Synthesis and anti-HIV activity of β-D-3′-azido-2′, 3′-unsaturated nucleosides and β-D-3′-azido-3′- deoxyribofuranosylnucleosides

Article abstract of DOI:10.1080/15257770500267170

□ Since the discovery of 3′-azido-3′-deoxythymidine (AZT) and 2′,3′-didehydro-2prime;,3′-dideoxythymidine (d4T) as potent and selective inhibitors of the replication of human immunodeficiency virus (HIV), there has been a growing interest for the synthesis of 2′,3′-didehydro-2′,3′-dideoxynucleosides with electron withdrawing groups on the sugar moiety. Here we described an efficient method for the synthesis of such nucleoside analogs bearing structural features of both AZT and d4T. The hey intermediate, 3-azido-1,2-bis-O-acetyl-5-O-benzoyl-3- deoxy-D-ribofuranose, 5 was synthesized from commercially available D-xylose in five steps, from which a series of pyrimidine and purine nucleosides were synthesized in high yields. The resultant protected nucleosides were converted to target nucleosides using appropriate chemical modifications. The final nucleosides were evaluated as potential anti-HIV agents. Copyright Taylor & Francis Group, LLC.

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Synthesis and Anti-HIV Activity of β-D-3′-Azido-2′,3′-
unsaturated Nucleosides and β-D-3′-Azido-3′-
deoxyribofuranosylnucleosides
Srinivas Gadthula a , Chung K. Chu a & Raymond F. Schinazi b
a Department of Pharmaceutical and Biomedical Sciences , College of Pharmacy, The
University of Georgia , Athens, Georgia, USA
b Emory University School of Medicine/Veterans Affairs Medical Center , Decatur, Georgia,
USA
Published online: 16 Aug 2006.
To cite this article: Srinivas Gadthula , Chung K. Chu & Raymond F. Schinazi (2005) Synthesis and Anti-HIV Activity of β-
D-3′-Azido-2′,3′-unsaturated Nucleosides and β-D-3′-Azido-3′-deoxyribofuranosylnucleosides, Nucleosides, Nucleotides and
Nucleic Acids, 24:10-12, 1707-1727, DOI: 10.1080/15257770500267170
To link to this article: http://dx.doi.org/10.1080/15257770500267170
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Nucleosides, Nucleotides, and Nucleic Acids, 24:1707–1727, 2005
c
Copyright ꢀ Taylor & Francis Group, LLC
ISSN: 1525-7770 print/1532-2335 online
DOI: 10.1080/15257770500267170
SYNTHESIS AND ANTI-HIV ACTIVITY OF
β-D-3 -AZIDO-2 ,3 -UNSATURATED NUCLEOSIDES AND
β-D-3 -AZIDO-3 -DEOXYRIBOFURANOSYLNUCLEOSIDES
ᮀ
Srinivas Gadthula, and Chung K. Chu
Department of Pharmaceutical and
Biomedical Sciences, College of Pharmacy, The University of Georgia, Athens, Georgia, USA
ᮀ
Raymond F. Schinazi
Emory University School of Medicine/Veterans Affairs Medi-
cal Center, Decatur, Georgia, USA
ᮀ
Since the discovery of 3 -azido-3 -deoxythymidine (AZT) and 2 ,3 -didehydro-2 ,3 -dideoxy-
thymidine (d4T) as potent and selective inhibitors of the replication of human immunodeficiency
virus (HIV), there has been a growing interest for the synthesis of 2 ,3 -didehydro-2 ,3 -
dideoxynucleosides with electron withdrawing groups on the sugar moiety. Here we described an
efficient method for the synthesis of such nucleoside analogs bearing structural features of both AZT
and d4T. The key intermediate, 3-azido-1,2-bis-O-acetyl-5-O-benzoyl-3-deoxy-D-ribofuranose, 5 was
synthesized from commercially available D-xylose in five steps, from which a series of pyrimidine
and purine nucleosides were synthesized in high yields. The resultant protected nucleosides were
converted to target nucleosides using appropriate chemical modifications. The final nucleosides
were evaluated as potential anti-HIV agents.
Keywords Nucleosides; -D-3 -azido-2 ,3 -unsaturated nucleosides; -D-3 -azido-3 -de-
oxyribofuranosylnucleosides; Anti-HIV activity
INTRODUCTION
Nucleoside analogs have been extensively used as chemotherapeu-
tic agents for the treatment of HIV infection. Since the discovery of 3ꢁ-
azido-3ꢁ-deoxythymidine (AZT)[1] and 2ꢁ,3ꢁ-didehydro-2ꢁ,3ꢁ-dideoxythymi-
dine (d4T)[2] as potent and selective inhibitors of the replication of HIV,
This article is dedicated to the memory of Dr. John A. Montgomery.
Received 12 January 2005; accepted 19 April 2005.
This research was supported in part by the U.S. Public Health Service grant (AI 32351) from the
National Institute of Allergy and Infectious Diseases, NIH.
Address correspondence to Dr. C. K. Chu, Distinguished Research Professor, College of Pharmacy,
The University of Georgia, Athens, GA 30602. Fax: (706) 542-5381; E-mail: dchu@rx.uga.edu
1707

1708
S. Gadthula et al.
several 2ꢁ,3ꢁ-unsaturated and 2ꢁ,3ꢁ-dideoxy nucleoside analogs have been syn-
thesized and evaluated. For example, most of the FDA approved nucleoside
reverse transcriptase inhibitors[3] for the treatment of AIDS can be consid-
ered as 2ꢁ,3ꢁ-unsaturated and/or 2ꢁ,3ꢁ-dideoxy nucleoside analogs. In addi-
tion, the nucleoside analogs with electron withdrawing groups like azide[1]
or fluorine[4–11] on the carbohydrate moiety have been proven as potent
antiviral agents.
In recent years, we have extensively explored the synthesis and biologi-
cal activity of such substituents, particularly F or CNgroups in 2 ꢁ,3ꢁ-dideoxy-
2ꢁ,3ꢁ-didehydro-nucleoside analogs.[4–12] For example, synthesis and evalu-
ation of D- and L-2ꢁ(or 3ꢁ)-fluoro-2ꢁ,3ꢁ-unsaturated nucleosides [D- and L-2ꢁ
(or 3ꢁ)-F-d4Ns],[5–8] D- and L-2ꢁ,3ꢁ-unsaturated 2ꢁ(or 3ꢁ)-fluoro-4ꢁ-thionucleo-
sides [D- and L-2ꢁ(or 3ꢁ)-F-4ꢁSd4Ns][9–11] and L-3ꢁ-C-cyano-2ꢁ,3ꢁ-unsaturated
nucleosides (L-3ꢁ-C-CN-d4Ns)[12] have been reported by our group and a
number of nucleosides from the above classes displayed moderate to po-
tent anti-HIV activity and anti-hepatitis B virus (HBV) activities. Particularly
in the D-2ꢁ-F-d4Ns series, the adenine and hypoxanthine derivatives exhib-
ited potent anti-HIV-1 activities (EC50 0.04 and 0.5 µM, respectively) and
showed favorable cross-resistance profiles with respect to the 2ꢁ,3ꢁ-dideoxy-
3ꢁ-thiacytidine (3TC) resistant viral isolates.[6] Furthermore, the cytosine
and 5-fluorocytosine derivatives from the L-2ꢁ-F-d4Ns series displayed po-
tent HBV (EC50 = 0.002 and 0.004 µM, respectively) as well as anti-HIV-1
activities without significant cytotoxicities.[5]
In view of these interesting biological results, we were prompted to ex-
plore the synthesis and biological activity of a series of β-D-3ꢁ-azido-2ꢁ,3ꢁ-
unsaturated nucleosides and β-D-3ꢁ-azido-3ꢁ-deoxyribofuranosylnucleosides.
To our knowledge, β-D-3ꢁ-azido-2ꢁ,3ꢁ-unsaturated nucleosides were unknown
except 3ꢁ-azido-2ꢁ,3ꢁ-dideoxy-2ꢁ,3ꢁ-didehydrothymidine,[13] of which a syn-
thetic method was not amenable for the synthesis of the same series of
compounds. Herein, we report a general synthetic method and biological
evolution of 3ꢁ-azido-2ꢁ,3ꢁ-didehydro-2ꢁ,3ꢁ-dideoxynucleoside analogs and 3ꢁ-
azido-3ꢁ-deoxyribofuranosylnucleosides.
RESULTS AND DISCUSSION
To synthesize the target compounds, a versatile carbohydrate precursor
5 was used as a key intermediate, which was prepared in five steps from
D-xylose (Scheme 1). The conversion of D-xylose to 1,2-O-isopropylidene-β-
D-xylofuranose 1 was achieved in 90% yield by the reported procedure.[14]
The primary hydroxyl group of compound 1 was selectively protected with
benzoyl chloride and pyridine to produce the benzoyl derivative 2 in 85%
yield. In order to introduce an 3-azido group, the 3-hydroxy group of com-
pound 2 was converted to a triflate 3 with trifluoromethanesulfonic anhy-

