Efficient synthesis of novel chalcogen-containing derivatives of DNA nucleobases

Article abstract of DOI:10.1016/j.tet.2015.02.005

The formation of a library of chalcogen-containing DNA nucleobase derivatives is presented. Reacting easily accessible 9-(2-bromoethyl)adenine with chalcogen-containing nucleophilic reagents led to a series of novel heteroatom derivatives incorporating S,

Full text of DOI:10.1016/j.tet.2015.02.005

Accepted Manuscript
Efficient Synthesis of Novel Chalcogen-Containing Derivatives of DNA Nucleobases
Guoxiong Hua, Junyi Du, David B. Cordes, Alexandra M.Z. Slawin, J.Derek Woollins
PII:
S0040-4020(15)00139-8
10.1016/j.tet.2015.02.005
TET 26393
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 17 December 2014
Revised Date: 19 January 2015
Accepted Date: 2 February 2015
Please cite this article as: Hua G, Du J, Cordes DB, Slawin AMZ, Woollins JD, Efficient Synthesis
of Novel Chalcogen-Containing Derivatives of DNA Nucleobases, Tetrahedron (2015), doi: 10.1016/
j.tet.2015.02.005.
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ACCEPTED MANUSCRIPT
Graphical Abstract
Efficient Synthesis of Novel Chalcogen-Containing Derivatives of DNA Nucleobases
Guoxiong Hua, Junyi Du, David B. Cordes, Alexandra M. Z. Slawin, J. Derek Woollins*
A number of novel DNA nucleobase derivatives containing chalcogens (S, Se and Te) have been synthesized in satisfactory yields.

1
ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
Efficient Synthesis of Novel Chalcogen-Containing Derivatives of DNA Nucleobases
Guoxiong Hua, Junyi Du, David B. Cordes, Alexandra M. Z. Slawin, J. Derek Woollins*
EaStCHEM School of Chemistry, University of St Andrews, Fife, KY16 9ST, UK
*Corresponding author. Tel.: (+44)-1334-463384; email: jdw3@st-and.ac.uk
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
The formation of a library of chalcogen-containing DNA nucleobase derivatives is
presented. Reacting easily accessible 9-(2-bromoethyl)adenine with chalcogen-containing
nucleophilic reagents led to a series of novel heteroatom derivatives incorporating S, Se
and Te atoms prepared in satisfactory yields. Two representative X-ray structures are
reported.
Available online
2009 Elsevier Ltd. All rights reserved
.
Keywords:
DNA nucleobases
9-(2-Bromoethyl)adenine
Adenine derivatives
Chalcogens
Woollins’ reagent
inhibitors.23
In
addition,
9-(2-fluorobenzyl)-N6-methyl-2-
1. Introduction
trifluoromethyladenine and several 9-substituted adenine derivatives
elicited a concentration-dependent inhibition of the TNFa release
from mononuclear cells stimulated with lipopolysaccharide (LPS).23
To our knowledge, chalcogen-containing derivatives substituted in
position 9 have not been reported. In this paper, we report the
synthesis of a series of chalcogen-containing adenine derivatives
substituted in position 9 and two related X-ray single crystal
structures.
