intensity when excited at 320 nm.
(a)
(b)
(c)

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Figure 3: (a) Absorption spectra of compounds 10-11 and 14-17; (b) Emission spectra of
azidonucleosides 5a and 5b and alkynyloxy-compounds 6-9; (c) Emission spectra of
coumarintriazolyl-bicyclonucleoside conjugates 10-17. All spectra were recorded in methanol at
-5
1
0 M concentration.
Table 1: Photophysical data of eight synthesized coumarintriazolyl-bicyclonucleosides 10-17
Compd Absorbance Excitation Emission λem (nm)/
Stoke Shift
(nm)
No.
λ
abs (nm)
λ
ex (nm)
Intensity (au)
390/118
395/153
391/55
10
11
12
13
14
15
16
17
322
320
70
75
71
77
70
74
70
78
322
320
324
320
326
320
397/6
323
320
390/123
394/288
390/118
398/8
321
320
330
320
325
320
Further, structure-fluorescence intensity relationship of the synthesized conjugates 10-17 has been
studied. The electron donating methyl group on C-4 position of coumarin increases the
fluorescence intensity. The electron withdrawing phenyl moiety and chloro-group at C-4 / C-6
positions of coumarin moiety decreases the extent of conjugation by decreasing the electron density
on the coumarin and so the fluorescence emission intensity was decreased. Conjugates having 5-
methyluracil nucleobase were possessing slightly higher fluorescence intensity than conjugates having
uracil nucleobase. The results of spectral studies demonstrate the importance of these triazole-
linked analogues, as the starting sugar azides and alkynyloxy-coumarins possesses lesser
fluorescence intensity than the conjugates.
3
.
Conclusion
A small library of novel coumarintriazolyl-bicyclonucleosides 10-17 has been synthesized by
using very simple and efficient, Cu(I)-catalyzed azide-alkyne cycloaddition reaction between 3'-
azido-3'-deoxy-2'-O,4'-C-methylene-nucleosides and 7-propargyloxy coumarins in 82-88% yields.
The X-ray crystal structure studies on one of the coumarintriazolyl-bicyclonucleoside conjugates
1
7 revealed that the sugar moiety is puckered in N-type conformation. This pre-organization may
have resulted due to the presence of the bridging methylene group between C-2' oxygen and C-4'

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carbon in these coumarintriazolyl-bicyclonucleoside conjugates 10-17. Photophysical studies of
these compounds revealed that they possess useful level of fluorescence properties.
4.
Experimental
Melting points were determined on Buchi M-560 instrument and are uncorrected. The IR spectra
were recorded on a Perkin-Elmer model 2000 FT-IR spectrometer by making KBr disc for solid
samples and thin film for oils. The optical rotations were measured with Rudolph autopol II
1
13
automatic polarimeter using light of 546 nm wavelength. The H- and C NMR spectra were
recorded on a Jeol alpha-400 spectrometer at 400 and 100.6 MHz, respectively, using TMS as
internal standard. The chemical shift values are on δ scale and the coupling constants (J) are in Hz.
1
Signals from -OH groups in H NMR spectra recorded in CDCl and DMSO-d were verified by
3
6
2
removing them by shaking the solution with D O. HR-ESI-TOF-MS analyses were recorded on a
MicroTOF instrument from Bruker Daltonics, Bremen on ESI positive mode. Analytical TLCs
were performed on precoated Merck silica-gel 60F254 plates; the spots were detected under UV
light as well as by charring using 4% H SO in ethanol solution. Silica gel (100-200 mesh) was
2
4
used for column chromatography. Chemicals were obtained from commercial suppliers and were
used without any further purification unless otherwise noted.
Absorption spectra were recorded between 250 nm and 600 nm using a Perkin-Elmer UV/Vis
spectrometer Lambda 45 at scan speed 240 nm/min. All measurements were carried out in PE-
UV/Vis Spectroscopy cells (1 cm). Fluorescence emission spectra were taken on Varian Cary
eclipse Fluorescence spectrophotometer at 10 nm slit width with 150 Watt DC powered Xenon
lamp. Absorption and fluorescence spectra were developed by Origin 6.0 software. HPLC grade
solvents were used for all solution preparation.