Synthesis and Anti-HIV Activity of Nucleosides
1709
SCHEME 1 Reagents and conditions: (a) H2SO4, CuSO4, acetone, rt; (ii) 0.1 M HCl solution in
MeOH, 40 C; (b) BzCl, Py, CH2Cl2, 0 C; (c) Tf2O, Py, CH2Cl2, −10 C; (d) NaN3, Bu4NCl (cat),
DMF, 60 C; (e) (i) 75% HCOOH, 50 C; (ii) Ac2O, Py, rt.
dride, which was subsequently converted to an 3-azido derivative 4 in ap-
proximately 52% yield with sodium azide and catalytic amount of phase
transfer catalyst (Bu4NCl) in DMF at 60◦C.[15] The azide 4 was converted
to 3-azido-1,2-bis-O-acetyl-5-O-benzoyl-3-deoxy-D-ribofuranose 5 in 75% yield
as an epimeric mixture with 75% formic acid, followed by acetylation with
acetic anhydride in pyridine.[16] Condensation of the key intermediate 5
with persilylated pyrimidines with trimethylsilyl triflate as Lewis acid gave the
corresponding nucleosides 6, 7, and 8 in 79–83% yield (Scheme 2). The con-
densation reaction gave exclusively the β-anomer, which can be explained
by the neighboring 2-acetyl group participation. Then we attempted the
elimination reaction on the compound 6 to obtain the intermediate 15 with
DBU and DMAP in CH2Cl2.[12] It was thought that the 3ꢁ-β-proton would be
acidic enough to be abstracted by base (DBU or DMAP) and subsequently
the 2ꢁ-acetyl group would be expected to leave. Unfortunately, this reaction
did not proceed and only starting material was isolated. However, Hasegawa
et al.[17] reported a similar elimination reaction on 2-O-triflate sugar deriva-
tive with tetrabutyl ammonium fluoride. Thus, a similar protocol was used
for the introduction of 2ꢁ,3ꢁ-unsaturation in our target nucleosides. In order
to synthesize the 2ꢁ-O-triflate derivatives 12, 13, and 14, compounds 6, 7, and
8 were treated with hydrazine hydrate in buffered acetic acid and pyridine
to produce the desired nucleosides 9 and 11 in 84% and 86% yields, re-
spectively. In the case of compound 7, in addition to the 2ꢁ-O-acetyl group,
the N-benzoyl group was also affected under the reaction conditions and
compound 10 was obtained in 71% yield. The resulting nucleosides 9, 10,
and 11 were treated with trifluoromethanesulfonic anhydride and pyridine
in CH2Cl2 at −40◦C to produce triflate derivatives 12 and 14 in 78% and
82% yields, respectively. In the case of compound 10, an undesired black
mass was observed under similar reaction conditions due to the presence
of a primary amino group. Since the cytosine analog 10 did not give the

1710
S. Gadthula et al.
SCHEME 2 Reagents and conditions: (a) BSA, pyrimidines, TMSOTf, CH3CN, 50–70 C; (b) DBU,
DMAP, CH2Cl2, rt; (c) N2H4.H2O, AcOH-Py, rt; (d) Tf2O, Py, CH2Cl2, −40 C; (e) TBAF, THF,
rt; (f) (i) 2,4,6-triisopropylbenzenesulfonyl chloride, DMAP, Et3N , CHCN, rt; (ii) 30% NH4OH, rt;
3
(g) NH3/MeOH, rt.
expected triflate derivative 13, we decided to synthesize the cytosine analog
19 from the uracil analog 11. The nucleosides 12 and 14 were treated with
2 equivalents of tetrabutylammonium fluoride (TBAF) in THF to give the
desired compounds 15 and 16 in 87% and 85% yields, respectively. The re-
sulting 2ꢁ,3ꢁ-unsaturated uracil analog 16 was converted to the cytosine ana-
log 17 by amination with triisopropylbenzenesulfonyl chloride, DMAP and
triethylamine.[18] Finally, compounds 15 and 17 were treated with saturated
methanolic ammonia to afford the desired nucleosides 18 and 19 in 84%
and 82% yields, respectively. On the other hand, compounds 6 and 7 were
treated with saturated methanolic ammonia to obtain the final nucleosides
20 and 21 in 79% and 75% yields, respectively.

Synthesis and Anti-HIV Activity of Nucleosides
1711
For the synthesis of purine nucleosides, we first attempted the synthesis
of adenine analog 28. Key intermediate 5 was treated with 6-chloropurine
under similar reaction conditions used for the pyrimidine nucleosides to
obtain nucleoside 22 exclusively as the N-9 glycosylation product in 90%
yield (Scheme 3). Since the preparation of the triflate of cytosine (13) was
problematic, it was of interest to convert compound 22 to 25 by a similar
sequence of reactions used for pyrimidines, and it was expected that am-
ination and deprotection would give final compound 28 in a single step.
Accordingly, compound 22 was treated with hydrazine hydrate in buffered
acetic acid and pyridine to give the desired compound 23 in only 20% yield.
Alternatively, compound 22 was converted to the desired compound 23 in
86% yield with partially saturated methanolic ammonia at 0◦C. Compound
23 was converted to the triflate derivative 24, and subsequently treated with
TBAF in THF to give only hydrolyzed products 26 and 27. TLC studies re-
vealed that the expected product was formed in the reaction medium, but
unfortunately it was not stable enough to be isolated. We also tried to con-
vert 25 to desired compound 28 in situ by treating with saturated methano-
lic ammonia in a steel bomb at 100◦C but without success. In an alternative
approach, key intermediate 5 was treated with silylated N-benzoyladenine
under similar reaction conditions with trimethylsilyltriflate as Lewis acid to
give the desired compound 29 in only 30% yield along with unidentified side
products. However, much improved yields were achieved when the key in-
termediate 5 was treated with N-benzoyladenine in the presence of tin(IV)
chloride in anhydrous acetonitrile (Scheme 4). The resulting compound
29 was first chemo-selectively deacylated with partially saturated methanolic
ammonia to give compound 30. Compound 30 was treated with trifluoro-
SCHEME 3 Reagents and conditions: (a) 6-Chloropurine, BSA, TMSOTf, CH3CN, 50–70 C; (b) par-
tially saturated NH3/MeOH, 0 C; (c) Tf2O, Py, CH2Cl2, −40 C; (d) TBAF, THF, rt; (e) work up;
(f) NH3/MeOH, steel bomb, 100 C.

1712
S. Gadthula et al.
SCHEME 4 Reagents and conditions: (a) N-Benzoyladenine, SnCl4, CH3CN, rt; (b) partially saturated
NH3/MeOH, 0 C; (c) Tf2O, Py, CH2Cl2, −40 C; (d) TBAF, THF, rt; (e) work up; (f) K2CO3, MeOH,
rt; (g) NH3/MeOH, rt.
methanesulfonic anhydride in a mixture of pyridine and methylene chlo-
ride at −40◦C to obtain triflate derivative 31, which was treated with TBAF
in THF. After usual work up and purification, a similar cleavage product 26
was obtained along with the corresponding free base N 6-benzoyladenine.
Since the elimination product was not stable enough to isolate, we searched
for an alternative method where both elimination and deprotection would
take place in a single step. Such triflate elimination reaction was reported
with potassium carbonate in methanol[19] and it was also known in the
literature that the same potassium carbonate would work for the depro-
tection of a benzoyl group. The same method was applied to the triflate
sugar 31, which gave the desired final product 28 along with the depro-
tected product 34 in 30% and 22% yields, respectively. Since the yield of
the final nucleoside 28 was poor, an alternative method was tried in which
the unstable eliminated compound 32 was treated with saturated methano-
lic ammonia in situ without work up to give the desired final compound
28 in 75% yield. On the other hand, compound 29 was treated with sat-
urated methanolic ammonia to give the final nucleoside 34 in 87% yield.
For the synthesis of guanine analogs 41 and 42 (Scheme 5), initially the
condensation of persilylated-protected guanine with the key intermediate
5 was carried out using (trimethylsilyl) trifluoromethane sulfonate in ace-
tonitrile to give compound 36 in 74% yield. In order to obtain the final
compound 41, a similar sequence of reactions were followed, in which com-
pound 36 was first treated with hydrazine hydrate in buffered acetic acid and
pyridine to give compound 37 in 78% yield. Compound 37 was converted

Synthesis and Anti-HIV Activity of Nucleosides
1713
SCHEME 5 Reagents and conditions: (a) 35, BSA, TMSOTf, CH3CN, 50–70 C; (b) N2H4.H2O, AcOH-
Py; (c) Tf2O, Py, CH2Cl2, −40 C; (d) TBAF, THF, rt; (e) work up; (f) NH3/MeOH, rt.
to the triflate derivative 38 in 81% yield, which was subsequently treated
with TBAF in THF. After work up, similar elimination product 26 and the
corresponding free base 40 were observed. To obtain the final compound, a
similar strategy (i.e., compound 32 to 28) was followed, where the elimina-
tion compound 39 was treated with saturated methanolic ammonia to afford
the final nucleoside 41 in 72% yield. Compound 36 was directly converted
to the final nucleoside 42 with saturated methanolic ammonia in 83% yield.
ANTI-HIV ACTIVITY
The synthesized β-D-3ꢁ-azido-2ꢁ,3ꢁ-unsaturated nucleosides (18, 19, 28,
and 41) and β-D-3ꢁ-azido-3ꢁ-deoxyribofuranosylnucleosides (20, 21, 34, and
42) were evaluated against HIV-1 in human PBM cells in vitro, as well as
their cytotoxicity and the results are summarized in Table 1. Among these
nucleosides, compounds 42 (9.03 µM), 34 (13.9 µM), 18 (31.0 µM), 19
(44.9 µM), and 41 (46.5 µM) exhibited moderate anti-HIV activity with
significant cytotoxicity in PBM, CEM and vero cells. Adenine analog 28
exhibited weak anti-HIV activity with significant cytotoxicity. Compounds
20 and 21 exhibited weak anti-HIV activities without significant cytotoxicity.
In summary, we have developed an efficient synthetic methodology for
the synthesis of β-D-3ꢁ-azido-2ꢁ,3ꢁ-unsaturated nucleosides and β-D-3ꢁ-azido-3ꢁ-
deoxyribofuranosylnucleosides and evaluated their anti-HIV activities. Some
of the synthesized compounds exhibited moderate anti-HIV activity.

