A simple synthesis of 2-deoxy-3-thioinosine and its phosphorothioamidite

Article abstract of DOI:10.1055/s-0032-1317713

5-O-{[Bis(4-methoxyphenyl)(phenyl)methyl])-2-deoxy-3-thioinosine and its S-phosphorothioamidite were prepared in five and six steps, respectively, from commercially available 2-deoxyinosine. The key 3-thio intermediate was synthesized by two sequential configuration inversions: a one-pot oxidation/reduction reaction and an S reaction. This intermediate was readily converted into the target compound with a high yield. Compared with other methods, this synthetic strategy has the advantages of brief reaction steps, a relatively high overall yield, and regioselectivity for the configuration inversions. The products might be useful as intermediates for the preparation of new functionalized nucleosides. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0032-1317713

106▌
PAPER
paper
A Simple Synthesis of 2′-Deoxy-3′-Thioinosine and Its Phosphorothioamidite
2′-Deoxy-3′-Thioinosine and Its Phosphorothioamidite
Qianfu Luo,* Renjun Cheng, Qiu Wang, Shuming Bao
Key Lab for Advanced Materials and Institute of Fine Chemicals, East China University of Science and Technology, Shanghai 200237,
P. R. of China
Fax +86(021)64250597; E-mail: luoqf@ecust.edu.cn
Received: 10.07.2012; Accepted after revision: 09.11.2012
nucleotides to study the mechanism of a ribozyme
Abstract: 5′-O-{[Bis(4-methoxyphenyl)(phenyl)methyl])-2′-de-
reaction in Tetrahymena. Inspired by this design, we de-
oxy-3′-thioinosine and its S-phosphorothioamidite were prepared in
veloped an efficient method for the synthesis of a new ino-
sine-containing 2′-deoxy-3′-thionucleoside analogue 6,
five and six steps, respectively, from commercially available 2′-de-
oxyinosine. The key 3′-thio intermediate was synthesized by two
sequential configuration inversions: a one-pot oxidation/reduction together with its phosphorothioamidite 7, as shown in Fig-
reaction and an SN2 reaction. This intermediate was readily convert-
ed into the target compound with a high yield. Compared with other
methods, this synthetic strategy has the advantages of brief reaction
any the four base pairs associated with the hybridization
steps, a relatively high overall yield, and regioselectivity for the
configuration inversions. The products might be useful as interme-
ure 1. This product can act as a general base that can pair
with any of the four nucleobases10 and it can also match
effect in any position.11 Furthermore, the design of the
synthesis of 6 provides an alternative method for the syn-
thesis of nucleoside analogues. We hope that these prod-
ucts will be useful as intermediates and building blocks
for the preparation of other functionalized nucleosides.
diates for the preparation of new functionalized nucleosides.
Key words: stereoselective synthesis, heterocycles, medicinal
chemistry, nucleosides
O
The preparation and functionalization of oligonucleotide
analogues have attracted an increasing degree of interest
because of the variety of potential applications of such
compounds. Oligonucleotide analogues have been widely
used, for example, in exploring the catalytic mechanisms
of enzymes and ribozymes,1 in studying physical and bio-
logical properties of nucleic acids and RNA,2 in control-
ling gene expression,3 in identifying catalytic metal ions,4
and in probing hydrogen-bonding interactions.5 The bio-
logical, biochemical, physical, and medicinal importance
of oligonucleotide analogues has fostered the develop-
ment of various nucleoside modifications.In general, the
two primary strategies that are used to prepare structural
modifications of nucleotide analogues involve modifica-
tion of the nucleobase or modification of the sugar resi-
due, respectively. A classical method for modification of
the sugar residues involves the removal or replacement of
