A new synthetic approach for the synthesis of N2-modified guanosines

Article abstract of DOI:10.1055/s-2005-869905

A new universal route for generating N²-modified guanosines is developed and the synthesis of two examples is shown. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-869905

PAPER
1797
A New Synthetic Approach for the Synthesis of N2-Modified Guanosines
A
N
ew Syntheti
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A
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h for th
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Synth
a
esis of
N
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2 n
M
odified G
u
a
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nosines Hofmann, Karin Zweig, Joachim W. Engels*
Institute for Organic Chemistry and Chemical Biology, Johann Wolfgang Goethe-University, Marie-Curie-Str. 11, 60439 Frankfurt am
Main, Germany
Fax +49(69)79829148; E-mail: joachim.engels@chemie.uni-frankfurt.de
Received 24 November 2005; revised 7 March 2005
yields obtained.11 By using protecting groups like benzyl
Abstract: A new universal route for generating N2-modified gua-
or nitrophenylethyl (NPE) at the O6-position better yields
nosines is developed and the synthesis of two examples is shown.
are achieved, especially with polyvinylpyridinium poly-
Key words: alkylations, alkyl halides, DNA , nucleosides, synthe-
hydrogenfluoride (PVPHF) as the fluorination reagent.12
sis
Therefore this route has been used, even for biological ap-
plications.13
A simpler and shorter approach for the synthesis of N2-
modified guanosines uses wyosine as the protected inter-
regions of DNA is of great importance for understanding
The insertion of appropriate reporter groups into specific
mediate. This motive has been known for 30 years.14,15
Several derivatives have been synthesized because of
their analogy to the tricyclic acyclovir and were proven to
be active against herpes infections.16 The wyosine motive
can be also used as a protecting group for guanosine, as
the tricycle (1) generated protects the N1-position as well
as the N2-position. Therefore the possibility of double
alkylations in the next step is prevented. Scheme 1 shows
the route for the synthesis of N2-modified guanosines. In
connection with this guanosine reacts with freshly synthe-
sized bromoacetone,17 which is a teargas. Wyosine (1) is
generated easily and in good yield. The following alkyla-
tion is universally applicable; aliphatic or arylalkyl bro-
mides can be used as electrophilic agents. The alkylated
wyosine 2 can be deprotected using mild conditions and
then the modified N2-guanosine 3 is readily obtained in a
good yield (44% over three steps).
its structural motives and biological functions.1 These
markers usually possess physical properties, which allow
detection and/or quantification. For example the marker
can be a fluorophoric or paramagnetic group, so that they
can be measured by fluorescence or EPR (electron para-
magnetic resonance) spectroscopy.2,3 Modified oligo-
deoxynucleotides are also of great interest for therapeutic
use.4
Reporter groups for DNA are mainly either tethered to the
5-position of pyrimidines or the 7-position of deazapu-
rines. This results in derivatization of the major groove of
the B-helix. For labeling nucleosides in the minor groove
especially, guanosine is an interesting candidate, because
of its exocyclic amino function; this group points to the
minor groove in a B-helix. Monoalkylation of this amino
group of guanosine does not seem to impair its Watson–
Crick base pairing capacity. When we tested the 2¢,3¢-
dideoxy derivative of 3 in a T7-DNA-polymerase assay,
we found adequate termination.5
The N2-function of 2¢-deoxyguanosine cannot be directly
alkylated. Indeed the reaction at the N7-position predomi-
nates and in some cases significant amounts of the O6-
alkylation products can be obtained.6 Even in the presence
of a weak base like potassium carbonate and with methyl
iodide as alkylating agent, the reaction preferentially oc-
curs at the N1-position.7
For that reason a special strategy is needed for the synthe-
sis of N2-modified guanosines. The synthesis of 2-fluo-
roguanosine is possible; the fluorine can be replaced by an
amine afterwards. This nucleophilic substitution works
best with fluorine derivatives, in contrast to bromine or io-
dine derivatives.8 Several attempts were necessary to op-
timize the fluorination step.9,10 However, fluorination of
O6-unprotected guanosines is not convenient for the syn-
thesis of N2-modified guanosines, because of the low
Scheme 1 Reagents and conditions: a) NaH, CH3C(O)CH2Br,
NH4OH, r.t.; b) K2CO3, Br(CH2)4CN, 2 d, r.t.; c) CH3CN–H2O, NBS,
NH4OH, r.t., 30 min.