1714
S. Gadthula et al.
TABLE 1 In Vitro Anti-HIV-1 Activity and Toxicity of -D-3 -Azido-2 ,3 -Unsaturated
Nucleosides and -D-3 -Azido-3 -Deoxyribofuranosylnucleosides
Anti-HIV-1 activity (PBM)
Toxicity ( M)
CEM
Comp. (B)
EC50 ( M)
EC90 ( M)
PBM
VERO
Thymine (18)
Cytosine (19)
Adenine (28)
Guanine (41)
Thymine (20)
Cytosine (21)
Adenine (34)
Guanine (42)
AZT
31.0
44.9
100
46.5
100
91.0
13.9
9.03
0.0024
83.5
100
100
100
100
100
48.3
100
24.2
∼100
42.4
28
100
100
59.4
14.5
100
11.7
20.7
4.1
11.3
100
100
100
33.8
14.3
100
100
100
15.5
100
100
84.1
100
28
0.014
EXPERIMENTAL
Melting points were determined on a Mel-temp II apparatus and were
uncorrected. Nuclear magnetic resonance spectra were recorded on Bruker
1
500 AMX spectrophotometer at 500 MHz for H NMR and at 125 MHz
for 13C NMR with tetramethylsilane as internal standard. Chemical shifts
(δ) are reported in parts per million (ppm), and signals are reported as
s (single), d (double), t (triple), q (quartet), m (multiplet), br (broad
singlet), and dd (doublet of doublets). UV spectra were recorded on a
Beckman DU-650 spectrophotometer. Optical rotation was measured on
a Jasco DIP-370 digital polarimeter. Mass spectra were recorded on a
LCT premier electrospray ionization high-resolution mass spectrometer.
TLC was performed on uniplates (silica gel) purchased from Analtech
Co. Silica gel G (TLC grade, >440 mesh) was used for vacuum column
chromatography as well as for flash column chromatography. Elemental
analysis were performed by Atlantic Microlab Inc., Norcross, Georgia.
3 -Azido-2 -O -acetyl-5 -O -benzoyl-3 -deoxy-β-D-ribofuranosylthymine
(6). N,O-Bis(trimethylsilyl)acetamide (BSA, 2.0 mL, 8.0 mmol) was added
at room temperature to a mixture of compound 5 (1.0 g, 2.74 mmol) and
thymine (0.40 g, 3.20 mmol) in anhydrous acetonitrile (30 mL) under
argon, then stirred for 1 h at 50–60◦C to form a clear solution. After
being cooled to room temperature, trimethylsilyl trifluoromethanesulfonate
(TMSOTf, 0.54 mL, 3.0 mmol) was added and the resulting mixture was

Synthesis and Anti-HIV Activity of Nucleosides
1715
heated to 65–70◦C for 6 h. The reaction mixture was cooled to room
temperature, then quenched with saturated aqueous sodium bicarbonate
solution (15 mL) and stirred until the evolution of CO2 ceased. The
resulting mixture was diluted with ethyl acetate (80 mL). The organic
phase was separated and the aqueous phase was extracted with ethyl acetate
(50 mL). The combined organic phases were washed with brine (20 mL),
dried over Na2SO4, filtered, and concentrated. The residue was purified by
silica gel column chromatography eluting with dichloromethane/methanol
(100:1 v/v) to give compound 6[20] (0.98 g, 83%) as a white foam. mp 58–
60◦C; [α]D25 31.3◦ (c, 0.56, CHCl3); UV (MeOH) λmax 264.0 nm; IR (neat):
2111.82 cm−1 (azide); 1H NMR (CDCl3) δ 1.68 (s, 3 H, 5-CH3), 2.21 (s, 3 H,
2ꢁ-OAc), 4.27 (m, 1 H, 4ꢁ-H), 4.48 (t, J = 6 Hz, 1 H, 3ꢁ-H), 4.60 (dd, J = 4,
12 Hz, 1 H, 5ꢁ-Ha), 4.74 (dd, J = 3, 12 Hz, 1 H, 5ꢁ-Hb), 5.54 (dd, J = 5, 6 Hz,
1 H, 2ꢁ-H), 5.85 (d, J = 4.5 Hz, 1 H, 1ꢁ-H), 7.03 (d, J = 1.5 Hz, 1 H, 6-H),
7.47–7.50 (m, 2 H, Ar-H), 7.60–7.64 (m, 1 H, Ar-H), 8.07 (dd, J = 1.5, 8 Hz,
2 H, Ar-H), 8.54 (bs, 1 H, 4-OH), 13C NMR (CDCl3) δ 12.24, 20.51, 60.17,
63.36, 74.98, 79.79, 89.47, 111.86, 128.77, 129.16, 129.69, 133.74, 135.98,
150.14, 163.67, 166.05, 170.09; MS (ESI) m/z 452 (M+Na).
3 -Azido-2 -O-acetyl-5 -O-benzoyl-3 -deoxy-β-D-ribofuranosyl-N4-ben-
zoyl Cytosine (7). Using the same procedure as described for 6, compound
5 (1.10 g, 3.0 mmol) was condensed with N4-benzoyl cytosine (0.75 g, 3.5
mmol) using BSA (2.21 mL, 9.0 mmol) and TMSOTf (0.60 mL, 3.3 mmol)
for 4 h to produce compound 7 (1.23 g, 79%) as a white foam. Rf = 0.55
(CH2Cl2/MeOH, 10:1); mp 80-82◦C; [α]D 46.3◦ (c, 0.51, CHCl3); UV
25
(MeOH) λmax 261.0 nm; IR (neat): 2115.47 cm−1 (azide); 1H NMR (CDCl3)
δ 2.18 (s, 3 H, 2ꢁ-OAc), 4.32–4.35 (m, 1 H, 4ꢁ-H), 4.42 (dd, J = 5, 9 Hz, 1 H,
3ꢁ-H), 4.65 (dd, J = 4, 12 Hz, 1 H, 5ꢁ-Ha), 4.73 (dd, J = 3, 12.5 Hz, 1 H,
5ꢁ-Hb), 5.76 (dd, J = 2.5, 5.5 Hz, 1 H, 2ꢁ-H), 5.92 (d, J = 2 Hz, 1 H, 1ꢁ-
H), 7.44–7.54 (m, 5 H, 5,6-H, Ar-H), 7.60–7.66 (m, 2 H, Ar-H), 7.93 (dd,
J = 7, 28 Hz, 3 H, Ar-H), 8.07–8.09 (m, 2 H, Ar-H), 8.88 (bs, 1 H, NH),
13C NMR (CDCl3) δ 20.51, 59.79, 62.82, 75.57, 80.17, 91.53, 127.70, 128.77,
129.02, 129.19, 129.72, 133.26, 133.76, 144.60, 162.81, 166.09, 169.58; ES
HRMS calcd C25H22N6O7 [M+H+] 519.1629, found 519.1601.
3 -Azido-2 -O-acetyl-5 -O-benzoyl-3 -deoxy-β-D-ribofuranosyluracil (8).
Using the same procedure as described for 6, compound 5 (1.95 g, 5.37
mmol) was condensed with uracil (0.69 g, 6.20 mmol) using BSA (3.71
mL, 15.0 mmol) and TMSOTf (1.0 mL, 5.60 mmol) for 4 h to produce
compound 8[20] (1.78 g, 80%) as a white foam. Rf = 0.6 (CH2Cl2/MeOH,
10:1); mp 73–75◦C; [α]D 56.3◦ (c, 1.3, MeOH); UV (MeOH) λmax 258.0
25
1
nm; IR (neat): 2115.30 cm−1 (azide); H NMR (CDCl3) δ 2.22 (s, 3 H, 2ꢁ-
OAc), 4.27–4.29 (m, 1 H, 4ꢁ-H), 4.42 (dd, J = 6.5, 7.5 Hz, 1 H, 3ꢁ-H), 4.56

