A simple method for C-6 modification of guanine nucleosides

Article abstract of DOI:10.1039/b905298d

A facile method for the introduction of various substituents at the C-6 position of guanosine and 2′-deoxyguanosine is reported. In a simple, 1-step transformation, tert-butyldimethylsilyl protected guanosine and 2′-deoxyguanosine were converted to the O<

Full text of DOI:10.1039/b905298d

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Volume 7 | Number 14 | 21 July 2009 | Pages 2821–2992
ISSN 1477-0520
ChemicalScience
FULL PAPER
Mahesh K. Lakshman and Josh Frank
A simple method for C-6 modification
of guanine nucleosides
In this issue...
1477-0520(2009)7:14;1-D

PAPER
www.rsc.org/obc | Organic & Biomolecular Chemistry
A simple method for C-6 modification of guanine nucleosides†
Mahesh K. Lakshman* and Josh Frank
Received 16th March 2009, Accepted 23rd April 2009
First published as an Advance Article on the web 1st June 2009
DOI: 10.1039/b905298d
A facile method for the introduction of various substituents at the C-6 position of guanosine and
2¢-deoxyguanosine is reported. In a simple, 1-step transformation, tert-butyldimethylsilyl protected
guanosine and 2¢-deoxyguanosine were converted to the O6-(benzotriazol-1-yl) derivatives via reaction
with 1H-benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP) and
1,8-diazabicyclo[5.4.0]undec-7ene (DBU). The easily isolated, stable and storable,
O6-(benzotriazol-1-yl) guanosine derivatives upon exposure to a range of nucleophiles, under
appropriate conditions, led to the C-6 modified 2-amino purine nucleoside analogues in good yields.
to N,N-modified adenosine analogues via reaction of protected
Introduction
inosine and 2¢-deoxyinosine with hexaalkylphosphorus triamides
produced in situ and I2.19 In this paper, we report our find-
ings on the synthesis of O6-(benzotriazol-1-yl)guanosine and
2¢-deoxyguanosine, and their applications leading to C-6 modified
2-amino purine nucleoside analogues. While this work was in
progress, preparation of O6-(benzotriazol-1-yl)-3¢,5¢-di-O-(tert-
butyldimethylsilyl)-2¢-deoxyguanosine and its use for the synthesis
of C-8 acetylarylamine adducts was reported.20 However, no use
of the O6-(benzotriazol-1-yl)guanine nucleosides for other types of
functionalization is currently known.
The development of chemical methods to modify nucleosides con-
tinues to attract attention since unnatural and unusual nucleosides
play a prominent role in biochemistry, biology and medicine.1
Typically, modification at the C-6 position of the guanine nucleus
requires the introduction of a suitable leaving group at that
position, followed by SNAr displacement with nucleophiles.
Although chlorination of guanosine can be readily accom-
plished from its triacetate derivative,2,3 chlorination of the
2¢-deoxy analogue has been reported to be low yielding.4 There-
fore, improved methods have been reported for C-6 chlorination of
2¢-deoxyguanosine 3¢,5¢-diacetate with careful control of reaction
conditions.5,6 In addition to C-6 chlorination of the guanine
nucleosides, facile synthesis of the O6-arylsulfonates is also
known.6–12 Thus, the 6-chloro and O6-arylsulfonyl derivatives have
served as the principal electrophilic nucleoside derivatives used in
displacement reactions leading to C-6 modified 2-amino purine
nucleosides.
Results and discussion
In our initial work, we had shown that conversion of inosine
and deoxyinosine to the O6-(benzotriazol-1-yl) derivatives could
be accomplished via the use of BOP and i-Pr2NEt as base.
Although the reactions of the hypoxanthine nucleosides proceeded
to completion,13 similar reactions of the guanine nucleosides
proved to be quite slow. In fact, the literature reports reaction times
of 72 h even in a solvent such as DMF.20 Therefore, we decided to
reassess this reaction at the outset.
Table 1 summarizes the results from these initial experi-
ments. In order to avoid formation of the N6,N6-dimethyl-2,6-
diaminopurine derivate from decomposition of DMF, we chose to
conduct our first experiment in DMSO (Table 1, entry 1). In this
solvent, elevated temperature and a prolonged reaction time were
necessary. Upon switching to THF as solvent (entry 2), practically
no reaction was observed, but when DBU was used as base a
significantly fast reaction was observed (entry 3) that reached
completion within 4 h. Finally, replacing THF with CH3CN led to
an improvement in reaction time and yield. In CH3CN as solvent
and with DBU as base, the reaction was complete within 2 h with
a 65% isolated yield of 3 (entry 4). Under these conditions the
2¢-deoxy analogue 4 could be prepared in 85% yield (the previously
reported yield for 4 was 67%20).
Recently, we have developed a new class of O6-(benzotriazol-
1-yl)inosine analogues that are easily prepared via a reaction
of either protected or unprotected inosine and 2¢-deoxyinosine
with 1H-benzotriazol-1-yloxy-tris(dimethylamino)phosphonium
hexafluorophosphate (BOP).13 The basis for this chemistry resides
in the postulated formation of C-6 phosphonium salts in the
reaction of the hypoxanthine moiety with PPh3/I2 or BOP.15
14
We reasoned that in the absence of other nucleophiles, the
hydroxybenzotriazole from BOP should react as a nucleophile
on the nucleoside phosphonium salts. This was indeed the
case and not only were we able to synthesize O6-(benzotriazol-
1-yl)inosine analogues, but we have been able to utilize the
underlying chemistry to load inosine and 2¢-deoxyinosine onto
a polymer linker.16,17 The intermediacy of nucleoside phospho-
nium salts has also proven important in our recently described
N2-modification of 2¢-deoxyguanosine,18 and in chemistry leading
Department of Chemistry, The City College and The City University of
New York, 160 Convent Avenue, New York, NY, 10031-9198. E-mail:
lakshman@sci.ccny.cuny.edu; Fax: +1 212 650-6107; Tel: +1 212 650-7835
† Electronic supplementary information (ESI) available: NMR spectra
of compounds 3–19 and 1H-1H COSY spectrum of 3. See DOI:
10.1039/b905298d
Our observations on optimal solvent and base parallel those
reported for the amination of 4-hydroxyquinazoline using BOP
and n-BuNH2.21 Besides solubility considerations, one major
contributor to the differences in the reactions of inosine and
guanosine derivatives should be the pKa values of the acidic
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Table 1 Initial studies at determining optimal conditions for the synthesis of O6-(benzotriazol-1-yl)guanosine analogues 3 and 4a
Entry
Substrate
Solvent
Base
Temperature
Time
Yieldb
1
2
3
4
5
1
1
1
1
2
DMSO
THF
THF
CH3CN
CH3CN
i-Pr2NEt
i-Pr2NEt
DBU
DBU
DBU
55 ◦
rt
rt
rt
rt
C
24 h
96 h
4 h
2 h
1 h
54%
NRc
45%
65%
85%
a Reactions were performed using 2.0 molar equiv each of BOP and DBU at ~0.1 M nucleoside concentration. b Where reported, yield is of isolated and
purified products. c No reaction was observed and only 1 was present.
amide protons. Inosine is more acidic, with the amide pKa of
~8; in guanosine it is ~9.22,23 Nevertheless, both nucleosides can be
conveniently converted to the O6-(benzotriazol-1-yl) derivatives
under the appropriate conditions.