SYNTHESIS 2005, No. 11, pp 1797–1800
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Advanced online publication: 19.05.2005
DOI: 10.1055/s-2005-869905; Art ID: T14304SS
© Georg Thieme Verlag Stuttgart · New York

1798
T. Hofmann et al.
PAPER
2¢-Deoxy-4-desmethylwyosine (1)
Due to the high polarity of guanosine, protecting the hy-
droxyl groups is advisable. Unfortunately, conversion to
acetyl was not successful, because of the alkaline work-up
required. To show the general applicability of this meth-
od, a second linker and nucleophilic agent was used
(Scheme 2). In generating the N2-modified guanosine 8
(23% over five steps), TBS groups were used as protect-
ing groups for the hydroxyl groups of the sugar and p-io-
dobenzylbromide was used as an alkylating agent. The
cleavage of the wyosine was performed analogously to
Scheme 1.
The reaction was carried out in a dry flask under an argon atmo-
sphere. 2¢-Deoxyguanosine (5 g; 18.71 mmol) was dissolved in an-
hyd DMSO (60 mL) and NaH (60% suspension; 940 mg, 19.64
mmol) was added. After stirring the solution for 1 h, bromoacetone
(2.69 g; 19.64 mmol) was added and the mixture was stirred for 1 h.
Then the reaction was completed by adding NH4OH (30 mL). After
2 h the solution was reduced to a volume of 30 mL. The residue was
dissolved in acetone (30 mL) and added to a stirred mixture of ace-
tone (400 mL) and anhyd Et2O (100 mL). After stirring at 0 °C for
3 h the resulting oil was isolated by decanting the solvent. The oil
was washed with Et2O (2 × 250 mL) and dried under reduced pres-
sure. The powder obtained was taken up in H2O (200 mL) and ab-
sorbed onto 15 g of silica gel by several co-evaporations with EtOH;
column chromatography (CH2Cl2 → CH2Cl2–MeOH, 9:1) gave 4.7
g (82%) of 1.
The difference between the yields obtained can be ex-
plained by the different reactivities and the size of the
electrophilic reagents used. This new synthetic approach
for the synthesis of N2-modified guanosines can be used
for N2-monoalkylation of guanosine, giving rise to minor
groove labeling, which is yet almost unexplored. This
might be especially helpful for monitoring DNA protein
interactions whether they take place in the minor or major
groove.
1H NMR (250 MHz, DMSO-d6): d = 2.28 (d, 3 H, C8-CH3), 2.32–
2.68 (m, 2 H, H-2¢), 3.51–3.63 (m, 2 H, 2 H-5¢), 3.87–3.88 (m, 1 H,
H-4¢), 4.41 (m, 1 H, H-3¢), 5.00–5.16 (t, 1 H, 5¢-OH), 5.34–5.35 (d,
1 H, 3¢-OH), 6.23–6.29 (t, 1 H, J = 6.8 Hz, H-1¢), 7.37 (d, 1 H, H-
9), 8.14 (s, 1 H, H-2), 12.38 (s, 1 H, N-H).
13C NMR (62.8 MHz, DMSO-d6): d = 10.5 (C8-CH3), 38.5–40.7
(C-2¢ and C-3¢ covered by DMSO), 70.76 (C-5¢), 83.0 (C-4¢), 87.6
(C-1¢), 103.3 (C-9), 115.5 (C-12), 126.1 (C-8), 136.9 (C-2), 145.5
(C-6), 149.5 (C-4), 151.2 (C-11).
MS-ESI: m/z = 304.3 [M – H]–.
Anal. Calcd for C13H15N5O4: C, 51.15; H, 4.95; N, 22.94. Found: C,
51.32; H, 4.95; N, 22.69.