the oxygen atom in the 3′-position with a larger, more-
electropositive, sulfur atom.6 By this approach, a variety
of 3′-S-modified nucleosides containing diverse function-
alized bases have been prepared as building blocks and in-
termediates for oligonucleotides. These compounds have
been widely used to mimic RNA, to investigate the mech-
anistic properties of ribozymes, and to increase the resis-
tance of ribozymes to degradation by nucleases.7
However, 3′-thio nucleoside analogues that contain
inosine-derived bases have received little attention.8
N
NH
N
N
DMTO
O
H
H
H
H
H
6
SH
OMe
O
N
N
N
NH
MeO
O
O
N
H
H
H
H
H
S
P
O
NC
7
Figure 1 5′-O-{[Bis(4-methoxyphenyl)(phenyl)methyl])-2′-deoxy-
3′-thioinosine 6 and its S-phosphorothioamidite 7
In our synthetic route to the required compounds, the
preparation of intermediate 3 (Scheme 1) through inver-
sion of the configuration of the hydroxy group at the 3′-
position of the sugar moiety is vital. According to the lit-
erature, there are several methods for realizing a configu-
rational inversion of a 3′-hydroxy group. First, we
examined the approach reported by Challa and Bruice12
for the synthesis of N2-isobutyryl-2′-deoxy-xylo-guano-
sine. Treatment 2′-deoxyinosine (1) with benzoyl chloride
in anhydrous pyridine at room temperature gave 5′-O-
benzoyl-2′-deoxyinosine (Scheme 1, path a). Treatment of
Recently, Piccirilli and co-workers9 reported the synthesis
and biochemical applications of 2′-O-methyl-3′-thio-
guanosine. The product was incorporated into oligo-
SYNTHESIS 2013, 45, 0106–0110
Advanced online publication: 11.12.2012
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0032-1317713; Art ID: SS-2012-H0579-OP
© Georg Thieme Verlag Stuttgart · New York

PAPER
2′-Deoxy-3′-Thioinosine and Its Phosphorothioamidite
107
this product with 1.5 equivalents of triflic anhydride in di- we opted to perform the configuration inversion at C3′ by
chloromethane containing 10% pyridine gave 2′-deoxy- means of an oxidation–reduction sequence13 (Scheme 1,
xylo-inosine, which has an inverted configuration at the path c).
3′-position. Although we obtained a small amount of this
required intermediate, we did not take this route any fur-
ther because of the low yields and the laborious proce-
dures involved in chromatographic purifications.
The complete preparation began with commercially avail-
able 2′-deoxyinosine (1). Although oligonucleotide syn-
theses involving 5′-silyl protecting groups are known, we
choose the bis(4-methoxyphenyl)(phenyl)methyl (4,4′-di-
We then tried another synthetic route developed by methoxytrityl; Dmt) protecting group for the 5′-O-hy-
Piccirilli and coworkers9 (Scheme 1, path b). In the pres- droxyl group, instead of a tert-butyl(dimethyl)silyl or tert-
ence of 4-(N,N-dimethylamino)pyridine, the reaction of butyl(diphenyl)silyl group, which would have to have
5′-O-[tert-butyl(diphenyl)silyl]-2′-deoxyinosine with tri- been deprotected by treatment with tetrabutylammonium
flic chloride in dichloromethane at 0 °C gave the 3′-tri- fluoride during subsequent steps. Experiments showed
flate intermediate. Subsequent SN2 substitution with protection with a Dmt group ensured regioselectivity and
sodium bromide in acetone resulted in a product with an prevented partial deprotection during oxidation by Dess–
inverted configuration at the 3′-position. However, the Martin periodinane [1,1,1-triacetoxy-1,1-dihydro-1,2-
conversion was very low, even after prolonged reaction benziodoxol-3(1H)-one]. After reduction by sodium bo-
times. This might have been due to the low reactivity and rohydride propan-2-ol, the desired intermediate product 3,
low solubility of 5′-O-[tert-butyl(diphenyl)silyl]-3′-O-tri- with the inverted configuration, was obtained in high
flyl-2′-deoxy-xylo-inosine in the reaction solvent. Finally yield and with high regioselectivity.
