Pyrimidine-purine and pyrimidine heterodinucleosides synthesis containing a triazole linkage

Article abstract of DOI:10.1080/15257771003708579

This article describes a synthetic route to generate two purine-pyrimidine and pyrimidine heterodinucleosides. Both microwave activated regioselective alkylation using hydride and copper-catalyzed-azide-alkyne-cycloaddition (CuAAC) were used in order to perform the synthesis.

Full text of DOI:10.1080/15257771003708579

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Pyrimidine-Purine and Pyrimidine
Heterodinucleosides Synthesis
Containing a Triazole Linkage
R. Lucas a , P. H. Elchinger a , P. A. Faugeras a & R. Zerrouki a
a Université de Limoges, Laboratoire de Chimie des Substances
Naturelles, Faculté des Sciences et Techniques , 123, Limoges,
France
Published online: 19 Apr 2010.
To cite this article: R. Lucas , P. H. Elchinger , P. A. Faugeras & R. Zerrouki (2010) Pyrimidine-Purine
and Pyrimidine Heterodinucleosides Synthesis Containing a Triazole Linkage, Nucleosides, Nucleotides
and Nucleic Acids, 29:3, 168-177, DOI: 10.1080/15257771003708579
To link to this article: http://dx.doi.org/10.1080/15257771003708579
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Nucleosides, Nucleotides and Nucleic Acids, 29:168–177, 2010
Copyright ꢀC Taylor and Francis Group, LLC
ISSN: 1525-7770 print / 1532-2335 online
DOI: 10.1080/15257771003708579
PYRIMIDINE-PURINE AND PYRIMIDINE HETERODINUCLEOSIDES
SYNTHESIS CONTAINING A TRIAZOLE LINKAGE
R. Lucas, P. H. Elchinger, P. A. Faugeras, and R. Zerrouki
Universite´ de Limoges, Laboratoire de Chimie des Substances Naturelles, Faculte´ des Sciences
et Techniques, 123Limoges, France
This article describes a synthetic route to generate two purine-pyrimidine and pyrimidine heterod-
2
inucleosides. Both microwave activated regioselective alkylation using hydride and copper-catalyzed-
azide-alkyne-cycloaddition (CuAAC) were used in order to perform the synthesis.
Keywords Oligonucleotides analogues; click chemistry; microwave-activated synthesis
INTRODUCTION
Synthetic oligonucleotide analogues are of considerable importance be-
cause of their ability to inhibit gene expression through the antisense ef-
fect.[1] One of the most important modifications is the complete substitu-
tion of the phosphate internucleoside bridge,[2] in order to achieve stronger
affinity for the nucleic acid target, enhanced resistance, and improved mem-
brane permeability and cellular uptake. The Huigsen 1,3-dipolar cycload-
dition between azides and alkynes, performed by recently discovered cop-
per (I) catalysis[3] appears as a promising way to generate oligomers and
particularly oligonucleotide analogues, which can resist chemical or enzy-
matic depolymerization. Moreover the exclusive regioselective formation of
1,4-disubstituted-1,2,3-triazole conserves the directional character of DNA
strands. In addition the introduction of a dT-A or pyrimidine-purine step
into a straight and rigid A-tract of oligonucleoside can cause a positive roll
deformation that kinks the DNA helix at this step.[4] In this way, our research
effort in this area has focused on the synthesis of an anti HIV-1 sequence
(Figure 1)[5] and the introduction of a dT-A step in this sequence. Pre-
vious studies, introducing a triazole linkage in oligonucleosides backbone,
have been realized using thymidine as nucleoside (homothymidines) in both
Received 4 February 2010; accepted 10 February 2010.
Address correspondence to R. Zerrouki, Universite´ de Limoges, Laboratoire de Chimie des Sub-
stances Naturelles, Faculte´ des Sciences et Techniques, 123, Av. Albert Thomas, 87060 Limoges, France.