With the synthesis of the O6-(benzotriazol-1-yl)guanine deriva-
tives 3 and 4 optimized, the next step was an evaluation of their
use for modification at the C-6 position. For this amine, alcohol,
phenol and thiol nucleophiles were selected. In addition, our prior
work13 provided a basis for this analysis and the results are shown
in Table 2.
displacement with morpholine.15 Similarly, we attempted a 2-step,
1-pot synthesis of the methyl ether 16 under identical conditions.
However, this reaction only showed a trace of product after 52 h
at room temperature. Thus it appears that the 1-pot protocol is
currently only feasible with amines, although at this time we have
not performed any extensive experiments on the etherification. In
this context, reaction of 4 with MeNH2 was performed using a
40 wt% solution in water (entry 10). The good product recovery
indicates that any competing reaction with water was minimal in
the presence of the amine.
Our first examples on the SNAr displacement involved reactions
of the ribose derivative 3 and secondary amines (morpholine,
diethylamine and 1-methylpiperazine) in 1,2-dimethoxyethane
(DME) as solvent, without additional base. These reactions
were complete at room temperature or at 55 ◦C, with good
to high product yields (Table 2, entries 1–3). Reaction with
S-(-)-a-methylbenzylamine also proceeded smoothly (entry 4),
indicating that steric bulk proximal to the nitrogen atom does
not interfere with the reaction. Displacements with alcohols
Reactions with phenols (entries 14 and 15) also proceed
smoothly. On the basis of these results, it becomes clear that
isolation of the nucleoside O6-(benzotriazol-1-yl) derivatives is
important for fully exploiting their reactivity with a wide range of
nucleophiles. The isolated compounds 3 and 4 possess excellent
reactivity towards the range of nucleophiles as exemplified in
Table 2.
We then became interested in evaluating the mechanistic
pathway involved in the formation of 3 and 4 for comparison
to the reactions of inosine and 2¢-deoxyinosine.13 For this we
=
(CH3OH, CH3CH2OH and CH2 CHCH2OH) were conducted
1
using the alcohol as solvent with Cs2CO3 as base, and each
proceeded smoothly (entries 5–7). Reaction with benzyl mercaptan
was conducted in DME with Cs2CO3 as base (entry 8). These
results clearly demonstrated the utility of the O6-(benzotriazol-1-
yl)guanosine derivative 3 for the synthesis of C-6 modified 2-amino
purine nucleosides.
utilized 31P{ H} NMR (Fig. 1). The resonances for BOP appear
-
at 45.1 ppm and -143.1 ppm (PF6 ) in CD3CN (panel A in
Fig. 1). Upon addition of 1, no change was observed (panel B).
However, two new signals at 35.7 ppm and 26.1 ppm were observed
immediately upon addition of DBU (panel C). The resonance at
26.1 ppm corresponding to hexamethylphosporamide (HMPA)
continued to grow (pure HMPA in CH3CN appears at 25.6 ppm)
as the one at 35.7 ppm was depleted (panel D), indicating the likely
intermediacy of a nucleoside phosphonium salt (I in Scheme 1).
Finally, this room temperature reaction appears to be complete
at 120 minutes (panel E). Therefore, the plausible mechanism is
one that parallels that reported previously for the hypoxanthine
nucleosides,13 involving formation of a nucleoside phosphonium
salt.
With disilyl 2¢-deoxyguanosine 2, we initially explored the
possibility of a 2-step, 1-pot transformation where the O6-
(benzotriazol-1-yl) derivative was generated in situ. Thus, 2 was
exposed to BOP and DBU in CH3CN. After disappearance of 2
(1 h), 4 molar equiv of morpholine was added. This reaction was
complete within an additional 2 h and yielded the 6-morpholinyl
product 13 in 91% yield. This is consistent with the reported
1-pot reaction of inosine with BOP and i-Pr2NEt, followed by
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Table 2 Reactions of 3 and 4 with various nucleophilesa
Entry
1
Substrate
Nucleophile
Conditions
Yieldb
3
DME, 4 molar equiv morpholine, rt, 2 h
5: 87%
2
3
4
3
3
3
DME, 4 molar equiv Et2NH, rt, 19 h
6: 69%
7: 82%
8: 92%
DME, 4 molar equiv 1-methylpiperazine, 55 ◦C, 3.5 h
DME, 4 molar equiv S-(-)-a-methylbenzylamine, rt, 20.5 h
5
6
7
8
3
3
3
3
CH3OH
CH3OH solvent, 2 molar equiv Cs2CO3, 55 ◦C, 2 h
9: 95%
CH3CH2OH
CH3CH2OH solvent, 2 molar equiv Cs2CO3, 55 ◦C, 2.5 h
10: 71%
11: 88%
12: 89%
=
=
CH2 CHCH2OH
CH2 CHCH2OH solvent, 2 molar equiv Cs2CO3, rt, 20 h
DME, 2 molar equiv benzyl mercaptan, 2 molar equiv Cs2CO3, rt, 24 h
9
4
1-Pot reaction: CH3CN, 2 molar equiv BOP, 2 molar equiv DBU, 4 molar
equiv morpholine, rt, 3 h
13: 91% (94%)d
10
11
4
4
DME, 4 molar equiv Me2NH,c rt, 22 h
DME, 4 molar equiv benzyl amine, rt, 4 h
14: 83% (86%)d
15: 81% (80%)d
12
13
14
4
4
4
CH3OH
CH2 CHCH2OH
CH3OH solvent, 2 molar equiv Cs2CO3, rt, 4 h
16: 79% (80%)d
17: 82% (71%)d
18: 89% (86%)d
=
=
CH2 CHCH2OH solvent, 2 molar equiv Cs2CO3, rt, 7 h
DME, 2 molar equiv phenol, 2 molar equiv Cs2CO3, 60 ◦C, 2.5 h
15
4
DME, 2 molar equiv 4-chlorophenol, 2 molar equiv Cs2CO3, 60 ◦C, 2.5 h
19: 88% (90%)d
a Reaction times have not been optimized for each entry. b Yields of isolated and purified products. c A 40 wt% solution of Me2NH in water was used.
d Yields in parentheses are those obtained from 3¢,5¢-di-O-(tert-butyldimethylsilyl)-O6-[(2,4,6-trimethylphenyl)sulfonyl]-2¢-deoxyguanosine (reported in
ref. 24).