7-Valerianacidnitrile-2¢-deoxy-7-desmethylwyosine (2)
The reaction was carried out in a dry flask under an argon atmo-
sphere. K2CO3 (0.48 g; 3.5 mmol) was added to a solution of 1 (1.00
g; 3.3 mmol) in anhyd DMF (25 mL). The suspension was stirred
for 2 d. The mixture was filtered through celite and washed with
warm DMF until UV-activity disappeared. The solvent was re-
moved by using a nitrogen rotary evaporator and recrystallization of
the residue from MeOH gave 0.96 g (75%) of 2.
1H NMR (250 MHz, DMSO-d6): d = 1.54–1.65 (m, 2 H, H-15),
1.77–1.89 (m, 2 H, H-14), 2.34 (d, 3 H, C8-CH3), 2.49–2.59 (m, 3
H, H-2¢, H-16), 2.67–2.77 (m, 1 H, H-2¢), 3.49–3.66 (m, 2 H, H-5¢),
3.84–3.89 (m, 1 H, H-4¢), 4.07–4.11 (t, 2 H, J = 7.1 Hz, H-13),
4.41–4.43 (m, 1 H, H-3¢), 4.92–4.96 (t, 1 H, J = 5.3 Hz, 5¢-OH),
5.32–5.34 (d, 1 H, 3¢-OH), 6.23–6.29 (t, 1 H, J = 7.0 Hz, H-1¢), 7.48
(d, 1 H, H-9), 8.12 (s, 1 H, H-2).
13C NMR (62.8 MHz, DMSO-d6): d = 6.2 (C8-CH3), 9.6 (C-16),
21.9 (C-15), 27.5 (C-14), 38.4–40.6 (C-2¢ and C-3¢ covered by
DMSO), 41.1 (C-13), 61.8 (C-5¢), 83.6 (C-4¢), 87.7 (C-1¢), 103.1 (C-
9), 115.9 (C-12), 120.4 (CN), 127.3 (C-8), 137.3 (C-2), 144.9 (C-6),
149.1 (C-4), 150.9 (C-11).
MS-ESI: m/z = 385.3 [M – H]–.
Anal. Calcd for C18H21N6O3: C, 59.48; H, 7.49; N, 17.34. Found: C,
59.28; H, 7.55; N, 17.36.
Scheme 2 Reagents and conditions: a) TBSCl, imidazole, DMF,
r.t., 4 h; b) NaH, CH3C(O)CH2Br, NH4OH, r.t.; c) K2CO3, p-iodoben-
zylbromide, r.t.; d) THF–H2O, NBS, NH4OH, r.t., 30 min; e) THF,
TBAF, r.t., 20 min.
2-Valerianacidnitrile-2¢-deoxyguanosine (3)
To a solution of 2 (0.25 g; 0.65 mmol) in MeCN (5 mL) and H2O (5
mL), NBS (0.14 g; 0.78 mmol) was added and the solution was
stirred for 30 min. Afterwards a concd aq solution of NH4OH was
added and the mixture was stirred for another 30 min. The solvent
was evaporated under reduced pressure and the residue was ab-
sorbed onto silica gel by several co-evaporations with EtOH; col-
umn chromatography (CH2Cl2–MeOH, 9:1) gave 0.16 g (72%) of 3.
All 1H and 13C NMR spectra were measured on a Bruker AM 250
(250 MHz) spectrometer or on a Bruker Avance 400 (400 MHz)
spectrometer. J values are given in Hz. MALDI-mass spectra were
recorded on a Fisons VG Tofspec spectrometer and ESI-mass spec-
tra on a Fisons VG Plattform II spectrometer. Column chromatog-
raphy was carried out on silica gel 60 (Merck 9385, 34–62 mm).
