Synthesis of 2′-deoxyuridine and 2′-deoxycytidine Nucleosides bearing bipyridine and terpyridine ligands at position 5

Article abstract of DOI:10.1055/s-0028-1083266

A methodology for the syntheses of pyrimidine (C or U) 2- deoxyribonucleosides bearing bipyridine or terpyridine ligands attached via acetylene or phenylene linkers was developed based on single step cross-coupling reactions of unprotected 5-iodopyrimidin

Full text of DOI:10.1055/s-0028-1083266

PAPER
105
Synthesis of 2¢-Deoxyuridine and 2¢-Deoxycytidine Nucleosides Bearing
Bipyridine and Terpyridine Ligands at Position 5
Nucleosides
Be
u
b
ine and Terp
i
yridin
c
Ligands
a
a
t
Position
5
Kalachova, Radek Pohl, Michal Hocek*
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Gilead & IOCB Research Center,
Flemingovo nám. 2, 16610 Prague 6, Czech Republic
Fax +420(2)20183559; E-mail: hocek@uochb.cas.cz
Received 3 November 2008
sides bearing bpy or terpyridine (tpy) ligands linked via
acetylene or phenylene linkers.
Abstract: A methodology for the syntheses of pyrimidine (C or U)
2-deoxyribonucleosides bearing bipyridine or terpyridine ligands
attached via acetylene or phenylene linkers was developed based on
single step cross-coupling reactions of unprotected 5-iodopyrimi-
dine nucleosides with bipyridine or terpyridine acetylenes of phenyl
boronates. The Sonogashira reactions with acetylenes were per-
formed in DMF, while the Suzuki reactions with boronates in
water–acetonitrile mixtures. Photophysical properties of the title
modified nucleosides have been studied and (2,2¢-bipyridin-5-
yl)ethynyl or (2,2¢-bipyridin-5-yl)phenyl derivatives exerting ab-
sorption at >300 nm and bright emission at 421–451 nm were se-
lected as the best candidates for luminescent DNA labeling.
Our selected approach of choice for the synthesis of the
target modified nucleosides consists in the application of
cross-coupling reactions of unprotected 5-iodopyrimidine
nucleosides. Both Sonogashira9–11 and Suzuki12 cross-
coupling of 5-iodopyrimidines with diverse terminal acet-
ylenes or boronic acids have been extensively used in the
synthesis of 5-modified pyrimidine nucleosides. In recent
years, unprotected nucleosides11–13 are preferentially used
for the cross-couplings in DMF or in aqueous solutions to
save two steps (protection and deprotection). Our goal to
attach bpy or tpy ligands via the cross-coupling reaction is
more challenging due to possible chelation of the Pd cat-
alyst to the bpy/tpy ligand which can terminate the cata-
lytic cycle. Therefore in some cases, a thorough
optimization of the catalytic system, solvent, and condi-
tions must have been performed to achieve good conver-
sions.
Key words: nucleosides, pyrimidines, bipyridines, N-ligands,
cross-coupling reactions
Complexes of 2,2¢-bipyridine (bpy) and related ligands
with transition metals possess1 unique electrochemical
and photophysical properties and thus could be used for
electrochemical or luminescent labeling of biomolecules.
Covalently bound conjugates of pyrimidine nucleotides
with bipyridine or phenanthroline complexes of Ru and
Os have been extensively studied as luminescence probes
for DNA hybridization and charge transfer through
DNA.2 Recently, we have reported on the synthesis of
purine3 and 7-deazapurine4 nucleosides and nucleoside
triphosphates bearing Ru(II)bpy3 and Os(II)bpy3 and their
enzymatic incorporation to DNA by polymerase primer
extension.5 Considerably less attention has been paid to
conjugates of nucleosides with free (nonchelated) bpy-
type ligands, which could be very useful in post synthetic
complexations of nucleosides, nucleotides or nucleic ac-
ids with metals, self assembly and/or catalysis. In purine
bases6 and nucleosides3 and 7-deazapurine nucleosides,4
we have reported all the bipyridine, phenanthroline, and
terpyridine conjugates linked via acetylene or phenylene
tether. However, only two isolated examples of pyrimi-
dine nucleosides bearing N-ligands have been reported so
far: synthesis of 5-[(phenanthrolin-3-yl)ethynyl]-2¢-de-
oxyuridine (including chemical incorporation of its phos-
phoramidite to oligonucleotides)7 and 5-[(bipyridin-6-
yl)ethynyl]-2¢-deoxyuridine.8 To complement the series
of bpy-nucleoside conjugates, we report here on the syn-
thesis of 2¢-deoxyuridine and 2¢-deoxycytidine nucleo-
Terminal acetylenes 1a–c bearing bpy ligand attached via
positions 6 or 5, as well as tpy ligand were the reagents of
choice for the Sonogashira coupling, while the corre-
sponding 4-(pinacolboronato)phenyl derivatives of the
same ligands (compounds 2a–c) were used for the
Suzuki–Miyaura coupling. The synthesis of these starting
building blocks have been reported previously.6 The
cross-coupling partners for these reagents were commer-
cially available unprotected 5-iodo-2¢-deoxycytidine (3)
and -deoxyuridine (4).
The Sonogashira reactions of iodinated pyrimidine nu-
cleosides 3 and 4 with terminal acetylenes 1a–c
(Scheme 1, Table 1) were performed under previously
developed6,4 conditions using 5 mol% of Pd(OAc)2,
water-soluble tris(3-sulfonatophenyl)phosphane (TPPTS)
ligand, CuI, and Hünig’s base in DMF (which in the So-
nogashira reactions of purine bases and nucleosides
worked better6,4 than the aqueous-phase conditions13 us-
ing water–acetonitrile mixtures). All the reactions pro-
ceeded reasonably well at 75 °C to reach full conversion
in 2 hours. The products 5a–c and 6a–c were isolated in
acceptable yields of 63–75% after column chromatogra-
phy. Minor parts of the products were probably lost on
chromatography as complexes with Cu and/or Pd, but also
some minor products of decomposition of rather labile 2¢-
deoxyribonucleosides have also been observed. Taking
into consideration that the synthesis of the target bpy-
SYNTHESIS 2009, No. 1, pp 0105–0112
0
2
.
0
1
.2
0
0
9
Advanced online publication: 12.12.2008
DOI: 10.1055/s-0028-1083266; Art ID: C05508SS
© Georg Thieme Verlag Stuttgart · New York

106
L. Kalachova et al.
PAPER
NH2
N
NH2
NH2
N
R
R
I
I
NH2
N
N
N
N
N
O
O
N
O
HO
HO
HO
O
O
O
O
HO
O
R
1a–c
OH
OH
3
OH
O
O
3
5a–c
7a–c
R
O
N
B
i)
OH
O
R
O
N
R
I
O
N
2a–c
HN
HN
i) A or B
HN
O
N
O
I
HO
HO
O
HN
O
O
HO
O
O
OH
N
HO
OH
O
4
6a–c
OH
8a–c
OH
4
N
N
N
a
b
R =
N
N
N
N
a
b
N
R =
N
N
c
N
N
N
Scheme 1 Reagents and conditions: i) Pd(OAc)2 (5 mol%), TPPTS
(2.5 equiv to Pd), CuI (10 mol%), (i-Pr)2NEt (10 equiv), DMF, 75 °C,
c
2 h.
Scheme 2 Reagents and conditions: i) A: Pd(OAc)2 (5 mol%),
TPPTS (2.5 equiv to Pd), Cs2CO3 (3 equiv), H2O–MeCN (2:1), 80 °C;
B: Pd(OAc)2 (10 mol%), TPPTS (5 equiv to Pd), Cs2CO3 (3 equiv),
H2O–MeCN (1:2), 90 °C.
Table 1 The Sonogashira Reactions of Nucleosides 3 and 4 with
Alkynes 1a–c
Entry
Nucleoside
Alkyne
1a
Product
5a
Yield (%)
Table 2 The Suzuki Reactions of Nucleosides 3 and 4 with
Boronates 2a–c
1
2
3
4
5
6
3
4
3
4
3
4
70
75
67
70
63
67
1a
6a
Entry Nucleoside
Boronate
Product Yield A Yield B
(%)a
65
60
12
7
(%)b
1b
5b
1
2
3
4
5
6
3
4
3
4
3
4
2a
2a
2b
2b
2c
2c
7a
8a
7b
8b
7c
8c
75
1b
6b
75
1c
5c
55
1c
6c
35
28
24
70
modified nucleosides 5 and 6 is just a single-step proce-
dure without any use of protecting groups, the yields were
satisfactory.
70
a Conditions A (see Scheme 2).
b Conditions B (see Scheme 2).
The second class of target compounds were the corre-
sponding phenylene linked conjugates 7 and 8. At first the
Suzuki–Miyaura reactions of boronates 2a–c with nu- prolonged reaction time, the conversions were incomplete
cleosides 3 and 4 were performed under previously and only very low yields of products 7b,c and 8b,c were
developed3,6,13 aqueous-phase conditions using 5 mol% of obtained (entries 3–6).
Pd(OAc)2, TPPTS, and Cs2CO3 in water–acetonitrile 2:1
at 80 °C (Scheme 2, Table 2, conditions A). While the re-
actions of 6-(4-boronatophenyl)bpy 2a with 3 and 4 gave
good conversions and the products 7a and 8a were isolat-
ed in acceptable 60–65% yields (entries 1,2), the other bo-
ronates 2b and 2c reacted very slowly and even after
Therefore, the conditions of the Suzuki reaction were fur-
ther optimized for the reaction of 3 with boronates 2b or
2c. At first several sources of Pd and several ligands suc-
cessful in other aqueous Suzuki reactions with different
boronic acids/boronates have been tested. The reactions
using Pd(PPh3)4 or Pd(OAc)2 in combination with
Synthesis 2009, No. 1, 105–112 © Thieme Stuttgart · New York

PAPER
Nucleosides Bearing Bipyridine and Terpyridine Ligands at Position 5
107
Buchwald’s ligands (S-Phos,14 dicyclohexylphosphino-
biphenyl15) or catalytic system prepared from Na2PdCl4
and disulfonated fluorenyldialkylphosphine16 using dif-
ferent bases (Cs2CO3, NaOH, K2CO3, K3PO4) did not
bring any improvement (the yields varied from 0 to 15%).