1
4.1 General procedure for the preparation of
N
-(3'-deoxy-2'-O,4'-C-methylene-
β-D-
4
ribofuranosyl-nucleoside-3'-yl)-
C
-(coumarin-7-oxymethyl)-1,2,3-triazoles (10-17).
Azidobicyclo nucleosides 5a/5b (0.67 mmol) and 5'-propargylated coumarin 6-9 (0.81 mmol), as
desired were suspended in a mixture of THF:tert-BuOH:H O (1:1:1) (30 mL). Sodium ascorbate
2
(
0.54 mmol) was added into the reaction mixture followed by the addition of CuSO
4 2
.5H O (0.27
mmol). The heterogeneous mixture was stirred vigorously for 10-12 h. After completion of the

ACCEPTED MANUSCRIPT
reaction as shown on analytical TLC, excess of solvents was evaporated under reduced pressure
and traces of any residual moisture were removed by co-evaporation with toluene. The crude
product thus obtained was purified by using silica gel column chromatography to afford the title
compounds in pure form.
1
4
4.1.1.
N -(3'-Deoxy-2'-O,4'-C-methyleneuridin-3'-yl)-C -(coumarin-7-oxymethyl)-1,2,3-
triazole (10). It was obtained as white solid in 85% yield; R
f
3
= 0.45 (10% MeOH in CHCl ); mp:
o
-1
28
D
1
78-180 C; IR (cm , KBr): 3422, 1701, 1400, 1277, 1128, 1053, 1014, 836, 761; [α] = + 4.64
1
(
c 0.05, MeOH); H NMR (400 MHz, DMSO-d ): δ 3.60 (1H, d, J = 8.4 Hz), 3.88 (1H, d, J = 8.4
6
Hz), 3.97-4.09 (2H, m), 4.83 (1H, s), 5.13 (1H, s), 5.28 (2H, s), 5.68 (2H, s), 6.30 (1H, d, J = 2.3
Hz), 7.02 (1H, dd, J = 2.0 & 8.4 Hz), 7.16 (1H, d, J = 3.2 Hz), 7.64 (1H, d, J = 8.4 Hz), 7.85 (1H,
13
d, J = 8.4 Hz), 7.99 (1H, d, J = 9.2 Hz), 8.44 (1H, s), 11.43 (1H, s); C NMR (100.6 MHz, DMSO-
d6): 56.61, 59.53, 61.47, 71.00, 79.24, 86.23, 90.30, 101.14, 101.55, 112.62, 112.72, 112.89, 125.52,
29.82, 138.82, 141.91, 144.16, 149.94, 155.29, 160.09, 161.36, 163.33; HR-ESI-TOF-MS: m/z
δ
1
5
+
+
04.1137 ([M+Na] ), calcd. for [C H N O +Na] 504.1126.
22
19
5
8
1
4
4.1.2.
N
-(3'-Deoxy-2'-
O
,4'-
C
-methyleneuridin-3'-yl)-
C
-(4-methylcoumarin-7-oxymethyl)-
1
,2,3-triazole (11). It was obtained as white solid in 86% yield; R
f
= 0.45 (10% MeOH in CHCl );
3
o
-1
28
D
mp: 166-168 C; IR (cm , KBr): 3424, 2345, 1701, 1389, 1275, 1146, 1054, 848, 567; [α] = +
1
0
.46 (c 0.05, MeOH); H NMR (400 MHz, DMSO-d ): δ 2.40 (3H, s), 3.61 (1H, d, J = 9.2 Hz),
6
3.88 (1H, d, J = 8.4 Hz), 3.96-4.10 (2H, m), 4.83 (1H, s), 5.14 (1H, s), 5.29 (2H, s), 5.46 (1H, t, J
=
6.0 Hz), 5.68 (2H, s), 6.22 (1H, s), 7.05 (1H, dd, J = 2.4 and 8.2 Hz), 7.14 (1H, d, J = 2.4 Hz),
1
3
7
.69 (1H, d, J = 9.2 Hz), 7.85 (1H, d, J = 7.6 Hz), 8.44 (1H, s), 11.43 (1H, s); C NMR (100.6
MHz, DMSO-d6): 18.14, 56.61, 59.54, 61.46, 71.01, 79.25, 86.24, 90.30, 101.14, 101.58,
11.17, 112.59, 113.57, 125.49, 126.51, 138.93, 141.95, 149.62, 153.03, 154.58, 159.82, 161.23,
δ
1
1
+
+
63.65. HR-ESI-TOF-MS: m/z 518.1292 ([M+Na] ), calcd. for [C H N O +Na] 518.1282.
2
3
21
5
8
1
4
4.1.3.