1H NMR (250 MHz, DMSO-d6): d = 1.61–1.62 (m, 4 H, H-14 and
H-15), 2.11–2.17 (m, 1 H, H-2¢), 2.50–2.56 (m, 3 H, H-2¢, H-16),
3.22-3.31 (m, 2 H, H-13), 3.42–3.63 (m, 2 H, H-5¢), 3.84–3.89 (m,
Synthesis 2005, No. 11, 1797–1800 © Thieme Stuttgart · New York

PAPER
A New Synthetic Approach for the Synthesis of N2-Modified Guanosines
1799
1 H, H-4¢), 4.42–4.46 (m, 1 H, H-3¢), 4.70–4.73 (t, 1 H, J = 5.8 Hz,
5¢-OH), 5.27–5.28 (d, 1 H, 3¢-OH), 6.12–6.16 (t, 1 H, J = 7.1 Hz, H-
1¢), 6.59–6.62 (t, 1 H, N2-H), 7.89 (s, 1 H, H-8), 10.72 (s, 1 H, N1-
H).
13C NMR (62.8 MHz, DMSO-d6): d = 15.9 (C-16), 22.2 (C-15),
27.8 (C-14), 36.1 (C-2¢), 38.6–40.4 (C-13 covered by DMSO), 61.9
(C-5¢), 70.8 (C-3¢), 85.1 (C-1¢), 87.5 (C-4¢), 117.6 (C-5), 120.5
(CN), 151.5 (C-4), 152.2 (C-2), 155.4 (C-6).
3¢,5¢-O-Di-tert-butyldimethylsilyl-2¢-deoxy-7-(p-iodobenzyl)-4-
desmethylwyosine (6)
The reaction was carried out in a dry flask under an argon atmo-
sphere. To a solution of 5 (3.65 g; 6.84 mmol) in anhyd DMF (40
mL) were added K2CO3 (1.23 g; 8.88 mmol) and p-iodobenzylbro-
mide (2.23 g; 7.52 mmol). After 30 min a precipitate formed; after
stirring for a further 2 h, the solvent was removed under reduced
pressure and column chromatography (CH2Cl2–i-PrOH, 40:1) of
the residue gave 1.93 g (57%) of 6.
1H NMR (250 MHz, CDCl3): d = –0.02 (s, 6 H, SiCH3), 0.00 (s, 6
H, SiCH3), 0.81 (s, 18 H, Si-t-Bu), 2.12 (s, 3 H, 8-CH3), 2.15–2.30
(m, 1 H, H-2¢), 2.35–2.50 (m, 1 H, H-2¢), 3.68–3.69 (m, 2 H, H-5¢),
3.87–3.89 (m, 1 H, H-4¢), 4.47–4.48 (m, 1 H, H-3¢), 5.12 (s, 2 H, 13-
CH2), 6.20–6.30 (t, 1 H, J = 6.5 Hz, H-1¢), 6.87 (d, 2 H, J = 8.3 Hz,
ArH-15/19), 7.32 (s, 1 H, H-9), 7.56 (d, 2 H, J = 8.3 Hz, Ar-H-16/
18), 7.87 (s, 1 H, H-2).
13C NMR (100.6 MHz, CDCl3): d = –5.5 (2 s, SiCH3), –4.8 (2 s,
SiCH3), 10.3 (8-CH3), 17.9 (SiC, quaternary), 18.4 (SiC, quaterna-
ry), 25.9 (2 s, Si-t-Bu), 41.1 (C-2¢), 45.3 (C-13), 62.9 (C-5¢), 71.9
(C-3¢), 83.6 (C-1¢), 87.6 (C-4¢), 93.6 (C-17), 104.0 (C-9), 116.9 (C-
12), 126.2 (C-8), 128.9 (C-15/19), 135.4 (C-14), 136.4 (C-2), 138.0
(C-16/18), 145.7 (C-6), 149.3 (C-4), 151.7 (C-11).
MS-ESI: m/z = 348.9 [M – H]+.
Anal. Calcd for C15H20N6O3: C, 54.21; H, 6.07; N, 25.29. Found: C,
54.40; H, 6.31; N, 25.18.