Further optimization experiments were performed using
the original Pd(OAc)2/TPPTS catalytic system and fo-
cused on changing the ratio of the reagents and catalyst
and solvent mixtures. These experiments showed that us-
ing 10 mol% of the catalyst and higher amount of the
TPPTS ligand (5 equiv to Pd), as well as changing the sol-
vent mixture to water–acetonitrile (1:2) had a beneficial
effect on the conversion.
Table 3 Absorption and Emission Band Positions in Methanol
Compd Absorption
Emission
max (nm)
l
max (nm) e (L·mol–1·cm–1)
l
f
5a
5b
5c
6a
6b
6c
7a
7b
7c
8a
8b
8c
326
329
283
316
327
282
286
306
286
309
315
285
2.1 × 10–4
5.4 × 10–4
3.7 × 10–4
3.1 × 10–4
3.9 × 10–4
4.4 × 10–4
3.9 × 10–4
3.7 × 10–4
1.2 × 10–4
3.6 × 10–4
5.3 × 10–4
3.4 × 10–4
397
435
445
389
421
408
389
451
444
399
437
427
<0.01
0.11
0.02
<0.01
0.16
0.01
The final optimized conditions (Scheme 2, Table 2, con-
ditions B) then involved the use of 10 mol% of Pd(OAc)2,
50 mol% of TPPTS and Cs2CO3 in water–acetonitrile
(1:2) at 90 °C. In all cases, the yields of the products 7 and
8 were substantially improved compared to the conditions
A. The reactions of 6-linked bpy boronate 2a and tpy-
boronate 2c gave full conversions and satisfactory isolat-
ed yields of products 7a,c and 8a,c (70–75%). Only in the
case of 5-linked bpy-boronate 2b, the conversions were
incomplete and the products 7b and 8b were isolated in
moderate yields of 55 or 35%, respectively.
<0.01
0.18
0.04
<0.01
0.29
0.08
Preliminary study of photophysical properties of the mod-
ified nucleosides has been performed. The UV-VIS ab-
sorption spectra of the compounds revealed absorption
maxima at 282–329 nm. All compounds showed some
luminescence with emission maxima at 389–451 nm
(Table 3). The 6-linked bpy-nucleosides 5a–8a exerted
very low luminescence with negligible quantum yields
and the shortest wavelengths of emission (<400 nm). The
tpy-linked nucleosides 5c–8c gave moderately bright
(f = 1–8%) emission in VIS region. The most interesting
class of compounds were the 5-linked bpy-nucleosides
5b–8b that absorbed at 306–329 nm (and thus in principle
could be selectively excited in DNA) and provided very
bright emission at 421–451 with quantum yields of 11–
29%.
Melting points were determined on a Kofler block. NMR spectra
were measured at 500 MHz for 1H and 125.7 MHz for 13C, or at 600
MHz for 1H and 151 MHz for 13C in DMSO-d6 (referenced to the
1
residual solvent signal: d = 2.50 for H NMR and 39.7 for 13C
NMR). Chemical shifts are given in ppm (d-scale) and coupling
constants (J) in Hz. Complete assignments of all NMR signals (see
Figure 1 for numbering) were performed using a combination of H,
H-COSY, H,C-HSQC, and H,C-HMBC experiments. Preparative
flash chromatography on reverse phase was performed on Biotage
SP1 flash purification system.
5'''
6'''
4'''
N1'''
3'''
2'''
6''
1''
5''
N
In conclusion, aqueous-phase cross-coupling methodolo-
gy for attachment of bpy and tpy ligands to position 5 of
2¢-deoxyuridine and 2¢-deoxycytidine via acetylene or
phenylene spacer has been developed. While the Sono-
gashira reactions worked reasonably well with bpy- or
tpy-acetylenes under standard conditions in DMF, the
aqueous-phase Suzuki reactions were much more prob-
lematic and only after thorough optimization, efficient
procedure has been developed using higher catalyst load-
ing, higher temperature and different ratio of solvents.
Most importantly, at least the Sonogashira protocol is
suitable for the use in modification of nucleoside triphos-
phates.17 All the nucleoside-bpy/tpy conjugates are lumi-
nescent and in particular the 5-linked bpy derivatives
exert very high level of luminescence. We will further
prepare the corresponding dNTPs, study their polymerase
incorporation to DNA17 and use these building blocks for
fluorescent labeling of DNA, for complexation with
metals, self-assembly and catalysis.
2''
N
O
4
4''
3''
5
HN
4''
3
3''
2''
5''
6''
6
2
1'''
O
N1
5'
N
HO
6'''
5'''
N
1''
p
2'''
3'''
O
4'
1'
m
i
o
3'
4'''
2'
OH
Figure 1 Numbering scheme for NMR assignment
Sonogashira Cross-Coupling Reactions; General Procedure
DMF (1 mL) and (i-Pr)2NEt (0.22 mL, 1.25 mmol, 10 equiv) were
added to an argon-purged flask containing nucleoside 3 or 4 (44 mg,
0.125 mmol), an alkyne 1a–c (0.188 mmol, 1.5 equiv), and CuI (2.4
mg, 0.0125 mmol, 10 mol%). In a separate flask, Pd(OAc)2 (1.4 mg,
6.25 mmol, 5 mol%) and TPPTS (8.9 mg, 0.0156 mmol, 2.5 equiv
to Pd) were combined, evacuated and purged with argon followed
by addition of DMF (0.5 mL). The mixture of catalyst was then in-
Synthesis 2009, No. 1, 105–112 © Thieme Stuttgart · New York

108
L. Kalachova et al.
PAPER
jected into the reaction mixture and the resulting mixture was stirred
at 75 °C for 2 h. The solvent was then evaporated in vacuo. Products
were directly purified by flash chromatography on reverse phase us-
ing H2O–MeOH (0 to 100%) as an eluent.
139.58 (CH-4¢¢), 145.79 (CH-6), 149.68 (CH-6¢¢¢), 151.46 (CH-6¢¢),
153.57 (C-2), 154.11 (C-2¢¢), 154.69 (C-2¢¢¢), 163.93 (C-4).
MS (ESI): m/z (%) = 405 (3, [M+]), 428 (16, [M+ + Na]), 833 (100,
[2 M+ + Na]).
HRMS-ESI: m/z [M+ + H] calcd for C21H20N5O4: 406.1510; found:
406.1512.
5-[(2,2¢-Bipyridin-6-yl)ethynyl]-2¢-deoxycytidine (5a)
Prepared from deoxycytidine 3 and bipyridinyl acetylene 1a. It was
isolated as a brown powder in a yield of 70% (35 mg), which was
then crystallized from a mixture of MeOH–H2O; mp 139–146 °C.
Anal. Calcd for C21H19N5O4·0.5H2O: C, 60.86; H, 4.86; N, 16.90;
Found C, 61.13; H, 4.67; N, 16.60.
IR (KBr): 3392, 1645, 1500, 1094, 780 cm–1.
5-[(2,2¢:6¢,2¢¢-Terpyridin-4¢-yl)ethynyl]-2¢-deoxycytidine (5c)
Prepared from deoxycytidine 3 and terpyridinyl acetylene 1c. It was
isolated as a slightly brownish powder in a yield of 63% (38 mg),
which was then crystallized from a mixture of DMSO–H2O; mp
284–295 °C.
1H NMR (500 MHz, DMSO-d6): d = 2.07 (ddd, Jgem = 13.2 Hz,
J2¢b,1¢ = 7.0 Hz, J2¢b,3¢ = 6.1 Hz, 1 H, H-2¢b), 2.19 (ddd, Jgem = 13.2
Hz, J2¢a,1¢ = 6.1 Hz, J2¢a,3¢ = 3.7 Hz, 1 H, H-2¢a), 3.59 (ddd,
Jgem = 11.9 Hz, J5¢b,OH = 5.1 Hz, J5¢b,4¢ = 3.7 Hz, 1 H, H-5¢b), 3.67
(ddd, Jgem = 11.9 Hz, J5¢a,OH = 5.1 Hz, J5¢a,4¢ = 3.5 Hz, 1 H, H-5¢a),
3.82 (ddd, J4¢,5¢ = 3.7, 3.5 Hz, J4¢,3¢ = 3.3 Hz, 1 H, H-4¢), 4.24 (dddd,
IR (KBr): 3422, 2214, 1645, 1602, 1583, 1567, 1502, 1468, 1393,
1264, 1097, 792 cm–1.
