Preparation of ribavirin analogues by copper- and ruthenium-catalyzed azide-alkyne 1,3-dipolar cycloaddition

Article abstract of DOI:10.1016/j.tet.2008.07.007

In this study, we described the synthesis of 1,4- and 1,5-disubstituted-1,2,3-triazolo-nucleosides from various alkynes with 1′-azido-2′,3′,5′-tri-O-acetylribose using either copper-catalyzed azide-alkyne cycloaddition (CuAAC) or ruthenium-catalyzed azide-alkyne cycloaddition (RuAAC), respectively. Optimized RuAAC conditions were realized with the commercially available [Cp^*RuCl(PPh₃)₂] under microwave heating, which allows a significant acceleration of the reaction times (from 6 h to 5 min). This reaction can work under water-containing system. RuAAC and CuAAC are useful tools for the synthesis of 1,2,3-triazolyl-nucleosides small libraries.

Full text of DOI:10.1016/j.tet.2008.07.007

Tetrahedron 64 (2008) 9044–9051
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Preparation of ribavirin analogues by copper- and ruthenium-catalyzed
azide-alkyne 1,3-dipolar cycloaddition
,
,
,
*
Ugo Pradere a, Vincent Roy a, Tamara R. McBrayer b c, Raymond F. Schinazi b c, Luigi A. Agrofoglio a
a Institut de Chimie Organique et Analytique, Universite´ d’Orle´ans, UMR CNRS 6005, BP 6759, 45067 Orle´ans, France
b Emory University School of Medicine, Atlanta, GA 30033, USA
c Veterans Affairs Medical Center, Atlanta, GA 30033, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 11 May 2008
Received in revised form 23 June 2008
Accepted 1 July 2008
Available online 5 July 2008
In this study, we described the synthesis of 1,4- and 1,5-disubstituted-1,2,3-triazolo-nucleosides from
various alkynes with 10-azido-20,30,50-tri-O-acetylribose using either copper-catalyzed azide-alkyne
cycloaddition (CuAAC) or ruthenium-catalyzed azide-alkyne cycloaddition (RuAAC), respectively.
Optimized RuAAC conditions were realized with the commercially available [Cp RuCl(PPh3)2] under
*
microwave heating, which allows a significant acceleration of the reaction times (from 6 h to 5 min). This
reaction can work under water-containing system. RuAAC and CuAAC are useful tools for the synthesis of
1,2,3-triazolyl-nucleosides small libraries.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
conditions for the synthesis of 1,5-regiomers. All obtained com-
pounds were evaluated for their anti-HCV activity in vitro.
In recent years, many nucleoside analogues have been suc-
cessfully developed into DNA virus and retrovirus therapeutic
agents,1 against different human immunodeficiency virus (HIV)
strains and viruses with related-polymerases such as hepatitis B
(HBV) or C (HCV). In the case of HCV, the template and substrate
specificity of HCV RNA-dependent RNA polymerase differs from the
host DNA-dependent polymerase, increasing thus the probability of
developing potent HCV-specific nucleoside chain terminator.
Figure 1 shows some examples of anti-HCV nucleosides and some
triazolo derivatives (Fig. 1). The first nucleoside to show a thera-
peutic effect in HCV infection was ribavirin2 (1) whose mechanism
of action is a subject of debate.
NHOH
NH
NH2
N
O
N
N
NH2
N
HO
O
HO
N
O
HO
N
O
O
O
Me
HO OH
HO OH
HO OH
(1)
(2)
(3)
N
H2N
N
(CH2)7CH3
N
N
N
N
N
Stuyver et al.3 reported the activity of a N4-hydroxycytidine
(NHC) analogue (2), meanwhile several reports4 describe the anti-
HCV replicon activity of nucleosides modified at the 20-position (3).
Another approach to discover a potent anti-HCV compounds was
reported by Smith et al.5 in which analogues of triciribine (4),
a cyclic sangivamycin analog with anti-cancer and anti-viral ac-
tivity was reported. The synthesis of various triazolo compounds
has been reported by Schinazi et al. (for 5),6 Benhida et al. (for 6),7
and by our team (for 7).8 As part of our drug discovery program, we
report herein the synthesis of new 1,4-disubstituted-1,2,3-triazolo-
nucleosides through well established Cu(I)-catalyzed azide-alkyne
cycloaddition (CuAAC). We have then investigated the Ru(II)-cata-
lyzed azide-alkyne cycloaddition (RuAAC) under microwave
N
N
HO
HO
N
N
O
O
N
O
O
HO OH
HO OH
(4)
HO OH
(5)
(6)
O
R
N
N
N
N
NH2
N
O
R'
HO
HO
N
OH
HO OH
(7)
(12a-h) 1,4-regioisomers
(13a-h) 1,5-regioisomers
* Corresponding author. Tel.: þ33 2 3849 4582; fax: þ33 2 3841 7281.
E-mail address: luigi.agrofoglio@univ-orleans.fr (L.A. Agrofoglio).
Figure 1. Some anti-HCV triazolo-nucleosides and target compounds (12 and 13).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.07.007

U. Pradere et al. / Tetrahedron 64 (2008) 9044–9051
9045
2. Results and discussion
mainly to 1,5-regioisomers.13 Generally, the common approaches to
1,5-regioisomers were based on Grignard reagents,14 or 1-trime-
thylsilylalkynes;15 nevertheless, these approaches suffer from some
limitations including the number of steps and the chemical be-
havior of some functional groups toward those conditions. Thus,
under classical heating, the azido-ribose (8) was reacted with var-
The Huisgen 1,3-dipolar cycloaddition of alkynes and azides
(AAC)9 to give substituted-1,2,3-triazoles has emerged as a power-
ful linking reaction in both uncatalyzed10 and copper (I)-catalyzed
leading to the sole 1,4-regioisomers.11 The copper-catalyzed version
of the reaction (CuAAC) has proven to be popular in many condi-
tions, ranging from drug discovery to surface science, where rapid
and reliable bond formation is required. Such 1,4 selectivity has
been already reported in a very similar system under microwave
conditions by Benhida et al.7 Nevertheless, we have synthesized
new compounds and evaluated them against HCV. Starting with the
ious alkynes and 5 mol % Cp
RuCl(PPh3)2 catalyst16 (11) in THF at
*
50 ꢀC. After 6 h, the desired triazolo compounds 10a–h were
obtained in moderate to good yield (54–83%), after purification by
column chromatography. Except for the ethyl ethynyl ether de-
rivative (54%), the yields of all other alynes are almost identical
(from 71 to 83%) for the RuAAc reaction showing that the influence
of the steric hindrance of alkyne is low.
protected b
-azido-ribose (8),12 the synthesis of various protected
1,4-disubstituted-1,2,3-triazolyl-nucleosides (Scheme 1) was per-
formed regioselectively with Cu(0)/CuSO4 as catalyst precursor. The
desired new compounds 9a–h were obtained in yields ranging from
83 to 93% (Table 1, entries 1–7) except for ethoxy-ethyne (Table 1,
entry 8). This system has the advantage of being simple and the
products can be obtained from the reaction mixture by simple
extraction.
During the RuAAC, 3 to 7% of the 1,4-regioisomers, separable by
column chromatography on silica gel, were obtained. Their struc-
tures were unambiguously confirmed by NMR (e.g., dH1¼6.44 ppm
(for 1,4-isomer) and dH1¼6.15 ppm (for 1,5-isomer)) and TLC com-
parison with those obtained under CuAAC conditions. It should be
noted that some catalyst deactivation has been encountered during
long heating times. Thus, to circumvent this limitation, we decided
to work under microwave activation17 (Table 1). Microwave heating
is known as powerful tool to promote a variety of chemical
We then turn our attention to the ruthenium-catalyzed version
of the reaction (RuAAC), which is less extensively described and led
N
N
R
N
O
CuAAc
BzO
(see Table)
BzO OBz
BzO
N3
O
9a-h
+
R
N
N
BzO OBz
Ru
Cl
11, RuAAc
PPh3
Ph3P
BzO
N
heating or MW
(see Table)
O
R
8
11
RuAAC catalyst [Cp*RuCl(PPh3)2]
BzO OBz
10a-h
Scheme 1.
Table 1
Survey of CuAAC and RuAAC reactiona,b
Entry
Alkyne
R
1,4-Regioisomers (CuAAC) (%)
1,5-Regioisomers (RuAAC)b
Ratio 1,4/1,5
D
D
MW yield % (Conv. %)
1
2
3
4
a
b
c
86
88
93
87
79
88 (93)
4:96
3:93
4:96
5:95
F
83
71
79
92 (100)
92 (100)
87 (100)
d
5
6
7
e
f
89
83
92
63
82
68
77
54
91 (96)
4:96
5:95
5:95
3:97
87 (100)
95 (100)
93 (100)
Cl
g
h
O
8
a
Conditions: azide 1 (1 equiv), alkyne (1.1 equiv), Cu powder (4 equiv), CuSO4$5H2O (0.2 equiv), tBuOH/H2O.
b
Conditions: azide 1 (1 equiv, 0.1 M in THF), alkyne (1.5 equiv), Cp
*
RuCl(PPh3)2 (0.05 equiv), THF, thermal heating (
D
): 6 h, T¼50 ꢀC or microwave conditions (MW): 5 min,
T¼100 ꢀC.

9046
U. Pradere et al. / Tetrahedron 64 (2008) 9044–9051
reactions.18 While yields and purities of the coupling products were
comparable to heating conditions, microwave heating allows
a significant acceleration of the reaction from 6 h to 5 min (Table 1).
Working in THF at 100 ꢀC, we first investigated the optimal con-
ditions for the cycloaddition of azido-ribose 8 and hexyne with dif-
ferent concentration of catalyst 11 (Table 2). A 95% conversion was
obtained after only 3 min of reaction with 5% catalyst. The total con-
version of starting azido-ribose was obtained after 10 min with 3.5%
catalystloadingandin5 minfor5%catalystloading. Forlowercatalyst
loading, conversion was not complete, even after 10 min reaction.