O
N
O
N
N
N
N
N
NH
NH
HO
BzO
HO
a'
O
O
H
H
H
H
H
H
H
H
a
OH
O
N
O
N
N
N
NH
NH
O
N
HO
N
N
N
N
DmtO
DmtO
NH
O
O
c'
c
H
H
H
Scheme 2
HO
H
H
H
H
H
OH
O
H
H
3
2
H
H
O
N
OH
O
N
1
N
N
N
N
NH
NH
TBDPSO
TBDPSO
b1
O
O
H
H
H
H
H
H
H
H
b
OH
OTf
b2
O
N
N
NH
Br
N
TBDPSO
O
H
H
H
H
Scheme 1 Reaction conditions: (a) BzCl, py; (a) Tf2O, py, CH2Cl2, then H2O; (b) TBDPSCl, py; (b1) TfCl, DMAP, CH2Cl2; (b2) NaBr, acetone,
reflux; (c) DMTCl, pyridine, ; (c′) 1. Dess–Martin periodinane, CH2Cl2; 2. i-PrOH, NaBH4, acetone, –45 °C. Dmt = 4,4′-dimethoxytrityl.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 106–110

108
Q. Luo et al.
PAPER
Next, we used an O-mesyl group as a leaving group and blocks and intermediates for the preparation of new func-
potassium thioacetate as a nucleophile to realize the sec- tionalized nucleosides.
ond inversion at the 3′-position (from 4 to 5). In this pro-
cedure, compound 3 was converted into compound 4 by
All chemicals were obtained commercially and used as received un-
treatment with mesyl chloride in pyridine. Compound 4
was treated with potassium thioacetate in N,N-dimethyl-
formamide at 60 °C for 24 hours to give the thioacetate in-
termediate 5 (Scheme 2).
less otherwise mentioned. DMF was dried over MgSO4 and dis-
tilled. Pyridine was refluxed over KOH and then distilled. CH2Cl2
was heated with CaH2 for 6 h, decanted, and then distilled. Solvents
and liquid reagents were introduced from oven-dried microsyrin-
ges. TLC analyses were carried out on silica gel 60 F254, and spots
were examined under UV radiation. Column chromatography was
carried out on silica gel (200–300 mesh).
1H and 13C NMR spectra were recorded on a Bruker AM-500 spec-
trometer. All mass spectrometric analyses were performed on a
ThermoStar mass spectrometer.
The target phosphorothioamidite 7 was efficiently ob-
tained in two steps (Scheme 2). First, thioacetate 5 was de-
protected by reduction with lithium aluminum hydride to
give the sulfanyl derivative 6 in high yield (91.5%). A so-
lution of 6 in dichloromethane was stirred with N,N-diiso-
propylethylamine and 2-cyanoethyl diisopropylamido-
chloridophosphite at room temperature for three hours to
give the target compound 7 in an overall yield of 18.1%.
5′-O-[Bis(4-methoxyphenyl)(phenyl)methyl]-2′-deoxyinosine
(2)14
A stirred soln of 2′-deoxyinosine (1; 0.252 g, 1.0 mmol) in anhyd
pyridine (10 mL) was treated with DMTCl (0.406 g, 1.2 mmol). Af-
ter 19 h, MeOH (2 mL) was added and stirring was continued for 5
min. The mixture was then transferred into CH2Cl2 (20 mL) and the
Compared with literature methods, this synthetic design
has advantages of brief reaction steps, a relatively high
overall yield, and regioselectivity in the configuration- soln was washed successively with H2O (2 × 20 mL) and brine (2 ×
20 mL) then dried (Na2SO4), filtered, and concentrated under vacu-
um. The resulting yellow oil was purified by chromatography [silica
inversion steps. The products should be useful as building
O
N
O
N
O
N
N
N
N
N
N
N
NH
NH
NH
HO
DmtO
HO
DmtO
O
O
O
b
H
H
H
a
H
H
H
H
H
H
H
85.2%
H
H
H
81.4%
OH
OH
2
3
1
c
44.0%
O
O
N
N
N
NH
NH
N
MsO
N
N
DmtO
DmtO
O
d
O
H
H
H
H
H
67.4%
H
H
SAc
H
4
5
OMe
O
N
e
91.5%
N
N
NH
O
N
N
N
NH
MeO
O
O
N
H
H
f
DmtO
H
H
O
H
S
P
H
95.2%
H
H
H
O
H
NC
SH
7
6
Scheme 2 Reaction conditions: (a) DmtCl, py, r.t., 19 h (81.4%); (b) (1) Dess–Martin periodinane, CH2Cl2, r.t. 3 h; (2) i-PrOH, NaBH4, acetone,
–45 °C, 13 h (85.2%); (c) MsCl, i-PrOH, r.t., 12 h (44.0%); (d) KSAc, DMF, 60 °C, 24 h (67.4%); (e) LiAlH4, THF–HOAc, argon, r.t. 3 h
(91.5%); (f) i-Pr2NP(Cl)O(CH2)2CN, DIPEA, CH2Cl2, r.t., 3 h (95.2%).