J
J
3¢,2¢ = 6.1, 3.7 Hz, J3¢,OH = 4.3 Hz, J3¢,4¢ = 3.3 Hz, 1 H, H-3¢), 5.17 (t,
OH,5¢ = 5.1 Hz, 1 H, OH-5¢), 5.26 (d, J3¢,OH = 4.3 Hz, 1 H, OH-3¢),
1H NMR (500 MHz, DMSO-d6): d = 2.09 (dt, Jgem = 13.1 Hz,
6.15 (dd, J1¢,2¢ = 7.0, 6.1 Hz, 1 H, H-1¢), 7.17 (br s, 1 H, NHaHb), 7.49
(ddd, J5¢¢¢4¢¢¢ = 7.5 Hz, J5¢¢¢,6¢¢¢ = 4.7 Hz, J5¢¢¢,3¢¢¢ = 1.2 Hz, 1 H, H-5¢¢¢),
7.87 (dd, J5¢¢4¢¢ = 7.7 Hz, J5¢¢3¢¢ = 1.1 Hz, 1 H, H-5¢¢), 7.90 (br s, 1 H,
NHaHb), 7.97 (ddd, J4¢¢¢,3¢¢¢ = 8.0 Hz, J4¢¢¢,5¢¢¢ = 7.5 Hz, J4¢¢¢,6¢¢¢ = 1.8 Hz,
1 H, H-4¢¢¢), 8.00 (dd, J4¢¢,3¢¢ = 8.0 Hz, J4¢¢,5¢¢ = 7.7 Hz, 1 H, H-4¢¢),
8.36 (dd, J3¢¢,4¢¢ = 8.0 Hz, J3¢¢,5¢¢ = 1.1 Hz, 1 H, H-3¢¢), 8.38 (ddd,
J
J
2¢b,1¢ = J2¢b,3¢ = 6.4 Hz, 1 H, H-2¢b), 2.21 (ddd, Jgem = 13.1 Hz,
2¢a,1¢ = 5.9 Hz, J2¢a,3¢ = 3.6 Hz, 1 H, H-2¢a), 3.62 (ddd, Jgem = 11.9
Hz, J5¢b,OH = 4.9 Hz, J5¢b,4¢ = 3.9 Hz, 1 H, H-5¢b), 3.70 (ddd,
Jgem = 11.9 Hz, J5¢a,OH = 5.4 Hz, J5¢a,4¢ = 3.7 Hz, 1 H, H-5¢a), 3.83
(ddd, J4¢,5¢ = 3.9, 3.7 Hz, J4¢,3¢ = 3.1 Hz, 1 H, H-4¢), 4.26 (m,
J3¢,2¢ = 6.4, 3.6 Hz, J3¢,OH = 4.3 Hz, J3¢,4¢ = 3.1 Hz, 1 H, H-3¢), 5.19
J3¢¢¢,4¢¢¢ = 8.0 Hz, J3¢¢¢,5¢¢¢ = 1.2 Hz, J3¢¢¢,6¢¢¢ = 1.0 Hz, 1 H, H-3¢¢¢), 8.43 (s,
(dd, JOH,5¢ = 5.4, 4.9 Hz, 1 H, OH-5¢), 5.24 (d, J3¢,OH = 4.3 Hz, 1 H,
OH-3¢), 6.15 (dd, J1¢,2¢ = 6.4, 5.9 Hz, 1 H, H-1¢), 7.52 (br s, 1 H,
NHaHb), 7.53 (ddd, J5¢¢¢,4¢¢¢ = 7.5 Hz, J5¢¢¢,6¢¢¢ = 4.7 Hz, J5¢¢¢,3¢¢¢ = 1.2 Hz,
2 H, H-5¢¢¢), 7.82 (br s, 1 H, NHaHb), 8.03 (ddd, J4¢¢¢,3¢¢¢ = 8.0 Hz,
1 H, H-6), 8.71 (ddd, J6¢¢¢,5¢¢¢ = 4.7 Hz, J6¢¢¢,4¢¢¢ = 1.8 Hz, J6¢¢¢,3¢¢¢ = 1.0
Hz, 1 H, H-6¢¢¢).
13C NMR (125.7 MHz, DMSO-d6): d = 41.10 (CH2-2¢), 61.13 (CH2-
5¢), 70.21 (CH-3¢), 81.62 (C5-C≡C–C6¢¢), 85.76 (CH-1¢), 87.75
(CH-4¢), 88.79 (C-5), 93.86 (C5–C≡C–C6¢¢), 120.10 (CH-3¢¢),
120.90 (CH-3¢¢¢), 124.79 (CH-5¢¢¢), 128.05 (CH-5¢¢), 137.67 (CH-
4¢¢¢), 137.95 (CH-4¢¢), 142.42 (C-6¢¢), 146.22 (CH-6), 149.61 (CH-
6¢¢¢), 153.53 (C-2), 154.72 (C-2¢¢¢), 155.70 (C-2¢¢), 164.05 (C-4).
MS (ESI): m/z (%) = 428 (15, [M+ + Na]), 833 (100, [2 M+ + Na]).
HRMS-ESI: m/z [M+ + H] calcd for C21H20N5O4: 406.1510; found:
J
4¢¢¢,5¢¢¢ = 7.5 Hz, J4¢¢¢,6¢¢¢ = 1.8 Hz, 2 H, H-4¢¢¢), 8.49 (s, 1 H, H-6), 8.62
(s, 2 H, H-3¢¢,5¢¢), 8.63 (ddd, J3¢¢¢,4¢¢¢ = 8.0 Hz, J3¢¢¢,5¢¢¢ = 1.2 Hz,
J
3¢¢¢,6¢¢¢ = 0.9 Hz, 2 H, H-3¢¢¢), 8.74 (ddd, J6¢¢¢,5¢¢¢ = 4.7 Hz, J6¢¢¢,4¢¢¢ = 1.8
Hz, J6¢¢¢,3¢¢¢ = 0.9 Hz, 2 H, H-6¢¢¢).
13C NMR (125.7 MHz, DMSO-d6): d = 41.02 (CH2-2¢), 61.09 (CH2-
5¢), 70.10 (CH-3¢), 85.78 (CH-1¢), 87.27 (C5–C≡C–C4¢¢), 87.75
(CH-4¢), 88.85 (C-5), 92.15 (C5–C≡C–C4¢¢), 121.10 (CH-3¢¢¢),
121.99 (CH-3¢¢,5¢¢), 124.89 (CH-5¢¢¢), 133.13 (C-4¢¢), 137.74 (CH-
4¢¢¢), 146.85 (CH-6), 149.51 (CH-6¢¢¢), 153.52 (C-2), 154.78 (C-
2¢¢¢), 155.30 (C-2¢¢,6¢¢), 163.93 (C-4).
406.1514.
Anal. Calcd for C21H19N5O4·1H2O·1MeOH: C, 58.01; H, 5.53; N,
15.38. Found: C, 57.97; H, 5.13; N, 15.20.
MS (ESI): m/z (%) = 483 (37, [M+ + H]), 505 (100, [M+ + Na]), 982
(86, [2 M+ + Na]).
5-[(2,2¢-Bipyridin-5-yl)ethynyl]-2¢-deoxycytidine (5b)
HRMS-ESI: m/z [M + H]+ calcd for C26H23N6O4: 483.1775; found:
483.1780.
Prepared from deoxycytidine 3 and bipyridinyl acetylene 1b. It was
isolated as a slightly yellow powder in a yield of 67% (34 mg), and
was then crystallized from a mixture of EtOH–H2O; mp >300 °C.
5-[(2,2¢-Bipyridin-6-yl)ethynyl]-2¢-deoxyuridine (6a)
IR (KBr): 3448, 1656, 1634, 1501, 1462, 1101, 794, 781, 742 cm–1.
1H NMR (500 MHz, DMSO-d6): d = 2.05 (dt, Jgem = 13.3 Hz,
Prepared from deoxyuridine 4 and bipyridinyl acetylene 1a. Product
was isolated as yellow crystals in a yield of 75% (38 mg) and crys-
tallized from a mixture of MeOH–H2O; mp 129–136 °C.
J
J
2¢b,1¢ = J2¢b,3¢ = 6.4 Hz, 1 H, H-2¢b), 2.20 (ddd, Jgem = 13.3 Hz,
2¢a,1¢ = 6.1 Hz, J2¢a,3¢ = 3.9 Hz, 1 H, H-2¢a), 3.60 and 3.68 (2 br dt,
IR (KBr): 3424, 3061, 1699, 1626, 1454, 1429, 1274, 1094, 1056,
778 cm–1.