1716
S. Gadthula et al.
(dd, J = 4, 12.5 Hz, 1 H, 5ꢁ-Ha) 4.70 (dd, J = 3, 13 Hz, 1 H, 5ꢁ-Hb), 5.55
(dd, J = 4, 6 Hz, 1 H, 2ꢁ-H), 5.60 (dd, J = 2.5, 8.5 Hz, 1 H, 5-H), 5.79 (d,
J = 3.5 Hz, 1 H, 1ꢁ-H), 7.31 (d, J = 8.5 Hz, 1 H, 6-H), 7.47-7.50 (m, 2 H,
Ar-H), 7.61–7.64 (m, 1 H, Ar-H), 8.05–8.07 (m, 2 H, Ar-H), 8.85 (bs, 1 H,
4-OH); 13C NMR (CDCl3) δ 20.46, 60.02, 63.08, 75.19, 79.94, 90.32, 103.07,
128.71, 129.18, 129.69, 133.70, 140.39, 150.01, 163.14, 166.05, 169.89.
3 -Azido-5 -O-benzoyl-3 -deoxy-β-D-ribofuranosylthymine (9). Hydra-
zine hydrate (0.7 mL, 12.0 mmol) was added to a stirred solution of
compound 6 (0.86 g, 2.0 mmol) in an acetic acid-pyridine (10 mL, v/v, 1:4)
mixture. After being stirred for 24 h, acetone (5 mL) was added and stirred
further for 30 min. The resulting mixture was diluted with chloroform (100
mL) and washed with saturated aqueous sodium hydrogen carbonate (20
mL) followed by water (30 mL). The organic layer was dried over sodium
sulfate, evaporated to dryness and coevaporated with anhydrous toluene (20
mL). The residue was purified by silica gel column chromatography using
dichloromethane/methanol (100:1 v/v) obtained compound 9 (0.65 g,
84%) as a white foam. mp 78–80◦C; [α]D 26.6◦ (c, 1.2, CHCl3); UV
25
(MeOH) λmax 266.0 nm; IR (neat): 2109.62 cm−1 (azide); 1H NMR (CDCl3)
δ 1.54 (s, 3 H, 5-CH3), 4.16 (t, J = 6 Hz, 1 H, 3ꢁ-H), 4.49–4.51 (m, 1 H, 4ꢁ-H),
4.59 (dd, J = 4, 12.5 Hz, 1 H, 5ꢁ-Ha), 4.76 (dd, J = 2.5, 12.5 Hz, 1 H, 5ꢁ-Hb),
4.63 (t, J = 5 Hz, 1 H, 2ꢁ-H), 5.10 (bs, 1 H, 2ꢁ-OH), 5.86 (d, J = 3.5 Hz,
1 H, 1ꢁ-H), 7.26 (s, 1 H, 6-H), 7.48 (t, J = 8 Hz, 2 H, Ar-H), 7.61–7.64 (m,
1 H, Ar-H), 8.06 (d, J = 8 Hz, 2 H, Ar-H), 10.41 (bs, 1 H, NH); 13C N MR
(CDCl3) δ 12.27, 60.48, 63.61, 75.92, 80.01, 90.40, 111.06, 128.81, 129.29,
129.67, 133.71, 134.89, 151.51, 163.79, 166.10; ES HRMS calcd C17H17N5O6
[M+H+] 388.1258, found 388.1277.
3 -Azido-5 -O-benzoyl-3 -deoxy-β-D-ribofuranosylcytosine (10). Using
the same procedure as described for 9, compound 7 (1.20 g, 2.30 mmol)
was deprotected with hydrazine hydrate (0.7 mL, 12.0 mmol) in acetic acid-
pyridine (10 mL, 1:4 v/v) to give compound 10 (0.61 g, 71%) as a white
solid. Rf = 0.50 (CH2Cl2/MeOH, 10:1); mp 182-184◦C; [α]D 30.15◦ (c,
25
0.73, MeOH); UV (MeOH) λmax 272.0 nm; IR (neat): 2112.64 cm−1 (azide);
1H NMR (DMSO-d6) δ 4.20 (t, J = 5.5 Hz, 1 H, 3ꢁ-H), 4.24–4.26 (m, 1 H,
4ꢁ-H), 4.45–4.47 (m, 1 H, 2ꢁ-H), 4.49 (dd, J = 5, 12.5 Hz, 1 H, 5ꢁ-Ha) 4.60
(dd, J = 3, 12 Hz, 1 H, 5ꢁ-Hb), 5.63 (d, J = 7.5 Hz, 1 H, 2ꢁ-OH), 5.80 (d,
J = 3.5 Hz, 1 H, 1ꢁ-H), 6.25 (d, J = 5.5 Hz, 1 H, 5-H), 7.23 (d, J = 13.5
Hz, 2 H, N H), 7.55–7.58 (m, 3 H, 6-H, and Ar-H), 7.70-7.73 (m, 1 H, Ar-
2
H), 8.02–8.04 (m, 2 H, Ar-H); 13C NMR (DMSO-d6) δ 60.97, 64.42, 74.57,
78.42, 91.23, 94.82, 129.29, 129.75, 129.79, 134.07, 141.83, 155.55, 165.98,
166.11; MS (ESI) m/z 373 (M+H+); ES HRMS calcd C16H16N6O5 [M+H+]
373.1261, found 373.1220.

Synthesis and Anti-HIV Activity of Nucleosides
1717
3 -Azido-5 -O-benzoyl-3 -deoxy-β-D-ribofuranosyluracil (11). Using the
same procedure as described for 9, compound 8 (1.66 g, 4.0 mmol) was
deprotected with hydrazine hydrate (1.1 mL, 18.0 mmol) in acetic acid-
pyridine (15 mL, 1:4 v/v) to give compound 11 (1.28 g, 86%) as a white
foam. Rf = 0.55 (CH2Cl2/MeOH, 10:1); mp 99–101◦C; [α]D25 48.4◦ (c, 1.0,
MeOH); UV (MeOH) λmax 261.0 nm; IR (neat): 2111.36 cm−1 (azide); 1H
NMR (CDCl3) δ 4.16 (dd, J = 6, 7 Hz, 1 H, 3ꢁ-H), 4.53–4.55 (m, 1 H, 4ꢁ-H),
4.64 (dd, J = 3.5, 12.5 Hz, 1 H, 5ꢁ-Ha), 4.68–4.70 (m, 1 H, 2ꢁ-H), 4.70–
4.73 (m, 1 H, 5ꢁ-Hb), 5.16 (bs, 1 H, 2ꢁ-OH), 5.36 (d, J = 8 Hz, 1 H, 5-H),
5.87 (d, J = 3.5 Hz, 1 H, 1ꢁ-H), 7.45–7.48 (m, 2 H, Ar-H), 7.55–7.60 (m,
2 H, Ar-H, and 6-H), 8.06–8.08 (m, 2 H, Ar-H), 10.62 (bs, 1H, NH); 13C
NMR (CDCl3) δ 60.14, 63.41, 75.74, 79.98, 90.66, 102.53, 128.69, 129.32,
129.70, 133.69, 139.39, 151.63, 163.25, 166.06; ES HRMS calcd C16H15N5O6
[M+H+] 374.1101, found 374.1163.
3 -Azido-2 -O -triflyl-5 -O -benzoyl-3 -deoxy-β-D-ribofuranosylthymine
(12). Trifluoromethanesulfonic anhydride (0.22 mL, 1.30 mmol) in anhy-
drous CH2Cl2 (2 mL) was added dropwise during 5 min. to a stirred solution
of compound 9 (0.39 g, 1.0 mmol) and anhydrous pyridine (0.16 mL, 2.0
mmol) in anhydrous CH2Cl2 (15 mL) at −40◦C (acetone/dry ice bath).
After being stirred for 30 min. at 20–30◦C, the reaction temperature was
allowed to 0◦C and diluted with CH2Cl2 (50 mL), washed with a saturated
aqueous solution of NaHCO3 (20 mL), and dried (Na2SO4). After evapora-
tion of the solvent the crude was purified by silica gel column chromatogra-
phy with CH2Cl2/MeOH (100:3) as eluent, afforded nucleoside 12 (0.40 g,
78%) as a pale red solid. UV (MeOH) λmax 263.0 nm; IR (neat): 2117.34
cm−1 (azide); 1H NMR (CDCl3) δ 1.88 (s, 3 H, 5-CH3), 4.30–4.36 (m, 2 H,
5ꢁ-H), 4.51 (dd, J = 4, 6 Hz, 1 H, 3ꢁ-H), 5.41 (dd, J = 2, 6 Hz, 1 H, 2ꢁ-H),
4.53–4.55 (m, 1 H, 4ꢁ-H), 6.30 (d, J = 6 Hz, 1 H, 1ꢁ-H), 7.22 (d, J = 1.5,
1 H, 6-H), 7.44 (t, J = 7 Hz, 2 H, Ar-H), 7.57–7.60 (m, 1 H, Ar-H), 7.93 (dd,
J = 1, 8.5 Hz, 2 H, Ar-H); 13C NMR (CDCl3) δ 14.01, 62.73, 65.99, 83.04,
86.50, 90.30, 119.61, 128.65, 128.82, 129.65, 130.19, 133.73, 158.93, 165.73,
172.00.
3 -Azido-2 -O -triflyl-5 -O -benzoyl-3 -deoxy-β-D-ribofuranosylcytosine
(13). Using the same procedure as described for 12, compound 10 (0.37 g,
1.0 mmol) was also reacted with trifluoromethanesulfonic anhydride (0.22
mL, 1.30 mmol) under similar reaction conditions. After standard work up
desired compound was not obtained.
3 -Azido-2 -O-triflyl-5 -O-benzoyl-3 -deoxy-β-D-ribofuranosyluracil (14).
Using the same procedure as described for 12, trifluoromethanesulfonic an-
hydride (0.44 mL, 2.60 mmol) was added dropwise to a stirred solution of