E-mail: Rachida.zerrouki@unilim.fr
168

Pyrimidine-Purine and Pyrimidine Heterodinucleosides
169
FIGURE 1 Anti HIV-1 sequence.
solution-phase and solid phase synthesis.[6] However, no other pyrimidine or
purine nucleosides have been inserted in aoligonucle´oside sequences using
a “click backbone.”
In this article, we are interested in the feasibility of coupling two differ-
ent nucleosides by click chemistry and synthesis of two hetero-dinucleoside
analogues (dC-dT and dT-A) in which glycosidic moieties are linked by a
triazole group between positions 3ꢁ and 5ꢁ.
RESULTS AND DISCUSSION
Toward a Cytidine-Thymidine heterodimer (dC-dT)
The synthesis of the first precursor 3 began benzoylating commer-
cially available 2ꢁ-deoxycytidine, using an established transient protection
method,[7] in order to protect the exo-cyclic amine on the nucleobase
to give compound 1 (87%). Then tosylation[8] of resultant N 4-benzoyl-2ꢁ-
deoxycytidine 1 using tosyl chloride (1.6 equiv.) and standard conditions in
pyridine, at 0◦C produced compound 2 in low yield (49%; Scheme 1). In
addition to 5ꢁ-O-tosyldeoxycytidine, 3ꢁ,5ꢁ-di-O-tosyldeoxycytidine also is ob-
served. This result strongly suggest that the slight difference in reactivity
between 5ꢁ and 3ꢁ positions is the cause of relative low yield of tosylation
of primary hydroxyl group. Alkyne 3 was obtained by regioselective 3ꢁ-O-
alkylation using a two-step method.[9] During the first step compound 2 was
activated with 2.5 equivalents of NaH in THF, then, for the second step, 2.5
equivalents of propargyl bromide was added and the mixture was activated
again. No evolution of hydrogen gas was observed and a large amount of
reactant (5 equiv.) was necessary in order to obtain the compound 3 in
51% yield. This strategy is not efficient to prepare compound 3 because
the over yield is very low (22% from deoxycytidine). Finally, for obtention
of the alkyne compound, we decided to use another strategy (Scheme 2).
Precursor 5 was synthesized from N 4-benzoyl-2ꢁ-deoxycytidine 1, first by se-
lective protection of 5ꢁ-hydroxyl group with tert-butyldimethylsilyl chloride
(1.6 equiv.) in dry dimethylformamide (DMF) in the presence of imidazole
(3.0 equiv.) giving compound 4 in 84% yield.[10] The 3ꢁ-hydroxyl group was

170
R. Lucas et al.
SCHEME 1 Synthesis of propargylated 2ꢁ-deoxycytidin precursor (3). Reagents and conditions: (i) 1-
Me3SiCl (5 equiv.), 2-BzCl (5 equiv.), Py (10 mL); (ii) TsCl (1.6 equiv.), Py, 0◦C; (iii) 1-NaH (2.5 equiv.),
THF, MW (2 minutes, 200 W, 40◦C) 2-propargylbromide (2.5 equiv.); (6 minutes, 200 W, 40◦C).
SCHEME 2 Synthesis of the second propargylated 2ꢁ-deoxycytidine precursor (5). Reagents and condi-
tions: (i) Imidazole (3 equiv.), TBDMSCl (1.6 equiv.), DMF; (ii) 1-NaH (2.5 equiv.), THF, MW (2 minutes,
200 W, 40◦C) 2-propargylbromide (2.5 equiv.), MW (6 minutes, 200 W, 40◦C).
then alkylated using Chattopadhyaya’s method[9] with NaH (2.5 equiv.) and
propargylbromide (2.5 equiv.) in THF under MW activation to give alkyne
compound 5 in 91% yield (67% from deoxycytidine). The azido-precursor
was 5ꢁ-azido-5ꢁ-deoxythymidine.[6] Tosylation of thymidine followed by an
azidation gave the expected precursor 6 in a two steps good yield of 67%
from thymidine.