Jgem = 11.9 Hz, J5¢,OH = J5¢,4¢ = 3.5 Hz, 2 H, H-5¢), 3.82 (q,
J4¢,5¢ = J4¢,3¢ = 3.5 Hz, 1 H, H-4¢), 4.25 (br m, J3¢,2¢ = 6.4, 3.9 Hz,
1H NMR (500 MHz, DMSO-d6): d = 2.17 (ddd, Jgem = 13.3 Hz,
J3¢,OH = 4.3 Hz, J3¢,4¢ = 3.5 Hz, 1 H, H-3¢), 5.17 (br t, JOH,5¢ = 3.5 Hz,
1 H, OH-5¢), 5.26 (br d, J3¢,OH = 4.3 Hz, 1 H, OH-3¢), 6.13 (dd,
J2¢b,1¢ = 6.2 Hz, J2¢b,3¢ = 3.9 Hz, 1 H, H-2¢b), 2.21 (ddd, Jgem = 13.3
Hz, J2¢a,1¢ = 6.9 Hz, J2¢a,3¢ = 5.9 Hz, 1 H, H-2¢a), 3.60 (ddd,
Jgem = 12.1 Hz, J5¢b,OH = 4.5 Hz, J5¢b,4¢ = 3.6 Hz, 1 H, H-5¢b), 3.68
(ddd, Jgem = 12.1 Hz, J5¢a,OH = 4.8 Hz, J5¢a,4¢ = 3.6 Hz, 1 H, H-5¢a),
3.83 (td, J4¢,5¢ = 3.6 Hz, J4¢,3¢ = 3.0 Hz, 1 H, H-4¢), 4.27 (m,
J
J
1¢,2¢ = 6.4, 6.1 Hz, 1 H, H-1¢), 7.21 (br s, 1 H, NHaHb), 7.47 (ddd,
5¢¢¢,4¢¢¢ = 7.5 Hz, J5¢¢¢,6¢¢¢ = 4.8 Hz, J5¢¢¢,3¢¢¢ = 1.2 Hz, 1 H, H-5¢¢¢), 7.85
(br s, 1 H, NHaHb), 7.97 (ddd, J4¢¢¢,3¢¢¢ = 7.9 Hz, J4¢¢¢,5¢¢¢ = 7.5 Hz,
J4¢¢¢,6¢¢¢ = 1.8 Hz, 1 H, H-4¢¢¢), 8.14 (dd, J4¢¢,3¢¢ = 8.3 Hz, J4¢¢,6¢¢ = 2.1 Hz,
J
3¢,2¢ = 5.9, 3.9 Hz, J3¢,OH = 4.3 Hz, J3¢,4¢ = 3.0 Hz, 1 H, H-3¢), 5.21 (br
1 H, H-4¢¢), 8.40 (ddd, J3¢¢¢,4¢¢¢ = 7.9 Hz, J3¢¢¢,5¢¢¢ = 1.2 Hz, J3¢¢¢,6¢¢¢ = 1.0
Hz, 1 H, H-3¢¢¢), 8.41 (dd, J3¢¢,4¢¢ = 8.4 Hz, J3¢¢,6¢¢ = 0.9 Hz, 1 H, H-3¢¢),
8.42 (s, 1 H, H-6), 8.70 (ddd, J6¢¢¢,5¢¢¢ = 4.8 Hz, J6¢¢¢,4¢¢¢ = 1.8 Hz,
dd, JOH,5¢ = 4.8, 4.5 Hz, 1 H, OH-5¢), 5.30 (br d, J3¢,OH = 4.3 Hz, 1 H,
OH-3¢), 6.14 (dd, J1¢,2¢ = 6.9, 6.2 Hz, 1 H, H-1¢), 7.49 (ddd,
J
5¢¢¢,4¢¢¢ = 7.5 Hz, J5¢¢¢,6¢¢¢ = 4.8 Hz, J5¢¢¢,3¢¢¢ = 1.2 Hz, 1 H, H-5¢¢¢), 7.61
(dd, J5¢¢,4¢¢ = 7.7 Hz, J5¢¢,3¢¢ = 1.0 Hz, 1 H, H-5¢¢), 7.97 (ddd,
4¢¢¢,3¢¢¢ = 8.0 Hz, J4¢¢¢,5¢¢¢ = 7.5 Hz, J4¢¢¢,6¢¢¢ = 1.8 Hz, 1 H, H-4¢¢¢), 7.99
(dd, J4¢¢,3¢¢ = 8.0 Hz, J4¢¢,5¢¢ = 7.7 Hz, 1 H, H-4¢¢), 8.36 (ddd,
3¢¢¢,4¢¢¢ = 8.0 Hz, J3¢¢¢,5¢¢¢ = 1.2 Hz, J3¢¢¢,6¢¢¢ = 1.0 Hz, 1 H, H-3¢¢¢), 8.37
(dd, J3¢¢,4¢¢ = 8.0 Hz, J3¢¢,5¢¢ = 1.0 Hz, 1 H, H-3¢¢), 8.50 (s, 1 H, H-6),
J
6¢¢¢,3¢¢¢ = 1.0 Hz, 1 H, H-6¢¢¢), 8.88 (dd, J6¢¢,4¢¢ = 2.1 Hz, J6¢¢,3¢¢ = 0.9 Hz,
1 H, H-6¢¢).
J
13C NMR (125.7 MHz, DMSO-d6): d = 41.12 (CH2-2¢), 61.06 (CH2-
5¢), 70.09 (CH-3¢), 85.77 (CH-1¢), 86.36 (C5–C≡C–C5¢¢)), 87.70
(CH-4¢), 89.22 (C-5), 91.18 (C5–C≡C–C5¢¢), 120.05 (CH-3¢¢),
120.09 (C-5¢¢), 121.00 (CH-3¢¢¢), 124.71 (CH-5¢¢¢), 137.68 (CH-4¢¢¢),
J
Synthesis 2009, No. 1, 105–112 © Thieme Stuttgart · New York

PAPER
Nucleosides Bearing Bipyridine and Terpyridine Ligands at Position 5
109
8.70 (ddd, J6¢¢¢,5¢¢¢ = 4.8 Hz, J6¢¢¢,4¢¢¢ = 1.8 Hz, J6¢¢¢,3¢¢¢ = 1.0 Hz, 1 H, H-
6¢¢¢).
(dd, JOH,5¢ = 5.1, 4.6 Hz, 1 H, OH-5¢), 5.33 (d, J3¢,OH = 4.4 Hz, 1 H,
OH-3¢), 6.14 (dd, J1¢,2¢ = 6.8, 6.2 Hz, 1 H, H-1¢), 7.53 (ddd,
5¢¢¢,4¢¢¢ = 7.4 Hz, J5¢¢¢,6¢¢¢ = 4.7 Hz, J5¢¢¢,3¢¢¢ = 1.2 Hz, 2 H, H-5¢¢¢), 8.03
(ddd, J4¢¢¢,3¢¢¢ = 7.9 Hz, J4¢¢¢,5¢¢¢ = 7.4 Hz, J4¢¢¢,6¢¢¢ = 1.8 Hz, 2 H, H-4¢¢¢),
8.41 (s, 2 H, H-3¢¢,5¢¢), 8.58 (s, 1 H, H-6), 8.63 (ddd, J3¢¢¢,4¢¢¢ = 7.9 Hz,
J
13C NMR (125.7 MHz, DMSO-d6): d = 40.48 (CH2-2¢), 61.02 (CH2-
5¢), 70.11 (CH-3¢), 82.52 (C5–C≡C–C6¢¢), 85.24 (CH-1¢), 87.86
(CH-4¢), 91.76 (C5–C≡C–C6¢¢), 97.51 (C-5), 120.27 (CH-3¢¢),
120.95 (CH-3¢¢¢), 124.83 (CH-5¢¢¢), 127.66 (CH-5¢¢), 137.70 (CH-
4¢¢¢), 138.25 (CH-4¢¢), 142.24 (C-6¢¢), 145.31 (CH-6), 149.62 (CH-
6¢¢¢), 149.68 (C-2), 154.67 (C-2¢¢¢), 155.97 (C-2¢¢), 161.70 (C-4).
J
3¢¢¢,5¢¢¢ = 1.2 Hz, J3¢¢¢,6¢¢¢ = 1.0 Hz, 2 H, H-3¢¢¢), 8.74 (ddd, J6¢¢¢,5¢¢¢ = 4.7
Hz, J6¢¢¢,4¢¢¢ = 1.8 Hz, J6¢¢¢,3¢¢¢ = 1.0 Hz, 2 H, H-6¢¢¢), 11.83 (br s, 1 H,
NH).
13C NMR (151 MHz, DMSO-d6): d = 40.49 (CH2-2¢), 61.02 (CH2-
5¢), 70.09 (CH-3¢), 85.34 (CH-1¢), 87.93 (CH-4¢), 88.10 (C5–C≡C–
C4¢¢), 90.20 (C5–C≡C–C4¢¢), 97.40 (C-5), 121.15 (CH-3¢¢¢), 121.66
(CH-3¢¢,5¢¢), 125.13 (CH-5¢¢¢), 132.87 (C-4¢¢), 137.90 (CH-4¢¢¢),
145.79 (CH-6), 149.70 (C-2), 149.74 (CH-6¢¢¢), 154.48 (C-2¢¢¢),
155.62 (C-2¢¢,6¢¢), 161.68 (C-4).
MS (ESI): m/z (%) = 406 (9, [M+]), 429 (100, [M+ + Na]), 835 (21,
[2 M+ + Na]).
HRMS-ESI: m/z [M + H]+ calcd for C21H19N5O4: 407.1350; found:
407.1357.
Anal. Calcd for C21H18N5O4·1H2O: C, 59.43; H, 4.75; N, 13.20.
Found: C, 59.73; H, 4.67; N, 13.12.
MS (ESI): m/z (%) = 483 (57, [M+]), 506 (100, [M+ + Na]), 989 (77,
[2 M+ + Na]).
5-[(2,2¢-Bipyridin-5-yl)ethynyl]-2¢-deoxyuridine (6b)
Prepared from deoxyuridine 4 and acetylene 1b and isolated as a
yellowish solid in a yield of 70% (35 mg) and crystallized from a
mixture of CHCl3–MeOH–heptane; mp 134–139 °C.
HRMS-ESI: m/z [M + H]+ calcd for C26H22N5O5: 484.1615; found:
484.1614.
Anal. Calcd for C26H21N5O5·0.5H2O: C, 63.41; H, 4.5; N, 14.22.
Found: C, 63.49; H, 4.36; N, 14.07.
IR (KBr): 3419, 3056, 2974, 1716, 1697, 1624, 1458, 1306, 1274,
1092, 1051, 795, 747 cm–1.
Suzuki–Miyaura Cross-Coupling Reactions; General Proce-
dure
1H NMR (500 MHz, DMSO-d6): d = 2.16 (ddd, Jgem = 13.3 Hz,
J2¢b,1¢ = 6.3 Hz, J2¢b,3¢ = 4.3 Hz, 1 H, H-2¢b), 2.20 (ddd, Jgem = 13.3
Conditions A: A mixture of H2O–MeCN (2:1) (1 mL) was added to
an argon-purged flask containing nucleoside 3 or 4 (44 mg, 0.125
mmol), a boronate 2a–c (0.15 mmol, 1.2 equiv), and Cs2CO3 (122
mg, 0.38 mmol, 3 equiv). In a separate flask, Pd(OAc)2 (1.4 mg, 6.3
mmol, 5 mol%) and TPPTS (8.9 mg, 15.6 mmol, 2.5 equiv to Pd)
were combined, evacuated and purged with argon followed by the
addition of H2O–MeCN (2:1, 0.5 mL). The mixture of catalyst was
then injected into the reaction mixture and the resulting mixture was
heated at 80 °C for appropriate time. The solvent was then evapo-
rated in vacuo. Products 7a,b and 8a–c were directly purified by
flash chromatography on reverse phase using H2O–MeOH (0 to
100%) as an eluent. Product 7c was purified by column chromatog-
raphy on silica gel using CHCl3–MeOH (10 to 100%) as an eluent.