1718
S. Gadthula et al.
compound 11 (0.75 g, 2.0 mmol) and anhydrous pyridine (0.4 mL, 5 mmol)
in anhydrous CH2Cl2 (25 mL) under similar reaction conditions. After stan-
dard work up and purification produced compound 14 (0.83 g, 82%) as a
light red solid. Rf = 0.53 (CH2Cl2/MeOH, 10:1); UV (MeOH) λmax 257.0
nm; IR (neat): 2112.28 cm−1 (azide); 1H NMR (CDCl3) δ 4.32 (d, J = 6 Hz,
2 H, 5ꢁ-H), 4.51–4.53 (m, 1 H, 3ꢁ-H), 4.53–4.55 (m, 1 H, 4ꢁ-H), 5.50 (dd,
J = 1.5, 6 Hz, 1 H, 2ꢁ-H), 5.97 (d, J = 7.5 Hz, 1 H, 5-H), 6.41 (d, J = 6 Hz,
1 H, 1ꢁ-H), 7.42–7.45 (m, 3 H, 6-H, and Ar-H), 7.56–7.59 (m, 1 H, Ar-H),
7.93–7.95 (m, 2 H, Ar-H); 13C NMR (CDCl3) δ 62.83, 65.79, 83.13, 86.83,
90.25, 110.40, 128.63, 128.86, 129.68, 133.68, 135.10, 159.40, 165.77, 171.60.
3 -Azido-5 -O-benzoyl-2 ,3 -didehydro-2 ,3 -dideoxy-β-D-ribofuranosyl-
thymine (15). To a stirred solution of nucleoside 12 (0.35 g, 0.67 mmol) in
anhydrous tetrahydrofuran (20 mL) was added TBAF in THF solution (1 M)
(1.34 mL, 1.34 mmol). The mixture was stirred for 20 h at room temperature
and then evaporated to dryness. The resulting residue was dissolved in
chloroform (100 mL) and washed with water (30 mL). The organic layer
was dried and evaporated to dryness under reduced pressure. The crude
was purified by silica gel column chromatography with dichloromethane/
MeOH (100:3) afforded the title compound 15 (0.22 g, 87%) as a white
foam. mp 68–70◦C; [α]D −119.9◦ (c, 1.6, CHCl3) UV (MeOH) λmax 261.0
25
1
nm; IR (neat): 2119.86 cm−1 (azide); H NMR (CDCl3) δ 1.43 (s, 3 H, 5-
CH3), 4.40 (dd, J = 4, 13 Hz, 1 H, 5ꢁ-Ha), 4.70 (dd, J = 2, 12.5 Hz, 1 H,
5ꢁ-Hb), 4.90–4.95 (m, 1 H, 4ꢁ-H), 5.54 (t, J = 2 Hz, 1 H, 1ꢁ-H), 7.04 (dd,
J = 1.5, 4 Hz, 1 H, 2ꢁ-H), 7.20 (d, J = 1 Hz, 1 H, 6-H), 7.46–7.48 (m, 2 H,
Ar-H), 7.59–7.62 (m, 1 H, Ar-H), 7.99–8.02 (m, 2 H, Ar-H), 9.18 (bs, 1 H, 4-
OH); 13C NMR (CDCl3) δ 11.83, 63.37, 80.52, 88.05, 108.05, 111.58, 128.77,
129.51, 129.61, 133.63, 134.83, 143.95, 150.67, 163.60, 165.96; ES HRMS
calcd C17H15N5O5 [M+Na+] 392.0970, found 392.0919.
3 -Azido-5 -O-benzoyl-2 ,3 -didehydro-2 ,3 -dideoxy-β-D-ribofuranosyl-
uracil (16). Using the same procedure as described for 15, compound 14
(0.75 g, 1.50 mmol) was treated with TBAF/THF (1 M) solution (3 mL, 3.0
mmol) in anhydrous THF obtained compound 16 (0.45 g, 85%) as a white
foam. Rf = 0.56 (CH2Cl2/MeOH, 10:1); mp 122–124◦C; [α]D −146.5◦ (c,
25
1.1, CHCl3); UV (MeOH) λmax 259.0 nm; IR (neat): 2110.28 cm−1 (azide);
1H NMR (CDCl3) δ 4.45 (dd, J = 3, 13 Hz, 1 H, 5ꢁ-Ha), 4.69 (dd, J = 2.5, 13.5
Hz, 1 H, 5ꢁ-Hb), 4.89–4.4.91 (m, 1 H, 4ꢁ-H), 5.23 (dd, 1.5, 8 Hz, 1 H, 5-H),
5.49 (t, J = 1.5 Hz, 1 H, 1ꢁ-H), 7.05 (dd, J = 1.5, 3.5 Hz, 1 H, 2ꢁ-H), 7.47–7.50
(m, 3 H, 6-H, and Ar-H), 7.60–7.64 (m, 1 H, Ar-H), 7.97–7.99 (m, 2 H, Ar-H),
9.54 (bs, 1 H, 4-OH); 13C NMR (CDCl3) δ 62.91, 80.75, 88.06, 102.84, 107.63,
128.77, 129.44, 129.54, 133.74, 139.72, 144.23, 150.68, 163.26, 165.88; ES
HRMS calcd C16H13N5O5 [M+Na+] 378.0814, found 378.0746.

Synthesis and Anti-HIV Activity of Nucleosides
1719
3 -Azido-5 -O-benzoyl-2 ,3 -didehydro-2 ,3 -dideoxy-β-D-ribofuranosyl-
cytosine (17). A mixture of 16 (0.36 g, 1.0 mmol), 4-dimethylamino
pyridine (0.24 g, 2.0 mmol), triethylamine (0.20 g, 2.0 mmol) and 2,4,6-
triisopropylbenzene sulfonyl chloride (0.61 g, 2.0 mmol) in anhydrous
acetonitrile (30 mL) was stirred at room temperature for 24 h. After
the addition of 30% NH4OH (7 mL), the mixture was further stirred
for 5 h, then CHCl3 (150 mL) and water (35 mL) were added and
the resulting mixture was partitioned. The organic phase was washed
with saturated aqueous NH4Cl solution, dried (Na2SO4), and evaporated
to dryness under reduced pressure. The residue was purified by silica
gel column chromatography with dichloromethane/MeOH (100:4) and
obtained the desired nucleoside 17 (0.28 g, 78%) as a white solid. mp 104–
106◦C; [α]D −148.4◦ (c, 0.55, MeOH), UV (MeOH) λmax 272.0 nm; IR
25
1
(neat): 2121.96 cm−1 (azide); H NMR (CD3OD) δ 4.44 (dd, 3.5, 13 Hz,
1 H, 5ꢁ-Ha), 4.70 (dd, J = 2.5, 13 Hz, 1 H, 5ꢁ-Hb), 4.98–5.00 (m, 1 H, 4ꢁ-H),
5.45 (d, 8 Hz, 1 H, 5-H), 5.75 (t, J = 2 Hz, 1 H, 1ꢁ-H), 7.03 (dd, J = 2, 3.5
Hz, 1 H, 2ꢁ-H), 7.54 (t, 8 Hz, 2 H, Ar-H), 7.66–7.69 (m, 2 H, 6-H, and Ar-H),
8.01 (dd, 1.5, 8 Hz, 2 H, Ar-H); 13C NMR (CD3OD) δ 61.53, 79.08, 87.69,
93.42, 106.84, 126.86, 127.66, 128.06, 131.71, 139.52, 141.83, 155.46, 164.39,
164.67; Anal. calcd for C16H14N6O4: C, 54.24; H, 3.98; N, 23.72; Found C,
53.91; H, 4.40; N, 23.47.
3 -Azido-2 ,3 -didehydro-2 ,3 -dideoxy-β-D-ribofuranosylthymine (18).
A solution of compound 15 (0.17 g, 0.46 mmol) in methanolic ammonia
(previously saturated at 0◦C) (20 mL) was stirred for 16 h at room tem-
perature. Upon completion of the reaction, the solvent was removed un-
der reduced pressure. The resulting crude was purified by silica gel column
chromatography with dichloromethane/MeOH (100:4) afforded the target
nucleoside 18 (0.10 g, 84%) as a white solid. Rf = 0.45 (CH2Cl2/MeOH,
10:1); mp 52–54◦C, [lit.[13] mp 145◦C (Decomposition)]; [α]D −265.2◦
25
(c, 0.6, MeOH); UV (MeOH) λmax 261.0 nm, (ε 14,813) (pH 2), 261.0 nm,
(ε 15,190) (pH 7), 260.0 nm, (ε 13,116) (pH 11); IR (neat): 2112.32 cm−1
(azide); 1H NMR (DMSO-D6) δ 1.76 (d, J = 0.5 Hz, 3 H, 5-CH3), 3.56–3.64
(m, 2 H, 5ꢁ-Hs), 4.64–4.67 (m, 1 H, 4ꢁ-H), 5.25 (t, J = 2.5 Hz, 1 H, 5ꢁ-OH,
D2O exch), 5.73 (t, J = 1.75 Hz, 1 H, 2ꢁ-H), 6.86 (dd, J = 1.75, 3.25 Hz, 1 H,
1ꢁ-H), 7.86 (d, J = 1.5 Hz, 1 H, 6-H), 11.35 (bs, 1 H, NH, D2O exch); 13C
NMR (CD3OD) δ 11.09, 60.80, 61.06, 74.82, 82.41, 89.10, 110.21, 136.80,
151.22, 165.00; MS (ESI) m/z 288 (M+Na+); Anal. calcd for C10H11N5O4:
C, 45.28; H, 4.18; N, 26.41; Found C, 45.06; H, 4.44; N, 26.17.
3 -Azido-2 ,3 -didehydro-2 ,3 -dideoxy-β-D-ribofuranosylcytosine (19).
Using the same procedure as described for 18, compound 17 (0.20 g, 0.57
mmol) was treated with saturated methanolic ammonia (20 mL) obtained