It is also instructive to compare the reactions of 4 with those
Conclusions
of 3¢,5¢-di-O-(tert-butyldimethylsilyl)-O6-[(2,4,6-trimethylphenyl)-
In this paper we have demonstrated that silyl-protected guanosine
(1) and 2¢-deoxyguanosine (2) can be conveniently converted to the
O6-(benzotriazol-1-yl) derivatives 3 and 4. Use of DBU as base in
CH3CN as solvent leads to fast conversion in good to high yield.
These O6-(benzotriazol-1-yl) derivatives are excellent reagents
sulfonyl]-2¢-deoxyguanosine (yields shown in parentheses in
Table 2).24 In this comparison 4 performs just as well as the
nucleoside O6-arylsulfonate, although synthesis and utilization
of the O6-(benzotriazol-1-yl) guanosine derivatives are generally
operationally simpler.
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1
Fig. 1 Monitoring the course of the reaction between 1 and BOP at room temperature using 31P{ H} NMR: (A) BOP in 0.5 mL CD3CN; (B) after
addition of 1 (0.1 M in CD3CN); (C) immediately after addition of DBU; (D) 60 minutes after addition of DBU; (E) 120 minutes after addition of DBU;
(F) pure HMPA in CD3CN.
Experimental
General experimental considerations
All reactions were carried out in oven-dried glassware. Reactions
were monitored on glass-backed TLC plates coated with silica
gel (250 mm), containing a fluorescent indicator. Column chro-
matographic purifications were performed on 200–300 mesh silica
gel. CH3CN and i-Pr2NEt were distilled over CaH2, CH2Cl2 was
distilled over CaCl2, THF was distilled over LiAlH4 and then over
Na. Commercially available anhydrous DMSO and DME were
used without further purification. All other reagents were obtained
from commercial sources and used without further purification.
1H NMR spectra were recorded at 500 MHz and are referenced
to residual protonated solvent. Chemical shifts are reported in
parts per million (d) and coupling constants (J) are in hertz. 13
C
NMR spectra were obtained at 125 MHz and are referenced to
the solvent resonance. The imidazolyl proton in the nucleoside is
labeled H-8 and the sugar protons are numbered 1¢–5¢ beginning at
the anomeric carbon atom and proceeding to the primary carbinol
carbon atom.
Scheme 1 Plausible reaction pathway and chemical shifts from 31P{ H}
1
NMR.
General procedure for the synthesis of O6-(benzotriazol-1-yl)-
2¢,3¢,5¢-tri-O-(tert-butyldimethylsilyl)guanosine (3) and O6-(benzo-
triazol-1-yl)-3¢,5¢-di-O-(tert-butyldimethylsilyl)-2¢-deoxyguanosine
(4). In a clean, dry round-bottomed flask equipped with a
stirring bar were placed the silylated nucleoside (1 or 2), BOP
(2.0 molar equiv), and DBU (2.0 molar equiv) in dry CH3CN
(8.5 mL/mmol). The reaction mixture was flushed with nitrogen
gas, stoppered and stirred at room temperature for 1 to 2 h. The
reaction progress was monitored by TLC. Upon completion, the
mixture was diluted with EtOAc and washed with deionized water
containing a small amount of NaCl. The aqueous layer was back
extracted (2¥) with EtOAc. The combined organic layer was dried
over Na2SO4, filtered and evaporated to leave a yellowish oil that
for SNAr displacements and a variety of C-6 modified 2-amino
purine nucleosides can be efficiently synthesized. It appears that
amination reactions can be conducted as a 2-step, 1-pot procedure
but a similar reaction with an alcohol was not successful. Extensive
experimentation has not presently been conducted on a 1-pot
synthesis of C-6 ethers via amide group activation by BOP, and
work is in progress on this aspect. However, the readily isolated
and stable O6-(benzotriazol-1-yl) guanosine derivatives undergo
efficient conversion to a wide variety of products using relatively
simple methods.
2936 | Org. Biomol. Chem., 2009, 7, 2933–2940
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was dried under oil pump vacuum. Chromatographic purification
then provided products 3 and 4.
SiCH3); dC (125 MHz; CDCl3) 159.3, 154.5, 153.3, 135.3, 115.6,
88.0, 85.1, 75.6, 72.2, 67.3, 62.9, 45.7 (br), 26.4, 26.1, 26.0, 18.8,
18.4, 18.2, -4.1, -4.4, -4.5, -4.6, -5.0, -5.1; HRMS (ESI) calcd
for C32H62N6O5Si3 [M + H]+: 695.4163, found: 695.4173.
O6 -(Benzotriazol-1-yl)-2¢,3¢,5¢-tri-O-(tert-butyldimethylsilyl)-
guanosine (3). Chromatography on a silica gel column using 20%
EtOAc in hexanes gave a white solid (65% yield). Rf (silica, 20%
EtOAc in hexanes) = 0.46; dH (500 MHz; CDCl3) 8.23 (1H, s,
H-8), 8.11 (1H, d, J 8.3, Ar–H), 7.54–7.48 (2H, m, Ar–H), 7.44
(1H, dt, J 1.5, 8.3, Ar–H), 5.95 (1H, d, J 4.4, H-1¢), 4.75 (2H, s,
NH2), 4.47 (1H, t, J 4.2, H-2¢), 4.30 (t, 1H, J 4.2, H-3¢), 4.12 (1H,
q, J 3.9, H-4¢), 4.00 (1H, dd, J 3.4, 11.3, H-5¢), 3.80 (1H, dd, J
3.0, 11.3, H-5¢), 0.97, 0.93 and 0.84 (27H, 3 s, tert-Bu), 0.16, 0.15,
0.11, 0.09, 0.00 and -0.11 (18H, 6 s, SiCH3); dC (125 MHz; CDCl3)
159.6, 159.0, 156.2, 143.7, 140.2, 129.1, 128.7, 124.9, 120.6, 113.3,
109.2, 87.8, 85.9, 77.1, 72.3, 62.9, 26.4, 26.0, 25.9, 18.8, 18.3, 18.2,
-4.1, -4.4, -4.6,-4.8, -5.1; HRMS (ESI) calcd for C34H58N8O5Si3
[M + H]+: 743.3911, found: 743.3898.