Products were crystallized from a mixture MeOH–H2O, unless oth-
erwise stated.
Hz, J2¢a,1¢ = 6.8 Hz, J2¢a,3¢ = 5.8 Hz, 1 H, H-2¢a), 3.60 (br ddd,
Jgem = 12.1 Hz, J5¢b,OH = 4.0 Hz, J5¢b,4¢ = 3.5 Hz, 1 H, H-5¢b), 3.68 (br
ddd, Jgem = 12.1 Hz, J5¢a,OH = 4.4 Hz, J5¢a,4¢ = 3.5 Hz, 1 H, H-5¢a),
3.82 (td, J4¢,5¢ = 3.5 Hz, J4¢,3¢ = 3.2 Hz, 1 H, H-4¢), 4.27 (br m,
J
3¢,2¢ = 5.8, 4.3 Hz, J3¢,OH = 4.2 Hz, J3¢,4¢ = 3.2 Hz, 1 H, H-3¢), 5.23 (br
dd, JOH,5¢ = 4.4, 4.0 Hz, 1 H, OH-5¢), 5.31 (br d, J3¢,OH = 4.2 Hz, 1 H,
OH-3¢), 6.13 (dd, J1¢,2¢ = 6.8, 6.3 Hz, 1 H, H-1¢), 7.48 (ddd,
J5¢¢¢,4¢¢¢ = 7.5 Hz, J5¢¢¢,6¢¢¢ = 4.8 Hz, J5¢¢¢,3¢¢¢ = 1.2 Hz, 1 H, H-5¢¢¢), 7.97
(ddd, J4¢¢¢,3¢¢¢ = 8.0 Hz, J4¢¢¢,5¢¢¢ = 7.5 Hz, J4¢¢¢,6¢¢¢ = 1.8 Hz, 1 H, H-4¢¢¢),
8.03 (dd, J4¢¢,3¢¢ = 8.3 Hz, J4¢¢,6¢¢ = 2.2 Hz, 1 H, H-4¢¢), 8.39 (ddd,
J3¢¢¢,4¢¢¢ = 8.0 Hz, J3¢¢¢,5¢¢¢ = 1.2 Hz, J3¢¢¢,6¢¢¢ = 0.9 Hz, 1 H, H-3¢¢¢), 8.42
(dd, J3¢¢,4¢¢ = 8.3 Hz, J3¢¢,6¢¢ = 1.0 Hz, 1 H, H-3¢¢), 8.50 (s, 1 H, H-6),
8.71 (ddd, J6¢¢¢,5¢¢¢ = 4.8 Hz, J6¢¢¢,4¢¢¢ = 1.8 Hz, J6¢¢¢,3¢¢¢ = 0.9 Hz, 1 H, H-
6¢¢¢), 8.76 (dd, J6¢¢,4¢¢ = 2.2 Hz, J6¢¢,3¢¢ = 1.0 Hz, 1 H, H-6¢¢).
13C NMR (125.7 MHz, DMSO-d6): d = 40.51 (CH2-2¢), 60.99 (CH2-
5¢), 70.06 (CH-3¢), 85.23 (CH-1¢), 87.17 (C5–C≡C–C5¢¢), 87.84
(CH-4¢), 89.04 (C5–C≡C–C5¢¢), 97.85 (C-5), 119.94 (C-5¢¢), 120.34
(CH-3¢¢), 121.05 (CH-3¢¢¢), 124.80 (CH-5¢¢¢), 137.73 (CH-4¢¢¢),
139.68 (CH-4¢¢), 144.97 (CH-6), 149.66 (C-2), 149.73 (CH-6¢¢¢),
151.32 (CH-6¢¢), 154.39 (C-2¢¢), 154.60 (C-2¢¢¢), 161.61 (C-4).
Conditions B: A mixture of H2O–MeCN (1:2) (1 mL) was added to
an argon-purged flask containing nucleoside 3 or 4 (44 mg, 0.125
mmol), a boronate 2a–c (0.15 mmol, 1.2 equiv), and Cs2CO3 (122
mg, 0.38 mmol, 3 equiv). In a separate flask, Pd(OAc)2 (2.8 mg,
12.5 mmol, 10 mol%) and TPPTS (35.5 mg, 62.5 mmol, 5 equiv to
Pd) were combined, evacuated and purged with argon followed by
the addition of H2O–MeCN (1:2, 0.5 mL). The mixture of catalyst
was then injected into the reaction mixture and the resulting mixture
was heated at 90 °C until complete consumption of the starting ma-
terial. The reaction was monitored by TLC, and at the end of the re-
action the solvent was evaporated in vacuo. Products 7a,b and 8a–
c were directly purified by flash chromatography on reverse phase
using H2O–MeOH (0 to 100%) as an eluent. Product 7c was purified
by column chromatography on silica gel using CHCl3–MeOH (10
to 100%) as an eluent. Products were crystallized from a mixture
MeOH–H2O, unless otherwise stated.
MS (ESI): m/z (%) = 407 (17, [M+ + H]), 429 (19, [M+ + Na]), 835
(21, [2 M+ + Na]).
HRMS-ESI: m/z [M + H]+ calcd for C21H19N 4O5: 407.1350; found:
407.1358
Anal. Calcd for C21H18N4O5·3H2O: C, 54.78; H, 5.25; N, 12.17.
Found: C, 54.72; H, 5.19; N, 12.04.
5-[(2,2¢:6¢,2¢¢-Terpyridin-4¢-yl)ethynyl]-2¢-deoxyuridine (6c)
Prepared from deoxyuridine 4 and bipyridinyl acetylene 1c and iso-
lated as a yellowish powder in a yield of 67% (40 mg) and crystal-
lized from a mixture of MeOH–H2O; mp 234–242 °C.
5-[4-(2,2¢-Bipyridin-6-yl)phenyl]-2¢-deoxycytidine (7a)
Prepared from deoxycytidine 3 and bipyridinyl boronate 2a.
IR (KBr): 3405, 2923, 2228, 1704, 1586, 1568, 1462, 1396, 1282,
1054, 790 cm–1.
Conditions A: Reaction was heated for 2 h and the product was then
isolated as a white powder in a yield of 65% (37 mg).
1H NMR (600 MHz, DMSO-d6): d = 2.18 (ddd, Jgem = 13.4 Hz,
J
2¢b,1¢ = 6.2 Hz, J2¢b,3¢ = 4.0 Hz, 1 H, H-2¢b), 2.23 (ddd, Jgem = 13.4
Conditions B: Reaction mixture was heated for 1 h and 7a was iso-
Hz, J2¢a,1¢ = 6.8 Hz, J2¢a,3¢ = 5.8 Hz, 1 H, H-2¢a), 3.62 (ddd,
Jgem = 12.0 Hz, J5¢b,OH = 4.6 Hz, J5¢b,4¢ = 3.7 Hz, 1 H, H-5¢b), 3.70
(ddd, Jgem = 12.0 Hz, J5¢a,OH = 5.1 Hz, J5¢a,4¢ = 3.5 Hz, 1 H, H-5¢a),
3.84 (ddd, J4¢,5¢ = 3.7, 3.5 Hz, J4¢,3¢ = 3.2 Hz, 1 H, H-4¢), 4.28 (m,
lated as a white powder in a yield of 75% (43 mg).
Mp >300 °C.
IR (KBr): 3462, 3370, 1649, 1599, 1581, 1470, 1456, 1429, 1097,
778 cm–1.
J3¢,2¢ = 5.8, 4.0 Hz, J3¢,OH = 4.4 Hz, J3¢,4¢ = 3.2 Hz, 1 H, H-3¢), 5.29
Synthesis 2009, No. 1, 105–112 © Thieme Stuttgart · New York

110
L. Kalachova et al.
PAPER
MS (ESI): m/z (%) = 457 (48, [M+]), 480 (100, [M+ + Na]).
HRMS-ESI: m/z [M + H]+ calcd for C25H24N5O4: 458.1823; found:
458.1821.
1H NMR (500 MHz, DMSO-d6): d = 2.11 (ddd, Jgem = 13.3 Hz,
J
2¢b,1¢ = 6.9 Hz, J2¢b,3¢ = 6.0 Hz, 1 H, H-2¢b), 2.18 (ddd, Jgem = 13.3
Hz, J2¢a,1¢ = 6.7 Hz, J2¢a,3¢ = 3.7 Hz, 1 H, H-2¢a), 3.54 and 3.60 (2 ddd,
Jgem = 11.8 Hz, J5¢,OH = 4.8 Hz, J5¢,4¢ = 3.6 Hz, 2 H, H-5¢), 3.80 (td,
Anal. Calcd for C25H23N5O4: C, 65.63; H, 5.07; N, 15.31. Found: C,
65.34; H, 5.09; N, 15.05.
J4¢,5¢ = 3.6 Hz, J4¢,3¢ = 3.1 Hz, 1 H, H-4¢), 4.25 (m, J3¢,2¢ = 6.0, 3.7 Hz,
J3¢,OH = 4.2 Hz, J3¢,4¢ = 3.1 Hz, 1 H, H-3¢), 5.02 (t, JOH,5¢ = 4.8 Hz, 1
H, OH-5¢), 5.24 (br d, J3¢,OH = 4.2 Hz, 1 H, OH-3¢), 6.23 (dd,
5-[4-(2,2¢:6¢,2¢¢-Terpyridin-4¢-yl)phenyl]-2¢-deoxycytidine (7c)
Prepared from deoxycytidine 3 and terpyridinyl boronate 2c and af-
ter chromatography was crystallized from a mixture of DMSO–
H2O.