N -(3'-Deoxy-2'-O,4'-C-methyleneuridin-3'-yl)-C -(6-chloro-4-methylcoumarin-7-
oxymethyl)-1,2,3-triazole (12). It was obtained as off white solid in 82% yield; R = 0.45 (10%
f
o
-1
MeOH in CHCl ); mp: 165-167 C; IR (cm , KBr): 3448, 2345, 1707, 1605, 1387, 1279, 1163,
3
2
D
8
1
1047, 826; [α]
6
= + 3.99 (c 0.05, MeOH); H NMR (400 MHz, DMSO-d ): δ 2.39 (3H, s), 3.62
(
1H, d, J = 8.4 Hz), 3.89 (1H, d, J = 8.8 Hz) 3.98-4.11 (2H, m), 4.85 (1H, s), 5.15 (1H, s), 5.39
2H, s), 5.47 (1H, t, J = 5.6 Hz), 5.68 (2H, s), 6.29 (1H, s), 7.47 (1H, s), 7.82 (1H, s), 7.85 (1H, s),
(

ACCEPTED MANUSCRIPT
1
3
8
7
1
.47 (1H, s), 11.43 (1H, s); C NMR (100.6 MHz, DMSO-d ): δ 18.13, 56.62, 59.58, 62.44, 71.03,
6
9.27, 86.23, 90.31, 101.13, 102.15, 112.26, 113.80, 117.73, 125.75, 125.97, 138.92, 141.28,
+
50.13, 152.75, 153.12, 155.74, 159.72, 163.41. HR-ESI-TOF-MS: m/z 552.0897 ([M+Na] ),
+
calcd. for [C H ClN O +Na] 552.0893.
23
20
5
8
1
4
4.1.4.
N -(3'-Deoxy-2'-O,4'-C-methyleneuridin-3'-yl)-C -(4-phenylcoumarin-7-oxymethyl)-
1
,2,3-triazole (13). It was obtained as off white solid in 84% yield; R = 0.45 (10% MeOH in
f
o
-1
3
CHCl ); mp: 169-171 C; IR (cm , KBr): 3422, 2345, 1701, 1458, 1376, 1274, 1153, 1052, 822,
-1
28
1
7
00 cm ; [α] = + 4.30 (c 0.05, MeOH); H NMR (400 MHz, DMSO-d ): δ 3.59 (1H, d, J = 9.2
D
6
Hz), 3.86 (1H, d, J = 8.8 Hz), 3.95-4.08 (2H, m), 4.81 (1H, s), 5.12 (1H, s), 5.29 (2H, s), 5.45 (1H,
t, J = 4.4 Hz), 5.66 (2H, s), 6.24 (1H, s), 6.98 (1H, dd, J = 2.0 and 8.9 Hz), 7.24 (1H, d, J = 2.0
Hz), 7.34 (1H, d, J = 9.2 Hz), 7.49- 7.56 (5H, m), 7.84 (1H, d, J = 7.6 Hz), 8.43 (1H, s), 11.42 (1H,
13
s); C NMR (100.6 MHz, DMSO-d ):
δ
56.61, 59.54, 61.54, 70.01, 79.25, 86.25, 90.31, 101.15,
6
1
1
02.06, 111.54, 112.06, 112.98, 125.54, 127.87, 128.88, 129.70, 134.95, 138.94 , 141.70 , 150.14,
+
55.11, 155.40, 159.98, 161.12, 163.42; HR-ESI-TOF-MS: m/z 580.1443 ([M+Na] ), calcd. for
+
[
C H N O +Na] 580.1439.
2
8
23
5
8
1
4
4.1.5.