3. Biological results
The biological activity and toxicity of the synthesized triazoles
against HCV were investigated in a replicon system in Huh-7 cells,
and these compounds did not exhibit any marked activity or tox-
icity. The anti-viral19 and cytotoxicity20 assays were done as pre-
viously described.
4. Conclusion
In summary, we have used either the Cu(0)/CuSO4 catalytic
system for CuAAC or the Cp RuCl(PPh3)2 (11) under microwave
*
Table 2
Optimization of RuAAC under microwave conditions for 11e
conditions for RuAAC to reach hitherto unknown 1,4- and 1,5-di-
substituted-1,2,3-triazolyl-nucleosides. The cooperative effect of
the catalyst 11 and the microwave activation afforded the desired
compounds in a few minutes in high yields. This approach allows an
Catalyst loading
(mol %)
Irradiation time
3 min
5 min
10 min
1
d
d
36%
57%
100%
d
easy access to
a small library of 1,5-disubstituted-triazolo
2
d
d
derivatives under RuAAC and 1,4-regioisomers under CuAAC.
3.5
5
d
84%
100%
94%
5. Experimental
5.1. General
Thus, 5 mol % catalyst and 1.5 equiv of alkyne in THF at 100 ꢀC for
5 min under microwave irradiation allowed the isolation of the de-
sired compound 10e. It is interesting to note that anhydrous condi-
tions are not necessary (e.g., undistilled THF, or THF-containing
2 equiv of water can be used to run this RuAAC). With this optimized
conditions in hand, we probed the scope of the reaction onprotected
azido-ribose (8) with various alkynes. The desired 1,5-disubstituted-
1,2,3-triazolyl-nucleosides 10a–h were obtained in good yields
(Table 1). In most examples (Table 1, entries 1–7), microwave irra-
diation had evident beneficial effects in terms of reaction time and
yield. For example, using classical heating, sluggish reactions with
ethyl ethynyl ether were observed (54% after 6 h), meanwhile under
microwave irradiation, complete conversion was achieved with
Commercially available chemicals were of reagent grade and
used as received. THF was distilled from sodium/benzophenone
ketyl; CH2Cl2 from CaH2 immediately prior use and benzene over
Na. The microwave was a Biotage AB Initiator EXP EU with a max-
imum power of 300 W. The vials used in the microwave were
EmrysÔ process vials 0.5–2 mL. The reactions were monitored by
thin layer chromatography (TLC) analysis using silica gel plates
(Kieselgel 60F254, E. Merck). Column chromatography was per-
formed on Silica Gel 60M (0.040–0.063 mm, E. Merck). Melting
points are uncorrected and were measured on a Kofler apparatus.
The 1H and 13C NMR spectra were recorded on a Bruker AVANCE
DPX 250 and Varian InovaUnity 400 spectrometer (1H: 250 MHz, 13C:
100 MHz) in (d4) methanol and CDCl3, shift values in parts per
million relative to SiMe4 as internal reference, the 31P spectra were
reported using aqueous phosphoric acid as external reference (31P:
161.97 MHz) in CD3OD, unless otherwise stated; J in hertz. Evidence
of purity has been done from a proton-decoupled 13C NMR spec-
trum with a signal-to-noise ratio sufficient to permit seeing peak
with 5% of the intensity of the strongest peak.
[Cp RuCl(PPh3)2] after short reaction time (5 min). The deacylation
*
of 1,4-regioisomers (9a–h) and 1,5-regioisomers (10a–h) was car-
ried out using a 7 N solution of ammonia in methanol at 0 ꢀC over
12 h and led quantitatively to the final 1,4-disubstituted-1,2,3-
triazolo-nucleosides (12a–h) and 1,5-disubstituted-1,2,3-triazolo-
nucleosides (13a–h), respectively (Scheme 2).
N
N
N
N
N
O
R
N
O
R
5.2. General procedure under CuAAC condition
BzO
HO
NH3 / MeOH
To a solution of selected alkyne (1.1 mmol) and azido-ribose (8)
(1 mmol) in H2O/tBuOH (1 mL) were added Cu powder (4 mmol)
and CuSO4 (0.2 mmol). The resulting suspension was stirred over-
night at room temperature, then the mixture was extracted twice
with ethyl acetate (50 mL), and dried over MgSO4. The solvents
were removed under reduced pressure and the obtained residue
was purified on silica gel (petroleum ether/ethyl acetate, 8:2, v/v) to
give the desired compound.
BzO OBz
9a-h or 10a-h
HO OH
12a-h or 13a-h
Scheme 2. Cleavage of benzoyl protective group.
Finally, the scope of this reaction with respect to unprotected
azido-ribose (14) was next investigated on the hexyne and after
5 min of irradiation with 5 mol % RuAAC catalyst, the desired
product (13e) was obtained in 95% yield (Scheme 3). This result
confirms the robustness of the RuACC reaction conditions.
5.2.1. 20,30,50-Tri-O-benzoyl-10-[4-phenyl-[1,2,3]triazol-1-
yl]ribofuranose (9a)
Prepared from compound 8 with the typical procedure de-
scribed before to give 9a (86%) as an oil. IR: 1717, 1451, 1316, 1124,
HO
N3
N
N
O
Bu
+
N
N
1093, 1040, 703 cmꢁ1; 1H NMR (CDCl3):
d
8.06 (d, J¼7.2 Hz, 2H, HAr),
N
O
N
8.00–7.95 (m, 5H, HAr and H5), 7.65 (d, J¼7.5 Hz, 2H, HAr), 7.58–7.50
HO
Bu
HO
O
0
HO OH
14
(m, 3H, HAr), 7.41–7.30 (m, 9H, HAr), 6.53 (d, J¼3.8 Hz, 1H, H1 ), 6.30
RuAAc
0
0
(dd, J¼05.3, 3.80Hz, 1H, H2 ), 6.18 (t, J¼5.3 Hz, 1H, H3 ), 4.86–4.92 (m,
microwaves
irradiation
5 min
0
OH
HO
13e
(95%)
2H, H4 and H5 ), 4.62 (dd, J¼12.0, 3.6 Hz, 1H, H5 ); 13C NMR (CDCl3):
HO OH
12e
+
d
166.0 (C(O)),165.1 (C(O)),165.0 (C(O)),148.2 (C4),133.8 (CAr),133.6
(5%)
(CAr), 133.3 (CAr), 129.8 (2C, CAr), 129.7 (CAr), 129.6 (CAr), 129.2 (CAr),
128.6 (2C, CAr), 128.5 (2C, CAr), 128.4 (CAr), 128.4 (CAr), 128.3 (CAr),
Scheme 3. RuAAC on deprotected azido-ribose under thermal heating.

U. Pradere et al. / Tetrahedron 64 (2008) 9044–9051
9047
0
0
0
0
0
0
0
0
125.7 (CAr), 118.4 (C5), 90.3 (C1 ), 81.1 (C4 ), 75.2 (C2 ), 71.5 (C3 ), 63.5
1H, H2 ), 6.15 (t, J¼5.3 Hz, 1H, H3 ), 4.90–4.80 (m, 2H, H4 and H5 ),
0
0
(C5 ); CAS: 26295-47-6; MS (ESI): m/z [MþNa]þ calcd for
4.60 (dd, J¼12.1, 4.2 Hz, 1H, H5 ), 2.64 (td, J¼7.6, 2.3 Hz, 2H,
CH2CH2CH2CH3), 1.59–1.50 (m, 2H, CH2CH2CH2CH3), 1.39–1.28 (m,
2H, CH2CH2CH2CH3), 0.89 (t, J¼7.3 Hz, 3H, CH2CH2CH2CH3); 13C
C
34H27N3NaO7: 612.6, found: 612.5.
5.2.2. 20,30,50-Tri-O-benzoyl-10-[4-4-fluoro-3-methylphenyl-
[1,2,3]triazol-1-yl]ribofuranose (9b)
NMR (CDCl3): d
166.0 (C(O)), 165.0 (C(O)), 164.9 (C(O)), 148.9 (C4),
133.7 (CAr), 133.6 (CAr), 133.3 (CAr), 129.7 (2C, CAr), 129.6 (CAr), 1290.2
(CAr), 128.6 (CAr), 0128.5 (CAr0), 128.4 (2C, CAr), 119.5 (C5), 90.0 (C1 ),
Prepared from compound 8 with the typical procedure described
before to give 9b (88%) as a slight yellow oil. IR: 1720, 1602, 1493,
0
0
80.9 (C4 ), 75.1 (C2 ), 71.6 (C3 ), 63.6 (C5 ), 31.0 (CH2CH2CH2CH3), 25.1
(CH2CH2CH2CH3), 22.2 (CH2CH2CH2CH3), 13.7 (CH2CH2CH2CH3); MS
(ESI): m/z [MþNa]þ calcd for C32H31N3NaO7: 592.6, found: 592.5.