J
1¢,2¢ = 6.9, 6.2 Hz, 1 H, H-1¢), 6.54 and 7.42 (2 br s, 2 H, NH2), 7.49
(ddd, J5¢¢¢,4¢¢¢ = 7.5 Hz, J5¢¢¢,6¢¢¢ = 4.8 Hz, J5¢¢¢,3¢¢¢ = 1.2 Hz, 1 H, H-5¢¢¢),
7.51 (m, 2 H, H-o-phenylene), 7.99 (s, 1 H, H-6), 8.01 (ddd,
J4¢¢¢,3¢¢¢ = 7.9 Hz, J4¢¢¢,5¢¢¢ = 7.5 Hz, J4¢¢¢,6¢¢¢ = 1.8 Hz, 1 H, H-4¢¢¢), 8.07
(dd, J4¢¢,5¢¢ = 7.9 Hz, J4¢¢,3¢¢ = 6.8 Hz, 1 H, H-4¢¢), 8.08 (dd, J5¢¢,4¢¢ = 7.9
Hz, J5¢¢,3¢¢ = 1.9 Hz, 1 H, H-5¢¢), 8.30 (m, 2 H, H-m-phenylene), 8.36
(dd, J3¢¢,4¢¢ = 6.8 Hz, J3¢¢,5¢¢ = 1.9 Hz, 1 H, H-3¢¢), 8.59 (ddd,
Conditions A: Reaction mixture was heated for 5 h. Even if the start-
ing material was not fully consumed, product 7c was isolated as a
white solid in a yield of 28% (19 mg).
J3¢¢¢,4¢¢¢ = 7.9 Hz, J3¢¢¢,5¢¢¢ = 1.2 Hz, J3¢¢¢,6¢¢¢ = 0.9 Hz, 1 H, H-3¢¢¢), 8.72
Conditions B: Reaction mixture was heated for 3 h. Product 7c was
isolated as a white solid in a yield of 70% (47 mg).
(ddd, J6¢¢¢,5¢¢¢ = 4.8 Hz, J6¢¢¢,4¢¢¢ = 1.8 Hz, J6¢¢¢,3¢¢¢ = 0.9 Hz, 1 H, H-6¢¢¢).
13C NMR (125.7 MHz, DMSO-d6): d = 40.90 (CH2-2¢), 61.24 (CH2-
5¢), 70.35 (CH-3¢), 85.37 (CH-1¢), 87.51 (CH-4¢), 107.45 (C-5),
119.40 (CH-3¢¢), 120.60 (CH-5¢¢), 120.85 (CH-3¢¢¢), 124.57 (CH-
5¢¢¢), 127.41 (CH-m-phenylene), 129.42 (CH-o-phenylene), 135.10
(C-i-phenylene), 137.64 (CH-4¢¢¢), 137.69 (C-p-phenylene), 138.77
(CH-4¢¢), 140.51 (CH-6), 149.54 (CH-6¢¢¢), 154.65 (C-2), 155.24
and 155.27 (C-2¢¢,6¢¢), 155.50 (C-2¢¢¢), 163.49 (C-4).
Mp >300 °C.
IR (KBr): 3464, 3382, 2919, 2852, 1648, 1602, 1587, 1566, 1468,
1392, 1268, 1096, 1063, 1040, 788, 744, 517 cm–1.
1H NMR (500 MHz, DMSO-d6): d = 2.11 (ddd, Jgem = 13.5 Hz,
J2¢b,1¢ = 6.7 Hz, J2¢b,3¢ = 6.0 Hz, 1 H, H-2¢b), 2.19 (ddd, Jgem = 13.5
Hz, J2¢a,1¢ = 6.3 Hz, J2¢a,3¢ = 4.0 Hz, 1 H, H-2¢a), 3.55 and 3.62 (2 ddd,
Jgem = 11.9 Hz, J5¢,OH = 5.0 Hz, J5¢,4¢ = 3.7 Hz, 2 × 1 H, H-5¢), 3.80
(td, J4¢,5¢ = 3.7 Hz, J4¢,3¢ = 2.8 Hz, 1 H, H-4¢), 4.26 (m, J3¢,2¢ = 6.0, 4.0
Hz, J3¢,OH = 4.2 Hz, J3¢,4¢ = 2.8 Hz, 1 H, H-3¢), 5.02 (t, JOH,5¢ = 5.0 Hz,
1 H, OH-5¢), 5.22 (d, J3¢,OH = 4.2 Hz, 1 H, OH-3¢), 6.25 (dd,
MS (ESI): m/z (%) = 457 (20, [M+]), 915 (100, [2 M+]), 937 (87, [2
M+ + Na]).
HRMS-ESI: m/z [M + H]+ calcd for C25H24N5O4: 458.1823; found:
458.1831.
J1¢,2¢ = 6.7, 6.3 Hz, 1 H, H-1¢), 6.56 and 7.44 (2 br s, 2 × 1 H, NH2),
Anal. Calcd for C25H23N5O4·1/3H2O: C, 64.78; H, 5.15; N, 15.11.
Found: C, 64.97; H, 5.04; N, 14.88.
7.54 (ddd, J5¢¢¢,4¢¢¢ = 7.5 Hz, J5¢¢¢,6¢¢¢ = 4.7 Hz, J5¢¢¢,3¢¢¢ = 1.1 Hz, 2 H, H-
5¢¢¢), 7.57 (m, 2 H, H-o-phenylene), 7.99 (m, 2 H, H-m-phenylene),
8.04 (s, 1 H, H-6), 8.05 (ddd, J4¢¢¢,3¢¢¢ = 7.9 Hz, J4¢¢¢,5¢¢¢ = 7.5 Hz,
5-[4-(2,2¢-Bipyridin-5-yl)phenyl]-2¢-deoxycytidine (7b)
Prepared from 2¢-deoxycytidine 3 and bipyridinyl boronate 2b.
J
4¢¢¢,6¢¢¢ = 1.8 Hz, 2 H, H-4¢¢¢), 8.69 (ddd, J3¢¢¢,4¢¢¢ = 7.9 Hz, J3¢¢¢,5¢¢¢ = 1.1
Hz, J3¢¢¢,6¢¢¢ = 0.9 Hz, 2 H, H-3¢¢¢), 8.76 (s, 2 H, H-3¢¢,5¢¢), 8.78 (ddd,
6¢¢¢,5¢¢¢ = 4.7 Hz, J6¢¢¢,4¢¢¢ = 1.8 Hz, J6¢¢¢,3¢¢¢ = 0.9 Hz, 2 H, H-6¢¢¢).
J
Conditions A: Reaction mixture was heated for 6 h. Even if the start-
ing material was not fully converted, the product 7b was isolated as
a white powder in a yield of 12% (7 mg).
13C NMR (125.7 MHz, DMSO-d6): d = 40.93 (CH2-2¢), 61.15 (CH2-
5¢), 70.25 (CH-3¢), 85.36 (CH-1¢), 87.46 (CH-4¢), 107.13 (C-5),
117.98 (CH-3¢¢,5¢¢), 121.16 (CH-3¢¢¢), 124.81 (CH-5¢¢¢), 127.68
(CH-m-phenylene), 129.91 (CH-o-phenylene), 135.45 (C-i-phe-
nylene), 136.60 (C-p-phenylene), 137.73 (CH-4¢¢¢), 140.68 (CH-6),
149.24 (C-4¢¢), 149.61 (CH-6¢¢¢), 154.57 (C-2), 155.11 (C-2¢¢¢),
155.99 (C-2¢¢,6¢¢), 163.41 (C-4).
Conditions B: Reaction mixture was heated for 3 h. Product was iso-
lated as a white powder in a yield of 55% (31 mg).
Mp >300 °C.
IR (KBr): 3389, 3176, 3068, 2932, 1661, 1631, 1503, 1459, 1263,
1196, 1082, 798, 750 cm–1.
1H NMR (500 MHz, DMSO-d6): d = 2.11 (ddd, Jgem = 13.3 Hz,
MS (ESI): m/z (%) = 534 (3, [M+]), 535 (20, [M+ + H]), 557 (100,
[M+ + Na]).
J
2¢b,1¢ = 6.9 Hz, J2¢b,3¢ = 6.0 Hz, 1 H, H-2¢b), 2.18 (ddd, Jgem = 13.3
HRMS-ESI: m/z [M+ + H] calcd for C30H27N5O4: 353.2088; found:
353.2090.
Hz, J2¢a,1¢ = 6.7 Hz, J2¢a,3¢ = 3.7 Hz, 1 H, H-2¢a), 3.54 and 3.60 (2 ddd,
Jgem = 11.8 Hz, J5¢,OH = 4.8 Hz, J5¢,4¢ = 3.6 Hz, 2 H, H-5¢), 3.80 (td,
J
4¢,5¢ = 3.6 Hz, J4¢,3¢ = 3.1 Hz, 1 H, H-4¢), 4.25 (m, J3¢,2¢ = 6.0, 3.7 Hz,
5-[4-(2,2¢-Bipyridin-6-yl)phenyl]-2¢-deoxyuridine (8a)
Prepared from deoxyuridine 4 and boronate 2a.
J3¢,OH = 4.2 Hz, J3¢,4¢ = 3.1 Hz, 1 H, H-3¢), 5.02 (t, JOH,5¢ = 4.8 Hz, 1
H, OH-5¢), 5.24 (br d, J3¢,OH = 4.2 Hz, 1 H, OH-3¢), 6.23 (dd,
Conditions A: The reaction mixture was heated for 2 h and then the
product was isolated as a white solid in a yield of 60% (34 mg).