Pyrimidine-Purine and Pyrimidine Heterodinucleosides
171
SCHEME 3 Synthesis of the dC-dT heterodinucleotide analogue (7). Reagents and conditions: (i)
CuSO4 (0.1 equiv.), Na ascorbate (0.6 equiv.), H2O/EtOH (1/1), MW (1 minutes, 200 W, 80◦C).
Derivatives 5 and 6 were then coupled using copper(I)-catalyzed cycload-
dition in order to obtain silylated heterodimer 7 (Scheme 3). Optimization
of this reaction has been described in a previous article.[11] Alkyne and azide
precursors were suspended in a 1:1 mixture of water and ethanol, together
with Cu(I) catalyst and sodium ascorbate. After 3 minutes of MW irradiation
the heterodimer 7 was isolated in 70% yield.
Synthesis of an Thymidine-Adenosine heterodimer (dT-A)
The synthesis of hetero-dinucleoside analogue dT-A is presented
in Scheme 4. The first precursor synthesized was 3ꢁ-O-propargyl-5ꢁ-O-
tosylthymidine. Selective tosylation of the primary hydroxyl group of thymi-
dine gave the already known product 8. Alkyne 9 was obtained by regios-
elective 3ꢁ-O-alkylation using Chattopadhyaya’s two-step method under mi-
crowave irradiation. During the first step compound 8 was activated (40◦C,
200 W, 3 minutes) with 2.5 equivalents of NaH in THF then in the sec-
ond step 2.5 equivalents of propargyl bromide was added and the mixture
was subjected to microwave irradiation for 3 minutes. The reaction pro-
duced compound 9 in 96% yield.[6] The synthesis of second precursor 11
began with tosylating commercially available 2ꢁ,3ꢁ-O-isopropylidene adeno-
sine. Then using previous method used for hydroxyl group protection, the
protected compound 10 was synthesized in moderate yield (50%). In addi-
tion to 5ꢁ-O-tosyl-2ꢁ,3ꢁ-O-isopropylidene adenosine, cycloadenosine 10ꢁ was
also is observed (Figure 2). Compound 10ꢁ results from the intramolecular
nucleophilic displacement by N 3 (Figure 2). It was reported that, upon ro-
tation of the adenine ring of 5ꢁ-protected adenosine, the N 3 of the base can

172
R. Lucas et al.
SCHEME 4 Synthesis of the dT-A heterodinucleotide analogue (12).

Pyrimidine-Purine and Pyrimidine Heterodinucleosides
173
FIGURE 2 Cycloadenosine 10ꢁ.
readily displace the 5ꢁ-activation to give the ionic cycloadenosine, causing a
steep decrease of the overall yield of 10.[12] In fact, intramolecular displace-
ment of sulfonate is so rapid that it interferes with product isolation and
purification.
Derivatives 9 and 11 were then clicked using copper(I)-catalyzed cy-
cloaddition in order to obtain silylated heterodimer 12. Alkyne and azide
precursors were suspended in a 1:1 mixture of water and ethanol, together
with Cu(I) catalyst and sodium ascorbate. After 3 minutes of irradiation, het-
erodimer 12 was obtained after purification in 87% yield. The tosyl group
in 5ꢁ of the dT-A could be used for further azidation in order to generate an
oligonucle´otides analogue.
CONCLUSION
In conclusion we have investigated the first total synthesis of two triazole
heterodimers (dC-dT and dT-A) using a “click chemistry” reaction and MW
irradiation to reduce reaction time. This work is presently continuing toward
solid-phase synthesis of a pyrimidine antisense sequence with promising
results.
EXPERIMENTAL
All the solvents and chemicals were commercially available and, unless
otherwise stated, were used as received. Reactions were monitored by thin
layer chromatography (TLC) on precoated 0.2 mm silica gel 60 F254 (Merck)
plates and visualized in several ways: with an ultraviolet light source at 254 nm,
by spraying with sulphuric acid (6N) and heating to 200◦C. Microwave irra-
diations were performed by the means of an Ethos 1600 MicroSynth reactor
from Milestone. Temperature was measured with a fiber optic thermome-
ter (ATC-FO)/Ethos. 1H NMR spectra were recorded at 400.13 MHz with a

174
R. Lucas et al.
Bru¨ker DPX spectrometer (Germany). Chemical shifts (δ) are expressed in
ppm with Me4Si as an internal standard (δ = 0). Data are reported as fol-
lows: chemical shift, multiplicity (s, singlet; d, doublet; t, triplet; q, quartet;
m, multiplet and br, broad), coupling constants (Hz) and assignment.