1451, 1259, 1091, 1069, 1024, 799, 705 cmꢁ1; 1H NMR (CDCl3):
d 8.07
(d, J¼8.3 Hz, 2H, HAr), 8.00 (d, J¼8.3 Hz, 2H, HAr), 7.97 (d, J¼8.3 Hz,
2H, HAr), 7.89 (s, 1H, H5), 7.61–7.50 (m, 4H, HAr), 7.44–7.37 (m, 7H,
0
HAr), 6.98 (t, J¼9.0 Hz, 1H, HAr), 6.53 (d, J¼3.9 Hz, 1H, H1 ), 6.28 (dd,
5.2.6. 20,30,50-Tri-O-benzoyl-10-[4-(3-chloropropyl)-[1,2,3]triazol-1-
yl]ribofuranose (9f)
Prepared from compound 8 with the typical procedure de-
scribed before to give 9f (83%) as white solid. Mp: 132 ꢀC (CHCl3);
IR: 1716, 1601, 1451, 1264, 1124,1099, 1070, 1047, 702 cmꢁ1; 1H NMR
0
0
J¼5.2, 3.9 Hz, 1H, H2 ), 6.15 (t, J¼5.2 Hz, 1H,0H3 ), 4.93–4.87 (m, 2H,
0
0
H4 and H5 ), 4.62 (dd, J¼13.2, 4.8 Hz, 1H, H5 ), 2.28 (d, J¼1.7 Hz, 3H,
CH3); 13C NMR (CDCl3):
d 166.1 (C(O)), 165.2 (C(O)), 165.1 (C(O)),
147.7 (C4), 133.9 (CAr), 133.8 (CAr), 133.5 (CAr), 129.9 (CAr), 129.8 (CAr),
129.7 (CAr), 129.2 (CAr), 129.0 (CAr), 128.9 (CAr), 128.7 (CAr), 128.6 (3C,
CAr), 128.5 (CAr), 125.8 (2C, CAr), 125.4 (CAr), 125.2 (CAr),0 124.9 (CAr0),
(CDCl3):
d
8.03 (d, J¼8.5 Hz, 2H, HAr), 7.98 (d, J¼8.4 Hz, 2H, HAr), 7.94
(d, J¼8.4 Hz, 2H, HAr), 7.58–7.52 (m, 4H, HAr and H5), 7.45–7.33 (m,
0
0
124.8 (CA0 r), 118.0 (C5), 115.5 (CA0 r), 115.2 (CAr), 90.4 (C1 ), 81.3 (C4 ),
6H, HAr), 6.44 (d, J¼3.5 Hz, 1H, H1 ), 6.24 (dd, J¼5.4, 3.5 Hz, 1H, H2 ),
0
0
0
0
75.3 (C2 ), 71.6 (C3 ), 63.6 (C5 ), 14.6, 14.5 (CH3); MS (ESI): m/z
6.14 (t, J¼5.4 Hz, 1H, H3 ), 4.90–4.79 (m, 2H, H4 and H5 ), 4.58 (dd,
0
[MþNa]þ calcd for C35H28FN3NaO7: 644.6, found: 644.5.
J¼12.2, 4.3 Hz, 1H, H5 ), 3.51 (t, J¼6.4 Hz, 2H, CH2CH2CH2Cl), 2.79 (t,
J¼6.4 Hz, 2H, CH2CH2CH2Cl), 2.07–2.00 (m, 2H, CH2CH2CH2Cl); 13C
5.2.3. 20,30,50-Tri-O-benzoyl-10-[4-benzyl-[1,2,3]triazol-1-
yl]ribofuranose (9c)
NMR (CDCl3): d
165.9 (C(O)), 165.0 (C(O)), 164.9 (C(O)), 146.7 (C4),
133.7 (CAr), 133.6 (CAr), 133.3 (CAr), 129.7 (CAr), 129.6 (2C, CAr), 1290.2
(CAr),128.5 (2C, CAr0),128.4 (2C, CAr),128.3 (CAr),120.1 (C5), 90.0 (C1 ),
Prepared from compound 8 with the typical procedure de-
scribed before to give 9c (93%) as white solid. Mp: 158 ꢀC (CHCl3);
IR: 1727,1708,1601,1450,1270,1123,1095,1068, 710 cmꢁ1; 1H NMR
0
0
0
80.9 (C4 ), 75.1 (C2 ), 71.5 (C3 ), 63.5 (C5 ), 44.0 (CH2CH2CH2Cl), 31.4
(CH2CH2CH2Cl), 22.5 (CH2CH2CH2Cl); MS (ESI): m/z [MþNa]þ calcd
for C31H28ClN3NaO7: 612.6, found: 612.5.
(CDCl3):
d
8.09–7.96 (m, 6H, HAr), 7.64–7.56 (m, 3H, HAr), 7.50–7.38
0
(m, 7H, HAr and H5), 07.33–7.21 (m, 5H, HAr), 6.43 (d, J¼3.1 Hz, H1 ),
0
6.28–6.25 (m, 1H, H2 ), 6.19 (t, J¼5.5 0Hz, 1H, H3 ), 4.95–4.88 (m, 1H,
5.2.7. 20,30,50-Tri-O-benzoyl-10-[4-terbutyl-[1,2,3]triazol-1-
yl]ribofuranose (9g)
0
H4 ), 4.83 (dd, J¼12.2, 3.3 Hz, 1H, H5 ), 4.63 (dd, J¼12.2, 4.5 Hz, 1H,
0
H5 ), 4.02–3.88 (m, 1H, CH2Ph); 13C NMR (CDCl3):
d
166.0 (C(O)),
Prepared from compound 8 with the typical procedure de-
scribed before to give 9g (92%) as white solid. Mp: 129 ꢀC (CHCl3);
165.6 (C(O)), 165.0 (C(O)), 138.4 (C4), 133.8 (CAr), 133.6 (CAr), 133.3
(CAr), 129.8 (CAr), 129.7 (2C, CAr), 129.2 (CAr),0128.7 (CAr), 128.6 (CAr0),
IR: 1718, 1600, 1450, 1265, 1094, 1069, 1037, 706 cmꢁ1 1H NMR
;
0
128.5 (CAr), 128.4 0(CAr), 126.5 (C5), 90.1 (C1 ), 81.0 (C4 ), 75.2 (C2 ),
(CDCl3):
d
8.07 (d, J¼8.0 Hz, 2H, HAr), 7.99 (d, J¼8.3 Hz, 2H, HAr), 7.94
0
71.6 (C3 ), 63.7 (C5 ), 32.1 (CH2Ph); MS (ESI): m/z [MþNa]þ calcd for
(d, J¼8.3 Hz, 2H, HAr), 7.59–7.51 (m, 3H, HAr), 7.46–7.33 (m, 7H, H0Ar
0
0
C
35H29N3NaO7: 626.6, found: 626.5.
and H5), 6.46 (d, J¼3.1 Hz, 1H, H1 ), 6.20–6.14 (m, 2H, H2 and H3 ),
0
0
0
4.90–4.80 (m, 2H, H4 and H5 ), 4.61 (dd, J¼11.9, 4.1 Hz, 1H, H5 ), 1.27
5.2.4. 20,30,50-Tri-O-benzoyl-10-[4-methylcyclopentyl-[1,2,3]triazol-
1-yl]ribofuranose (9d)
(s, 9H, C(CH3)3); 13C NMR (CDCl3):
d 166.1 (2C, C(O)), 165.1 (2C,
C(O)), 158.2 (C4), 133.8 (CAr), 133.7 (CAr), 133.4 (CAr), 129.8 (CAr),
129.7 (20C, CAr), 129.3 (CAr), 128.6 (2C, CAr0 ), 128.5 (3C, CAr), 117.4 (C5),
Prepared from compound 8 with the typical procedure described
before to give 9d (87%) as white solid. Mp: 121 ꢀC (CHCl3); IR: 1716,
1601, 1451, 1261, 1093, 1068, 1023, 803, 706 cmꢁ1; 1H NMR (CDCl3):
0
0
0
90.1 (C1 ), 81.0 (C4 ), 75.2 (C2 ), 71.8 (C3 ), 63.8 (C5 ), 30.7 (CHCH3),
30.1 (CHCH3); MS (ESI): m/z [MþNa]þ calcd for C32H31N3NaO7:
592.6, found: 592.0.
d
8.05 (d, J¼8.2 Hz, 2H, HAr), 7.97 (d, J¼8.2 Hz, 2H, HAr), 7.94 (d,
J¼8.2 Hz, 2H, HAr), 7.57–7.49 (m, 4H, HAr and H5), 7.44–7.31 (m, 6H,
0
0
HAr), 6.46 (d, J¼3.6 Hz, 1H, H1 ), 6.23 (dd, J¼5.2, 3.6 Hz, 1H, H2 ), 6.15
5.2.8. 20,30,50-Tri-O-benzoyl-10-[4-O-ethoxy-[1,2,3]triazol-1-
yl]ribofuranose (9h)
Prepared from compound 8 with the typical procedure de-
scribed before to give 9h (63%) as yellow solid. Mp: 117 ꢀC (CHCl3);
IR: 1715,1568, 1451,1282,1265,1127,1092,1024, 701 cmꢁ1; 1H NMR
0
0
0
(t, J¼5.4 Hz,1H, H3 ), 4.89–4.79 (m, 2H, H4 and H5 ), 4.59 (dd, J¼12.1,
0
4.2 Hz, 1H, H5 ), 2.63 (d, J¼6.9 Hz, 2H, CH2–CHCH2CH2), 2.11–2.01
(m, 1H, CH2–CHCH2CH2), 1.73–1.62 (m, 2H, CH2–CHCH2CH2), 1.60–
1.52 (m, 2H, CH2–CHCH2CH2), 1.50–1.42 (m, 2H, CH2–CHCH2CH2),
1.17–1.07 (m, 2H, CH2–CHCH2CH2); 13C NMR (CDCl3):
d
166.1 (C(O)),
(CDCl3):
d
8.06 (d, J¼8.4 Hz, 2H, HAr), 7.98 (d, J¼8.4 Hz, 2H, HAr), 7.95
165.2 (C(O)), 165.1 (C(O)), 148.6 (C4), 133.8 (CAr), 133.7 (CAr), 133.4
(CAr), 130.1 (CAr), 129.9 (CAr), 129.8 (2C, CAr), 129.3 (CAr),0128.7 (CAr0),
128.6 (2C, CAr),128.5 (CAr),128.3 (CAr),112.0 (C5), 90.2 (C1 ), 81.0 (C4 ),
(d, J¼8.4 Hz, 2H, HAr), 7.60–7.53 (m, 3H, HAr), 7.48–7.34 (m, 6H, HAr),
0
7.16 (s,1H, H5), 6.36 (d, J¼3.8 0Hz,1H, H1 ), 6.22 (dd, J¼05.3, 3.8 Hz,1H,
0
0
H2 ), 6.10 (t, J¼5.3 Hz, 1H,0H3 ), 4.88–4.79 (m, 2H, H4 and H5 ), 4.69
(dd, J¼12.1, 4.2 Hz, 1H, H5 ), 4.12 (q, J¼7.1 Hz, 2H, OCH2CH3), 1.35 (t,
0
0
0
75.2 (C2 ), 71.7 (C3 ), 63.8 (C5 ), 39.7 (CH2–CHCH2CH2), 32.5 (2C, CH2–
CHCH2CH2), 31.6 (CH2–CHCH2CH2), 25.1 (CH2–CHCH2CH2); MS
(ESI): m/z [MþNa]þ calcd for C34H33N3NaO7: 618.7, found: 618.5.