9-[2,3,5-Tri-O-(tert-butyldimethylsilyl)-b-D-ribofuranosyl]-
N6,N6-diethyl-2,6-diaminopurine (6). Yellow solid, prepared in
69% yield using Et2NH (28 mL, 0.27 mmol) in a reaction time of
19 h at room temperature. Rf (silica, 20% EtOAc in hexanes) =
0.47; dH (500 MHz; CDCl3) 7.68 (1H, s, H-8), 5.85 (1H, d, J 5.4,
H-1¢), 4.68 (1H, t, J 4.7, H-2¢), 4.48 (2H, br s, NH2), 4.29 (1H, t, J
4.2, H-3¢), 4.07 (1H, app q, J 3.9, H-4¢), 3.96 (1H, dd, J 4.4, 11.0,
H-5¢), 3.90 (4H, br, NCH2), 3.75 (1H, dd, J 3.4, 11.0, H-5¢), 1.23
(6H, t, J 7.0, CH3) 0.93, 0.92 and 0.82 (27H, 3 s, tert-Bu), 0.103,
0.097, 0.090, -0.03 and -0.15 (18H, 5 s, SiCH3); dC (125 MHz;
CDCl3) 159.4, 154.4, 152.8, 135.2, 115.5, 88.1, 85.0, 75.0, 72.2,
62.9, 42.8 (br), 26.3, 26.1, 26.0, 18.8, 18.4, 18.2, 13.8, -4.1, -4.4,
-4.5, -4.8, -5.0, -5.1; HRMS (ESI) calcd for C32H64N6O4Si3 [M +
H]+: 681.4370, found: 681.4380.
O6 -(Benzotriazol-1-yl)-3¢,5¢-di-O-(tert-butyldimethylsilyl)-2¢-
deoxyguanosine (4)20. Chromatography on a silica gel column
using 30% EtOAc in hexanes gave a white solid (85% yield). Rf
(silica, 30% EtOAc in hexanes) = 0.24; dH (500 MHz; CDCl3) 8.12
(1H, s, H-8), 8.11 (1H, d overlapping with the singlet at 8.12, J 7.3,
Ar–H), 7.54–7.48 (2H, m, Ar–H), 7.44 (1H, t, J 6.8, Ar–H), 6.35
(1H, t, J 6.6, H-1¢), 4.76 (2H, s, NH2), 4.60 (1H, m, H-3¢), 4.00
(1H, app q, J 3.4, H-4¢), 3.84 (1H, dd, J 3.9, 11.2, H-5¢), 3.77 (1H,
dd, J 2.9, 11.2, H-5¢), 2.57 (1H, app quint, J 6.5, H-2¢), 2.40 (1H,
ddd, J 3.4, 6.3, 13.7, H-2¢), 0.924 and 0.916 (18H, 2 s, tert-Bu),
0.108, 0.101, 0.098 (12H, 3 s, SiCH3); dC (125 MHz; CDCl3) 159.7,
158.8, 156.0, 143.6, 140.4, 129.1, 128.8, 124.9, 120.6, 113.7, 109.1,
88.1, 84.3, 72.0, 63.0, 41.4, 26.2, 26.0, 18.7, 18.3, -4.4, -4.5, -5.1,
-5.2.
2-Amino-9-[2,3,5-tri-O-(tert-butyldimethylsilyl)-b-D-ribofura-
nosyl]-6-(4-methylpiperazin-1-yl)purine (7). White solid, pre-
pared in 82% yield using 1-methylpiperazine (30 mL, 0.27 mmol)
in a reaction time of 3.5 h at 55 ◦C. Rf (silica, 20% EtOAc in
hexanes) = 0.05; dH (500 MHz; CDCl3) 7.74 (1H, s, H-8), 5.86
(1H, d, J 5.4, H-1¢), 4.61 (1H, t, J 4.7, H-2¢), 4.51 (2H, s, NH2),
4.29 (1H, t, J 4.2, H-3¢), 4.24 (4H, br s, piperazinyl–CH2), 4.08
(1H, app q, J 3.9, H-4¢), 3.99 (1H, dd, J 4.4, 11.2, H-5¢), 3.78
(1H, dd, J 3.0, 11.2, H-5¢), 2.51 (4H, br s, piperazinyl–CH2), 2.34
(3H, s, CH3), 0.93, 0.925 and 0.83 (27H, 3 s, tert-Bu), 0.103, 0.096,
0.087, -0.03 and -0.13 (18H, 5 s, SiCH3); dC (125 MHz; CDCl3)
159.3, 154.5, 153.3, 135.2, 115.7, 88.1, 85.1, 75.4, 72.2, 62.9, 55.4,
46.5, 45.0 (br), 26.4, 26.1, 26.0, 18.8, 18.4, 18.2, -4.1, -4.4, -4.5,
-4.6, -5.0, -5.1; HRMS (ESI) calcd for C33H65N7O4Si3 [M + H]+:
708.4479, found: 708.4486.
General procedure for the reaction of 3 with amines
In a clean, dry reaction vial equipped with a stirring bar were
placed 3 (50.0 mg, 67.3 mmol), amine (4.0 molar equiv) and
anhydrous DME (0.5 mL). The reaction mixture was flushed
with nitrogen gas, sealed with a Teflon-lined cap and stirred
either at room temperature or at 55 ◦C for 2–20.5 h. Progress
of the reaction was monitored by TLC. Upon completion, the
mixture was diluted with EtOAc and washed with deionized water
containing a small amount of NaCl. The aqueous layer was back
extracted (2¥) with EtOAc. The combined organic layer was dried
over Na2SO4, filtered and evaporated. Purification on a silica
gel column using 20% EtOAc in hexanes then provided the C-6
amino derivatives 5–8. Additional details and any deviations from
this general procedure are noted under the individual compound
headings.