Selenium, an essential micronutrient for humans and animals,1–6 is
a trace element nutrient that functions as selenocysteine for the
reduction of antioxidant enzymes such as glutathione peroxidases,7,8
thioredoxin reductase,9 and thyroid hormone deiodinases.10 The
entire selenoprotein gene population, designated the selenoproteome,
has been identified in humans and rodents,11 and numerous
selenoprotein genes have functions in development and health.12
Selenoproteins are also involved in different human genetic
disorders.12 The antioxidant activity of selenium plays a protective
role in 50 human diseases, including prostate, lung, and
intestine/colon cancer, immunodeficiency, and heart diseases.13–16 It
is well known that the adenine moiety provides a hydrogen bond
with a variety of biological molecules and contributes to the diverse
biological functions such as molecular recognition in DNA
replication and protein biosynthesis.17 Adenine derivatives
2. Results and Discussion
9-(2-Bromoethyl)adenine (2) was obtained from unprotected
adenine (1) according to the literature method.24 Starting from
unprotected adenine (1), selective alkylation with dibromoethane in
the presence of dry K2CO3 in DMF gave the derivative 2 in 45%
isolated yield. 2 was applied to the synthesis of many kinds of
chalcogen-containing molecules as a starting material as shown in
Scheme 1. Reaction of 2 with 0.5 equiv of sodium selenide or
sodium telluride in DMF at room temperature for 40 h gave the
substituted in position
9
have potent cyclic nucleotide
phosphodiesterase (PDE) inhibition properties with high selectivity
toward PDE-4.18 For instance, the 9-(2-fluorobenzyl)-N6-
methyladenine has been found to be used as
a
potent
corresponding
9,9'-(selenobis(ethane-2,1-diyl))bis(9H-purin-6-
anticonvulsant,19 anxiolytic and sedative properties,20 and was a
relatively potent PDE-4 inhibitor (IC50-2.0 mM).21 Furthermore,
initial structure activity relationship (SAR) studies around 9-
substituted adenine derivatives allowed to identify 9-(2-
fluorobenzyl)-N6-methyl-2-trifluoromethyladenine as a potent PDE-
4 inhibitor (IC50-0.042 mM), with a high selectivity vs PDE-3.21
Moreover, 9-(2-fluorobenzyl)-N6-methyl-2-trifluoromethyladenine
also elicited anti-inflammatory properties,22 and marked dose-
dependent inhibition of arachidonate release from human
mononuclear cells stimulated with N-formyl-Met-Leu-Phe, a suitable
model to investigate the in vitro anti-inflammatory activity of PDE-4
amine) (3) and 9,9'-(tellurobis(ethane-2,1-diyl))bis(9H-purin-6-
amine) (4) in respective 95% and 68% yields. The reactions can be
accelerated by warming up the reaction solutions; however, brown
selenium or dark tellurium found in the resulting suspension resulted
in reduced yields. Furthermore, lower yields were obtained when the
reactions were carried out in ethanol/THF (50/50, v/v), DMF
seemed to perform much better. The use of an excess of 9-(2-
bromoethyl)adenine also improves yields and conversions. Treating
a
suspension of potassium selenocyanate with 9-(2-
bromoethyl)adenine in dry acetone at 60°C led to the formation of 9-
(2-selenocyanatoethyl)adenine (5) in 93% yield. Reacting

2
Tetrahedron
ACCEPTED MANUSCRIPT
diphenyldisulfide or diphenyldiselenide with a excess of NaBH4 in
THF/EtOH gave 2-((2-(6-amino-9H-purin-9-yl)ethyl)selanyl)-1-
dry THF/EtOH at room temperature, followed by addition of 9-(2-
bromoethyl)adenine followed by stirring at room temperature for 24
h
(phenylselanyl)ethyl)adenine (7) 95% and 80% yields respectively. It
is noteworthy that the sulfur starting material proved to be more
reactive than its selenium analogue.
In addition, the reaction of 9-(2-bromoethyl)adenine with an
equivalent of 1-(naphthalen-2-yl)-2-selenocyanatoethanone, which
was obtained from a modified literature method,25 and NaBH4 in dry
(naphthalen-2-yl)ethanone (8) in 99% yield. Similarly, 11-((2-(6-
Amino-9H-purin-9-yl)ethyl)selanyl)undecan-1-ol (9) was formed
from 11-selenocyanatoundecan-1-ol with 9-(2-bromoethyl) adenine
under the identical reaction conditions in 99% yield. Both reactions
are very straightforward. Furthermore, the reaction of 9-(2-
bromoethyl)adenine with one equivalent of potassium selenocyanate
in ethanol, followed by hydrolysis with an aqueous solution of
NaOH produced 2-(6-amino-9H-purin-9-yl)ethyl diselane (10) from
in 87% yield.