Tosylation of N4-Benzoyl-2ꢁ-deoxycytidine
N 4-benzoyl-2ꢁ-deoxycytidine 1 (223 mg, 0.68 mmol) was solubilized in
anhydrous pyridine with 1.6 equivalents of tosyl chloride (206 mg, 1.08
mmol). This solution was placed under argon at 0◦C during 3 hours. Then
solvent was removed under reduced pressure and the crude residue purified
using flash chromatography (CH2Cl2/petroleum ether, from 8/2 to pure
petroleum ether). Pure product 2 was recovered as a white solid in 49%
yield (160 mg).
Silylation of N4-Benzoyl-2ꢁ-deoxycytidine
N 4-benzoyl-2ꢁ-deoxycytidine 1 (150 mg, 0.45 mmol) was solubilized in
anhydrous DMF with 3.0 equivalents of imidazole (92.5 mg, 1.36 mmol) and
1.6 equivalents of tert-butyldimethylsilyl chloride (109 mg, 0.73 mmol). This
solution was placed under argon at 0◦C during 3 hours. Then solvent was
removed under reduced pressure and the crude residue purified using flash
chromatography. Pure product 4 was recovered as a white solid in 84% yield
(184 mg).
General Procedure for Propargylation
To compound 4 (50 mg, 0.10 mmol) in dry THF (15 mL), were added
2.5 equivalents of NaH (60%, 10 mg, 0.26 mmol) and the mixture was
activated by microwave irradiation (2 minutes, 200 W, 40◦C). Two and half
equivalents of propargyl bromide (30 µL, 0.26 mmol) were then added and
the mixture was activated by microwave irradiation (6 minutes, 200W, 40◦C).
After work-up (NH4Cl/H2O), the product was purified by chromatography
(thick layer plates, AcOEt/MeOH (9/1)). Compound 5 was recovered in
91% yield (39 mg).
General Procedure for Click Reaction
Compounds 9 (217 mg, 0.50 mmol), 11 (167 mg, 0.50 mmol), sodium
ascorbate (300 µL, 1 M, 0.6 equiv.), and copper sulfate pentahydrate (7.5
mg, 0.1 equiv.) were suspended in a 1:1 mixture of water and ethanol (4
mL each) in a 25 mL bicol (open reaction vessel). The mixture was then
irradiated for 1 minutes at 80◦C, using an irradiation power of 200 W. After
work-up (THF), the crude residue was concentrated in vacuo and product
12 was recovered as a white solid in 85% yield (326.2 mg).