9-[2,3,5-Tri-O-(tert-butyldimethylsilyl)-b-D-ribofuranosyl]-N6-
[(1S)-phenylethyl]-2,6-diaminopurine (8). Light yellow solid, pre-
pared in 92% yield using (S)-(-)-a-methylbenzylamine (35 mL,
0.27 mmol) in a reaction time of 20.5 h at room temperature. Rf
(silica, 20% EtOAc in hexanes) = 0.13; dH (500 MHz; CDCl3) 7.85
(1H, s, H-8), 7.42 (2H, d, J 7.3, Ar–H), 7.31 (2H, t, J 7.3, Ar–H),
7.22 (1H, t, J 7.3, Ar–H), 6.53 (1H, br s, NH), 5.84 (1H, d, J 4.4,
H-1¢), 5.50 (1H, br s, NCH), 4.71 (2H, br s, NH2), 4.53 (1H, t, J 4.4,
H-2¢), 4.28 (1H, t, J 3.9, H-3¢), 4.07 (1H, app q, J 3.9, H-4¢), 3.99
(1H, dd, J 4.4, 11.5, H-5¢), 3.78 (1H, dd, J 3.0, 11.5, H-5¢), 1.60
(3H, d, J 6.8, CH3), 0.94, 0.92 and 0.83 (27H, 3 s, tert-Bu), 0.119,
0.114, 0.090, 0.00 and -0.11 (18H, 5 s, SiCH3); proton assignments
were made by 1H-1H COSY of this compound at 60 ◦C, where the
NH sharpened to a br d (5.97 ppm, J 7.8), the NCH became a
sharper br m (5.56 ppm) and the CH3 d sharpened (1.61 ppm,
J 7.3); dC (125 MHz; CDCl3) 160.0, 154.5, 144.5, 136.4, 128.7,
127.2, 126.5, 115.0, 88.4, 84.9, 75.7, 71.8, 62.6, 26.4, 26.1, 26.0,
22.9, 18.8, 18.4, 18.2, -4.1, -4.4, -4.5, -4.6, -5.1; HRMS (ESI)
calcd for C36H64N6O4Si3 [M + H]+: 729.4370, found: 729.4374.
2-Amino-9-[2,3,5-tri-O-(tert-butyldimethylsilyl)-b-D-ribofuran-
osyl]-6-(morpholin-4-yl)purine (5). Light orange solid, prepared
in 87% yield using 3 (70.0 mg, 94.2 mmol) and morpholine (33 mL,
0.38 mmol) in DME (0.7 mL), in a reaction time of 2 h at
room temperature. Rf (silica, 5% MeOH in CH2Cl2) = 0.46; dH
(500 MHz; CDCl3) 7.75 (1H, s, H-8), 5.88 (1H, d, J 5.4, H-1¢),
4.61 (1H, t, J 4.7, H-2¢), 4.54 (2H, s, NH2), 4.28 (1H, t, J 3.9, H-
3¢), 4.21 (4H, br s, morpholinyl–CH2), 4.08 (1H, app q, J 3.9, H-4¢),
3.97 (1H, dd, J 4.4, 11.2, H-5¢), 3.80 (4H, t, J 4.9, morpholinyl–
CH2), 3.76 (1H, dd, J 3.0, 11.2, H-5¢), 0.935, 0.925 and 0.83 (27H,
3 s, tert-Bu), 0.11, 0.106, 0.10, 0.09, -0.03 and -0.13 (18H, 6 s,
General procedure for the reaction of 3 with alcohols
In a clean, dry reaction vial equipped with a stirring bar were
placed 3 and Cs2CO3 (2.0 molar equiv) in the appropriate alcohol
as solvent. The reaction mixture was flushed with nitrogen gas,
This journal is
The Royal Society of Chemistry 2009
Org. Biomol. Chem., 2009, 7, 2933–2940 | 2937
©

sealed with a Teflon-lined cap and stirred at 55 ◦C for 2–20 h.
Progress of the reaction was monitored by TLC. Upon completion,
the mixture was diluted with EtOAc and washed with deionized
water containing a small amount of NaCl. The aqueous layer
was back extracted (2¥) with EtOAc. The combined organic layer
was dried over Na2SO4, filtered and evaporated. Purification on a
silica gel column using 20% EtOAc in hexanes then provided the
guanosine O6-alkyl ethers 9–11. Additional details are listed under
the specific compound headings.
nitrogen gas, sealed with a Teflon-lined cap and allowed to stir at
room temperature for 24 h. The mixture was diluted with EtOAc
and washed with deionized water containing a small amount of
NaCl. The aqueous layer was back extracted (2¥) with EtOAc.
The combined organic layer was dried over Na2SO4, filtered and
evaporated. Purification on a silica gel column using 20% EtOAc
in hexanes then provided 12 as a light yellow solid (89% yield). Rf
(silica, 10% EtOAc in hexanes) = 0.47; dH (500 MHz; CDCl3) 7.98
(1H, s, H-8), 7.43 (2H, d, J 7.3, Ar–H), 7.31–7.21 (3H, m, Ar–H),
5.90 (1H d, J 4.9, H-1¢), 4.81 (s, 2H, NH2), 4.57 (2H, ABquart, J 13.7,
SCH2), 4.54 (1H, t, J 4.4, H-2¢), 4.29 (t, 1H, J 4.2, H-3¢), 4.10 (1H,
app q, J 2.9, H-4¢), 3.97 (1H, dd, J 3.9, 11.2, H-5¢), 3.77 (1H, dd, J
2.9, 11.2, H-5¢), 0.93, 0.927 and 0.83 (27H, 3 s, tert-Bu), 0.12, 0.11,
0.010, 0.09, -0.02, -0.16 (18H, 5 s, SiCH3); dC (125 MHz; CDCl3)
161.1, 159.0, 150.8, 139.0, 138.1, 129.3, 128.7, 127.4, 126.2, 88.1,
85.3, 76.1, 72.1, 62.7, 32.9, 26.4, 26.1, 26.0, 18.8, 18.4, 18.2, -4.1,
-4.4, -4.5, -4.7, -5.0, -5.1; HRMS (ESI) calcd for C35H61N5O4Si3
[M + H]+: 732.3825, found: 732.3831.
2¢,3¢,5¢-Tri-O-(tert-butyldimethylsilyl)-O6-methylguanosine (9).