N
-(3'-Deoxy-2'-O,4'-C-methylene-5-methyluridin-3'-yl)-C -(coumarin-7-oxymethyl)-
1
,2,3-triazole (14). It was obtained as white solid in 86% yield; R = 0.5 (10% MeOH in CHCl );
f
3
o
-1
28
D
mp: 170-172 C; IR (cm , KBr): 3422, 2118, 1701, 1458, 1278, 1125, 1057, 835, 759; [α] = +
1
4
3
5
2
.24 (c 0.05, MeOH); H NMR (400 MHz, DMSO-d
6
): δ 1.78 (3H, s), 3.58 (1H, d, J = 9.2 Hz),
.86 (1H, d, J = 9.2 Hz), 3.97-4.11 (2H, s), 4.87 (1H, s), 5.10 (1H, s), 5.27 (2H, s), 5.46 (1H, t, J =
.2 Hz), 5.66 (1H, s), 6.28 (1H, d, J = 11.2 Hz), 6.99 (1H, dd, J = 2.4 and 6 Hz), 7.14 (1H, d, J =
.4 Hz), 7.62 (1H, d, J = 8.4 Hz), 7.70 (1H, s), 7.97 (1H, d, J = 9.2 Hz), 8.42 (1H, s), 11.40 (1H,
13
s); C NMR (100.6 MHz, DMSO-d ):
δ
12.65, 57.37, 59.68, 62.27, 71.95, 79.84, 86.71, 90.80,
6
102.11, 108.88, 112.99, 113.21, 113.54, 125.81, 130.57, 134.93, 142.29, 145.03, 150.61, 155.82,
+
+
1
60.97, 161.50; HR-ESI-TOF-MS: m/z 495.1473 ([M+H] ), calcd. for [C23
H
21
N
5
O
8
+H] 495.1463.
1
4
4.1.6.
N
-(3'-Deoxy-2'-O,4'-C
-methylene-5-methyluridin-3'-yl)-
C
-(4-methylcoumarin-7-
oxymethyl)-1,2,3-triazole (15). It was obtained as white solid in 88% yield; R = 0.5 (10% MeOH
f
o
-1
in CHCl ); mp: 166-168 C; IR (cm , KBr): 3154, 2372, 1701, 1458, 1389, 1277, 1145, 1057,
3
28
D
1
850, 760; [α]
6
= + 3.83 (c 0.05, MeOH); H NMR (400 MHz, DMSO-d ): δ 1.76 (3H, s), 2.34
(
3H, s), 3.57 (1H, d, J = 9.2 Hz), 3.84 (1H, d, J = 8.4 Hz), 3.96-4.09 (2H, m), 4.85 (1H, s), 5.08
1H, s), 5.24 (2H, s), 5.47 (1H , t, J = 6.0 Hz), 5.63 (1H, s), 6.16 (1H, s), 6.97 (1H, dd, J = 2.0 and
(

ACCEPTED MANUSCRIPT
9.2 Hz), 7.07 (1H, d, J = 2.4 Hz), 7.62 (1H, d, J = 9.2 Hz), 7.67 (1H, s), 8.39 (1H, s), 11.38 (1H, s);
13
6
C NMR (100.6 MHz, DMSO-d ): δ 12.50, 18.21, 56.82, 59.71, 61.53, 71.06, 79.37, 86.21, 90.39,
1
1
5
01.62, 108.76, 111.38, 112.68, 113.46, 125.56, 126.57, 134.73, 141.88, 150.16, 153.51, 154.70,
+
+
60.25, 161.02, 164.10; HR-ESI-TOF-MS: m/z 510.1620 ([M+H] ), calcd. for [C H N O +H]
24
23
5
8
10.1619.
1
4
4.1.7.