3¢,5¢-O-Di-tert-butyldimethylsilyl-2¢-deoxyguanosine (4)
The reaction was carried out in a dry flask under an argon atmo-
sphere. 2¢-Deoxyguanosine (5 g, 18.7 mmol) was suspended in an-
hyd DMF (23 mL). A TBS-solution (1 mol/L solution in THF; 75
mL, 4 equiv) and imidazole (8.9 g, 131 mmol, 7 equiv) was added
to the suspension. After 10 min the solution began to clear and the
product began to crystallize. The suspension was stirred overnight,
EtOH (30 mL) was added, and after stirring for 30 min the suspen-
sion was concentrated under reduced pressure. The crystals were
filtered off under vacuum and washed with cold EtOH. The residue
was dried under vacuum overnight and gave 8.36 g (90%) of 4.
MS-ESI: m/z = 750.3 [M – H]+.
Anal.Calcd for C32H48IN5O4Si2: C, 51.20; H, 6.41; N, 9.04. Found:
C, 51.18; H, 6.34; N, 8.77.
1H NMR (250 MHz, DMSO-d6): d = –0.06 (s, 6 H, SiCH3), 0.00 (s,
6 H, SiCH3), 0.77 (6 s, 18 H, Si-t-Bu), 2.05–2.20 (m, 1 H, H-2¢),
2.50–2.65 (m, 1 H, H-2¢), 3.50–3.62 (m, 2 H, H-5¢), 3.69–3.77 (m,
1 H, H-4¢), 4.38–4.40 (m, 1 H, H-3¢), 5.98–6.01 (t, 1 H, J = 6.0 Hz,
H-1¢), 6.43 (s, 2 H, NH2), 7.8 (s, 1 H, H-8), 10.57 (s, 1 H, NH).
13C NMR (62.8 MHz, DMSO-d6): d = –5.78 (2 s, SiCH3), –5.2 (2 s,
SiCH3), 17.3 (SiC, quaternary), 17.6 (s, SiC, quaternary), 25.4 (Si-
t-Bu), 39.2 (C-2¢), 62.6 (C-5¢), 71.9 (C-3¢), 82.1 (C-1¢), 86.8 (C-4¢),
116.6 (C-5), 134.5 (C-8), 150.7 (C-4), 153.5 (C-2), 156.3 (C-6).
3¢,5¢-O-Di-tert-butyldimethylsilyl-2-N-(p-iodobenzyl)-2¢-deoxy-
guanosine (7)
To a solution of 6 (1.53 g; 2.04 mmol) in THF (50 mL), H2O (20
mL) and NBS (0.45 g; 2.45 mmol) were added. After 40 min the re-
action was stopped by the addition of an aq solution of NH4OH
(32%; 10 mL). After stirring for 30 min the two phases were sepa-
rated and the aqueous phase was extracted with CH2Cl2 (2 × 100
mL). The combined organic phases were dried with Na2SO4, fil-
tered, and evaporated. Column chromatography (CH2Cl2–i-PrOH,
30:1) of the residue gave 1.06 g (73%) of 7.
1H NMR (250 MHz, CDCl3): d = –0.03 (s, 6 H, SiCH3), 0.00 (s, 6
H, SiCH3), 0.77 (2 s, 18 H, Si-t-Bu), 2.15–2.20 (m, 1 H, H-2¢), 2.21–
2.35 (m, 1 H, H-2¢), 3.64–3.66 (m, 2 H, H-5¢), 3.88–3.89 (m, 1 H,
H-4¢), 4.38–4.39 (m, 1 H, H-3¢), 4.46 (s, 2 H, N2-CH2), 6.07 (t, 1 H,
H-1¢), 7.03 (d, 2 H, J = 8.3 Hz, o-ArH), 7.39 (s, 1 H, H-8), 7.47 (d,
2 H, J = 8.3 Hz, m-Ar-H), 8.1 (s, 1 H, N2-H), 12.05 (s, 1 H, N1-H).
13C NMR (100.6 MHz, CDCl3): d = –5.5 (2 s, SiCH3), –4.8 (2 s,
SiCH3), 18.3 (SiC, quaternary), 18.4 (SiC, quaternary), 25.8 (s, Si-
t-Bu), 40.6 (C-2¢), 44.3 (C-10), 62.9 (C-5¢), 72.3 (C-3¢), 84.1 (C-1¢),
87.7 (C-4¢), 91.9 (C-14), 117.2 (C-5), 128.6 (C-12/16), 135.3 (C-8),
137.2 (C-13/15), 139.3 (C-2), 150.9 (C-4), 152.6 (C-11), 159.1 (C-
9).