Light orange solid, prepared in 95% yield using 3 (45.3 mg,
61.0 mmol) and Cs2CO3 (42.9 mg, 0.131 mmol) in MeOH
(0.45 mL), in a reaction time of 2 h at 55 ◦C. Rf (silica, 20%
EtOAc in hexanes) = 0.11; dH (500 MHz; CDCl3) 7.98 (1H, s, H-
8), 5.90 (1H, d, J 4.9, H-1¢), 4.79 (2H, s, NH2), 4.50 (1H, t, J 4.4,
H-2¢), 4.28 (1H, t, J 4.2, H-3¢), 4.08 (1H, app q, J 3.0, H-4¢), 4.05
(3H, s, OCH3), 3.97 (1H, dd, J 3.9, 11.2, H-5¢), 3.77 (1H, dd, J 2.4,
11.2, H-5¢), 0.94, 0.92 and 0.82 (27H, 3 s, tert-Bu), 0.12, 0.11, 0.09,
0.08, -0.04 and -0.16 (18H, 6 s, SiCH3); dC (125 MHz; CDCl3)
161.7, 159.5, 153.8, 138.2, 116.2, 88.0, 85.4, 76.4, 72.1, 62.8, 54.0,
26.4, 26.1, 26.0, 18.8, 18.4, 18.2, 14.8, -4.1, -4.4, -4.5, -4.7, -5.1;
HRMS (ESI) calcd for C29H57N5O5Si3 [M + H]+: 640.3741, found:
640.3745.
9-[3,5-Di-O-(tert-butyldimethylsilyl)-2-deoxy-b-D-ribofuran-
osyl]-6-(morpholin-4-yl)purine (13)24.
One-pot procedure. In a clean, dry, round-bottomed flask
equipped with a stirring bar were placed 2 (70.0 mg, 0.141 mmol)
and BOP (0.125 g, 0.283 mmol) in anhydrous CH3CN (1.2 mL).
DBU (47.3 mL, 0.316 mmol) was added to the stirring mixture,
the flask was flushed with nitrogen gas and stoppered. After being
stirred at room temperature for 1 h TLC showed consumption of 2.
At this time morpholine (49.7 ml, 0.568 mmol) was added. The flask
was again flushed with nitrogen gas, stoppered and the mixture
was allowed to stir at room temperature for an additional 2 h at
which time the reaction was complete as assessed by TLC. The
mixture was diluted with EtOAc and washed with deionized water
containing a small amount of NaCl. The aqueous layer was back
extracted (2¥) with EtOAc. The combined organic layer was dried
over Na2SO4, filtered and evaporated to leave a yellowish oil.
Purification on a silica gel column using 30% EtOAc in hexanes
then provided 13 as a yellow solid (91% yield). Rf (silica, 30%
EtOAc in hexanes) = 0.11; dH (500 MHz; CDCl3) 7.72 (1H, s,
H-8), 6.31 (1H, t, J 6.8, H-1¢), 4.60 (2H, s, NH2), 4.57 (1H, m,
H-3¢), 4.21 (4H, br s, morpholinyl–CH2), 3.96 (1H, app q, J 4.1,
H-4¢), 3.79 (4H, t, J 4.4, morpholinyl–CH2), 3.76 (1H, dd, J 4.6,
11.1, H-5¢), 3.75 (1H, dd, J 3.6, 11.1, H-5¢), 2.55 (1H, app quint, J
6.8, H-2¢), 2.33 (1H, ddd, J 3.4, 6.0, 13.0, H-2¢), 0.91 and 0.90 (18H,
2 s, tert-Bu), 0.10, 0.07 and 0.06 (12H, 3 s, SiCH3); dC (125 MHz;
CDCl3) 159.4, 154.4, 153.1, 134.6, 115.4, 87.8, 83.6, 72.4, 67.3,
63.2, 45.7 (br), 40.9, 26.2, 26.0, 18.7, 18.3, -4.4, -4.5, -5.1, -5.2.
2¢,3¢,5¢-Tri-O-(tert-butyldimethylsilyl)-O6-ethylguanosine (10).
White solid, prepared in 71% yield using3 (50.0mg, 67.3 mmol) and
Cs2CO3 (43.8 mg, 0.134 mmol) in EtOH (0.45 mL), in a reaction
time of 2.5 h at 55 ◦C. Rf (silica, 20% EtOAc in hexanes) = 0.20;
d
H (500 MHz; CDCl3) 7.98 (1H, s, H-8), 5.91 (1H, d, J 4.9, H-1¢),
4.76 (2H, br s, NH2), 4.55 (2H, q, J 7.0, OCH2), 4.52 (1H, t, J 4.4,
H-2¢), 4.29 (1H, t, J 4.3, H-3¢), 4.09 (1H, app q, J 2.9, H-4¢), 3.99
(1H, dd, J 3.4, 11.5, H-5¢), 3.76 (1H, dd, J 3.0, 11.5, H-5¢), 1.45
(3H, t, J 7.0, CH3), 0.95, 0.93 and 0.83 (27H, 3 s, tert-Bu), 0.13,
0.12, 0.095, 0.09, -0.03 and -0.15 (18H, 6 s, SiCH3); dC (125 MHz;
CDCl3) 161.5, 159.5, 153.9, 138.0, 116.1, 88.0, 85.4, 76.3, 72.2,
62.8, 26.4, 26.1, 26.0, 18.8, 18.4, 18.2, 14.8, -4.1, -4.4, -4.5, -4.7,
-5.1; HRMS (ESI) calcd for C30H59N65O5Si3 [M + H]+: 654.3897,
found: 654.3890.
O6-Allyl-2¢,3¢,5¢-tri-O-(tert-butyldimethylsilyl)guanosine (11).
Orange solid, prepared in 88% yield using 3 (70.0 mg, 94.2 mmol)
and Cs2CO3 (61.4 mg, 0.188 mmol) in allyl alcohol (0.7 mL), in a
reaction time of 20 h at room temperature. Rf (silica, 20% EtOAc
in hexanes) = 0.31; dH (500 MHz; CDCl3) 8.00 (1H, s, H-8), 6.15
=
(1H, m, CH), 5.93 (1H, d, J 4.6, H-1¢), 5.45 (1H, dd, J 1.5, 18.6,
CHtrans), 5.29 (1H, dd, J 1.5, 11.7, CHcis), 5.02 (2H, d, J 5.9,
=
=
OCH2), 4.79 (2H, s, NH2), 4.54 (1H, t, J 4.7, H-2¢), 4.31 (1H, t,
J 3.4, H-3¢), 4.11 (1H, app q, J 3.9, H-4¢), 4.01 (1H, dd, J 3.9,
11.2, H-5¢), 3.80 (1H, dd, J 2.4, 11.2, H-5¢), 0.97, 0.95 and 0.85
(27H, 3 s, tert-Bu), 0.15, 0.14, 0.12, 0.11, 0.00 and -0.13 (18H, 6 s,
SiCH3); dC (125 MHz; CDCl3) 161.0, 159.4, 154.1, 138.1, 133.1,
118.4, 116.0, 87.9, 85.4, 76.4, 72.2, 67.4, 62.8, 26.4, 26.1, 26.0,
18.8, 18.4, 18.2, -4.1, -4.4, -4.5, -4.7, -5.11, -5.14; HRMS (ESI)
calcd for C31H59N5O5Si3 [M + H]+: 666.3897, found: 666.3912.