Pyrimidine-Purine and Pyrimidine Heterodinucleosides
175
CHARACTERIZATIONS
Spectroscopic data of selected new compounds:
1
Compound 4: Rf = 0.52 (AcOEt/EtOH: 9/1); H NMR (DMSO d6): cy-
tidine: 11.22 (s, 1H, NH), 8.31 (br s, 1H, H5), 7.36 (br d, J = 6.8 Hz, H5);
benzoyl: 8.00 (dd, 2H, J = 1.2 Hz, J = 8.5 Hz, H2–6), 7.62 (br t, 1H, J = 7.5 Hz,
ꢁ
H4), 7.51 (br t, 2H, J = 7.5 Hz, H3–5); ose: 6.13 (t, 1H, J = 6.1 Hz, H1 ), 5.33
ꢁ
ꢁ
(d, 1H, J = 4.4 Hz, 1H, O3 -H), 4.22 (m, 1H, H3 ), 3.93 (br dd, 1H, J = 3.1
ꢁ
ꢁ
Hz, J = 11.5 Hz, H5 a), 3.87 (dd, 1H, J = 3.3 Hz, J = 11.5 Hz, H5 b), 2.36 (ddd,
ꢁ
1H, J = 4.8 Hz, J = 6.1 Hz, J = 13.3 Hz, H2 a), 2.07 (dt, 1H, J = 6.1 Hz, J =
13.3 Hz, H2 b); TBDMS: 0.88 (s, 9H, C-CH3), 0.09 (s, 6H, Si-CH3); 13C NMR
ꢁ
(DMSO d6): thymine: 162.9 (C4), 154.3 (C2), 144.4 (C6), 95.8 (C5); benzoyl:
167.3 (C O), 133.1 (C1), 132.7 (C4), 128.4 (C2, C3, C5, C6); ose: 87.3 (C4ꢁ),
86.2 (C1ꢁ), 69.6 (C3ꢁ), 62.6 (C5ꢁ), 41.2 (C2ꢁ); TBDMS: 25.7 (C CH3), 17.9
(C CH3a), −5.5 (Si CH3a), −5.6 (Si CH3b).
1
Compound 5: Rf = 0.45 (AcOEt/MeOH: 9/1); H NMR (DMSO d6):
cytidine: 11.26 (s, 1H, NH), 8.28 (br s, 1H, H5), 7.36 (br d, J = 7.4 Hz, H5);
benzoyl: 8.01 (dd, 2H, J = 7.2 Hz, J = 1.2 Hz, H2–6), 7.62 (br t, 1H, J = 7.4 Hz,
ꢁ
H4), 7.51 (br t, 2H, J = 7.6 Hz, H3–5); ose: 6.09 (br t, 1H, J = 6.4 Hz, H1 ),
ꢁ
ꢁ
4.27 (m, 1H, H3 ), 4.14 (br dd, 1H, J = 3.1 Hz, J = 6.2 Hz, H4 ), 3.87 (br dd,
ꢁ
1H, J = 3.7 Hz, J = 11.4 Hz, H5 a), 3.78 (br dt, 1H, J = J = 3.3 Hz, 11.4 Hz,
ꢁ
ꢁ
H5 b), 2.54 (ddd, 1H, J = 3.1 Hz, J = 6.1 Hz, J = 13.3 Hz, H2 a), 2.14 (dt, 1H,
ꢁ
J = 6.3 Hz, J = 13.3 Hz, H2 b); TBDMS: 0.89 (s, 9H, C CH3), 0.10 (s, 6H,
Si CH3a), 0.09 (s, 6H, Si CH3a); propargyl: 4.23 (br d, 1H, J = 2.3 Hz, J =
18,0 Hz, CH2), 3.47 (t, 1H, J = 2.3 Hz, C H); 13C NMR (DMSO d6): thymine:
163.0 (C4), 154.2 (C2), 144.3 (C6), 95.9 (C5); benzoyl: 167.3 (C O), 133.1
(C1), 132.7 (C4), 128.4 (C2, C3, C5, C6); ose: 86.5 (C1ꢁ), 84.5 (C4ꢁ), 77.7
(C3ꢁ), 62.8 (C5ꢁ), 40.4 (C2ꢁ); TBDMS: 25.7 (C CH3), 17,9 (C CH3), −5.6
(CH3a), −5.6 (CH3b); propargyl: 80.0 (C), 77.4 (CH), 55.9 (CH2); MS (IS)
m/z = 484.4 (MH+), 506.4 (MNa+), 989,7 (M2Na+).