MS-ESI: m/z = 496.4 [M – H]+
HRMS (ESI): m/z calcd for C30H41N5O4Si2 [M – H]+: 496.27698;
found: 496.27763.
3¢,5¢-O-Di-tert-butyldimethylsilyl-2¢-deoxy-4-desmethyl-
wyosine (5)
The reaction was carried out in a dry flask under an argon atmo-
sphere. By using a water bath (60 °C) 4 (4 g, 8.1 mmol) were dis-
solved in anhyd DMSO (80 mL). Subsequently NaH (95%; 224 mg;
8.9 mmol, 1.1 equiv) was added, which was accompanied by a ve-
hement reaction; the resulting solution was stirred for 1 h. Then bro-
moacetone (1.1 g, 8.1 mmol) was added dropwise, whereby the
solution changed color. The red solution was stirred overnight at r.t.
protected from light. The solvent was removed under reduced pres-
sure and column chromatography (CH2Cl2–MeOH, 40:1 → 20:1) of
the residue gave 3.7 g (85%) of 5.
1H NMR (250 MHz, DMSO-d6): d = –0.08 (s, 6 H, SiCH3), 0.00 (s,
6 H, Si-CH3), 0.75 (4 s, 18 H, Si-t-Bu), 2.14 (s, 3 H, 8-CH3), 2.15–
2.22 (m, 1 H, H-2¢), 2.55¢2.8 (m, 1 H, H-2¢), 3.50–3.65 (m, 2 H, H-
5¢), 3.70–3.80 (m, 1 H, H-4¢), 4.41–4.44 (m, 1 H, H-3¢), 6.11–6.17
(t, 1 H, J = 6.5 Hz, H-1¢), 7.24 (s, 1 H, H-9), 7.96 (s, 1 H, H-2), 12.20
(s, 1 H, NH).
13C NMR (100.6 MHz, DMSO-d6): d = –5.4 (2 s, SiCH3), –4.9 (2 s,
SiCH3), 10.5 (8-CH3), 17.7 (s, SiC, quaternary), 17.9 (s, SiC, qua-
ternary), 25.7 (Si-t-Bu), 39.7 (C-2¢), 62.7 (C-5¢), 71.9 (C-3¢), 82.4
(C-1¢), 86.9 (C-4¢), 103.3 (C-9), 115.5 (C-12), 125.9 (C-8), 136.4
(C-2), 145.6 (C-6), 149.6 (C-4), 151.1 (C-11).
MS-ESI: m/z = 534.3 [M – H]+
HRMS (ESI): m/z calcd for C32H42N5O4Si2 [M – H]+: 534.292634;
MS-ESI: m/z = 712.5 [M – H]+.
HRMS (ESI): m/z calcd for C36H45IN5O2 [M – H]+: 712.220578;
found: 712.22148
2-N-(p-Iodobenzyl)-2¢deoxyguanosine (8)
The reaction was carried out in a dry flask and under an argon atmo-
sphere. To a solution of 7 (1.05 g, 1.5 mmol) in anhyd THF (20 mL),
TBAF (1 M in THF; 3.1 mL, 3.1 mmol, 2.1 equiv) was added drop-
wise. After 20 min the reaction was complete. The solution was
evaporated and column chromatography (CH2Cl2–i-PrOH, 15:1) of
the residue gave 503 mg (71%) of 8.
1H NMR (250 MHz, DMSO-d6): d = 2.15–2.20 (m, 1 H, H-2¢),
2.50–2.65 (m, 1 H, H-2¢), 3.45–3.55 (m, 1 H, H-5¢), 3.75–3.85 (m,
1 H, H-5¢), 4,3 (s, 1 H, 5¢-OH), 4.44 (d, 2 H, J = 5.8 Hz, 10-CH2),
4.85 (s, 1 H, 3¢-OH), 5.26–5.27 (m, 1 H, H-4¢), 6.08–6.14 (m, 1 H,
found: 534.29285.