Synthesis 2013, 45, 106–110
© Georg Thieme Verlag Stuttgart · New York

PAPER
2′-Deoxy-3′-Thioinosine and Its Phosphorothioamidite
109
gel, CH2Cl2–EtOH (20:1)] to give a white solid; yield: 0.451
(81.4%).
ture was stirred at 60 °C for 24 h under argon, The mixture was then
transferred into CH2Cl2 (10 mL) and the soln with washed with aq
NaHCO3 (2 × 20 mL), H2O (2 × 20 mL), and brine (2 × 20 mL). The
organic layer was separated, dried (Na2SO4), filtered, concentrated,
and co-evaporated with toluene to remove the DMF. The residual
oil was purified by chromatography [silica gel, CH2Cl2–EtOH
(15:1)] to give a white foamy solid; yield: 86.6 mg (67.4%).
1H NMR (400 MHz, CDCl3): δ =12.13 (s, 1 H), 8.07 (s, 1 H), 7.99
(s, 1 H), 7.44–6.77 (m, 13 H), 6.33 (dd, J1 = 4.0 Hz, J2 = 8 Hz, 1 H),
4.27 (m, 1 H), 4.17 (dd, J1 = 4 Hz, J2 = 8 Hz, 1 H), 3.78 (s, 6 H),
3.40 (d, J = 4.0 Hz, 2 H), 3.03 (m, 1 H), 2.56 (m, 1 H), 2.34 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 194.04, 159.21, 158.53, 148.42,
144.99, 144.39, 139.48, 138.39, 135.57, 130.09, 129.15, 128.15,
127.84, 126.93, 125.14, 113.17, 86.64, 84.48, 84.02, 63.29, 55.25,
40.80, 39.61, 30.62.
MS (ESI): m/z [M + H]+ calcd for C33H33N4O6S: 613.2; found:
613.3.
1H NMR (400 MHz, DMSO-d6): δ = 12.37 (s, 1 H), 8.19 (s, 1 H),
7.99 (s, 1 H), 7.34–6.77 (m, 13 H), 6.34 (dd, J1 = 4.0 Hz, J2 = 12 Hz,
1 H), 5.38 (d, J = 4 Hz, 1 H), 4.42 (m, 1 H), 3.97 (dd, J1 = 4 Hz, J2 =
12 Hz, 1 H), 3.72 (s, 6 H), 3.15 (dd, J1 = 4.0 Hz, J2 = 12 Hz, 2 H),
2.77 (m, 1 H), 2.34 (m, 1 H).
13C NMR (100 MHz, DMSO-d6): δ = 157.94, 156.62, 147.90,
145.50, 144.75, 138.73, 135.47, 129.60, 127.70, 127.59, 126.62,
124.53, 113.01, 85.80, 85.35, 83.49, 70.41, 63.88, 56.06, 54.95.
MS (ESI): m/z [M + H]+ calcd for C31H31N4O6: 555.2; found: 555.3.
5′-O-[Bis(4-methoxyphenyl)(phenyl)methyl]-2′-deoxy-xylo-ino-
sine (3)15
Product 2 (0.554 g, 1.0 mmol) was added to a chilled stirred soln of
Dess–Martin periodinane (0.640 g, 1.5 mmol) in anhyd CH2Cl2 (8
mL) at 0 °C, and the soln was stirred at 0 °C for 1 h and then at r.t.
for 4 h. i-PrOH (8 mL) was added and the resulting white slurry was
cooled to –45 °C. After 20 min, freshly powdered NaBH4 (76 mg,
2.0 mmol) was added and the mixture was stirred for 12 h at –45 °C.