J¼7.1 Hz, 3H, OCH2CH3); 13C NMR (CDCl3):
d 166.0 (C(O)), 165.1
(C(O)), 165.0 (C(O)), 161.2 (C4), 133.8 (CAr), 133.7 (CAr), 133.4 (CAr),
129.8 (CAr), 129.70 (CAr), 128.6 (2C, CAr0), 128.5 (2C, CAr), 104.5 (C50),
0
0
5.2.5. 20,30,50-Tri-O-benzoyl-10-[4-butyl-[1,2,3]triazol-1-
yl]ribofuranose (9e)
90.7 (C1 ), 81.1 (C4 ), 74.9 (C2 ), 71.6 (C3 ), 66.3 (OCH2CH3), 63.7 (C5 ),
14.7 (OCH2CH3); MS (ESI): m/z [MþNa]þ calcd for C30H27N3NaO8:
580.6, found: 580.5.
Prepared from compound 8 with the typical procedure de-
scribed before to give 9e (89%) as white solid. Mp: 98 ꢀC (CHCl3); IR:
1726, 1601, 1451, 1254, 1124, 1090, 1068, 1045, 706 cmꢁ1
;
1H NMR
5.3. General procedure for the RuAAC reaction
(CDCl3):
d
8.05 (d, J¼8.5 Hz, 2H, HAr), 7.99 (d, J¼8.5 Hz, 2H, HAr), 7.95
(d, J¼8.5 Hz, 2H, HAr), 7.58–7.52 (m, 3H, HA0 r), 7.49 (s, 1H, H5), 7.46–
In a microwave sealed reactor, a mixture of azido-ribose (8)
(1 mmol), the selected alkyne (1.5 mmol), and Cp RuCl(PPh3)2
7.34 (m, 6H, HAr), 6.45 (d, J¼3.6 Hz, 1H, H1 ), 6.23 (dd, J¼5.3, 3.6 Hz,
*

9048
U. Pradere et al. / Tetrahedron 64 (2008) 9044–9051
(0.05 mmol) in THF (10 mL) was irradiated for 5 min at 100 ꢀC
(200 W, normal mode). The mixture was then evaporated under
reduced pressure and the residue purified on silica gel (petroleum
ether/ethyl acetate; 7:3) to give the desired product.
(CDCl3): d
166.1 (C(O)), 165.1 (C(O)), 165.0 (C(O)), 138.0 (C5), 133.7
(CAr), 133.5 (CAr), 133.1 (CAr), 132.8 (C4), 129.8 (CAr), 129.7 (CAr), 129.3
(CA0r), 128.8 (CAr0), 128.7 (CAr)0, 128.5 (CAr),0128.4 (CAr), 128.3 (CAr), 87.8
0
(C1 ), 80.8 (C4 ), 75.4 (C2 ), 72.1 (C3 ), 63.8 (C5 ), 38.7 (CH2–
CHCH2CH2), 32.5 (2C, CH2–CHCH2CH2), 28.9 (CH2–CHCH2CH2), 25.0
(CH2–CHCH2CH2); MS (ESI): m/z [MþNa]þ calcd for C34H33N3NaO7:
618.7, found: 618.5.
5.3.1. 20,30,50-Tri-O-benzoyl-10-[5-phenyl-[1,2,3]triazol-1-
yl]ribofuranose (10a)
Prepared from compound 8 with the typical procedure de-
scribed before to give 10a (see Table 1) as a slightly brown oil. IR:
5.3.5. 20,30,50-Tri-O-benzoyl-10-[5-butyl-[1,2,3]triazol-1-
yl]ribofuranose (10e)
1721, 1601, 1451, 1261, 1090, 1069, 704 cmꢁ1
;
1H NMR (CDCl3):
d
8.05–7.90 (m, 6H, HAr), 7.74 (s, 1H, H4), 7.59–7.47 (m, 8H, HAr),
Prepared from compound 8 with the typical procedure de-
scribed before to give 10e (see Table 1) as a brown oil. IR: 1721,1602,
0
0
7.43–7.30 (m, 60H, HAr), 6.54–6.47 (m, 2H, H2 and H3 ), 6.15 (d,
0
J¼1.6 Hz, 1H, H1 ), 4.91 (m, 1H, H4 ), 4.78 (dd, J¼12.12, 3.96 Hz, 1H,
1451, 1261, 1092, 706 cmꢁ1 1H NMR (CDCl3):
; d 8.05–7.93 (m, 6H,
0
0
H5 ), 4.61 (dd, J¼12.12, 5.13 Hz, 1H, H5 ); 13C NMR (CDCl3):
d
166.2
HAr), 7.62–7.50 (m, 3H, HAr), 7.46 (s, 1H, H4), 7.45–7.33 (m, 6H, HAr),
0
0
(C(O)), 165.0 (2C, C(O)), 139.1 (C5), 133.7 (CAr), 133.5 (CAr), 133.1
(CAr), 133.0 (C5), 129.9 (CAr), 129.8 (2C, CAr), 129.4 (CAr), 129.2 (2C,
CAr), 128.8 (CAr), 128.7 (CAr),0 128.5 (CAr0), 128.4 (CAr), 128.30 (CAr),
6.46 (dd, J¼5.2, 1.8 0Hz, 1H, H2 ), 6.35 (dd, J¼7.2, 5.2 Hz, 1H, H3 ), 6.19
0
(d, J¼1.08 Hz, 1H, H1 ), 4.92–4.88 (m, 1H, H4 ), 4.73 (dd, J¼12.1, 3.9 Hz,
0
1H, H5 ), 4.54 (dd, J¼12.1, 5.5 Hz, 1H, H5 ), 2.73 (t, J¼7.8 Hz, 2H,
0
0
126.0 (C4), 88.2 (C1 ), 80.9 (C4 ), 75.6 (C2 ), 72.2 (C3 ), 63.7 (C5 ); MS
CH2CH2CH2CH3), 1.71–1.62 (m, 2H, CH2CH2CH2CH3), 1.44–1.33 (m,
2H, CH2CH2CH2CH3), 0.96–0.89 (t, J¼7.4 Hz, 3H, CH2CH2CH2CH3);
(ESI): m/z [MþNa]þ calcd for C34H27N3NaO7: 612.6, found: 612.5.
13C NMR (CDCl3):
d 166.1 (C(O)), 165.2 (C(O)), 165.0 (C(O)), 138.4
5.3.2. 20,30,50-Tri-O-benzoyl-10-[5-4-fluoro-3-methylphenyl-
[1,2,3]triazol-1-yl]ribofuranose (10b)
(C5), 133.8 (CAr), 133.5 (CAr), 133.2 (CAr), 132.4 (C4), 129.8 (2C, CAr),
129.4 (CAr), 128.8 (2C, CAr), 128.6 (CAr), 128.40 (CAr), 128.3 (CAr), 87.9
0
0
0
0
Prepared from compound 8 with the typical procedure de-
scribed before to give 10b (see Table 1) as a slight brown oil. IR:
(C1 ), 80.8 (C4 ), 75.4 (C2 ), 72.0 (C3 ), 63.8 (C5 ), 30.2
(CH2CH2CH2CH3), 22.6 (CH2CH2CH2CH3), 22.2 (CH2CH2CH2CH3),
13.6 (CH2CH2CH2CH3); MS (ESI): m/z [MþNa]þ calcd for
1720, 1602, 1492, 1451, 1253, 1084, 705 cmꢁ1 1H NMR (CDCl3):
;
d
8.05–7.91 (m, 6H, HAr), 7.70 (s, 1H, H4), 7.60–7.48 (m, 3H, HAr),
C32H31N3NaO7: 592.6, found: 592.5.