1720
S. Gadthula et al.
the title nucleoside 19 (0.12 g, 82%) as a white solid. Rf = 0.35 (CH2Cl2/
MeOH, 10:1); mp 123–125◦C; [α]D −102.2◦ (c, 0.6, MeOH); UV (MeOH)
25
λmax 265.0 nm (ε 16,333) (pH 7), 268.0 nm (ε 2586) (pH 2) 265.0 nm (ε
1
16,233) (pH 11); IR (neat): 2124.26 cm−1 (azide); H NMR (CD3OD) δ
3.72 (dd, J = 2.5, 13 Hz, 1 H, 5ꢁ-Ha), 3.77 (dd, J = 2, 13 Hz, 1 H, 5ꢁ-Hb),
4.64–4.66 (m, 1 H, 4ꢁ-H), 5.62 (t, J = 2 Hz, 1 H, 1ꢁ-H), 5.89 (d, J = 7 Hz,
1 H, 5-H), 7.05 (dd, J = 1.25, 2.5 Hz, 1 H, 2ꢁ-H), 8.10 (d, J = 7 Hz, 1 H, 6-
H); 13C NMR (CD3OD) δ 60.58, 83.61, 88.93, 94.69, 108.16, 142.30, 144.02,
157.27, 166.40; Anal. calcd for C9H10N6O3, 0.1 H2O: C, 42.89; H, 4.08; N,
33.35; Found C, 42.95; H, 4.04; N, 32.98.
3 -Azido-3 -deoxy-β-D-ribofuranosylthymine (20). Using the same pro-
cedure as described for 18, compound 6 (0.15 g, 0.39 mmol) was treated
with saturated methanolic ammonia (15 mL) produced the title compound
20[21] (0.087 g, 79%) as a white solid. Rf = 0.34 (CH2Cl2/MeOH, 10:1); mp
56–58◦C; [α]D 62.2◦ (c, 0.47, MeOH); UV (MeOH) λmax 266.0 nm.
25
3 -Azido-3 -deoxy-β-D-ribofuranosylcytosine (21). Using the same pro-
cedure as described for 18, compound 7 (0.30 g, 0.58 mmol) was treated
with saturated methanolic ammonia (30 mL) produced the title compound
21 (0.12 g, 75%) as a white solid. Rf = 0.30 (CH2Cl2/MeOH, 10:1); mp 70–
72◦C; [α]D25 99.3◦ (c, 0.32, MeOH); UV (MeOH) λmax 270.0 nm (ε 11,086)
(pH 7), 270.0 nm (ε 10,523) (pH 11) 271.0 nm (ε 10,953) (pH 2); 1H N MR
(DMSO-d6) δ 3.55–3.59 (m, 1 H, 5ꢁ-Ha), 3.66–3.70 (m, 1 H, 5ꢁ-Hb), 3.89–3.92
(m, 1 H, 4ꢁ-H), 3.95 (t, J = 6 Hz, 1 H, 3ꢁ-H), 4.35 (q, J = 5 Hz, 1 H, 2ꢁ-H),
5.24 (t, J = 5.5 Hz, 1 H, 5ꢁ-OH, D2O exch), 5.72 (d, J = 7.5 Hz, 1 H, 5-H),
5.77 (d, J = 4 Hz, 1 H, 1ꢁ-H), 6.12 (d, J = 5.5 Hz, 1 H, 2ꢁ-OH, D2O exch),
7.17 (d, J = 25 Hz, 2 H, NH2, D2O exch), 7.82 (d, J = 7.5 Hz, 1 H, 6-H); 13
C
NMR (DMSO-d6) δ 61.05, 74.86, 81.83, 89.87, 94.59, 141.86, 142.33, 155.78,
166.07; ES HRMS calcd C9H12N6O4 [M+H+] 269.0999, found 269.0972;
Anal. calcd for C9H12N6O4 0.3 H2O: C, 39.50; H, 4.64; N, 30.71; Found C,
39.93; H, 4.64; N, 30.33.
3 -Azido-2 -O-acetyl-5 -O-benzoyl-3 -deoxy-β-D-ribofuranosyl-6-chloro-
9H-purine (22). Using the same procedure as described for 6, compound 5
(1.27 g, 3.50 mmol) was condensed with 6-chloropurine (0.62 g, 4.0 mmol)
using BSA (1.10 mL, 4.50 mmol) and TMSOTf (0.68 mL, 3.80 mmol) for
4 h to produce compound 22 (1.44 g, 90%) as a white foam. Rf = 0.6
(EtOAc/hexane, 4:6); mp 113–114◦C; [α]D 12.2◦ (c, 0.72, CHCl3); UV
25
(MeOH) λmax 264.0 nm; IR (neat): 2114.36 cm−1 (azide); 1H NMR (CDCl3)
δ 2.22 (s, 3 H, 2ꢁ-OAc), 4.40–4.43 (m, 1 H, 4ꢁ-H), 4.58 (dd, J = 4, 13 Hz,
1H, 5ꢁ-Ha), 4.78 (dd, J = 3.25, 12.5 Hz, 1H, 5ꢁ-Hb), 4.93 (dd, J = 6, 7.5
Hz, 1 H, 3ꢁ-H), 6.09–6.13 (m, 2 H, 1ꢁ-H, and 2ꢁ-H), 7.41–7.44 (m, 2 H,

Synthesis and Anti-HIV Activity of Nucleosides
1721
Ar-H), 7.57–7.62 (m, 1 H, Ar-H), 7.94–7.96 (m, 2 H, Ar-H), 8.17 (s, 1 H,
8-H), 8.52 (s, 1 H, 2-H); 13C NMR (CDCl3) δ 20.44, 60.07, 62.58, 74.97,
80.48, 88.07, 128.55, 129.05, 129.56, 132.41, 133.61, 144.58, 150.82, 151.57,
152.14, 166.01, 169.79; ES HRMS calcd C19H16ClN7O5 [M+H+] 458.0980,
found 458.1075.
3 -Azido-5 -O-benzoyl-3 -deoxy-β-D-ribofuranosyl-6-chloro-9H-purine
(23). To a solution of compound 22 (0.73 g, 1.60 mmol) in methanol
(40 mL) was added a saturated methanolic ammonia (6 mL) at 0◦C and
stirred at the same temperature for 10 min. The solvent was evaporated to
dryness under reduced pressure and the residue was purified by silica gel
column chromatography with 35% EtOAc/hexane as eluent, afforded the
compound 23 (0.57 g, 86%) as a white foam. Rf = 0.50 (EtOAc/hexane,
4:6); mp 142–144◦C; [α]D 20.6◦ (c,1.0, CHCl3); UV (MeOH) λmax 263.0
25
nm; IR (neat): 2113.03 cm−1 (azide); 1H NMR (CDCl3) δ 4.12 (bs, 1 H, 2ꢁ-
OH), 4.50–4.53 (m, 1 H, 4ꢁ-H), 4.58 (dd, J = 3.5, 13 Hz, 1H, 5ꢁ-Ha), 4.67 (t,
5.5 Hz, 1 H, 3ꢁ-H), 4.74 (dd, J = 3.5,12 Hz, 1 H, 5ꢁ-Hb), 5.10–5.12 (m, 1 H,
2ꢁ-H), 5.99 (d, J = 4 Hz, 1 H, 1ꢁ-H), 7.35–7.38 (m, 2 H, Ar-H), 7.53–7.57
(m, 1 H, Ar-H), 7.83–7.86 (m, 2 H, Ar-H,), 8.24 (s, 1 H, 8-H), 8.55 (s, 1 H,
2 H, 2-H); 13C NMR (CDCl3) δ 62.30, 63.19, 75.17, 81.23, 90.59, 128.55,
128.89, 129.50, 132.10, 133.68, 144.49, 150.58, 151.38, 151.86, 166.06; ES
HRMS calcd C17H14ClN7O4 [M+Na+] 438.0693, found 438.0753.
3 -Azido-2 -O -triflyl-5 -O -benzoyl-3 -deoxy-β-D-ribofuranosyl-9H -6-
chloropurine (24). Using the same procedure as described for 12, trifluoro-
methanesulfonic anhydride (0.25 mL, 1.50 mmol) was added dropwise to
a stirred solution of compound 23 (0.46 g, 1.10 mmol) and anhydrous
pyridine (0.5 mL, 6.0 mmol) in anhydrous CH2Cl2 (20 mL) under similar
reaction conditions obtained compound 24 (0.51 g, 84%) as a light red
color solid. Rf = 0.5 (EtOAc/hexane, 4:6); UV (MeOH) λmax 263.0 nm; IR
(neat): 2122.90 cm−1 (azide); 1H NMR (CDCl3) δ 4.44-4.47 (m, 1 H, 4ꢁ-H),
4.65 (dd, J = 3.25, 12.75 Hz, 1 H, 5ꢁ-Ha), 4.79 (dd, J = 3, 13 Hz, 1 H, 5ꢁ-Hb),
5.12 (dd, J = 5.5, 8.25 Hz, 1 H, 3ꢁ-H), 6.17 (dd, J = 2, 5.5 Hz, 1 H, 2ꢁ-H),
6.20 (d, J = 2.5 Hz, 1 H, 1ꢁ-H), 7.40–7.43 (m, 2 H, Ar-H), 7.59–7.63 (m, 1 H,
Ar-H), 7.86 (dd, J = 1.5, 8 Hz, 2 H, Ar-H), 8.21 (s, 1 H, 8-H), 8.44 (s, 1 H,
2-H); 13C NMR (CDCl3) δ 59.92, 61.43, 80.50, 85.45, 88.04, 128.63, 128.74,
129.53, 132.54, 133.87, 144.26, 150.38, 152.24, 152.35, 165.93.
COMPOUNDS 26 AND 27
Using the same procedure as described for 15, compound 24 (0.48 g,
0.87 mmol) was treated with TBAF/THF (1 M) solution (0.87 mL, 0.87
mmol) in anhydrous THF, after usual work up and purification obtained