Compound 7: Rf = 0.20 (CHCl3/EtOH: 9/1); 1H NMR (DMSO d6): 11.29
ꢁ
(s, 2H, NH), 2.52–2.06 (m, 4H, H2 cytidine and thymine); cytidine: 8.28 (d, 1H, J =
ꢁ
7.4 Hz, H5), 7.34 (d, 1H, J = 7.4, H6); ose: 6.10 (t, 1H, J = 6.4, H1 ), 4.29 (m,
ꢁ
ꢁ
ꢁ
1H, H3 ), 4.14 (m, 1H, H4 ), 3.85 (dd, 1H, J = 3.5, J = 11.5, H5 ), 3.75 (dd,
ꢁ
1H, J = 3.2, J = 11.5, H5 ); TBDMS: 0.86 (s, 9H, C (CH3)3), 0.07 (s, 3H,
Si CH3a), 0.06 (s, 3H, Si CH3b); benzoyl: 8.01 (dd, 2H, J = 1.2 Hz, J = 7.4
Hz), 7.62 (br. t, 1H, J = 7.4 Hz), 7.51 (br. t, 2H, J = 7.7 Hz); linker: 8.09 (s, 1H,
Htriazole), 4.57 (d, 2H, J = 12.1, CH2triazole); thymine: 7.35 (s, 1H, H6), 1.80 (s,
ꢁ
3H, CH3); ose: 6.15 (t, 1H, J = 6.9, H1 ), 5.50 (br. s, 1H, OH), 4.71 (dd, 1H, J =
ꢁ
ꢁ
4.3 Hz, J = 14.4 Hz, H5 ), 4.70 (dd, 1H, J = 3.4 Hz, J = 14.4 Hz, H5 ), 4.20 (m,
13
ꢁ
ꢁ
ꢁ
1H, H3 ), 4.08 (m, 1H, H4 ); C NMR (DMSO d6), 41.4 (C2 cytidine or thymidine),
37.5 (C2ꢁcytidine or thymidine); cytidine: 163.0 (C4), 154.2 (C2), 144.3 (C6), 95.9
(C5); ose: 86.5 (C1ꢁ), 84.9 (C4ꢁ), 78.1 (C3ꢁ); benzoyl: 167.2 (C O), 133.1 (C1),
132.7 (C4), 128.4 (C2, C3, C5, C6); TBDMS: 25.7 (C CH3), 17.9 (C CH3);

176
R. Lucas et al.
linker: 143.7 (Ctriazole), 124.7 (CHtriazole), 61.8 (CH2triazole), −5.6 (CH3a), −5.7
(CH3b); thymine: 163.6 (C4), 150.4 (C2), 136.0 (C6), 109.8 (C5), 12.1 (CH3);
ose: 84.0 (C1ꢁ), 83.9 (C4ꢁ), 79.1 (C3ꢁ).
1
Compound 10: Rf = 0.21 (CHCl3/EtOH: 9/1); H NMR (DMSO d6):
adenine: 8.21 (s, 1H, H8), 8.03 (s, 1H, H2), 7.36 (br s, NH2); ose: 6.18 (d, 1H,
ꢁ
ꢁ
J = 1.8 Hz, H1 ), 5.33 (dd, 1H, J = 1.8 Hz, J = 6.2 Hz, H2 ), 5.00 (m, 1H,
ꢁ
ꢁ
ꢁ
H3 ), 4.33 (m, 1H, H4 ), 4.33 (dd, 1H, J = J = 3.9 Hz, 12.2 Hz, H5 a), 4.22
ꢁ
(dd, 1H, J = 2.8 Hz, J = 7.0 Hz, H5 b); isopropylidene: 1.51 (s, 3H, CH3a), 1.29
(s, 1H, CH3b); tosyl: 7.56 (d, 2H, J = 8.2 Hz, Hortho/S), 7.25 (d, 2H, J = 8.2
Hz, Hmeta/S), 2.36 (s, 3H, CH3).