Acetone (8 mL) was added and the mixture was allowed to warm to
r.t., diluted with CH2Cl2 (20 mL), and washed sequentially with aq
NaHCO3 (2 × 20 mL), H2O (2 × 20 mL), and brine (2 × 20 mL). The
organic layer was separated, dried (Na2SO4), filtered, and concen-
trated under vacuum. The residue was purified by chromatography
[silica gel, CH2Cl2–EtOH (15:1)] to give a white foamy solid; yield:
0.472 g (85.2%).
5′-O-[Bis(4-methoxyphenyl)(phenyl)methyl]-2-deoxy-3′-thio-
inosine (6)16
A suspension of LiAH4 (15.2 mg, 0.4 mmol) in anhyd THF (5 mL)
was cooled to 0 °C and then a soln of compound 5 (61.2 mg, 0.1
mmol) in THF (5 mL) was added dropwise under argon. The mix-
ture was stirred for 4 h at r.t. then treated with 1 M aq HOAc (2 ×
20 mL). CH2Cl2 (10 mL) was added and the organic layer was sep-
arated, washed with brine (2 × 20 mL), dried (Na2SO4), filtered, and
concentrated under vacuum. The residue was purified by chroma-
tography [silica gel, CH2Cl2–EtOH (12:1)] to give a white foamy
solid; yield: 52.2 mg (91.5%).
1H NMR (400 MHz, DMSO-d6: δ = 12.39 (s, 1 H), 8.14 (s, 1 H),
8.09 (d, J = 4 Hz, 1 H), 7.41–6.77 (m, 13 H), 6.33 (dd, J1 = 4.0 Hz,
J2 = 12 Hz, 1 H), 5.42 (d, J = 4 Hz, 1 H), 4.33 (m, 1 H), 4.21 (dd,
J1 = 4 Hz, J2 = 12 Hz, 1 H), 3.73 (s, 3 H), 3.72 (s, 3 H), 3.18 (dd,
J1 = 4.0 Hz, J2 = 12 Hz, 2 H), 2.72 (m, 1 H), 2.26 (m, 1 H).
13C NMR (100 MHz, DMSO-d6): δ = 157.96, 156.60, 147.73,
145.76, 144.98, 138.78, 135.68, 135.54, 129.71, 127.68, 126.56,
124.02, 113.01, 85.42, 83.93, 83.01, 69.28, 63.14, 54.94, 40.82.
1H NMR (400 MHz, CDCl3): δ = 12.62 (s, 1 H), 8.10 (s, 1 H), 8.04
(s, 1 H), 7.43–6.80 (m, 13 H), 6.32 (dd, J1 = 4.0 Hz, J2 = 8 Hz, 1 H),
4.00 (m, 1 H), 3.78 (s, 6 H), 3.75–3.70 (m, 1 H), 3.53 (dd, J1 =
4.0 Hz, J2 = 8 Hz, 1 H), 3.42 (dd, J1 = 4.0 Hz, J2 = 8 Hz, 1 H), 2.93
(m, 1 H), 2.49 (m, 1 H), 1.65 (d, J = 8 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 158.21, 157.53, 147.16, 143.99,
143.38, 137.59, 134.52, 129.01, 127.07, 126.93, 125.94, 124.21,
112.21, 87.39, 85.61, 83.15, 60.75, 54.22, 41.68, 34.01.
MS (ESI): m/z [M + H]+ calcd for C31H31N4O6: 555.2; found: 555.3.
MS (ESI): m/z [M + H]+ calcd for C31H30N4O5S: 571.2; found:
571.3.
5′-O-[Bis(4-methoxyphenyl)(phenyl)methyl]-3′-O-mesyl-2′-de-
oxyinosine (4)16
A soln of MsCl (77 μL, 1.0 mmol) in pyridine (2 mL) was added
dropwise to a stirred soln of compound 3 (0.277 g, 0.5 mmol) in an-
hyd pyridine (4 mL) at 0 °C. The cooling bath was removed and the
mixture was stirred for 12 h at r.t. The mixture was then poured into
ice–water and stirred for another 10 min. The resulting mixture was
diluted with CH2Cl2 (20 mL) and the organic layer was separated,
washed with aq NaHCO3 (2 × 20 mL), H2O (2 × 20 mL), and brine
(2 × 20 mL) then dried (Na2SO4), filtered, and concentrated under
vacuum. The crude product was purified by chromatography [silica
gel, CH2Cl2–EtOH (20:1)] to give a white foamy solid; yield: 0.139
g (44.0%).