7.44–7.30 (m, 9H, HAr), 7.16–7.08 (t, J¼8.0 Hz,1H, HAr), 6.51–6.45 (m,
0
0
0
0
2H, H2 and H3 ), 6.10 (d, J¼1.2 Hz, 1H, H1 ), 4.93–4.89 (m, 1H, H4 ),
5.3.6. 20,30,50-Tri-O-benzoyl-10-[5-(3-chloropropyl)-[1,2,3]triazol-1-
yl]ribofuranose (10f)
0
0
4.78 (dd, J¼12.1, 3.9 Hz, 1H, H5 ), 4.61 (dd, J¼12.1, 5.2 Hz, 1H, H5 ),
2.32 (d, J¼1.8 Hz, 3H, CH3); 13C NMR (CDCl3):
d
166.2 (C(O)), 165.1
Prepared from compound 8 with the typical procedure de-
scribed before to give 10f (see Table 1) as a brown oil. IR: 1719,1602,
(C(O)), 165.0 (CAr), 163.5 (CAr), 161.0 (CAr), 138.4 (CAr), 133.8 (CAr),
133.5 (CAr), 133.2 (CAr), 132.9 (CAr), 132.6 (2C, CAr), 129.8 (3C, CAr),
129.4 (CAr), 128.7 (2C, CAr), 128.5 (CAr), 128.4 (CAr), 128.3 (CAr), 126.3
(C4), 126.1 (C40), 121.7 (CA0 r), 121.6 (CAr), 116.0 (CAr), 115.8 (CAr), 88.1
1451, 1260, 1092, 706 cmꢁ1 1H NMR (CDCl3):
; d 8.05–7.94 (m, 6H,
HAr), 7.61–7.50 (m, 3H, HAr), 7.50 (s, 1H, H4), 7.39 (m, 6H,0HAr), 6.50
0
(dd, J¼5.2, 1.8 Hz, 1H, H2 ), 6.34 (dd, J¼7.2, 5.2 Hz, 1H, H3 ), 6.25 (d,
0
0
0
0
0
(C1 ), 80.8 (C4 ), 75.7 (C2 ), 72.1 (C3 ), 63.7 (C5 ), 14.5 (2C, CH3); MS
(ESI): m/z [MþNa]þ calcd for C35H28FN3NaO7: 644.6, found: 644.5.
J¼1.8 H0z, 1H, H1 ), 4.94–4.90 (m, 1H, H4 ), 4.74 (dd, J¼12.2, 3.8 Hz,
0
1H, H5 ), 4.53 (dd, J¼12.2, 5.1 Hz, 1H, H5 ), 3.60–3.48 (m, 2H,
CH2CH2CH2Cl), 3.03–2.88 (m, 2H, CH2CH2CH2Cl), 2.20–2.09 (m, 2H,
5.3.3. 20,30,50-Tri-O-benzoyl-10-[5-methylbenzyl-[1,2,3]triazol-1-
yl]ribofuranose (10c)
CH2CH2CH2Cl); 13C NMR (CDCl3):
d 166.0 (C(O)), 165.1 (C(O)), 165.0
(C(O)), 136.7 (C5), 133.7 (CAr), 133.5 (CAr), 133.1 (CAr), 132.6 (C4),
129.7 (CAr), 129.6 (CAr), 129.2 (CAr), 128.6 (2C, CAr),0128.5 (CAr), 128.3
Prepared from compound 8 with the typical procedure de-
scribed before to give 10c (see Table 1) as a slight brown oil. IR:
0
0
0
0
(2C, CAr), 87.8 (C1 ), 80.8 (C4 ), 75.2 (C2 ), 71.8 (C3 ), 63.5 (C5 ), 43.4
(CH2CH2CH2Cl), 30.7 (CH2CH2CH2Cl),19.9 (CH2CH2CH2Cl); MS (ESI):
m/z [MþNa]þ calcd for C31H28ClN3NaO7: 612.6, found: 612.5.
1720, 1577, 1451, 1261, 1091, 705 cmꢁ1; 1H NMR (CDCl3):
d 7.93–7.80
(m, 6H, HAr), 7.51–7.40 (m, 3H, HAr), 7.34–7.22 (m, 7H, HAr and H4),
7.21–7.09 (m, 3H, HAr), 7.09–7.04 (m, 2H, 0 HAr), 6.35 (dd, J¼5.2,
0
2.1 Hz,1H, H2 ), 6.21 (dd, J¼0 7.0, 5.2 Hz,1H, H3 ), 6.07 (d, J¼2.1 Hz,1H,
5.3.7. 20,30,50-Tri-O-benzoyl-10-[5-tert-butyl-[1,2,3]triazol-1-
yl]ribofuranose (10g)
Prepared from compound 8 with the typical procedure described
before to give 10g (see Table 1) as a brown oil. IR: 1721, 1602, 1451,
0
0
H1 ), 4.80–4.74 (m, 1H, H4 ), 4.65 (dd, J¼12.1, 3.8 Hz, 1H, H5 ), 4.46
0
(dd, J¼12.1, 5.1 Hz, 1H, H5 ), 4.03 (q, J¼16.6 Hz, 2H, CH2Ph); 13C NMR
(CDCl3):
d
166.1 (C(O)), 165.0 (2C, C(O)), 137.0, 135.6 (CAr and C5),
133.8 (CAr), 133.7 (CAr), 133.5 (CAr), 133.1 (CAr), 129.7 (2C, CAr), 129.3
(CAr), 128.9, 128.7, 128.6, 128.5, 128.4 0(2C), 128.30(CAr and C4), 127.2
1250,1092,1069, 706 cmꢁ1; 1H NMR (CDCl3):
d
8.09 (d, J¼8.5 Hz, 2H,
HAr), 8.01 (d, J¼8.5 Hz, 2H, HAr), 7.97 (d, J¼8.5 Hz, 2H, HAr), 7.61–7.54
0
0
0
0
(CAr), 88.0 (C1 ), 80.8 (C4 ), 75.1 (C2 ), 71.8 (C3 ), 63.6 (C5 ), 29.0
(CH2Ph); MS (ESI): m/z [MþNa]þ calcd for C35H29N3NaO7: 626.6,
found: 626.5.
(m, 3H, HAr), 7.47–7.36 (m, 7H, HAr and H4), 6.45 (d, J¼3.1 Hz,1H, H2 ),
0
0
0
0
6.19–6.15 (m, 2H, H3 and0H1 ), 4.89–4.80 (m, 2H, H4 and H5 ), 4.61
(dd, J¼11.9, 4.1 Hz, 1H, H5 ), 1.27 (s, 9H, C(CH3)3); 13C NMR (CDCl3):
d
166.1 (C(O)), 165.1 (C(O)), 165.0 (C(O)), 146.5 (C5), 133.7 (CAr), 133.4
5.3.4. 20,30,50-Tri-O-benzoyl-10-[5-methylcyclopentyl-[1,2,3]triazol-
1-yl]ribofuranose (10d)
(CAr), 133.0 (CAr), 131.2 (C4), 129.8 (CAr), 129.7 (CAr), 129.4 (CAr), 128.8
0
(2C, CAr),128.5 (CAr),128.4 (CAr),128.3 (CAr),117.4 (C4), 89.2 (C1 ), 80.7
0
0
0
Prepared from compound 8 with the typical procedure de-
scribed before to give 10d (see Table 1) as a slight brown oil. IR:
(C4 ), 72.4 (C2 ), 63.8 (C5 ), 30.3 (C(CH3)3), 30.1 (C(CH3)3); MS (ESI):
m/z [MþNa]þ calcd for C32H31N3NaO7: 592.6, found: 592.0.
1721, 1601, 1580, 1451, 1262, 1091, 706 cmꢁ1 1H NMR (CDCl3):
;
d
8.06–7.92 (m, 6H, HAr), 7.62–7.49 (m, 3H, HAr), 7.470 (s, 1H, H4),
5.3.8. 20,30,50-Tri-O-benzoyl-10-[5-O-ethoxy-[1,2,3]triazol-1-
yl]ribofuranose (10h)
7.46–7.32 (m, 6H, HAr), 6.48 (dd, J¼5.2, 1.8 Hz, 1H, H2 ), 6.36 (dd,
0
0
J¼7.1, 5.2 Hz, 1H, H3 ), 6.20 (d, J¼1.8 Hz, 1H, H1 ), 4.93–4.87 (m, 1H,
Prepared from compound 8 with the typical procedure de-
scribed before to give 10h (see Table 1) as a brown oil. IR: 1720,
0
0
H4 ), 4.73 (dd, J¼12.1, 3.9 Hz, 1H, H5 ), 4.53 (dd, J¼12.1, 5.3 Hz, 1H,
0
H5 ), 2.73 (d, J¼7.4 Hz, 2H, CH2–CHCH2CH2), 2.25–2.12 (m, 1H, CH2–
CHCH2CH2), 1.85–1.73 (m, 2H, CH2–CHCH2CH2), 1.68–1.47 (m, 4H,
CH2–CHCH2CH2), 1.24–1.12 (m, 2H, CH2–CHCH2CH2); 13C NMR
1577, 1451, 1261, 1091, 1026, 705 cmꢁ1; 1H NMR (CDCl3):
d 8.07–7.98
(m, 4H, HAr), 7.96–7.90 (m, 2H, HAr), 7.55 (m, 3H, HAr), 7.44–7.31 (m,
0
6H, HAr), 7.07 (s, 1H, H4), 6.34 (dd, J¼5.3, 2.4 Hz, 1H, H2 ), 6.30–6.25

U. Pradere et al. / Tetrahedron 64 (2008) 9044–9051
9049
0
0
0
0
0
(m, 2H, H3 and H1 ), 4.88–4.82 (m, 1H, H4 ),04.72 (dd, J¼12.0, 4.1 Hz,
3.2 Hz, 1H, H5 ), 3.69 (dd, J¼12.2, 4.3 Hz, 1H, H5 ), 2.70 (d, J¼7.4 Hz,
2H, CH2–CHCH2CH2), 2.24–2.12 (m, 1H, CH2–CHCH2CH2), 1.82–1.72
(m, 2H, CH2–CHCH2CH2), 1.71–1.62 (m, 2H, CH2–CHCH2CH2), 1.61–
1.51 (m, 2H, CH2–CHCH2CH2), 1.31–1.18 (m, 2H, CH2–CHCH2CH2);
0
1H, H5 ), 4.60 (dd, J¼12.0, 5.4 Hz, 1H, H5 ), 4.23–4.16 (dq, J¼7.1,
1.4 Hz, 2H, OCH2CH3), 1.46 (t, J¼7.1 Hz, 3H, OCH2CH3); 13C NMR
(CDCl3): d
166.2 (C(O)), 165.0 (2C, C(O)), 152.0 (C5), 133.7 (CAr), 133.5
0
0
(CAr), 133.1 (CAr), 129.8 (CAr), 129.7 (CAr), 129.4 (CAr), 128.7 (2C, CAr),
128.5 (CAr), 128.4 (CAr), 128.3 (CAr), 113.8 (C4), 86.7, 80.2, 74.5, 71.8,
69.3, 63.9, 14.4; MS (ESI): m/z [MþNa]þ calcd for C30H27N3NaO8:
580.6, found: 580.5.