1722
S. Gadthula et al.
compound 26 (0.18 g, 84%) as a colorless oil (0.11 g, 82%) and 6-
chloropurine 27 as a yellow solid, respectively. Compound 26: Rf = 0.7
(EtOAc/hexane, 1:9); MS (ESI) m/z (M+Na) +266; IR (neat): 2122.72
cm−1 (azide); 1H NMR (CDCl3) δ 5.25 (s, 2 H), 6.40 (d, J = 2 Hz, 1 H), 7.38–
7.44 (m, 3 H), 7.53–7.57 (m, 1 H), 8.03–8.06 (m, 2 H); 13C NMR (CDCl3) δ
55.50, 104.98, 126.13, 128.37, 129.80, 133.13, 138.02, 143.36, 165.35, 166.19.
3 -Azido-2 -O-acetyl-5 -O-benzoyl-3 -deoxy-β-D-ribofuranosyl-N6 -ben-
zoyl Adenine (29). To a stirred solution of compound 5 (1.45 g, 4.0 mmol)
and N6-benzoyladenine (1.20 g, 5.0 mmol) in anhydrous acetonitrile (35
mL) was added 1 M stannic chloride solution in dichloromethane (9 mL,
9 mmol) at room temperature and the mixture was stirred for 2 h at same
temperature. The reaction was quenched with saturated aqueous solution
of NaHCO3 and stirred until the evolution of CO2 ceased. The reaction mix-
ture was diluted with EtOAc (75 mL) and the organic phase was separated
and the aqueous phase was back extracted with an additional amount of
EtOAc (100 mL). The combined organic phases were washed successively
with a saturated aqueous solution of NaHCO3 (40 mL) H2O (45 mL), dried
(Na2SO4) and evaporated to dryness under reduced pressure. The residue
was purified by silica gel column chromatography with dichloromethane/
MeOH (100:1) as eluent to give nucleoside 29[20] (1.54 g, 71%) as a white
foam. mp 108–110◦C; [α]D25 6.6◦ (c, 0.68, CHCl3); UV (MeOH) λmax 279.0
1
nm; IR (neat): 2113.39 cm−1 (azide); H NMR (CDCl3) δ 2.21 (s, 3 H, 2ꢁ-
OAc), 4.39–4.42 (m, 1 H, 4ꢁ-H), 4.58 (dd, J = 4.5, 12.5 Hz, 1 H, 5ꢁ-Ha),
4.77 (dd, J = 3.5, 12.5 Hz, 1 H, 5ꢁ-Hb), 4.98 (dd, J = 6, 7 Hz, 1 H, 3ꢁ-H),
6.11 (d, J = 3.5 Hz, 1 H, 1ꢁ-H), 6.14 (dd, 3.25, 6 Hz, 1 H, 2ꢁ-H), 7.40–
7.44 (m, 2 H, Ar-H), 7.50 (t, J = 8 Hz, 2 H, Ar-H), 7.54–7.61 (m, 2 H,
Ar-H), 7.97–8.02 (m, 4 H, Ar-H), 8.07 (s, 1 H, 8-H), 8.61 (s, 1 H, 2-H), 9.15
(bs, 1 H, N6HCOPh); 13C NMR (CDCl3) δ 20.50, 60.20, 62.89, 75.10, 80.29,
87.90, 123.73, 127.93, 128.58, 128.90, 129.16, 129.68, 132.91, 133.46, 133.57,
142.27, 149.84, 151.25, 152.89, 164.64, 166.11, 169.85.
3 -Azido-5 -O-benzoyl-3 -deoxy-β-D-ribofuranosyl-N6-benzoyl Adenine
(30). To a solution of compound 29 (1.39 g, 2.55 mmol) in methanol
(30 mL) was added a saturated methanolic ammonia (10 mL) at 0◦C
and stirred at the same temperature for 1 h. The solvent was evaporated
to dryness under reduced pressure and the residue was purified by silica
gel column chromatography with dichloromethane/MeOH (100-2 mL) as
eluent, afforded the compound 30 (0.96 g, 75%) as a white foam. mp 102–
104◦C; [α]D25 4.1◦ (c, 0.54, CHCl3); UV (MeOH) λmax 279.0 nm; IR (neat):
1
2110.31 cm−1 (azide); H NMR (CDCl3) δ 4.49–4.53 (m, 1 H, 4ꢁ-H), 4.55
(dd, J = 4, 12.5 Hz, 1 H, 5ꢁ-Ha), 4.60 (t, J = 5 Hz, 1 H, 3ꢁ-H), 4.71 (dd, J =
3.5, 12.5 Hz, 1 H, 5ꢁ-Hb), 5.00 (bs, 1 H, 2ꢁ-OH), 5.15 (t, J = 4.5 Hz, 1 H,

Synthesis and Anti-HIV Activity of Nucleosides
1723
2ꢁ-H), 6.01 (d, J = 5 Hz, 1 H, 1ꢁ-H), 7.36 (t, J = 8 Hz, 2 H, Ar-H), 7.52–7.55
(m, 3 H, Ar-H), 7.63 (t, J = 7.5 Hz, 1 H, Ar-H), 7.90 (dd, J = 1, 8.5 Hz,
2 H, Ar-H), 7.99 (d, J = 2.5 Hz, 2 H, Ar-H), 8.09 (s, 1 H, 8-H), 8.62 (s, 1 H,
2-H), 9.07 (bs, 1 H, N6HCOPh); 13C NMR (CDCl3) δ 62.09, 63.70, 75.00,
80.65, 89.67, 122.74, 127.91, 128.55, 128.89, 129.15, 129.16, 129.62, 133.03,
133.25, 133.52, 142.23, 149.16, 151.02, 152.40, 166.13; ES HRMS (M+H)+
calcd C24H20N8O5, 501.1636, found 501.1703.
3 -Azido-2 -O-triflyl-5 -O-benzoyl-3 -deoxy-β-D-ribofuranosyl-N6 -ben-
zoyl Adenine (31). Using the same procedure as described for 12, trifluoro-
methanesulfonic anhydride (0.43 mL, 2.60 mmol) was added dropwise to
a stirred solution of compound 30 (0.65 g, 1.30 mmol) and anhydrous
pyridine (0.5 mL, 6.0 mmol) in anhydrous CH2Cl2 (25 mL) under similar
reaction conditions obtained compound 31 (0.74 g, 90%) as a pale yellow
solid. Rf = 0.6 (CH2Cl2/MeOH, 10:1 mL); UV (MeOH) λmax 279.0 nm; IR
1
(neat): 2128.52 cm−1 (azide); H NMR (CDCl3) δ 4.42–4.45 (m, 1 H, 4ꢁ-
H), 4.62 (dd, J = 3.5, 13 Hz, 1 H, 5ꢁ-Ha), 4.79 (dd, J = 3, 13 Hz, 1 H,
5ꢁ-Hb), 5.23 (dd, J = 5.5, 8.5 Hz, 1 H, 3ꢁ-H), 6.19 (d, J = 2 Hz, 1 H,
1ꢁ-H), 6.22 (d, J = 5.5 Hz, 1 H, 2ꢁ-H), 7.39–7.43 (m, 2 H, Ar-H), 7.52–
7.59 (m, 3 H, Ar-H), 7.61–7.63 (m, 1 H, Ar-H), 7.90–7.92 (m, 2 H, Ar-H),
8.00 (d, J = 7.5 Hz, 2 H, Ar-H), 8.09 (s, 1 H, 8-H), 8.55 (s, 1 H, 2-H),
8.97 (bs, 1 H, N6HCOPh); 13C NMR (CDCl3) δ 60.03, 61.79, 80.13, 85.83,
87.96, 123.66, 127.91, 128.59, 128.89, 128.98, 129.63, 133.05, 133.31, 133.70,
142.21, 150.07, 150.82, 153.04, 164.51, 165.99.
3 -Azido-2 ,3 -didehydro-2 ,3 -dideoxy-β-D-ribofuranosyladenine (28)
and 3 -Azido-3 -deoxy-β-D-ribofuranosyladenine (34). To a stirred solution
of compound 31 (0.68 g, 1.10 mmol) in MeOH (30 mL) was added
K2CO3 (0.30 g, 2.17 mmol) at room temperature. After stirring for 6 h,
the reaction was neutralized with acetic acid (0.025 mL). After removal of
the solvent the residue was purified by silica gel column chromatography
with MeOH/dichloromethane (2:100–4:100 mL) obtained compound 28
(0.09 g, 30%) as a white solid and then compound 34 (0.07 g, 22%) as a
spongy solid. Compound 28: mp 128–130◦C; [α]D −96.5◦ (c, 0.7, MeOH);
25
UV (MeOH) λmax 258.0 nm (ε 21,726) (pH 7), 258.0 nm (ε 20,376) (pH
11), (unstable in pH 2); IR (neat): 2197.05 cm−1 (azide); 1H NMR (CDCl3)
δ 3.75 (dd, J = 2.5, 12.5 Hz, 1 H, 5ꢁ-Ha), 3.79 (dd, J = 2.5, 13 Hz, 1 H,
5ꢁ-Hb), 4.77–4.79 (m, 1 H, 4ꢁ-H), 5.83 (t, J = 2 Hz, 1 H, 1ꢁ-H), 7.09 (t, J =
2 Hz, 1 H, 2ꢁ-H), 8.23 (s, 1 H, 2-H), 8.43 (s, 1 H, 8-H); 13C NMR (CDCl3)
δ 61.56, 84.26, 86.42, 108.81, 119.15, 139.87, 143.17, 149.51, 153.04, 156.47;
Anal. calcd for C10H10N8O2: C, 43.80; H, 3.68; N, 40.86; Found C, 43.54; H,
3.94; N, 40.61. Compound 34: mp 210–213◦C, (lit.[22] mp 208–212), [α]D
25
19.5◦ (c, 0.2, MeOH); UV (MeOH) λmax 258 nm.