General procedure for the reaction of 4 with amines
In a clean, dry reaction vial equipped with a stirring bar were
placed 4 (50.0 mg, 81.6 mmol), amine (4.0 molar equiv) and
anhydrous DME (0.5 mL). The reaction mixture was flushed
with nitrogen gas, sealed with a Teflon-lined cap and stirred at
room temperature for 4–22 h (see details under specific compound
headings). Progress of the reaction was monitored by TLC. Upon
completion, the mixture was diluted with EtOAc and washed with
deionized water containing a small amount of NaCl. The aqueous
layer was back extracted (2¥) with EtOAc. The combined organic
layer was dried over Na2SO4, filtered and evaporated. Purification
on a silica gel column using 30% EtOAc in hexanes then provided
S6 -Benzyl-2¢,3¢,5¢-tri-O-(tert-butyldimethylsilyl)thioguanosine
(12). In a clean, dry reaction vial equipped with a stirring
bar were placed 3 (50.0 mg, 67.0 mmol), Cs2CO3 (43.8 mg,
0.134 mmol) and dry DME (0.5 mL). Benzyl mercaptan (16.0 mL,
0.134 mmol) was added, the reaction mixture was flushed with
2938 | Org. Biomol. Chem., 2009, 7, 2933–2940
This journal is
The Royal Society of Chemistry 2009
©

the C-6 amino derivatives 14 and 15. Additional details and
any deviations from this general procedure are noted under the
individual compound headings.
alcohol, in a reaction time of 7 h. Rf (silica, 5% MeOH in
CH2Cl2) = 0.59; dH (500 MHz; CDCl3) 7.90 (1H, s, H-8), 6.32
=
(1H, t, J 6.8, H-1¢), 6.12 (1H, m, CH), 5.42 (1H, dd, J 1.5, 18.5,
=
=
CHtrans), 5.26 (1H, dd, J 1.5, 11.7, CHcis), 5.01 (2H, d, J 5.4,
9-[3,5-Di-O-(tert-butyldimethylsilyl)-2-deoxy-b-D-ribofura-
nosyl]-N6,N6-dimethyl-2,6-diaminopurine (14)24. Light yellow
solid, prepared in 83% yield using a 40 wt% solution of Me2NH
in water (37.3 mL, 0.331 mmol) in a reaction time of 2 h. Rf (silica,
5% MeOH in CH2Cl2) = 0.43; dH (500 MHz; CDCl3) 7.69 (1H, s,
H-8), 6.30 (1H, t, J 6.1, H-1¢), 4.67 (2H, s, NH2), 4.56 (1H, m,
H-3¢), 3.95 (1H, app q, J 4.0, H-4¢), 3.78–3.71 (2H, m, H-5¢), 3.43
(6H, br s, NCH3), 2.54 (1H, app quint, J 6.6, H-2¢), 2.32 (1H, ddd,
J 3.4, 6.0, 13.1, H-2¢), 0.90 and 0.896 (18H, 2 s, tert-Bu), 0.09, 0.06
and 0.05 (12H, 3 s, SiCH3); dC (125 MHz; CDCl3) 159.4, 155.5,
152.7, 134.2, 115.7, 87.8, 83.5, 72.4, 63.2, 40.8, 38.5 (br), 26.2, 26.0,
18.7, 18.3, -4.4, -4.5, -5.1, -5.2.
OCH2), 4.81 (2H, s, NH2), 4.59 (1H, m, H-3¢), 3.97 (1H, app q,
J 3.3, H-4¢), 3.81 (1H, dd, J 4.4, 11.1, H-5¢), 3.75 (1H, dd, J 2.9,
11.1, H-5¢), 2.57 (1H, app quint, J 6.0, H-2¢), 2.35 (1H, ddd, J 3.7,
6.1, 13.1, H-2¢), 0.913 and 0.910 (18H, 2 s, tert-Bu), 0.10, 0.08 and
0.07 (12H, 3 s, SiCH3); dC (125 MHz; CDCl3) 161.1, 159.4, 154.0,
137.8, 133.0, 118.4, 116.2, 87.9, 83.9, 72.2, 67.5, 63.1, 41.2, 26.2,
26.0, 18.7, 18.3, -4.4, -4.5, -5.1, -5.2.
General procedure for the reaction of 4 with phenols
In a clean, dry reaction vial equipped with a stirring bar were
placed 4 (50.0 mg, 81.6 mmol), the appropriate phenol (2 molar
equiv) and Cs2CO3 (53.1 mg, 0.163 mmol) in anhydrous DME
(0.5 mL). The reaction mixture was flushed with nitrogen gas,
sealed with a Teflon-lined cap and stirred at 60 ◦C for 2–2.5 hours.
Progress of the reaction was monitored by TLC. Upon completion,
the mixture was diluted with EtOAc and washed with deionized
water containing a small amount of NaCl. The aqueous layer
was back extracted (2¥) with EtOAc. The combined organic layer
was dried over Na2SO4, filtered and evaporated. Purification on a
silica gel column using 30% EtOAc in hexanes then provided the
2¢-deoxyguanosine O6-aryl ethers 18 and 19.
N6 -Benzyl-9-[3,5-di-O-(tert-butyldimethylsilyl)-2-deoxy-b-D-
ribofuranosyl]purine (15)24. Light yellow solid, prepared in 81%
yield using benzylamine (35.6 mL, 0.33 mmol) in a reaction time
of 4 h. Rf (silica, 30% EtOAc in hexanes) = 0.08; dH (500 MHz;
CDCl3) 7.76 (1H, s, H-8), 7.37–7.27 (5H, m, Ar–H), 6.30 (1H, t, J
6.8, H-1¢), 5.89 (1H, br s, NH), 4.79 (2H, s, NH2), 4.71 (2H, br s,
NCH2), 4.58 (1H, m, H-3¢), 3.97 (1H, app q, J 3.4, H-4¢), 3.81 (1H,
dd, J 4.4, 11.0, H-5¢), 3.75 (1H, dd, J 2.9, 11.0, H-5¢), 2.59 (1H, app
quint, J 6.8, H-2¢), 2.34 (1H, ddd, J 3.7, 6.0, 13.0, H-2¢), 0.90 and
0.896 (18H, 2 s, tert-Bu), 0.10, 0.08 and 0.07 (12H, 3 s, SiCH3); dC
(125 MHz; CDCl3) 160.0, 155.2, 139.0, 136.0, 128.8, 128.0, 127.6,
115.1, 87.9, 83.8, 72.3, 63.1, 44.7 (br), 41.0, 26.2, 26.0, 18.7, 18.3,
-4.4, -4.5, -5.10, -5.2.