13C0 NMR (CD3OD):
d
148.9 (C4), 122.2 (C5), 94.3 (C1 ), 87.1 (C4 ), 77.1
0
0
(C2 ), 71.9 (C3 ), 62.9 (C5 ), 41.3 (CH2–CHCH2CH2), 33.4 (CH2–
CHCH2CH2), 32.4 (CH2–CHCH2CH2), 26.1 (CH2–CHCH2CH2); HRMS
(ESI): m/z [MþH]þ calcd for C13H22N3O4: 284.1610, found:
284.1608.
5.4. General procedure for sugar deprotection
5.4.5. 10-[4-Butyl-[1,2,3]triazol-1-yl]ribofuranose (12e)
To the protected compounds (9a–h and 10a–h) was added
a solution of 7 N NH3/MeOH. The reaction was followed by TLC.
After evaporation of the solvent under reduced pressure, the crude
product was purified by liquid chromatography on silica gel
(methanol/ethyl acetate, 1:9, v/v) to give the desired pure product.
Prepared from compound 9e with the typical procedure
described above to give 12e (>98%) as a white solid. Mp: 105 ꢀC
(MeOH); IR: 3316, 2930, 2870, 1456, 1043, 826 cmꢁ1; UV (MeOH)
20
lmax: 223 nm; [
a]
ꢁ50.7 (c 0.56, MeOH); 1H NMR (CD3OD):0 d 8.00
D
0
(s, 1H, H5), 6.00 (d,0J¼4.1 Hz, 1H, H1 ), 4.48 (t, J¼4.5 Hz, 1H, H2 ), 4.32
0
(t, J¼5.0 Hz, 1H, H3 ), 4.15–4.11 (m, 1H, H4 ), 3.82 (dd, J¼12.2, 3.2 Hz,
0
0
5.4.1. 10-[4-Phenyl-[1,2,3]triazol-1-yl]ribofuranose (12a)
Prepared from compound 9a with the typical procedure de-
scribed above to give 12a (>98%) as an oil. IR: 3368,1661,1447,1191,
1H, H5 ), 3.70 (dd, J¼12.2, 4.3 Hz, 1H, H5 ), 2.71 (t, J¼7.6 Hz, 2H,
CH2CH2CH2CH3), 1.70–1.61 (m, 2H, CH2CH2CH2CH3), 1.45–1.34
(m, 2H, CH2CH2CH2CH3), 0.95 (t, J¼7.4 Hz, 3H, CH2CH2CH2CH3);
0
0
1135, 799, 723 cmꢁ1
;
1H NMR (CD3OD):
d
8.58 (s, 1H, H5), 7.82 (d,
13C NMR (CD3OD):
d
149.4 (C4), 0121.8 (C5), 94.3 (C1 ), 87.1 (C4 ),
0
0
J¼8.3 Hz, 2H, HAr), 7.43 (t, J¼7.5 Hz, 2H, HAr), 7.35 (t, J¼7.4 Hz, 1H,
77.0 (C2 ), 71.9 (C3 ), 62.9 (C5 ), 32.7 (CH2CH2CH2CH3), 26.0
(CH2CH2CH2CH3), 23.3 (CH2CH2CH2CH3), 14.2 (CH2CH2CH2CH3);
HRMS (ESI): m/z [MþNa]þ calcd for C11H19N3NaO4: 280.1273,
found: 280.1269.
0
0
HAr), 6.09 (d, J¼04.0 Hz, 1H, H1 ), 04.57 (t, J¼4.5 Hz, 1H, H2 ), 4.37 (t,
0
J¼5.1 Hz, 1H, H3 ), 4.17 (m, 1H, H40 ), 3.86 (dd, J¼12.3, 3.2 Hz, 1H, H5 ),
3.73 (dd, J¼12.3, 4.2 Hz, 1H, H5 ); 13C NMR (CD3OD):
d
149.0 (C40),
131.6 (CA0 r), 130.0 (CAr), 129.5 (CAr), 126.07 (CAr), 120.9 (C5), 94.5 (C1 ),
0
0
87.2 (C4 ), 77.1 (C2 ), 71.9 (C3 ), 62.8 (C5 ); HRMS (ESI): m/z [MþH]þ
calcd for C13H16N3NO4: 278.1141, found: 278.1148. Known product
CAS: 26295-54-5.
5.4.6. 10-[4-(3-Chloropropyl)-[1,2,3]triazol-1-yl]ribofuranose (12f)
Prepared from compound 9f with the typical procedure de-
scribed above to give 12f (>98%) as colorless crystals. Mp: 91 ꢀC
(MeOH); IR: 3316, 2928, 2361, 1546, 1229, 1048 cmꢁ1; UV (MeOH)
20
5.4.2. 10-[4-4-Fluoro-3-methylphenyl-[1,2,3]triazol-1-
yl]ribofuranose (12b)
lmax: 223 nm; [
a
]
ꢁ46.7 (c 0.89, MeOH); 1H NMR (CD3OD):0 d 8.05
D
0
(s, 1H, H5), 6.01 (d, 0J¼4.1 Hz, 1H, H1 ), 4.49 (t, J¼4.5 Hz, 1H, H2 ), 4.31
0
Prepared from compound 9b with the typical procedure de-
scribed above to give 121b (>98%) as white solid. Mp: 158 ꢀC
(t, J¼5.0 Hz, 1H, H3 ), 4.15–4.11 (m, 1H, H4 ), 3.81 (dd, J¼12.2, 3.2 Hz,
0
0
1H, H5 ), 3.69 (dd, J¼12.2, 4.3 Hz, 1H, H5 ), 3.61 (t, J¼6.5 Hz, 2H,
CH2CH2CH2Cl), 2.87 (t, J¼7.5 Hz, 2H, CH2CH2CH2Cl), 2.17–2.08 (m,
(MeOH); IR: 3344, 2929, 1493, 1233, 1082, 1043, 817 cmꢁ1; UV
20
(MeOH) lmax: 241 nm; [
a
]
ꢁ76.4 (c 1.45, MeOH); 1H NMR
2H, CH2CH2CH2Cl); 13C 0NMR (CD3OD):
d
147.9 (C4), 122.2 (C5), 94.3
D
0
0
0
0
(CD3OD):
d
8.53 (s, 1H, H5), 7.71 (d, J¼7.3 Hz, 1H, HAr), 7.67–7.62 (m,
(C1 ), 87.1 (C4 ), 77.0 (C2 ), 71.9 (C3 ), 62.9 (C5 ), 44.8 (CH2CH2CH2Cl),
33.3 (CH2CH2CH2Cl), 23.6 (CH2CH2CH2Cl); HRMS (ESI): m/z [MþH]þ
calcd for C10H17ClN3O4: 278.0908, found: 278.0902.
0
1H, HAr), 7.10 (t, J¼9.1 Hz,1H, HAr), 6.08 (d, J¼4.0 Hz,1H, H1 ), 4.55 (t,
0
0
0
J¼4.5 Hz, 1H, H2 ), 4.35 (t, J¼5.0 Hz, 1H, H3 ), 4.18–4.13 (m, 1H, H4 ),
0
0
3.85 (dd, J¼12.2, 3.2 Hz, 1H, H5 ), 3.71 (dd, J¼12.2, 4.2 Hz, 1H, H5 ),
2.32 (s, 3H, CH3); 13C NMR (CDCl3):
d
148.3 (C4), 0130.0 (CAr), 126.1
5.4.7. 10-[4-tert-Butyl-[1,2,3]triazol-1-yl]ribofuranose (12g)
Prepared from compound 9g with the typical procedure de-
scribed above to give 12g (>98%) as a white solid. Mp: 114 ꢀC
0
(CA0r), 120.7 (C5), 116.6 0(CAr), 116.4 (CAr), 94.6 (C1 ), 87.3 (C4 ), 77.2
0
(C2 ), 71.9 (C3 ), 62.9 (C5 ), 14.6 (CH3); HRMS (ESI): m/z [MþH]þ calcd
for C14H17FN3O4: 310.1203, found: 310.1218.
(MeOH); IR: 3355, 2964, 2361, 1461, 1365, 1232, 1104, 1047 cmꢁ1
;
20
UV (MeOH) lmax: 221 nm; [
a]
ꢁ55.7 (c 0.88, MeOH); 1H NMR
D
0
5.4.3. 10-[4-Methylbenzen-[1,2,3]triazol-1-yl]ribofuranose (12c)
Prepared from compound 9c with the typical procedure de-
scribed above to give 12c (>98%) as white solid. Mp: 100 ꢀC
(400 MHz, CD3OD):
d
8.01 (s, 1H, H5), 6.00 (d, J¼4.2 Hz, 1H, H1 ),
0
0
4.49 (t, J¼4.6 Hz, 1H, H2 ), 4.30 (t, J¼5.0 0Hz, 1H, H3 ), 4.14–4.09 (m,
0
1H, H4 ), 3.82 (dd, J¼12.2, 3.2 Hz, 1H, H5 ), 3.69 (dd, J¼12.2, 4.3 Hz,
0
(MeOH); IR: 3355, 2928, 2360, 1454, 1230, 1047, 725 cmꢁ1; UV
1H, H5 ), 1.34 (s, 9H, C(C0H3)3); 13C 0NMR (1010MHz, CD3OD):
d
1580.7
0
(MeOH) lmax: 212 nm; [
a]
ꢁ58.0 (c 0.59, MeOH); 1H NMR
(C4), 119.9 (C5), 94.2 (C1 ), 87.1 (C4 ), 77.0 (C2 ), 71.9 (C3 ), 62.9 (C5 ),
20
D
(CD3OD):
d
7.97 (s, 1H, H5), 7.30–7.16 (m, 5H, HAr), 6.00 (d, J¼4.1 Hz,
31.7 (C(CH3)3), 30.7 (C(CH3)3); HRMS (ESI): m/z [MþH]þ calcd for
0
0
0
1H, H1 ), 4.48 (t, J¼4.6 Hz, 1H, H2 ), 4.30 (t, J¼5.0 Hz, 1H, H3 ), 4.14–
C11H20N3O4: 258.1454, found: 258.1457.