gave rise to 9-(2-(phenylthio)ethyl)adenine (6) and (9-(2-
Scheme 1. Synthesis of a series of new selenium-containing derivatives 2 - 10 of adenine
The synthesis of 9-(2-((2-bromobenzyl)selanyl)ethyl)adenine (11)
can be achieved from 9-(2-bromoethyl)adenine by two routes as
phenylphosphonodiselenoates 12 – 14 in high yields,27 the latter
were stirred with an equivalent of 9-(2-bromoethyl)adenine in dry
THF overnight at room temperature to generate Se-(2-(6-amino-9H-
purin-9-yl)ethyl) O-alkyl phenylphosphonodiselenoates 15 - 17 in
69% - 87% yields, respectively, as shown in Scheme 3. To reduce
the probability of any diselenide byproduct formation, these
reactions were performed in an inert atmosphere. It is noteworthy
that neither coupling of two O-alkyl phenylphosphonodiselenoate
molecules nor decomposed selenium were detected.
shown in Scheme
2 . Stirring a suspension of 1,2-bis(2-
bromobenzyl)diselane (which was prepared following a literature
method26) with NaBH4 and 9-(2-bromoethyl)adenine in a dry mixed
medium of THF/EtOH (1 : 1) at room temperature for 20 h led to the
formation of 9-(2-((2-bromobenzyl)selanyl)ethyl)adenine (11) in
86%
yield.
Alternately,
with
mixing
NaBH4
1-bromo-2-
and 9-(2-
(selenocyanatomethyl)benzene
bromoethyl)adenine in dry THF/EtOH (1 : 1) at room temperature
for 20 h gave the same product in 61% yield. It is noteworthy that
1,2-bis(2-bromobenzyl)diselane proved to be a more efficient
starting material than 1-bromo-2-(selenocyanatomethyl)benzene for
the synthesis of the targeted product with high yield. Both reactions
resulted in the expected products without noticeable byproduct.
Compounds 3 – 11, 15 – 17 were characterized by multi-nuclear
NMR and IR spectroscopy and accurate mass measurement. All of
new compounds showed the anticipated molecular ion peaks [M+H]+
or [M+Na]+ and were confirmed by satisfactory accurate mass
measurements. Two stereoisomers were observed by multinuclear
NMR in compound 9 (see Experimental Section). The 77Se NMR
chemical shifts in compounds 3, 5, 7 – 11 fall within the range from
121.6 to 297.9 ppm, the highest 77Se NMR chemical shift value is
one of two isomers in compound 9 with a long alkyl chain alcohol
group, whilst the lowest 77Se NMR chemical shift value is the
compound 3 with a symmetric conformation at the Se atom centre.
Surprisingly, one of two isomers in compound 9 has very low 77Se
NMR chemical shift (140.0 ppm). Another sample having a high
77Se NMR chemical shift value (282.8 ppm) is compound 10, in
which also adopts a symmetric conformation around the Se-Se
bridge. With the similar conformation as compound 3, the 125Te
NMR chemical shift value in compound 4 is 199.3 ppm. The 31P
NMR spectra of 15 – 17 show sharp singlets in the range of 79.3 –
83.6 ppm, flanked by two pairs of selenium satellites with 31P-77Se
Scheme 2. Synthesis of 9-(2-((2-bromobenzyl)selanyl)ethyl)-9H-
purin-6-amine 11
Breaking the four-membered ring in Woollins’ reagent with two
molar equivalents of sodium alkanolates formed the sodium O-alkyl

3
coupling constants in the ranges of 434 – 439 Hz and 825 – 831 Hz,
indicating the presence of both a P-Se single bond and P=Se double
bond in these three compounds. This was further supported by the
77Se NMR spectra which showed two pairs of doublets in the range
of 307.8 – 338.6 ppm and -105.9 – -92.1 ppm with matching 31P-77Se
determined.28 The structures of 16 (Figure 1a) and 17 (Figure 2a)
ACCEPTED MANUSCRIPT
are in the triclinic space group P-1 though 17 contains two
independent molecules. The structural conformations have the
phenyl ring and the adenine ring inclined to one another at 75.85° for
16 and 55.45° for 17. The P(1)-Se(1)-Se(2) mean planes are nearly
perpendicular to the Se(1)-C-C mean planes (88.26° for 16 and
86.35° for 17). The P(1)-Se(1) and P(1)-Se(2) distances [2.253(6)
and 2.118(5) Å for 16, 2.246(2) and 2.081(2) Å for 17] are typical P-
Se single bond and P=Se double bond characters, comparable to that
in the similar structures.29
1
coupling constants in compounds 15 – 17. The H NMR spectra of
15 – 17 showed two strong singlets ranging from 7.94 – 8.38 ppm,
accompanied by singlet peaks in the range of 7.15 – 7.53 ppm for
the adenine NH2 groups, indicated the presence of adenine ring in the
molecules. The presence of the adenine rings can be further
confirmed by their special five carbon chemical shift values in the
13C NMR spectra.