3¢,5¢-Di-O-(tert-butyldimethylsilyl)-O6 -phenyl-2¢-deoxyguano-
sine (18)24. Yellowish solid, prepared in 89% yield using phenol
(15.3 mg, 0.163 mmol), in a reaction time of 2.5 h. Rf (silica, 5%
MeOH in CH2Cl2) = 0.26; dH (500 MHz; CDCl3) 8.01 (1H, s, H-
8), 7.40 (2H, t, J 7.8, Ar–H), 7.25–7.23 (3H, m, Ar–H), 6.34 (1H,
t, J 6.4, H-1¢), 4.82 (2H, s, NH2), 4.60 (1H, m, H-3¢), 3.99 (1H,
app q, J 3.4, H-4¢), 3.83 (1H, dd, J 3.9, 11.2, H-5¢), 3.77 (1H, dd,
J 2.9, 11.2, H-5¢), 2.58 (1H, app quint, J 6.8, H-2¢), 2.37 (1H, ddd,
J 3.9, 6.4, 13.1, H-2¢), 0.92 and 0.91 (18H, 2 s, tert-Bu), 0.10 and
0.09 (12H, 2 s, SiCH3); dC (125 MHz; CDCl3) 160.7, 159.4, 154.7,
152.8, 138.7, 129.5, 125.5, 122.2, 116.2, 88.0, 84.0, 72.1, 63.1, 41.3,
26.3, 26.0, 18.7, 18.3, -4.4, -4.5, -5.1, -5.2.
General procedure for the reaction of 4 with alcohols
In a clean, dry reaction vial equipped with a stirring bar were
placed 4 (50.0 mg, 81.6 mmol) and Cs2CO3 (53.1 mg, 0.163 mmol)
in the appropriate alcohol as solvent (0.5 mL). The reaction
mixture was flushed with nitrogen gas, sealed with a Teflon-lined
cap and stirred for 4–7 hours at room temperature. Progress
of the reaction was monitored by TLC. Upon completion, the
mixture was diluted with EtOAc and washed with deionized
water containing a small amount of NaCl. The aqueous layer
was back extracted (2¥) with EtOAc. The combined organic layer
was dried over Na2SO4, filtered and evaporated. Purification on a
silica gel column using 30% EtOAc in hexanes then provided the
2¢-deoxyguanosine O6-alkyl ethers 16 and 17. Additional details
are listed under the specific compound headings.
3¢,5¢-Di-O-(tert-butyldimethylsilyl)-O6-(4-chlorophenyl)-2¢-deo-
xyguanosine (19)24. Yellow solid, prepared in 88% yield using
4-chlorophenol (21.0 mg, 0.163 mmol), in a reaction time of 2 h.
Rf (silica, 5% MeOH in CH2Cl2) = 0.28; dH (500 MHz; CDCl3)
8.02 (1H, s, H-8), 7.36 (2H, J 8.8, Ar–H), 7.19 (2H, d, J 8.8, Ar–
H), 6.34 (1H, t, J 6.4, H-1¢), 4.79 (2H, s, NH2), 4.61 (1H, m, H-3¢),
3.99 (1H, app q, J 3.9, H-4¢), 3.84 (1H, dd, J 4.4, 11.2, H-5¢),
3.77 (1H, dd, J 2.9, 11.2, H-5¢), 2.58 (1H, app quint, J 6.8, H-2¢),
2.38 (1H, ddd, J 3.9, 5.9, 13.2, H-2¢), 0.923 and 0.920 (18H, 2 s,
tert-Bu), 0.11 and 0.10 (12H, 2 s, SiCH3); dC (125 MHz; CDCl3)
160.3, 159.3, 154.9, 151.3, 138.9, 130.8, 129.6, 123.6, 116.1, 88.0,
84.0, 72.1, 63.0, 41.3, 26.2, 26.0, 18.7, 18.3, -4.4, -4.5, -5.1, -5.2.
3¢,5¢-Di-O-(tert-butyldimethylsilyl)-O6 -methyl-2¢-deoxyguano-
sine (16)24. Light yellow solid, prepared in 79% yield using
MeOH, in a reaction time of 4 h. Rf (silica, 5% MeOH in CH2Cl2) =
0.41; dH (500 MHz; CDCl3) 7.91 (1H, s, H-8), 6.32 (1H, t, J 6.4,
H-1¢), 4.83 (2H, s, NH2), 4.59 (1H, m, H-3¢), 4.08 (3H, s, OCH3),
3.97 (1H, app q, J 3.9, H-4¢), 3.81 (1H, dd, J 4.4, 11.2, H-5¢), 3.75
(1H, dd, J 3.4, 11.2, H-5¢), 2.57 (1H, app quint, J 6.3, H-2¢), 2.34
(1H, ddd, J 3.8, 6.1, 13.0, H-2¢), 0.912 and 0.910 (18H, 2 s, tert-
Bu), 0.10, 0.08 and 0.07 (12H, 3 s, SiCH3); dC (125 MHz; CDCl3)
161.8, 159.5, 153.7, 137.8, 116.2, 87.9, 83.9, 72.1, 63.1, 54.1, 41.2,
26.2, 26.0, 18.7, 18.3, -4.4, -4.5, -5.1, -5.2.
Acknowledgements
This work was partially supported by a NSF grant CHE-0640417,
a NIGMS SCORE grant S06 GM008168-29 and a PSC CUNY-
39 award. Infrastructural support at CCNY was provided by
NIH/NCRR/RCMI grant G12 RR03060. We thank Dr Cliff Soll
(Hunter College) for high-resolution mass spectral analysis.
O6 -Allyl-3¢,5¢-di-O-(tert-butyldimethylsilyl)-2¢-deoxyguanosine
(17)24. Light yellow solid, prepared in 82% yield using allyl
This journal is
The Royal Society of Chemistry 2009
Org. Biomol. Chem., 2009, 7, 2933–2940 | 2939
©

10 B. L. Gaffney and R. A. Jones, Tetrahedron Lett., 1982, 23, 2257–
2260.
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