N -(3'-Deoxy-2'-O,4'-C-methylene-5-methyluridin-3'-yl)-C -(6-chloro-4-
methylcoumarin-7-oxymethyl)-1,2,3-triazole (16). It was obtained as white solid in 82% yield;
o
-1
R = 0.45 (10% MeOH in CHCl ); mp: 165-167 C; IR (cm , KBr): 3454, 2345, 1704, 1459, 1388,
f
3
2
8
1
1
2
5
055, 840, 765; [α]
D
6
= + 0.38 (c 0.05, MeOH); H NMR (400 MHz, DMSO-d ): δ 1.76 (3H, s),
.36 (3H, s), 3.56 (1H, d, J = 8.4 Hz), 3.84 (1H, d, J = 8.8 Hz) 3.95-4.09 (2H, m), 4.85 (1H, s),
.09 (1H, s), 5.34 (2H, s), 5.45 (1H, t, J = 5.6 Hz), 5.63 (1H, s), 6.25 (1H, d, J = 1.2 Hz), 7.43 (1H,
13
s), 7.67 (1H, s), 7.79 (1H, s), 8.41 (1H, s), 11.37 (1H, s); C NMR (100.6 MHz, DMSO-d
6
):
2.30, 17.97, 56.54, 59.83, 62.58, 71.22, 79.07, 86.25, 90.46, 108.90, 112.28, 113.75, 118.06,
25.65, 126.30, 134.54, 141.50, 150.09, 153.00, 153.24, 155.61, 159.95, 163.71; HR-ESI-TOF-
δ
1
1
+
+
5 8
MS: m/z 544.1225 ([M+H] ), calcd. for [C24H22ClN O +H] 544.1230.
1
4
4.1.8.
N
-(3'-Deoxy-2'-O,4'-C
-methylene-5-methyluridin-3'-yl)-
C
-(4-phenylcoumarin-7-
oxymethyl)-1,2,3-triazole (17). It was obtained as white solid in 85% yield; R = 0.55 (10%
f
-1
MeOH in CHCl
3
); IR (cm , KBr): 3422, 2345, 1702, 1458, 1376, 1275, 1152, 1055, 859, 757;
28
1
[
α]D = + 4.84 (c 0.05, MeOH); H NMR (400 MHz, DMSO-d ): δ 1.79 (3H, s), 3.59 (1H, d, J =
6
8.8 Hz), 3.86 (1H, d, J = 9.2 Hz), 3.97-4.11 (2H, m), 4.87 (1H, s), 5.11 (1H, s), 5.29 (2H, s), 5.47
(1H, t, J = 5.2 Hz), 5.66 (1H, s), 6.23 (1H, s), 6.97 (1H, dd, J = 2.4 and 9.6 Hz), 7.24 (1H, d, J =
1
3
2
.4 Hz), 7.33 (1H, d, J = 9.2 Hz), 7.49- 7.56 (5H, m), 7.70 (1H, s), 8.43 (1H, s), 11.41 (1H, s); C
): 12.44, 56.76, 59.64, 61.56, 71.00, 79.18, 85.90, 90.31, 102.07,
08.79, 111.33, 112.08, 113.00, 125.34, 127.88, 128.45, 128.89, 129.56, 134.66, 134.85, 141.71,
NMR (100.6 MHz, DMSO-d
6
δ
1
1
+
50.10, 155.05, 155.40, 159.80, 161.35, 164.01; HR-ESI-TOF-MS: m/z 572.1763 ([M+H] ), calcd.
+
for [C29H N
25 5
O
8
+H] 572.1776.
1
4
4
.2. X-Ray diffraction studies on N -(3'-deoxy-2'-O,4'-C-methylene-5-methyluridine-3'-yl)-C -(4-
phenylcoumarin-7-oxymethyl)-1,2,3-triazole (17), 4-C-hydroxymethyl-1,2-O-isopropylidene-β-
threo-pentofuranose (1) and 3-azido-3-deoxy-1,2-O-isopropylidene-5-O-methanesulfonyl-4-C-
methanesulfonyloxymethyl- -ribofuranose (2).
L
-
α-D

ACCEPTED MANUSCRIPT
Single crystals suitable for X-ray diffraction studies were grown by dissolving compounds 1 and
2
in methanol and chloroform mixture, compound 17 in DMSO and by allowing slow
evaporation of the solutions at room temperature. The X-ray diffraction data were collected with
graphite-monochromated Mo Ka radiation (l ¼0.71073 ) at temperature 293 K. The structures
were solved by direct methods using SHELXS-97 and refined by the full-matrix least-squares
Å
2
5
method on F2 (SHELXL-97). All calculations were carried out using the WinGX package of
2
6
27
the crystallographic programs. For the molecular graphics, the program Mercury was used.