c
Scheme 3. Synthesis of Se-(2-(6-amino-9H-purin-9-yl)ethyl) O-alkyl
phenylphosphonodiselenoates 15 - 17
d
Figure 2. (c) Single crystal X-ray structure of 1-(n aphthalen-2-yl)-
2-selenocyanatoethanone 17. Selected bond lengths (Å) and angles
(˚) (esds in parentheses): Se(1)-P(1) 2.246(2), Se(2)-P(1) 2.081(2),
Se(1)-C(9) 1.938(8), P(1)-C(11) 1.774(8), P(1)-O(1) 1.609(8), O(1)-
C(8) 1.428(11); P(1)-Se(1)-C(1) 98.7(2), Se(1)-P(1)-O(1) 103.6(3),
Se(2)-P(1)-O(1) 116.8(3), O(1)-P(1)-C(11) 97.9(4), Se(1)-P(1)-Se(2)
114.14(9), Se(1)-P(1)-C(11) 107.3(3), Se(2)-P(1)-C(11) 115.4(3),
P(1)-O(1)-C(8) 124.7(6), Se(1)-C(1)-C(2) 114.1(5); (d) shows the
hydrogen bonding of intermomelecule within 17.
a
In conclusion, a series of new chalcogen-containing derivatives of
DNA nucleobases having the adenine functionality were successfully
prepared and characterized. Reaction of 9-(2-bromoethyl) adenine
with sodium selenide, sodium telluride, potassium selenocyanate,
diphenyldisulfide/ NaBH4, diphenyldiselenide/ NaBH4, 1-
b
(naphthalen-2-yl)-2-selenocyanateethanone
and
11-
Figure 1. (a) Single crystal X-ray structure of 1-(n aphthalen-2-yl)-
2-selenocyanatoethanone 16. Selected bond lengths (Å) and angles
(˚) (esds in parentheses): Se(1)-P(1) 2.253(6), Se(2)-P(1) 2.118(5),
Se(1)-C(9) 1.936(14), P(1)-C(1) 1.640(2), P(1)-O(1) 1.612(13),
O(1)-C(7) 1.420(3); P(1)-Se(1)-C(9) 100.1(5), Se(1)-P(1)-O(1)
103.5(6), Se(2)-P(1)-O(1) 113.2(6), O(1)-P(1)-C(1) 101.8(9), Se(1)-
P(1)-Se(2) 114.9(2), Se(1)-P(1)-C(1) 107.5(8), Se(2)-P(1)-C(1)
114.6(8), P(1)-O(1)-C(7) 124.5(16), Se(1)-C(9)-C(1) 114.5(8); (b)
shows the hydrogen bonding of intermomelecule within 16.
selenocyanatoundecan-1-ol with 9-(2-bromoethyl) adenine resulted
in the corresponding chalcogen-containing heteroatom compounds in
good to excellent yields. Furthermore, treating 9-(2-bromoethyl)
adenine with three Woollins’ reagent derivatives of alcohols led to
the expected formation of three phosphorus-selenium heteroatom
compounds in excellent yields. The new chalcogen-containing DNA
nucleobases derivatives might provide a valuable addition to the
library of selenium-containing heteroatom compounds known.