1
Compound 11: Rf = 0.50 (CH2Cl2/EtOH: 9/1); H NMR (DMSO d6):
adenine: 8.35 (s, 1H, H8), 8.18 (s, 1H, H2), 7.35 (s, NH2); ose: 6.22 (d, 1H, J =
ꢁ
ꢁ
2.6 Hz, H1 ), 5.52 (dd, 1H, J = 2.6 Hz, J = 6.2 Hz, H2 ), 5.01 (dd, 1H, J = 3.0
ꢁ
ꢁ
ꢁ
Hz, J = 6.2 Hz, H3 ), 4.31 (m, 1H, H4 ), 3.63 (dd, 1H, J = 7.2 Hz, 13.0 Hz, H5 a),
ꢁ
3.55 (dd, 1H, J = 4.9 Hz, J = 13.0 Hz, H5 b); isopropylidene: 1.55 (s, 3H, CH3a),
1.13 (s, 1H, CH3b); 13C NMR (DMSO d6): adenine: 156.2 (C6), 152.8 (C2),
148.8 (C4), 140.0 (C8), 119.2 (C5); ose: 84.3 (C1ꢁ), 80.6 (C2ꢁ), 77.8 (C3ꢁ),
69.9 (C4ꢁ), 35.3 (C5ꢁ); isopropylidene: 113.5 (C), 26.9 (CH3a), 25.1 (CH3b).
1
Compound 12: Rf = 0.27 (CHCl3/EtOH: 9/1); H NMR (DMSO d6):
adenine: 8.28 (s, 1H, H8), 8.19 (s, 1H, H2), 7.36 (s, NH2); ose: 6.23 (d, 1H, J =
ꢁ
ꢁ
2.0 Hz, H1 ), 5.45 (dd, 1H, J = 2.0 Hz, J = 6.2 Hz, H2 ), 5.15 (dd, 1H, J = 3.4
ꢁ
ꢁ
Hz, J = 6.2 Hz, H3 ), 4.77 (dd, 1H, J = 5.4 Hz, J = 14.1 Hz, H5 b), 4.67 (dd,
ꢁ
ꢁ
1H, J = 7.7 Hz, 14.1 Hz, H5 a), 4.55 (m, 1H, H4 ); isopropylidene: 1.53 (s, 3H,
CH3b), 1.31 (s, 1H, CH3a); linker: 7.95 (s, 1H, Htriazole), 4.47 (d, 2H, J = 12.4,
CH2triazole); thymine: 11.31 (s, 1H, NH), 7.39 (s, 1H, H6), 1.77 (s, 3H, CH3);
ꢁ
ose: 6.08 (d, 1H, J = 6.8 Hz, J = 7.4 Hz, H1 ), 4.26 (dd, 1H, J = 3.5 Hz, J =
ꢁ
ꢁ
10.9 Hz, H5 b), 4.20 (dd, 1H, J = 5.5 Hz, J = 10.9 Hz, H5 a), 4.13 (ddd, 1H, J
ꢁ
= 3.0 Hz, J = 5.5 Hz, J = 6.0 Hz, H3 ), 4.06 (ddd, 1H, J = 3.2 Hz, J = 5.4 Hz,
ꢁ
ꢁ
J = 6.2 Hz, H4 ), 2.19 (m, 1H, H2 ); tosyl: 7.78 (d, 2H, J = 8.2 Hz, Hortho/S),
7.45 (d, 2H, J = 8.2 Hz, Hmeta/S), 2.39 (s, 3H, CH3); 13C NMR (DMSO d6):
adenine: 156.2 (C6), 152.8 (C2), 148.6 (C4), 140.1 (C8), 119.2 (C5); ose:
89.0 (C1ꢁ), 84.5 (C4ꢁ), 83.3 (C2ꢁ), 81.5 (C3ꢁ), 51.0 (C5ꢁ); isopropylidene: 113.7
(C), 26.9 (CH3a), 25.2 (CH3b); linker: 143.5 (Ctriazole), 124.5 (CHtriazole), 62.0
(CH2triazole); thymine: 163.6 (C4), 150.3 (C2), 135.9 (C6), 109.9 (C5); ose: 84.3
(C1ꢁ), 80.8 (C4ꢁ), 78.2 (C3ꢁ), 70.1 (C5ꢁ), 35.6 (C2ꢁ), 12.1 (CH3); tosyl: 145.1
(Cp/S), 132.1 (Cipso/S), 130.2 (Cm/S), 127.6 (Co/S), 21.1 (CH3).
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