Synthesis 2005, No. 11, 1797–1800 © Thieme Stuttgart · New York

1800
T. Hofmann et al.
PAPER
H-3¢), 6.99 (t, 1 H, H-1¢), 7.16 (d, 2 H, J = 8.3 Hz, o-ArH), 7.67 (d,
2 H, J = 8.3 Hz, m-Ar-H), 7.89 (s, 1 H, H-8), 10.74 (s, 1 H, N1-H).
(7) Broom, A. D.; Townsend, L. B.; Jones, J. W.; Robins, R. K.
Biochemistry 1964, 3, 494.
(8) Harris, C. M.; Zhou, L.; Strand, E. A.; Harris, T. A. J. Am.
Chem. Soc. 1991, 113, 4328.
(9) Gerster, J. F.; Robins, R. K. J. Am. Chem. Soc. 1965, 87,
3752.
(10) Gerster, J. F.; Robins, R. K. J. Org. Chem. 1966, 31, 3258.
(11) Schering, A. G.; Vorbrüggen, H.; Krolikiewicz, K.;
Baumann, J. D.; Wirsching, R. C. German Patent DE
4141454A1, 1993.
13C NMR (100.6 MHz, DMSO-d6): d = 43.4 (C-2¢), 61.7 (C-10),
70.8 (C-5¢), 82.9 (C-3¢), 87.6 (C-1¢), 92.7 (C-4¢), 109.0 (C-14),
113.0 (C-5), 129.7 (C-12/16), 137.0 (C-13/15), 139.0 (C-2, C-8),
150.0 (C-4), 152.4 (C-11), 157.1 (C-6).
MS-ESI: m/z = 482.1 [M – H]–.
HRMS (ESI): m/z calcd for C16H16IN5O4 [M – H]+: 484.047624;
found: 484.04569.
(12) Adib, A.; Potier, P. F.; Doronina, S.; Huc, I.; Behr, J.-P.
Tedrahedron Lett. 1997, 38, 2989.
(13) Potier, P.; Abdennaji, A.; Behr, J.-P. Chem.–Eur. J. 2000, 6,
4188.
(14) Kasai, H.; Goto, M.; Ikeda, K.; Zama, M.; Mizuno, Y.;
Takemura, S.; Matsuura, S.; Sugimoto, T.; Goto, T.
Biochemistry 1976, 15, 898.
(15) Glemarec, C.; Wu, J.-C.; Remaud, G.; Bazin, H.; Oivanen,
M.; Lönnenberg, H.; Chattopadhyaya, J. Tetrahedron 1988,
44, 1273.
References
(1) Khan, S. I.; Grinstaff, M. W. J. Am. Chem. Soc. 1999, 121,
4704.
(2) Wojczewski, C.; Stolze, K.; Engels, J. W. Synlett 1999,
1667.
(3) Schiemann, O.; Piton, N.; Mu, Y.; Stock, G.; Engels, J. W.;
Prisner, T. F. J. Am. Chem. Soc. 2004, 126, 5722.
(4) Uhlmann, E.; Peyman, A. Chem. Rev. 1990, 90, 543.
(5) Schwarzer, K. Dissertation; Universität Frankfurt:
Germany, 2002.
(6) (a) Lawley, P. D.; Warren, W. In DNA Repair: A Laboratory
Manual of Research Procedures, 1; Friedberg, E. C.;
Hanawalt, P., Eds.; Dekker: New York, 1981, 129.
(b) Osborne, M. R.; Crosby, N. T. Benzopyrenes; Cambridge
University Press: Cambridge UK, 1987, 147.
(16) Ostrowski, T.; Zeidler, J.; Goslinski, T.; Golankiewicz, B.
Nucleosides, Nucleotides Nucleic Acids 2000, 19, 1911.
(17) Levene, P. A. Org. Synth. 1930, 10, 12.
Synthesis 2005, No. 11, 1797–1800 © Thieme Stuttgart · New York