J
1¢,2¢ = 6.9, 6.2 Hz, 1 H, H-1¢), 6.54 and 7.42 (2 br s, 2 H, NH2), 7.49
(ddd, J5¢¢¢,4¢¢¢ = 7.5 Hz, J5¢¢¢,6¢¢¢ = 4.8 Hz, J5¢¢¢,3¢¢¢ = 1.2 Hz, 1 H, H-5¢¢¢),
7.51 (m, 2 H, H-o-phenylene), 7.99 (s, 1 H, H-6), 8.01 (ddd,
Conditions B: The reaction mixture was heated for 1 h and then the
product was isolated as a white compound in a yield of 75% (43
mg).
J4¢¢¢,3¢¢¢ = 7.9 Hz, J4¢¢¢,5¢¢¢ = 7.5 Hz, J4¢¢¢,6¢¢¢ = 1.8 Hz, 1 H, H-4¢¢¢), 8.07
(dd, J4¢¢,5¢¢ = 7.9 Hz, J4¢¢,3¢¢ = 6.8 Hz, 1 H, H-4¢¢), 8.08 (dd, J5¢¢,4¢¢ = 7.9
Hz, J5¢¢,3¢¢ = 1.9 Hz, 1 H, H-5¢¢), 8.30 (m, 2 H, H-m-phenylene), 8.36
(dd, J3¢¢,4¢¢ = 6.8 Hz, J3¢¢,5¢¢ = 1.9 Hz, 1 H, H-3¢¢), 8.59 (ddd,
Mp 145–150 °C.
IR (KBr): 3385, 3185, 3059, 1707, 1581, 1457, 1434, 1288, 1093,
783, 599 cm–1.
J
3¢¢¢,4¢¢¢ = 7.9 Hz, J3¢¢¢,5¢¢¢ = 1.2 Hz, J3¢¢¢,6¢¢¢ = 0.9 Hz, 1 H, H-3¢¢¢), 8.72
(ddd, J6¢¢¢,5¢¢¢ = 4.8 Hz, J6¢¢¢,4¢¢¢ = 1.8 Hz, J6¢¢¢,3¢¢¢ = 0.9 Hz, 1 H, H-6¢¢¢).
1H NMR (500 MHz, DMSO-d6): d = 2.19 (ddd, Jgem = 13.5 Hz,
13C NMR (125.7 MHz, DMSO-d6): d = 40.90 (CH2-2¢), 61.24 (CH2-
5¢), 70.35 (CH-3¢), 85.37 (CH-1¢), 87.51 (CH-4¢), 107.45 (C-5),
119.40 (CH-3¢¢), 120.60 (CH-5¢¢), 120.85 (CH-3¢¢¢), 124.57 (CH-
5¢¢¢), 127.41 (CH-m-phenylene), 129.42 (CH-o-phenylene), 135.10
(C-i-phenylene), 137.64 (CH-4¢¢¢), 137.69 (C-p-phenylene), 138.77
(CH-4¢¢), 140.51 (CH-6), 149.54 (CH-6¢¢¢), 154.65 (C-2), 155.24
and 155.27 (C-2¢¢,6¢¢), 155.50 (C-2¢¢¢), 163.49 (C-4).
J2¢b,1¢ = 6.4 Hz, J2¢b,3¢ = 3.8 Hz, 1 H, H-2¢b), 2.28 (ddd, Jgem = 13.5
Hz, J2¢a,1¢ = 6.9, J2¢a,3¢ = 6.0 Hz, 1 H, H-2¢a), 3.62 (ddd, Jgem = 11.9
Hz, J5¢b,OH = 4.7 Hz, J5¢b,4¢ = 3.3 Hz, 1 H, H-5¢b), 3.67 (ddd,
Jgem = 11.9 Hz, J5¢a,OH = 5.0 Hz, J5¢a,4¢ = 3.3 Hz, 1 H, H-5¢a), 3.85 (td,
J4¢,5¢ = 3.3 Hz, J4¢,3¢ = 2.9 Hz, 1 H, H-4¢), 4.32 (m, J3¢,2¢ = 6.0, 3.8 Hz,
J3¢,OH = 4.3 Hz, J3¢,4¢ = 2.9 Hz, 1 H, H-3¢), 5.21 (dd, JOH,5¢ = 5.0, 4.7
Hz, 1 H, OH-5¢), 5.30 (br d, J3¢,OH = 4.3 Hz, 1 H, OH-3¢), 6.26 (dd,
Synthesis 2009, No. 1, 105–112 © Thieme Stuttgart · New York

PAPER
Nucleosides Bearing Bipyridine and Terpyridine Ligands at Position 5
111
J
1¢,2¢ = 6.9, 6.4 Hz, 1 H, H-1¢), 7.49 (ddd, J5¢¢¢,4¢¢¢ = 7.5 Hz, J5¢¢¢,6¢¢¢ = 4.7
Anal. Calcd for C25H22N4O5·1H2O: C, 63.02; H, 5.08; N, 11.76.
Found: C, 63.32; H, 4.92; N, 11.64.
Hz, J5¢¢¢,3¢¢¢ = 1.2 Hz, 1 H, H-5¢¢¢), 7.76 (m, 2 H, H-o-phenylene), 8.01
(ddd, J4¢¢¢,3¢¢¢ = 8.0 Hz, J4¢¢¢,5¢¢¢ = 7.5 Hz, J4¢¢¢,6¢¢¢ = 1.9 Hz, 1 H, H-4¢¢¢),
8.04 (dd, J4¢¢,5¢¢ = 7.9 Hz, J4¢¢,3¢¢ = 7.2 Hz, 1 H, H-4¢¢), 8.07 (dd,
5-[4-(2,2¢:6¢,2¢¢-Terpyridin-4¢-yl)phenyl]-2¢-deoxyuridine (8c)
Prepared from deoxyuridine 4 and boronate 2c.
J5¢¢,4¢¢ = 7.9 Hz, J5¢¢,3¢¢ = 1.5 Hz, 1 H, H-5¢¢), 8.25 (m, 2 H, H-m-phe-
nylene), 8.35 (dd, J3¢¢,4¢¢ = 7.2 Hz, J3¢¢,5¢¢ = 1.5 Hz, 1 H, H-3¢¢), 8.37 (s,
1 H, H-6), 8.60 (ddd, J3¢¢¢,4¢¢¢ = 8.0 Hz, J3¢¢¢,5¢¢¢ = 1.2 Hz, J3¢¢¢,6¢¢¢ = 1.0
Hz, 1 H, H-3¢¢¢), 8.72 (ddd, J6¢¢¢,5¢¢¢ = 4.7 Hz, J6¢¢¢,4¢¢¢ = 1.9 Hz,
Conditions A: The reaction mixture was heated for 7 h and even if
the starting material was not fully consumed, the product 8c was
then isolated as a brownish compound in a yield of 24% (16 mg).
J6¢¢¢,3¢¢¢ = 1.0 Hz, 1 H, H-6¢¢¢).
Conditions B: The reaction mixture was heated for 3 h. The product
was isolated as a brownish solid in a yield of 70% (47 mg).
13C NMR (125.7 MHz, DMSO-d6): d = 40.42 (CH2-2¢), 61.14 (CH2-
5¢), 70.37 (CH-3¢), 84.81 (CH-1¢), 87.75 (CH-4¢), 113.01 (C-5),
119.29 (CH-3¢¢), 120.54 (CH-5¢¢), 120.87 (CH-3¢¢¢), 124.56 (CH-
5¢¢¢), 126.57 (CH-m-phenylene), 128.33 (CH-o-phenylene), 134.40
(C-i-phenylene), 137.23 (C-p-phenylene), 137.63 (CH-4¢¢¢), 138.54
(CH-6), 138.70 (CH-4¢¢), 149.53 (CH-6¢¢¢), 150.10 (C-2), 155.19
and 155.27 (C-2¢¢,6¢¢), 155.50 (C-2¢¢¢), 162.31 (C-4).
Mp 240–249 °C.
IR (KBr): 3426, 3055, 2925, 1687, 1583, 1467, 1390, 1292, 1096,
840, 791, 749, 659, 595 cm–1.
1H NMR (500 MHz, DMSO-d6): d = 2.20 (ddd, Jgem = 13.4 Hz,
J2¢b,1¢ = 6.3 Hz, J2¢b,3¢ = 4.0 Hz, 1 H, H-2¢b), 2.29 (ddd, Jgem = 13.4
MS (ESI): m/z (%) = 459 (100, [M+ + H]), 481 (33, [M+ + Na]).
HRMS-ESI: m/z [M+ + H] calcd for C25H23N4O5: 459.1663; found:
Hz, J2¢a,1¢ = 6.7 Hz, J2¢a,3¢ = 6.0 Hz, 1 H, H-2¢a), 3.63 (ddd,
Jgem = 11.8 Hz, J5¢b,OH = 4.3 Hz, J5¢b,4¢ = 3.3 Hz, 1 H, H-5¢b), 3.70
(ddd, Jgem = 11.8 Hz, J5¢a,OH = 4.3 Hz, J5¢a,4¢ = 3.1 Hz, 1 H, H-5¢b),
3.86 (dt, J4¢,5¢ = 3.3, 3.1 Hz, J4¢,3¢ = 3.1 Hz, 1 H, H-4¢), 4.33 (m,
459.1660.
Anal. Calcd for C25H22N4O5·3/2H2O: C, 61.85; H, 5.19; N, 11.54.
Found: C, 61.90; H, 5.04; N, 11.35.