3. Experimental section
3.1. General
Single crystals of 16 (colorless) and 17 (colorless) obtained from
diffusion of hexane into dichloromethane solutions of the
compounds in air at room temperature were investigated by X-ray
diffraction method and the structures of two compounds were

4
Tetrahedron
Unless otherwise stated, all reactions were carried out under on
[M+H]+. Accurate mass measurement [CI+, m/z]: 455.0681 [M+H]+,
ACCEPTED MANUSCRIPT
oxygen free nitrogen atmosphere using pre-dried solvents and
standard Schlenk techniques, subsequent chromatographic and work
up procedures were performed in air. 1H (270 MHz), 13C (67.9
MHz), 31P-{1H} (109 MHz) and 77Se-{1H} (51.4 MHz referenced to
calculated mass for C14H17N10Te: 455.0695.
3.2.3. Synthesis of 9-(2-Selenocyanatoethyl)adenine (5).
º
external Me2Se) NMR spectra were recorded at 25 C (unless stated
otherwise) on a JEOL GSX 270. IR spectra were recorded as KBr
pellets in the range of 4000-250 cm-1 on a Perkin-Elmer 2000
FTIR/Raman spectrometer. Mass spectrometry was performed by the
EPSRC National Mass Spectrometry Service Centre, Swansea and
the University of St Andrews Mass Spectrometry Service. X-ray
crystal structures were determined for compounds 16 and 17 at -
148(1) °C on a Rigaku ACTOR-SM, Saturn 724 CCD area detector
A suspension of potassium selenocyanate (0.145 g, 1.0 mmol) in
dry acetone (30 mL) was heated to 60°C, and 9-(2-
bromoethyl)adenine (0.241 g, 1.0 mmol) in dry acetone (5 mL) was
added dropwise. The resulting mixture was stirred at 60 °C for
another 7 h. Upon cooling to room temperature the mixture was
hydrolysed by adding water (10 mL) and extracted with diethyl
ether (2x30 mL). The ethereal layers were combined and dried over
MgSO4 overnight. The solvent was evaporated in vacuo and the
residue was purified by silica gel column (dichloromethane as
eluent) to give 0.250 g of the titled compound 5 as a pale purple solid
in 93% yield. M.p. 210-212°C. Selected IR (KBr, cm-1): 1675(s),
1645(m), 1607(s), 1573(m), 1478(m), 1420(m), 1331(m), 1306(m),
[the
St
Andrews
Automated
Robotic
Diffractometer
(STANDARD)]31 with SHINE optic using Mo Ka radiation (k =
0.71073 A). The data were corrected for Lorentz, polarisation and
absorption. The data was collected and processed using CrystalClear
(Rigaku).32 The structures were solved by direct methods33 and
expanded using Fourier techniques.34 Hydrogen atoms were refined
using the riding model. All calculations were performed using the
CrystalStructure35 and SHELXL 97.36 These data can be obtained
free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html or from
the Cambridge Crystallographic Data centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax (+44) 1223-336-033; e-mail:
deposit@ccdc.cam.ac.uk. CCDC 985908-985919
1
1235(m), 1072(m), 1016(m), 670(m), 599(m), 540(m), 504(m). H
NMR (DMF-d7, δ), 8.25 (s, 1H, adenine-H), 8.22 (s, 1H, adenine-H),
7.33 (s, 2H, NH2), 4.74 (t, J(H,H) = 6.6 Hz, 2H, NCH2), 3.73 (t,
J(H,H) = 6.6 Hz, 2H, SeCH2) ppm. 13C NMR (DMF-d7, δ), 156.6
(adenine-C), 152.8 (adenine-C), 150.2 (adenine-C), 141.1 (adenine-
C), 119.5 (adenine-C), 103.4 (C≡N), 44.2 (NCH2), 29.3 (SeCH2)
ppm. 77Se NMR (DMF-d7, δ), 197.1 ppm. Mass spectrum [CI+, m/z]:
269 [M+H]+. Accurate mass measurement [CI+, m/z]: 269.0046
[M+H]+, calculated mass for C8H8N6SeH: 269.0048.
3.2. Synthesis
3.2.1. Synthesis of 9,9'-(Selenobis(ethane-2,1-diyl))bisadenine (3).
3.2.4. Synthesis of 9-(2-(Phenylthio)ethyl)adenine (6).
A mixture of sodium selenide (0.127 g, 1.0 mmol) and 9-(2-
bromoethyl)adenine (0.482 g, 2.0 mmol) in dry DMF (10 mL) was
stirred at room temperature for 40 h. Upon filtering to remove the
solid the filtrate was diluted with water and extracted with
dichloromethane (3x50 mL). The combined organic layer was dried
over Na2SO4. After evaporative removal of solvent the crude product
was purified by column chromatography (silica gel) with 15%
MeOH in dichloromethane as eluent to give 0.385 g of the titled
compound 3 as a peach yellow solid in 95% yield. M.p. 193-195°C.