1724
S. Gadthula et al.
3 -Azido-2 ,3 -didehydro-2 ,3 -dideoxy-β-D-ribofuranosyladenine (28).
Using the same procedure as described for 15, compound 31 (0.25 g, 0.39
mmol) was treated with TBAF/THF (1 M) solution (0.39 mL, 0.39 mmol)
in anhydrous THF (15 mL), after being stirred for 45 min, the solvent was
removed under reduced pressure and the resulting residue was treated with
saturated methanolic ammonia (20 mL) for 20 h. After removal of the
solvent the crude was purified by silica gel column chromatography with
dichloromethane/MeOH (100:3 mL) afforded the desired nucleoside 28
(0.08 g, 75%) as a white solid. The mp, UV and NMR spectral data were
similar to the previously obtained compound 28.
3 -Azido-3 -deoxy-β-D-ribofuranosyladenine (34). Using the same pro-
cedure as described for 18, compound 29 (0.35 g, 0.65 mmol) was treated
with saturated methanolic ammonia (25 mL) obtained the title compound
34 (0.17 g, 87%) as a white spongy solid. The spectral data was similar to
the previously obtained compound 34.
3 -Azido-2 -O-acetyl-5 -O-benzoyl-3 -deoxy-β-D-ribofuranosyl-N2-acetyl-
6-O-diphenylcarbamoylguanine (36). Using the same procedure as described
for 6, compound 5 (0.73 g, 2.0 mmol) was condensed with N2-acetyl-6-O-
diphenylcarbamoyl guanine[23] (0.85 g, 2.20 mmol) using BSA (1.1 mL,
4.50 mmol) and TMSOTf (0.40 mL, 2.20 mmol) for 4 h to produce com-
pound 36 (1.02 g, 74%) as a white foam. Rf = 0.6 (CH2Cl2/MeOH, 10:1);
mp 110–112◦C; [α]D −2.4◦ (c, 0.58, CHCl3); UV (MeOH) λmax 277.0 nm;
25
1
IR (neat): 2117.40 cm−1 (azide); H NMR (CDCl3) δ 2.21 (s, 6 H, NHAc,
and 2ꢁ-OAc), 4.34–4.42 (m, 1 H, 4ꢁ-H), 4.62 (dd, J = 5, 13 Hz, 1 H, 5ꢁ-
Ha), 4.71 (dd, J = 3.5, 13 Hz, 1 H, 5ꢁ-Hb), 5.30 (s, 1 H, 3ꢁ-H), 5.91 (d,
J = 1.5 Hz, 1 H, 1ꢁ-H), 5.95 (dd, J = 1.5, 6 Hz, 1 H, 2ꢁ-H), 7.22–7.51 (m,
13 H, Ar-H), 7.79 (s, 1 H, 8-H), 7.86–7.88 (m, 2 H, Ar-H), 8.57 (bs, 1 H, 2-
NHAc); 13C NMR (CDCl3) δ 20.63, 25.00, 53.49, 59.52, 63.23, 76.13, 80.37,
88.75, 121.22, 126.51, 128.32, 129.26, 129.47, 129.57, 133.17, 143.56, 150.08,
151.74, 153.55, 156.03, 166.11, 170.04; Anal. calcd for C34H29N9O8: C, 59.04;
H, 4.23; N, 18.23; Found C, 59.05; H, 4.27; N, 18.02.
3 -Azido-5 -O -benzoyl-3 -deoxy-β-D-ribofuranosyl-N2 -acetyl-guanine
(37). Using the same procedure as described for 9, compound 36 (1.0 g,
1.45 mmol) was deprotected with hydrazine hydrate (0.7 mL, 12.0 mmol) in
acetic acid–pyridine (10 mL, 1:4 v/v) to give compound 37 (0.51 g, 78%) as
a white solid. Rf = 0.4 (CH2Cl2/MeOH, 10:1); mp 98–100◦C; [α]D 14.7◦
25
(c, 0.58, CHCl3); UV (MeOH) λmax 278.0 nm, 257.0 nm; IR (neat): 2110.62
cm−1 (azide); 1H NMR (CDCl3) δ 2.41 (s, 3 H, 2-NHAc), 4.32 (d, J = 5.5 Hz,
1 H, 5ꢁ-Ha), 4.48–4.52 (m, 2 H, 5ꢁ-Hb, and 4ꢁ-H), 5.20 (dd, J = 10, 12.5 Hz,
1 H, 3ꢁ-H), 5.58 (t, J = 6.5 Hz, 1 H, 2ꢁ-H), 5.74 (d, J = 7 Hz, 1 H, 1ꢁ-H), 6.85

Synthesis and Anti-HIV Activity of Nucleosides
1725
(bs, 1 H, 2ꢁ-OH), 7.44 (t, J = 8 Hz, 2 H, Ar-H) 7.48 (s, 1 H, 8-H), 7.56–7.60
(m, 1 H, Ar-H), 7.99 (dd, J = 1.5, 8 Hz, 2 H, Ar-H), 9.70 (s, 1 H, 2-NHAc),
11.92 (bs, 1 H, 6-OH); 13C NMR (CDCl3) δ 24.25, 62.93, 65.38, 73.65, 80.84,
91.27, 121.33, 128.65, 129.18, 129.74, 133.79, 139.42, 147.02, 147.26, 154.76,
167.77, 173.04; ES HRMS (M+H)+ calcd C19H18N8O6, 453.1270, found
453.1208.
3 -Azido-2 -O-triflyl-5 -O-benzoyl-3 -deoxy-β-D-ribofuranosyl-N2-acetyl
Guanine (38). Using the same procedure as described for 12, trifluoro-
methanesulfonic anhydride (0.25 mL, 1.40 mmol) was added drop wise
to a stirred solution of compound 37 (0.32 g, 0.70 mmol) and anhydrous
pyridine (0.5 mL, 6.0 mmol) in anhydrous CH2Cl2 (20 mL) under similar
reaction conditions obtained compound 38 (0.33 g, 81%) as a yellow solid.
Rf = 0.5 (CH2Cl2/MeOH, 10:1 mL); UV (MeOH) λmax 278.0 nm, 256.0 nm;
1H NMR (CDCl3) δ 2.27 (s, 3 H, 2-NHAc), 4.42–4.46 (m, 1 H, 4ꢁ-H), 4.59
(dd, J = 5, 12 Hz, 1 H, 5ꢁ-Ha), 4.99 (dd, J = 6, 12 Hz, 1 H, 3ꢁ-H), 5.26–5.30
(m, 1 H, 5ꢁ-Hb), 5.89 (d, J = 5.5 Hz, 1 H, 2ꢁ-H), 6.07 (d, J = 2 Hz, 1 H,
1ꢁ-H), 7.44 (t, J = 8 Hz, 2 H, Ar-H), 7.59–7.62 (m, 1 H, Ar-H), 7.69 (s, 1 H,
8-H), 7.97–7.99 (m, 2 H, Ar-H); 13C NMR (CDCl3) δ 24.28, 60.12, 62.73,
79.65, 87.30, 88.38, 121.98, 128.54, 128.94, 129.62, 133.73, 138.51, 147.95,
148.30, 155.99, 166.50, 172.94.
3 -Azido-2 ,3 -didehydro-2 ,3 -dideoxy-β-D-ribofuranosylguanine (41).
Using the same procedure as described for 28, compound 38 (0.30 g, 0.51
mmol) was treated with TBAF/THF (1 M) solution (0.51 mL, 0.51 mmol)
in anhydrous THF (15 mL), after being stirred for 45 min, the solvent was
removed under reduced pressure and the resulting residue was treated with
saturated methanolic ammonia (25 mL) for 20 h. After removal of the
solvent the crude was purified by silica gel column chromatography with
MeOH/dichloromethane (12%) afforded the desired nucleoside 41 (0.11 g,
72%) as a white solid. mp 180–182◦C; [α]D −86.5◦ (c, 0.34, DMSO); UV
25
(MeOH) λmax 250.0 nm (ε 15,551) (pH 7), 253.0 nm (ε 12,356) (pH 11)
1
(unstable in pH 2). H NMR (DMSO-d6) δ 3.53–3.57 (m, 2 H, 5ꢁ-H), 4.71
(t, J = 2.5 Hz, 1 H, 4ꢁ-H), 5.12 (bs, 1 H, 5ꢁ-OH, D2O exch), 5.88 (t, J =
2 Hz, 1 H, 1ꢁ-H), 6.53 (bs, 2 H, 2-NH2, D2O exch), 6.71 (t, J = 2.5 Hz, 1 H,
2ꢁ-H), 7.89 (s, 1 H, 8-H); 13C NMR (DMSO-d6) δ 61.63, 84.09, 85.86, 108.75,
116.83, 136.13, 143.10, 151.23, 154.25, 157.20; Anal. calcd for C10H10N8O3
1.3 H2O: C, 38.29; H, 4.05; N, 35.72; Found C, 38.44; H, 4.02; N, 35.46.
3 -Azido-3 -deoxy-β-D-ribofuranosylguanine (42). Using the same pro-
cedure as described for 18, compound 36 (0.30 g, 0.63 mmol) was treated
with saturated methanolic ammonia (30 mL) obtained the title nucleoside
42 (0.16 g, 83%) as a white solid. Rf = 0.25 (CH2Cl2/MeOH, 10:1); mp

1726
S. Gadthula et al.
246–248◦C; [α]D 56.9◦ (c, 0.37, DMSO); UV (MeOH) λmax 250.0 nm (ε
25
1
11,428) (pH 7), 256.0 nm (ε 9760) (pH 11), (unstable in pH 2); H N MR
(DMSO-d6) δ 3.56 (dd, J = 3.5, 9 Hz, 1 H, 5ꢁ-Ha), 3.63 (dd, J = 4, 12 Hz, 1 H,
5ꢁ-Hb), 3.92 (q, J = 4 Hz, 1 H, 4ꢁ-H), 4.25 (dd, J = 4, 5.5 Hz, 1 H, 3ꢁ-H), 4.82
(q, J = 5 Hz, 1 H, 2ꢁ-H), 5.22 (t, J = 5.5 Hz, 1 H, 5ꢁ-OH, D2O exch), 5.72 (d,
J = 6.5 Hz, 1 H, 1ꢁ-H), 6.21 (d, J = 5.5 Hz, 1 H, 2ꢁ-OH, D2O exch), 6.52 (bs,
2 H, 2-NH2, D2O exch), 7.96 (s, 1 H, 8-H), 10.67 (s, 1 H, 1-NH, D2O exch);
13C NMR (DMSO-d6) δ 61.88, 62.48, 74.73, 82.81, 86.94, 117.18, 136.00,
151.76, 154.23, 157.20; ES HRMS (M+H)+ calcd C19H18N8O6, 453.1270,
found 453.1208. Anal. calcd for C10H12N8O4 1.0 H2O: C, 36.81; H, 4.32; N,
34.34; Found C, 36.96; H, 4.34; N, 34.12.
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