Molecular structures were drawn as given in Figures 1 and 2, using Mercury software. The
selected bond lengths, bond angles, etc. are given in Table 2.
Table 2: X-ray crystal data and structure refinement for compounds 17, 1 and 2
17
1
2
Compounds
C
29
H
25
N
5
O
8
C
9
H
16
O
6
11 19 3 9 2
C H N O S
Empirical
formula
Formula
weight
571.17
220.22
401.41
Temperature
Wavelength
293(2) K
293(2) K
0.71073 Å
Monoclinic
298(2) K
0.71073 Å
0.71073 Å
Crystal
system
Monoclinic
P 21
Monoclinic
P 21
Space group
P 21
a = 7.8521(15) Å,
α
= 90°
a = 5.6443(5) Å,
b = 9.4753(6) Å,
α
= 90°
= 90°
a = 5.6530 (4) Å, α = 90°
b = 14.5640(7) Å,
β
=
β
b = 15.0897(5) Å,
95.92°
β =
Unit cell
dimensions
78.99(6)°
c = 14.4304(9) Å,
γ
= 90°
c = 9.7937(2) Å,
γ
= 90°
c = 10.141(3) Å, γ = 90°
3
3
3
Volume
Z
1619.88(17) Å
2
519.33(6) Å
2
860.42(6) Å
2
3
3
3
Density
1.367 mg / m
1.408 mg / m
1.549 mg / m
(calculated)
-1
-1
-1
Absorption
coefficient
0.164 mm
0.119 mm
0.361 mm
F(000)
698.0
236.0
420.0

ACCEPTED MANUSCRIPT
Theta range
for data
2.99 to 24.99°.
3.64 to 24.99°
3.86 to 28.46°
collection
Index ranges
-9≤h
≤
9, -17
≤
k
≤
17, -
-6≤h≤6, -11≤k≤11, -
-6≤h
≤6, -17≤k≤17, -
17≤l≤1
11≤l≤7
12≤l≤12
Reflections
collected
5047
99.8%
3215
9811
Independent
reflections
99.8%
99.8%
Reflections
collected /
unique
19474 / 5694 [R(int) =
0.0326]
3215 / 1468 [R(int) =
.0126]
9811 / 3019 [R(int) =
0.0195]
0
Refinement
method
Full-matrix least-squares
Full-matrix least-squares
Full-matrix least-squares
2
2
2
on F
on F
on F
Data /
restraints /
parameters
5694 / 1 / 432
1.053
2650 / 1 / 136
3019 / 1 / 226
0.867
Goodness-
of-fit on F
1.206
2
Final R
indices
R1 = 0.0752, wR2 =
0.2159
R1 = 0.0405, wR2 =
R1 = 0.0568, wR2 =
0.1236
0.1605
[I>2σ(I)]
R indices
R1 = 0.0918, wR2 =
0.2300
R1 = 0.0412, wR2 =
.1247
R1 = 0.0589, wR2 =
(
all data)
0
0.1644
Absolute
structure
parameter
-0.04(8)
1.5(13)
0.332 and -0.242 e.Å
1535099
0.04(2)
-3
-3
-3
Largest diff.
peak and
hole
-0.749 e.Å
1.719 and -0.741 e.Å
CCDC No.
1547973
1535166
5
. Acknowledgements:
We are grateful to University of Delhi for providing financial support under DU-DST Purse
Grant and under scheme to strengthen research and development. We are also thankful to CIF-
USIC University of Delhi, Delhi for providing crystallographic data and NMR spectral recording
facility. S.S. thanks CSIR for the award of Junior/Senior Research Fellowships. V.K.M. thanks

ACCEPTED MANUSCRIPT
CFEES-DRDO for his research fellowship. R.K. thanks UGC for the award of Junior/Senior
Research Fellowships.
6
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Highlights:
1
2
3
4
. A series of novel coumarintriazolyl-bicyclonucleosides have been synthesized.
. Crystal structure of one coumarintriazolyl-bicyclonucleoside has been reported.
. Synthesis of nucleoside monomers with N-configuration.
. Photo-physical studies of eight coumarintriazolyl-bicyclonucleoside conjugates.