Selected IR (KBr, cm-1): 1680(s), 1655(s), 1602(s), 1574(m),
1485(s), 1417(s), 1328(s), 1308(s), 1252(m), 1224(m), 1074(m),
796(m), 650(s). 1H NMR (DMF-d7, δ), 8.23 (s, 2H, adenine-H), 8.22
(s, 2H, adenine-H), 7.35 (s, 4H, NH2), 4.53 (t, J(H,H) = 6.9 Hz, 4H,
CH2), 3.18 (t, J(H,H) = 6.9 Hz, 4H, CH2) ppm. 13C NMR (DMF-d7,
δ), 156.6 (adenine-C), 152.9 (adenine-C), 150.1 (adenine-C), 141.1
(adenine-C), 119.5 (adenine-C), 43.7 (CH2), 22.5 (CH2) ppm. 77Se
NMR (DMF-d7, δ), 121.6 ppm. Mass spectrum [CI+, m/z]: 405
[M+H]+. Accurate mass measurement [CI+, m/z]: 405.0799 [M+H]+,
calculated mass for C14H17N10Se: 405.0797.
A suspension of diphenyldisulfide (0.107 g, 0.5 mmol) and NaBH4
(0.041 g, 1.1 mmol) in dry THF (30 mL) and dry EtOH (5 mL) was
stirred at room temperature until a pale yellow solution was formed,
then 9-(2-bromoethyl)adenine (0.241 g, 1.0 mmol) was added. The
mixture was stirred at room temperature for 24 h. Upon evaporating
to remove solvent the residue was purified by silica gel column (1 : 4
methanol/dichloromethane as eluent) to give 0.256 g of the titled
compound 6 as a white solid in 95% yield. M.p. 150-152°C. Selected
IR (KBr, cm-1): 1683(vs), 1607(vs), 1574(s), 1477(s), 1418(s),
1331(m), 1302(s), 1239(m), 1071(m), 1020(m), 881(m), 795(m),
1
747(s), 692(s). H NMR (DMF-d7, δ), 8.27 (s, 1H, adenine-H), 8.24
(s, 1H, adenine-H), 7.48 (d, J(H,H) = 8.0 Hz, 1H, Ar-H), 7.41 (d,
J(H,H) = 8.0 Hz, 1H, Ar-H), 7.35 (s, 2H, NH2), 7.26-7.21 (m, 3H,
Ar-H), 4.71 (t, J(H,H) = 6.9 Hz, 2H, NCH2), 3.59 (s, 2H, SCH2)
ppm. 13C NMR (DMF-d7, δ), 156.6 (adenine-C), 153.0 (adenine-C),
150.2 (adenine-C), 141.3 (adenine-C), 135.3 (Ar-C), 129.3 (Ar-C),
129.0 (Ar-C), 126.4 (Ar-C), 119.5 (adenine-C), 45.3 (NCH2), 31.4
(SeCH2) ppm. Mass spectrum [CI+, m/z]: 272 [M+H]+. Accurate
mass measurement [CI+, m/z]: 272.0962 [M+H]+, calculated mass
for C13H13N5SH: 272.0964.
3.2.2. Synthesis of
(4).