0
4.09 (m, 1H, H4 ), 4.04 (s, 2H, CH2Ph), 3.79 (dd, J¼12.2, 3.2 Hz, 1H,
0
0
H5 ), 3.67 (dd, J¼12.2, 4.3 Hz, 1H, H5 ); 13C NMR (CD3OD): d0 148.6
5.4.8. 10-[4-O-Ethoxy-[1,2,3]triazol-1-yl]ribofuranose (12h)
Prepared from compound 9h with the typical procedure de-
scribed above to give 12h (>98%) as colorless crystals. Mp: 127 ꢀC
(C4),140.3 (CA0r),129.6 (2C, CAr),127.5 (CAr), 122.6 (C5), 94.8 (C1 ), 87.1
0
0
0
(C4 ), 77.0 (C2 ), 71.9 (C3 ), 62.9 (C5 ), 32.6 (CH2Ph); HRMS (ESI): m/z
[MþH]þ calcd for C14H18N3O4: 292.1297, found: 292.1283.
(MeOH); IR: 3348, 2927, 2361,1667,1571,1381,1340,1045 cmꢁ1; UV
20
(MeOH) lmax: 233 nm; [
a
]
D
ꢁ63.1 (c 1.12, MeOH); 1H0 NMR
5.4.4. 10-[4-Methylcyclopentyl-[1,2,3]triazol-1-yl]ribofuranose
(12d)
(400 MHz, CD3OD):
d
7.71 (s, 1H, H5), 5.91 (d, J¼4.1 Hz, 1H, H1 ), 4.46
20
(t, J¼4.6 Hz, 1H, H ), 4.29 (t, J¼5.0 Hz, 1H, H30), 4.17 (q, J¼7.1 Hz, 2H,
0
0
Prepared from compound 9d with the typical procedure de-
scribed above to give 12d (>98%) as a white solid. Mp: 87 ꢀC
OCH2CH3), 4.13–4.09 (m, 1H, H4 ), 3.81 (dd, J¼12.2, 3.2 Hz, 1H, H5 ),
0
3.69 (dd, J¼12.2, 4.2 Hz,1H, H5 ), 1.38 (t, 3H, J¼7.1 Hz, OCH2CH3); 13
C
0
(MeOH); IR: 3349, 1298, 2868, 1452, 1228, 1048 cmꢁ1; UV (MeOH)
NMR (101 MHz, CD3OD): d 0 162.4 (C4), 106.4 (C5), 95.0 (C10 ), 87.2
0
0
20
lmax: 223 nm; [
a
]
ꢁ51.5 (c 1.37, MeOH); 1H NMR (CD3OD):
d
8.00
(C4 ), 76.9 (C2 ), 71.9 (C3 ), 67.9 (OCH2CH3), 62.8 (C5 ), 15.1
(OCH2CH3); HRMS (ESI): m/z [MþNa]þ calcd for C9H15N3NaO5:
268.0909, found: 268.0915.
D
0
0
(s, 1H, H5), 6.00 (d, J¼4.0 Hz, 1H, H1 ), 4.47 (t,0 J¼4.5 Hz, 1H, H2 ),
0
4.30 (t, J¼5.1 Hz, 1H, H3 ), 4.15–4.09 (m, 1H, H4 ), 3.81 (dd, J¼12.2,

9050
U. Pradere et al. / Tetrahedron 64 (2008) 9044–9051
0
5.4.9. 10-[5-Phenyl-[1,2,3]triazol-1-yl]ribofuranose (13a)
(dd, J¼12.1, 5.6 Hz, 1H, H5 ), 2.79 (t, J¼7.8 Hz, 2H, CH2CH2CH2CH3),
Prepared from compound 10a with the typical procedure de-
scribed above to give 13a (>98%) as a white solid. Mp: 151 ꢀC
1.73–1.64 (m, 2H, CH2CH2CH2CH3), 1.48–1.39 (m, 2H,
CH2CH2CH2CH3), 0.98 (t, J¼7.4 Hz, 3H, CH2CH2CH2CH3); 13C NMR
0
0
0
(MeOH); IR: 3332, 2930, 1486, 1454, 1243, 1058, 765, 699 cmꢁ1; UV
(CD3OD):
d
140.9 (C5), 132.9 (C4), 91.1 (C1 ), 87.3 (C4 ), 75.8 (C2 ), 72.5
0
0
20
(MeOH) lmax: 242 nm; [
a
]
ꢁ116.5 (c 0.83, MeOH); 1H NMR
(C3 ), 63.7 (C5 ), 31.7 (CH2CH2CH2CH3), 23.3 (2C, CH2CH2CH2CH3 and
CH2CH2CH2CH3), 14.0 (CH2CH2CH2CH3); HRMS (ESI): m/z [MþH]þ
calcd for C11H20N3O4: 258.1454, found: 2258.1448.
D
(CD3OD):
d
7.84 (s, 1H, H4), 7.64–7.60 (m, 2H, HAr), 7.58–7.52 (0m, 3H,
0
HAr), 5.81 (d, J¼3.70Hz, 1H, H1 ), 4.91 (dd, J¼5.1, 3.7 Hz, 1H, H2 ), 4.51
0
(t, J¼5.1 Hz, 1H, H3 ), 4.16–4.12 (m, 1H, H4 ), 3.80 (dd, J¼12.1, 3.9 Hz,
0
0
1H, H5 ), 3.66 (dd, J¼12.1, 5.8 Hz, 1H, H5 ); 13C NMR (CD3OD):
d
141.2
5.4.14. 10-[5-(3-Chloropropyl)-[1,2,3]triazol-1-yl]ribofuranose (13f)
Prepared from compound 10f with the typical procedure de-
scribed above to give 13f (>98%) as an yellow oil. IR: 3315, 2927,
0
(C5), 133.4 (CA0 r), 131.0 (CAr), 130.3 (2C, CAr), 127.4 (C4), 91.4 (C1 ), 87.3
0
0
0
(C4 ), 75.9 (C2 ), 72.6 (C3 ), 63.7 (C5 ); HRMS (ESI): m/z [MþH]þ calcd
for C13H16N3O4: 278.1141, found: 278.1142.
2360, 1717, 1446, 1276, 1242, 1058, 833 cmꢁ1; UV (MeOH) lmax
:
20
220 nm; [
a]
ꢁ50.5 (c 0.39, MeOH); 1H NMR (CD3OD):
d 7.59 (s, 1H,
D
0
0
5.4.10. 10-[5-4-Fluoro-3-methylphenyl-[1,2,3]triazol-1-
yl]ribofuranose (13b)
H4), 5.91 (d, J¼3.9 Hz, 1H, H1 ), 4.88 (dd, J¼5.0, 3.9 Hz, 1H, H2 ), 4.43
0
0
(t, J¼5.0 Hz, 1H, H3 ), 4.15–4.10 (m, 1H, H4 ), 3.73 (dd, J¼12.1, 3.8 Hz,
0
Prepared from compound 10b with the typical procedure de-
scribed above to give 13b (>98%) as yellow crystals. Mp: 69 ꢀC
1H, H5 ), 3.67–3.60 (m, 2H, CH2CH2CH2Cl), 3.58 (dd, J¼12.1, 5.6 Hz,
0
1H, H5 ), 3.01–2.95 (t, J¼7.6 Hz, 2H, CH2CH2CH2Cl), 2.20–2.11 (m,
(MeOH); IR: 3332, 2929, 1493, 1243, 1124, 1059, 824 cmꢁ1; UV
2H, CH2CH2CH2Cl); 13C 0NMR (CD3OD):
d
139.5 (C5), 133.2 (C4), 91.2
0
0
0
0
20
(MeOH) lmax: 243 nm; [
a]
ꢁ91.3 (c 0.67, MeOH); 1H NMR
(C1 ), 87.3 (C4 ), 75.7 (C2 ), 72.4 (C3 ), 63.6 (C5 ), 44.6 (CH2CH2CH2Cl),
32.4 (CH2CH2CH2Cl), 21.0 (CH2CH2CH2Cl); HRMS (ESI): m/z [MþH]þ
calcd for C10H17ClN3O4: 278.0908, found: 278.0892.
D
(CD3OD):
d
7.86 (s, 1H, H4), 7.57–7.49 (m, 2H, HAr), 7.30–7.23 (t,
0
J¼9.0 Hz, 1H, HAr), 5.83 (d, J¼3.7 Hz, 1H, H1 ), 4.95 (dd, J¼04.9, 3.8 Hz,
0
0
1H, H2 ), 4.55 (t, J¼5.20 Hz, 1H, H3 ), 4.22–4.17 (m, 1H, H4 ), 3.84 (dd,
0
J¼12.1, 3.8 Hz, 1H, H5 ), 3.70 (dd, J¼12.1, 5.9 Hz, 1H, H5 ), 2.40 (d,
5.4.15. 10-[5-tert-Butyl-[1,2,3]triazol-1-yl]ribofuranose (13g)
Prepared from compound 10g with the typical procedure de-
J¼1.8 Hz, 3H, CH3); 13C NMR (CD3OD):
d
164.8 (CAr), 162.4 (CAr),
140.4 (C5), 133.7 (2C, CAr), 133.5 (CAr), 129.9 (CAr), 129.8 (CAr), 127.4
scribed above to give 13g (>98%) as an yellow oil. IR: 3346, 2969,
0
20
(C4), 127.2 (C4), 123.4 (2C, CAr), 116.9 (CAr), 116.7 (CAr), 91.3 (C1 ), 87.4
2360, 1371, 1057 cmꢁ1; UV (MeOH) lmax: 221 nm; [
a
]
ꢁ70.9 (c
D
0
0
0
0
(C4 ), 75.9 (C2 ), 72.6 (C3 ), 63.7 (C5 ), 14.4 (2C, CH3); HRMS (ESI): m/z
[MþH]þ calcd for C14H17FN3O4: 310.1203, found: 310.1216.