1H NMR (400 MHz, CDCl3): δ = 11.91 (s, 1 H), 8.02 (s, 1 H), 7.99
(s, 1 H), 7.44–6.82 (m, 13 H), 6.43 (m, 1 H), 5.46 (m, 1 H), 4.37 (m,
1 H), 3.80 (s, 6 H), 3.66 (dd, J1 = 4.0 Hz, J2 = 8 Hz, 1 H), 3.36 (dd,
J1 = 4.0 Hz, J2 = 8 Hz, 1 H), 2.93 (m, 2 H), 2.74 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 153.44, 153.24, 142.34, 140.10,
139.41, 135.22, 130.63, 130.52, 124.79, 122.86, 122.62, 121.61,
119.99, 107.91, 81.36, 79.11, 78.85, 65.71, 57.10, 49.97, 35.83,
24.47.
S-[5′-O-[Bis(4-methoxyphenyl)(phenyl)methyl]-2-deoxy-3′-
thioinosinyl] O-(2-Cyanoethyl) Diisopropylamidothiophosphite
(7)
DIPEA (68.4 μL, 0.40 mmol) and i-Pr2NP(Cl)(CH2)2CN (31.8 μL,
0.14 mmol) were added to a stirred soln of compound 6 (40 mg,
0.070 mmol) in anhyd CH2Cl2 (5 mL), and the mixture was stirred
at r.t. for 3 h. The mixture was then diluted with CH2Cl2 (10 mL)
and washed successively with H2O (2 × 20 mL) and brine (2 × 20
mL) then dried (Na2SO4), filtered, and concentrated under vacuum.
The residue was purified by chromatography (silica gel, 0.5% Et3N
in 5% EtOH–CH2Cl2) to give a white solid; yield: 51.3 mg (95.2%
yield).
1H NMR (400 MHz, CDCl3): δ = 13.17 (s, 1 H), 8.15–8.06 (s, 2 H),
7.40–6.76 (m, 13 H), 6.39 – 6.29 (m, 1 H), 4.54–4.44 (m, 1 H),
4.24–4.17 (m, 1 H), 3.76 (s, 6 H), 3.66–3.52 (m, 4 H), 3.48–3.36 (m,
2 H), 3.04–2.95 (m, 1 H), 2.75–2.66 (m, 1 H), 2.60–2.55 (m, 1 H),
2.45–2.41 (m, 1 H), 1.28–1.02 (m, 12 H).
13C NMR (100 MHz, CDCl3): δ = 158.74, 158.54, 148.60, 145.28,
144.47, 138.37, 135.61, 130.06, 128.14, 127.87, 126.94, 125.13,
117.48, 113.15, 86.49, 84.57, 73.47, 63.33, 55.35, 55.25, 45.92,
43.27, 29.69, 24.62, 20.19.
MS (ESI): m/z [M + H]+ calcd for C32H33N4O8S: 633.2; found:
633.3.
31P NMR (162 MHz, CDCl3): δ = 165.42, 165.05.
HRMS: m/z [M]+ calculated for C40H47N6O6PS: 770.3015; found:
5′-O-[Bis(4-methoxyphenyl)(phenyl)methyl]-2-deoxy-3′-thio-
inosyl 3′-S-Acetate (5)16
KSAc (70.3 mg, 0.617 mmol) was added to a colorless soln of com-
pound 4 (0.130 g, 0.21 mmol) in anhyd DMF (8 mL), and the mix-
770.3038.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 106–110

110
Q. Luo et al.
PAPER
(7) Beevers, A. P. G.; Fettes, K. J.; O’Neil, I. A.; Roberts, S. M.;
Arnold, J. R. P.; Cosstick, R.; Fisher, J. Chem. Commun.
(Cambridge) 2002, 1458.
Acknowledgment
We thank the National Nature Science Foundation of China (No.
20702014) and the Fundamental Research Funds for the Central
Universities of China (WK1114053) for their financial support. We
are grateful to Professor H. Tian of the East China University of Sci-
ence and Technology for his valuable support for this project.