9,9'-(Tellurobis(ethane-2,1-diyl))bisadenine
3.2.5. Synthesis of (9-(2-(Phenylselanyl)ethyl)adenine (7).
A suspension of sodium telluride (0.176 g, 1.0 mmol) and 9-(2-
bromoethyl)adenine (0.482 g, 2.0 mmol) in dry DMF (10 mL) was
stirred at room temperature for 40 h. Upon filtering to remove the
solid the filtrate was diluted with water and extracted with
dichloromethane (3x50 mL). The combined organic layer was dried
over Na2SO4. After evaporative removal of solvent the crude product
was purified by column chromatography (silica gel) with 15%
MeOH in dichloromethane as eluent to give 0.310 g of the titled
compound 4 as a mustard yellow solid in 68% yield. M.p. 196-
198°C. Selected IR (KBr, cm-1): 1654(s), 1598(s), 1573(m), 1482(s),
1414(s), 1331(s), 1308(s), 1247(s), 1072(m), 1008(m), 796(m),
724(m), 645(s). 1H NMR (DMF-d7, δ), 8.22 (s, 2H, adenine-H), 8.20
(s, 2H, adenine-H), 7.32 (s, 4H, NH2), 4.59 (t, J(H,H) = 6.9 Hz, 4H,
CH2), 3.21(t, J(H,H) = 6.9 Hz, 4H, CH2) ppm. 13C NMR (DMF-d7,
δ), 156.6 (adenine-C), 152.9 (adenine-C), 150.0 (adenine-C), 140.8
(adenine-C), 119.5 (adenine-C), 45.7(CH2), 1.9(CH2) ppm. 125Te
NMR (DMF-d7, δ), 199.3 ppm. Mass spectrum [CI+, m/z]: 455
A suspension of diphenyldiselenide (0.156 g, 0.5 mmol) and
NaBH4 (0.041 g, 1.1 mmol) in dry THF (30 mL) and dry EtOH (5
mL) was stirred at room temperature until a pale yellow solution was
formed, then 9-(2-bromoethyl)adenine (0.241 g, 1.0 mmol) was
added. The mixture was stirred at room temperature for 24 h. Upon
evaporating to remove solvent the residue was purified by silica gel
column (1 : 4 methanol/dichloromethane as eluent) to give 0.256 g of
the titled compound 7 as a white solid in 80% yield. M.p. 149-
150°C. Selected IR (KBr, cm-1): 1677(s), 1643(m), 1602(vs),
1575(m), 1478(s), 1417(s), 1329(m), 1305(s), 1252(m), 1229(m),
1
1071(m), 1-19(m), 741(m), 691(m). H NMR (DMF-d7, δ), 8.26 (s,
1H, adenine-H), 8.24 (s, 1H, adenine-H), 7.63 (d, J(H,H) = 8.0 Hz,
1H, Ar-H), 7.55 (d, J(H,H) = 8.0 Hz, 1H, Ar-H), 7.36 (s, 2H, NH2),
7.32-7.17 (m, 3H, Ar-H), 4.70 (t, J(H,H) = 6.9 Hz, 2H, NCH2), 3.98
(s, 2H, SeCH2) ppm. 13C NMR (DMF-d7, δ), 156.7 (adenine-C),
152.9 (adenine-C), 150.1 (adenine-C), 141.3 (adenine-C), 141.1 (Ar-
C), 132.1 (Ar-C), 129.5 (Ar-C), 127.1 (Ar-C), 119.5 (adenine-C),

5
45.2 (NCH2), 31.4 (SeCH2) ppm. 77Se NMR (DMF-d7, δ), 267.7
ppm. Mass spectrum [CI+, m/z]: 320 [M+H]+. Accurate mass
measurement [CI+, m/z]: 320.0408 [M+H]+, calculated mass for
C13H13N5SeH: 320.0409.
14H, CH2) ppm. 13C NMR (CD2Cl2, δ), 101.7 (C≡N), 62.7 (OCH2),
ACCEPTED MANUSCRIPT
34.4 (SeCH2), 32.9 (CH2), 30.9 (CH2), 29.9 (CH2), 29.6 (CH2), 29.5
(CH2), 29.4 (CH2), 29.1 (CH2), 28.9 (CH2), 25.8 (CH2) ppm. 77Se
NMR (CD2Cl2, δ), 207.5 ppm. Mass spectrum [ES+, m/z]: 300
[M+Na]+. Mass spectrum [CI+, m/z]: 278 [M+H]+. Accurate mass
measurement [CI+, m/z]: 278.1018 [M+H]+, calculated mass for
C12H23NOSeH: 278.1018.
3.2.6. Synthesis of 2-((2-(6-Amino-9H-purin-9-yl)ethyl)selanyl)-1-
(naphthalen-2-yl)ethanone (8).