1.21, MeOH); 1H NMR (CD3OD):
d
7.49 (s, 1H, H4), 6.20 (d, J¼3.8 Hz,
0
0
0
1H, H1 ), 4.85 (dd, J¼5.0, 3.8 Hz, 1H, H2 ), 4.47 (t, J¼5.1 Hz, 1H, H3 ),
0
0
4.16–4.08 (m, 1H, H4 ), 3.76 (dd, J¼12.0, 4.0 Hz, 1H, H5 ), 3.64 (dd,
0
5.4.11. 10-[5-Benzyl-[1,2,3]triazol-1-yl]ribofuranose (13c)
Prepared from compound 10c with the typical procedure de-
scribed above to give 13c (>98%) as an yellow oil. IR: 3341, 2928,
J¼12.0, 5.7 Hz, 1H, H5 ), 1.44 (d, J¼6.2 Hz, 9H, C(CH3)3); 13C NMR
0
0
0
(CD3OD):
d
148.7 (C5), 131.5 (C4), 92.4 (C1 ), 87.4 (C4 ), 76.5 (C2 ), 72.6
0
0
(C3 ), 63.8 (C5 ), 31.4 (C(CH3)3), 30.5 (C(CH3)3); HRMS (ESI): m/z
[MþH]þ calcd for C11H20N3O4: 258.1454, found: 258.1451.
20
2361, 1455, 1242, 1058, 720. UV (MeOH) lmax: 214 nm; [
a
]
ꢁ50.6
D
(c 0.51, MeOH); 1H NMR (CD3OD):
d
7.38 (s, 1H, H4), 7.36–7.31 (m,
0
2H, HAr), 7.29–7.21 (m, 3H, HAr), 5.88 (d, J¼3.6 Hz, 1H, H1 ), 4.82 (dd,
5.4.16. 10-[5-O-Ethoxy-[1,2,3]triazol-1-yl]ribofuranose (13h)
Prepared from compound 10h with the typical procedure de-
scribed above to give 13h (>98%) as a white solid (MeOH). Mp:
0
0
J¼5.0, 3.6 Hz, 1H, H2 ), 4.42 (t, J¼0 5.2 Hz, 1H, H3 ), 4.18 (d, J¼2.7 Hz,
0
2H, CH2Ph), 4.13–4.08 (m, 1H, H4 ), 3.74 (dd, J¼12.1, 3.7 Hz, 1H, H5 ),
0
3.58 (dd, J¼12.1, 5.6 Hz, 1H, H5 ); 13C NMR (CD3OD):
d
139.8 (C50),
149 ꢀC; IR: 3357, 2936, 1579, 1458, 1325, 1056, 982 cmꢁ1; UV
20
137.8 (CAr), 134.1 (C4), 129.9 0(CAr), 129.7 (CAr), 128.2 (CAr), 91.5 (C1 ),
(MeOH) lmax: 231 nm; [
a
]
ꢁ56.2 (c 0.55, MeOH); 1H NMR
D
0
0
0
0
87.2 (C4 ), 75.7 (C2 ), 72.3 (C3 ), 63.6 (C5 ), 29.6 (CH2Ph); HRMS (ESI):
m/z [MþH]þ calcd for C14H18N3O4: 292.1297, found: 292.1298.
(CD3OD):
d
7.24 (s, 1H, H4), 5.83 (d, J¼3.9 Hz, 1H, H1 ), 4.68 (dd,
0
0
J¼5.0, 3.9 Hz, 1H, H2 ), 4.39 (t, J¼5.00Hz, 1H, H3 ), 4.25 (q, J¼7.5 Hz,
2H, OCH2CH3), 4.10–4.05 (m, 1H, H4 ), 3.75 (dd, J¼12.0, 3.9 Hz, 1H,
0
0
5.4.12. 10-[5-Methylcyclopentyl-[1,2,3]triazol-1-yl]ribofuranose
(13d)
H5 ), 3.62 (dd, J¼12.0, 5.8 Hz, 1H, H5 ), 1.45 (t, J¼7.5 H0z, 3H,
OCH2CH3); 13C NMR (CD3OD0): 153.9 (C5),114.8 (C4), 90.9 (C10 ), 86.9
d
0
0
Prepared from compound 10d with the typical procedure de-
(C4 ), 75.2 (C2 ), 72.3 (C3 ), 70.6 (OCH2CH3), 63.7 (C5 ), 14.8
(OCH2CH3); HRMS (ESI): m/z [MþNa]þ calcd for C9H15N3NaO5:
268.0909, found: 268.0909.
scribed above to give 13d (>98%) as an yellow oil. IR: 3315, 2946,
2867, 1449, 1241, 1050, 830 cmꢁ1; UV (MeOH) lmax: 221 nm; [
a]
20
D
ꢁ62.1 (c 1.04, MeOH); 1H NMR (CD3OD):
d
7.55 0(s, 1H, H4), 5.89 (d,
0
J¼4.0 Hz, 1H, H1 ), 4.83 (dd, J¼5.0, 4.0 Hz, 1H, H2 ), 4.43 (t, J¼5.0 Hz,
Acknowledgements
0
0
0
1H, H3 ), 4.14–4.10 (m, 1H, H4 ), 30.74 (dd, J¼12.0, 3.9 Hz, 1H, H5 ),
3.60 (dd, J¼12.0, 5.6 Hz, 1H, H5 ), 2.79 (d, J¼7.5 Hz, 2H, CH2–
CHCH2CH2), 2.29–2.16 (m, 1H, CH2–CHCH2CH2), 1.88–1.77 (m, 2H,
CH2–CHCH2CH2), 1.75–1.64 (m, 2H, CH2–CHCH2CH2), 1.64–1.53 (m,
2H, CH2–CHCH2CH2), 1.31–1.19 (m, 2H, CH2–CHCH2CH2); 13C NMR
This work was supported by an ‘ANR-05-BLAN-0368-03’ grant
(LAA), NIH CFAR grant 5P30-AI-50409 (RFS) and the Department of
Veterans Affairs (RFS).
0
0
0
(CD OD):
d
140.4 (C5), 133.3 (C4), 91.1 (C1 ), 87.4 (C4 ), 75.9 (C2 ), 72.5
0 3
References and notes
0
(C3 ), 63.6 (C5 ), 40.3 (CH2–CHCH2CH2), 33.5 (CH2–CHCH2CH2), 29.7
(CH2–CHCH2CH2), 26.0 (CH2–CHCH2CH2); HRMS (ESI): m/z [MþH]þ
calcd for C13H22N3O4: 284.1610, found: 284.1600.
1. (a) Simons, C. Nucleoside Mimetics: their Chemistry and Biological Properties;
Gordon and Breach Science: Amsterdam, 2001; Vol. 3, p 192; (b) Agrofoglio, L.
A.; Challand, S. R. Acyclic, Carbocyclic and L-Nucleosides; Kluwer Academic:
Dordrecht, 1998; (c) Agrofoglio, L. A.; Amblard, F.; Broggi, J.; Garnier, E. In
Modern Approaches to the Synthesis of O- and N-Heterocyles; Kaufman, T. S.,
Larghi, E. L., Eds.; Research Signpost: Trivandrum, India, 2007; Vol. 2, pp 195–
246; (e) De Clercq, E. Biochem. Pharmacol. 2007, 73, 911.
2. (a) Lau, J. Y.; Tam, R. C.; Liang, T. J.; Hong, Z. Hepatology 2002, 35, 1002; (b)
Borowski, P.; Lang, M.; Niebuhr, A.; Haag, A.; Schmitz, H.; Schulze zur Wiesch,
J.; Choe, J.; Siwecka, M. A.; Kulikowski, T. Acta Biochim. Pol. 2001, 48, 739; (c)
Contreras, A. M.; Hiasa, Y.; He, W.; Terella, A.; Schmidt, E. V.; Chung, R. T. J. Virol.
2002, 76, 8505; (d) Crotty, S.; Cameron, C. E.; Andino, R. Proc. Natl. Acad. Sci.
U.S.A. 2001, 98, 6895.
5.4.13. 10-[5-Butyl-[1,2,3]triazol-1-yl]ribofuranose (13e)
Prepared from compound 10e with the typical procedure de-
scribed above to give 13e (>98%) as an yellow oil. IR: 3331, 2932,
20
2871, 1428, 1243, 1056, 832 cmꢁ1; UV (MeOH) lmax: 221 nm; [
a]
D
ꢁ64.4 (c 0.70, MeOH); 1H NMR (CD3OD):
d
7.53 0(s, 1H, H4), 5.88 (d,
0
J¼3.9 Hz, 1H, H1 ), 4.84 (dd, J¼5.0, 3.9 Hz, 1H, H2 ), 4.33 (t, J¼5.0 Hz,
0
0
0
1H, H3 ), 4.14–4.11 (m, 1H, H4 ), 3.74 (dd, J¼12.1, 3.8 Hz, 1H, H5 ), 3.59

U. Pradere et al. / Tetrahedron 64 (2008) 9044–9051
9051
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