(8) (a) Sabbagh, G.; Fettes, K. J.; Gosain, R.; O’Neil, I. A.;
Cosstick, R. Nucleic Acids Res. 2004, 32, 495. (b) Ariza, X.;
Bou, V.; Vilarrasa, J. J. Am. Chem. Soc. 1995, 117, 3665.
(c) Terrazas, M.; Ariza, X.; Farràs, J.; Guisado-Yang, J. M.;
Vilarrasa, J. J. Org. Chem. 2004, 69, 5473. (d) Terrazas, M.;
Ariza, X.; Vilarrasa, J. Org. Lett. 2005, 7, 2477.
(9) Lu, J.; Li, N.-S.; Sengupta, R. N.; Piccirilli, J. A. Bioorg.
Med. Chem. 2008, 16, 5754.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnuIomprifgtooatrinSugpIoi
nnfomartit
(10) (a) Martin, F. H.; Castro, M. M.; Aboul-ela, F.; Tinoco, I.
Nucleic Acids Res. 1985, 13, 8927. (b) Kawase, Y.; Iwai, S.;
Inoue, H.; Miura, K.; Ohtsuka, E. Nucleic Acids Res. 1986,
14, 7727. (c) Ohtsuka, E.; Matsuki, S.; Ikehara, M.;
Takahashi, Y.; Matsubara, K. J. Biol. Chem. 1985, 260,
2605.
(11) Case-Green, S. C.; Southern, E. M. Nucleic Acids Res. 1994,
22, 131.
(12) Challa, H.; Bruice, T. C. Bioorg. Med. Chem. 2004, 12,
1475.
References
(1) Piccirilli, J. A.; Vyle, J. S.; Caruthers, M. H.; Cech, T. R.
Nature (London) 1993, 361, 85.
(2) (a) Thibaudeau, C.; Plavec, J.; Garg, N.; Papchikhin, A.;
Chattopadhyaya, J. J. Am. Chem. Soc. 1994, 116, 4038.
(b) Plavec, J.; Thibaudeau, C.; Chattopadhyaya, J. J. Am.
Chem. Soc. 1994, 116, 6558.
(3) (a) Liu, X.; Reese, C. B. Tetrahedron Lett. 1996, 37, 925.
(b) Weinstein, L. B.; Earnshaw, D. J.; Cosstick, R.; Cech, T.
R. J. Am. Chem. Soc. 1996, 118, 10341.
(13) Hansske, F.; Madej, D.; Robins, M. J. Tetrahedron 1984, 40,
125.
(4) Gordon, P. M.; Sontheimer, E. J.; Piccirilli, J. A. RNA 2000,
6, 199.
(5) Szewczak, A. A.; Kosek, A. B.; Piccirilli, J. A.; Strobel, S.
A. Biochemistry 2002, 41, 2516.
(6) (a) Butora, G.; Kenski, D. M.; Cooper, A. J.; Fu, W.; Qi, N.;
Li, J. J.; Flanagan, W. M.; Davies, I. W. J. Am. Chem. Soc.
2011, 133, 16766. (b) Kannan, A.; Burrows, C. J. J. Org.
Chem. 2010, 76, 720. (c) Wunderlich, C. H.; Spitzer, R.;
Santner, T.; Fauster, K.; Tollinger, M.; Kreutz, C. J. Am.
Chem. Soc. 2012, 134, 7558.
(14) (a) Bae, S.; Lakshman, M. K. J. Am. Chem. Soc. 2007, 129,
782. (b) Seela, F.; Kaiser, K. Nucleic Acids Res. 1986, 14,
1825. (c) Hansen, A. S.; Thalhammer, A.; El-Sagheer, A. H.;
Brown, T.; Schofield, C. J. Bioorg. Med. Chem. Lett. 2011,
21, 1181. (d) Lakshman, M. K.; Bae, S. WO 2008045535
2008; Chem. Abstr. 2008, 148, 449867.
(15) Eisenhuth, R.; Richert, C. J. Org. Chem. 2008, 74, 26.
(16) Xiao, P.; Bai, Y.; Chen, J.; Lu, Z. CN 102180926 2011;
Chem. Abstr. 2011, 155, 484417.
Synthesis 2013, 45, 106–110
© Georg Thieme Verlag Stuttgart · New York