J3¢,2¢ = 6.0, 4.0 Hz, J3¢,OH = 4.2 Hz, J3¢,4¢ = 3.1 Hz, 1 H, H-3¢), 5.24 (br
t, JOH,5¢ = 4.3 Hz, 1 H, OH-5¢), 5.30 (br d, J3¢,OH = 4.2 Hz, 1 H, OH-
3¢), 6.26 (dd, J1¢,2¢ = 6.7, 6.3 Hz, 1 H, H-1¢), 7.54 (ddd, J5¢¢¢,4¢¢¢ = 7.4
Hz, J5¢¢¢,6¢¢¢ = 4.7 Hz, J5¢¢¢3¢¢¢ = 1.1 Hz, 2 H, H-5¢¢¢), 7.82 (m, 2 H, H-o-
phenylene), 7.94 (m, 2 H, H-m-phenylene), 8.05 (s, 1 H, H-6), 8.05
(ddd, J4¢¢¢,3¢¢¢ = 7.9 Hz, J4¢¢¢,5¢¢¢ = 7.4 Hz, J4¢¢¢,6¢¢¢ = 1.8 Hz, 2 H, H-4¢¢¢),
8.68 (ddd, J3¢¢¢,4¢¢¢ = 7.9 Hz, J3¢¢¢,5¢¢¢ = 1.1 Hz, J3¢¢¢,6¢¢¢ = 0.9 Hz, 2 H, H-
3¢¢¢), 8.74 (s, 2 H, H-3¢¢,5¢¢), 8.77 (ddd, J6¢¢¢,5¢¢¢ = 4.7 Hz, J6¢¢¢,4¢¢¢ = 1.8
Hz, J6¢¢¢,3¢¢¢ = 0.9 Hz, 2 H, H-6¢¢¢).
5-[4-(2,2¢-Bipyridin-5-yl)phenyl]-2¢¢-deoxyuridine (8b)
Prepared from deoxyuridine 4 and boronate 2b.
Conditions A: The reaction mixture was heated for 6 h and even if
the starting material was not fully consumed, the product was iso-
lated as a white compound in a yield of 7% (4 mg).
Conditions B: The reaction mixture was heated for 3 h. The product
was isolated as a white compound in a yield of 35% (20 mg).
13C NMR (125.7 MHz, DMSO-d6): d = 40.49 (CH2-2¢), 61.06 (CH2-
5¢), 70.26 (CH-3¢), 84.87 (CH-1¢), 87.71 (CH-4¢), 112.69 (C-5),
117.89 (CH-3¢¢,5¢¢), 121.15 (CH-3¢¢¢), 124.76 (CH-5¢¢¢), 126.84
(CH-m-phenylene), 128.80 (CH-o-phenylene), 134.76 (C-i-phe-
nylene), 136.17 (C-p-phenylene), 137.69 (CH-4¢¢¢), 138.80 (CH-6),
149.25 (C-4¢¢), 149.57 (CH-6¢¢¢), 150.05 (C-2), 155.14 (C-2¢¢¢),
155.92 (C-2¢¢,6¢¢), 162.26 (C-4).
Mp 188–193 °C.
IR (KBr): 3427, 2923, 1694, 1589, 1464, 1289, 1265, 1088, 873,
796, 751, 603, 463 cm–1.
1H NMR (500 MHz, DMSO-d6): d = 2.19 (ddd, Jgem = 13.5 Hz,
J2¢b,1¢ = 6.4 Hz, J2¢b,3¢ = 3.7 Hz, 1 H, H-2¢b), 2.29 (ddd, Jgem = 13.5
MS (ESI): m/z (%) = 536 (96, [M+ + H]), 558 (100, [M+ + Na]).
HRMS-ESI: m/z [M+ + H] calcd for C30H26N5O5: 536.1928; found:
Hz, J2¢a,1¢ = 6.9 Hz, J2¢a,3¢ = 6.0 Hz, 1 H, H-2¢a), 3.61 and 3.66 (2 br
ddd, Jgem = 11.8 Hz, J5¢,OH = 4.4 Hz, J5¢,4¢ = 3.3 Hz, 2 H, H-5¢), 3.84
(td, J4¢,5¢ = 3.3 Hz, J4¢,3¢ = 3.1 Hz, 1 H, H-4¢), 4.32 (br m, J3¢,2¢ = 6.0,
3.7 Hz, J3¢,OH = 4.2 Hz, J3¢,4¢ = 3.1 Hz, 1 H, H-3¢), 5.18 (br t,
536.1925.
J
OH,5¢ = 4.4 Hz, 1 H, OH-5¢), 5.29 (br d, J3¢,OH = 4.2 Hz, 1 H, OH-3¢),
6.26 (dd, J1¢,2¢ = 6.9, 6.4 Hz, 1 H, H-1¢), 7.47 (ddd, J5¢¢¢,4¢¢¢ = 7.5 Hz,
5¢¢¢,6¢¢¢ = 4.7 Hz, J5¢¢¢,3¢¢¢ = 1.2 Hz, 1 H, H-5¢¢¢), 7.73 (m, 2 H, H-o-phe-
nylene), 7.83 (m, 2 H, H-m-phenylene), 7.97 (ddd, J4¢¢¢,3¢¢¢ = 7.9 Hz,
4¢¢¢,5¢¢¢ = 7.5 Hz, J4¢¢¢,6¢¢¢ = 1.8 Hz, 1 H, H-4¢¢¢), 8.27 (dd, J4¢¢,3¢¢ = 8.3
Hz, J4¢¢,6¢¢ = 2.4 Hz, 1 H, H-4¢¢), 8.32 (s, 1 H, H-6), 8.43 (ddd,
3¢¢¢,4¢¢¢ = 7.9 Hz, J3¢¢¢,5¢¢¢ = 1.2 Hz, J3¢¢¢,6¢¢¢ = 0.9 Hz, 1 H, H-3¢¢¢), 8.48
(dd, J3¢¢,4¢¢ = 8.3 Hz, J3¢¢,6¢¢ = 0.9 Hz, 1 H, H-3¢¢), 8.72 (ddd,
Fluorescence and UV-Vis Spectroscopy
The UV-Vis spectra were measured on Varian CARY 100 Bio
Spectrophotometer (e is the molar extinction coefficient in
L·mol–1·cm–1). The fluorescence measurements were performed on
a spectrofluorometer Aminco Bowman series 2 in 220–850 nm
range with Xenon source, excitation and emission wavelength
scans, spectral bandwidth 1–16 nm, PMT detector, scan rate 3–6000
nm/min, and Seya-Namioka grating monochromator. We used the
comparative method of Williams et al.18 for recording fluorescence
quantum yield of a sample fSA [a 10 mM solution of quinine sulfate
in 0.1 M H2SO4 (in H2O) was chosen as a standard: fST = 0.54].19
Thus, the fluorescence quantum yield of a sample fSA is calculated
by the formula of Equation 1, where the subscripts ST and SA de-
note standard and sample respectively, f is the fluorescent quantum
yield, IFI the integrated fluorescence intensity, Grad the gradient
from the plot of IFI versus absorbance A, and h the refractive index
of the solvent.
J
J
J
J
6¢¢¢,5¢¢¢ = 4.7 Hz, J6¢¢¢,4¢¢¢ = 1.8 Hz, J6¢¢¢,3¢¢¢ = 0.9 Hz, 1 H, H-6¢¢¢), 9.05
(dd, J6¢¢,4¢¢ = 2.4 Hz, J6¢¢,3¢¢ = 0.9 Hz, 1 H, H-6¢¢).
13C NMR (125.7 MHz, DMSO-d6): d = 40.32 (CH2-2¢), 61.15 (CH2-
5¢), 70.37 (CH-3¢), 84.78 (CH-1¢), 87.74 (CH-4¢), 112.94 (C-5),
120.60 (CH-3¢¢¢), 120.69 (CH-3¢¢), 124.40 (CH-5¢¢¢), 126.69 (CH-m-
phenylene), 128.73 (CH-o-phenylene), 133.52 (C-i-phenylene),
135.13 (CH-4¢¢), 135.39 (C-5¢¢), 135.44 (C-p-phenylene), 137.56
(CH-4¢¢¢), 138.43 (CH-6), 147.39 (CH-6¢¢), 149.59 (CH-6¢¢¢), 150.08
(C-2), 154.32 (C-2¢¢), 155.11 (C-2¢¢¢), 162.29 (C-4).
MS (ESI): m/z (%) = 459 (100, [M+ + H]), 481 (96, [M+ + Na]).
ηSA 2
ηST
IFI
A
HRMS-ESI: m/z [M+ + H] calcd for C25H23N4O5: 459.1663; found:
459.1661.
GradSA
φSA = φST
where Grad =
GradST
Equation 1 Fluorescence quantum yields calculation
Synthesis 2009, No. 1, 105–112 © Thieme Stuttgart · New York

112
L. Kalachova et al.
PAPER
(9) Review: Agrofoglio, A. L.; Gillaizeau, I.; Saito, Y. Chem.
Rev. 2003, 103, 1875.
(10) Crisp, G.; Flynn, B. L. J. Org. Chem. 1993, 58, 6614.
(11) Garg, N. K.; Woodroofe, C. C.; Lacenere, C. J.; Quake, S.
R.; Stoltz, B. M. Chem. Commun. 2005, 4551.
Acknowledgment
This work is a part of the research project Z04 055 905. It was sup-
ported by the Centre of Biomolecules and Complex Molecular
Systems (LC 512).
(12) (a) Amann, N.; Wagenknecht, H.-A. Synlett 2002, 687.
(b) Mayer, E.; Valis, L.; Huber, R.; Amann, N.;
Wagenknecht, H.-A. Synthesis 2003, 2335. (c) Wanninger-
Weiss, C.; Wagenknecht, H.-A. Eur. J. Org. Chem. 2008,
64.
(13) For aqueous-phase cross-coupling reactions of nucleosides,
see: (a) Western, E. C.; Daft, J. R.; Johnson, E. M. II;
Garnnett, P. M.; Shoughnessy, K. H. J. Org. Chem. 2003, 68,
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Synthesis 2009, No. 1, 105–112 © Thieme Stuttgart · New York