A suspension of 11-selenocyanatoundecan-1-ol (0.277 g, 1.0
mmol) and NaBH4 (0.041 g, 1.1 mmol) in dry THF (30 mL) and dry
EtOH (5 mL) was stirred at room temperature until a pale yellow
solution was formed, then 9-(2-bromoethyl)adenine (0.241 g, 1.0
mmol) was added. The mixture was stirred at room temperature for
20 h. Upon evaporating to remove solvent the residue was purified
A suspension of potassium selenocyanate (1.50 g, 10.3 mmol) in
dry acetone (30 mL) was heated to 60 °C, and 2-bromo-1-
(naphthalen-2-yl)ethanone (2.125 g, 8.57 mmol) in acetone (10 mL)
was added dropwise. The resulting mixture was stirred at 60 °C for
another 5 h. Upon cooling to room temperature the mixture was
hydrolysed by adding water (10 mL) and extracted ether (2 x 30
mL). The ethereal layers were combined and dried over MgSO4
overnight. The solvent was evaporated in vacuo and the residue was
purified by silica gel column (dichloromethane as eluent) to give
2.74 g of 1-(naphthalen-2-yl-)-2-selenocyanatoethanone as a pale
yellow solid in 99% yield. M.p. 100-102°C. Selected IR (KBr, cm-1):
2151(m), 1656(s), 1624(m), 1468(m), 1383(m), 1356(m), 1299(m),
1177(s), 1123(m), 996(m), 941(m), 850(m), 821(s), 744(m), 586(m),
474(s). 1H NMR (CD2Cl2, δ), 8.43 (s, 1H, Nap-H), 7.96-7.88 (m, 4H,
Nap-H), 7.70-7.59 (m, 2H, Nap-H), 5.00 (s, 2H, SeCH2) ppm. 13C
NMR (CD2Cl2, δ), 193.3 (C=O), 136.2 (Nap-C), 132.3 (Nap-C),
131.3 (Nap-C), 131.2 (Nap-C), 129.8 (Nap-C), 129.6 (Nap-C), 129.1
(Nap-C), 128.0 (Nap-C), 127.4 (Nap-C), 123.4 (Nap-C), 102.0
(C≡N), 39.1 (Se-C) ppm. 77Se NMR (CD2Cl2, δ), 155.7 ppm. Mass
spectrum [CI+, m/z]: 293 [M+NH4]+. Accurate mass measurement
[CI+, m/z]: 293.0191 [M+NH4]+, calculated mass for
C13H9NOSeNH4: 293.188.
by
silica
gel
column
chromatography
(1
:
4
methanol/dichloromethane as eluent) to give 0.405 g of the titled
compound 9 as a white cream solid in 98% yield. M.p. 118-119°C.
Two diastereoisomers were found in ca. 2 : 1 intensity ratio. Selected
IR (KBr, cm-1): 1674(m), 1642(m), 1601(s), 1575(m), 1470(s),
1419(m), 1305(s), 1253(m), 1059(s), 793(m), 716(m). 1H NMR
(DMF-d7, δ), 8.24 (s, 1H, adenine-H), 8.21 (s, 1H, adenine-H), 7.32
(s, 1H, adenine-H), 7.26 (s, 1H, adenine-H), 6.81 (s, 2H, NH2), 6.80
(s, 2H, NH2), 4.92 (t, J(H,H) = 6.1 Hz, 2H, NCH2), 4.50 (t, J(H,H) =
6.1 Hz, 2H, NCH2), 4.39 (t, J(H,H) = 6.1 Hz, 2H, SeCH2), 4.04 (t,
J(H,H) = 6.1 Hz, 2H, SeCH2), 3.49 (t, J(H,H) = 6.1 Hz, OCH2), 3.11
(t, J(H,H) = 6.1 Hz, 2H, SeCH2), 2.95 (t, J(H,H) = 6.1 Hz, OCH2),
2.75 (s, 1Hx2, OH), 2.58 (t, J(H,H) = 6.1 Hz, 2H, SeCH2), 1.76-1.30
(m, 18Hx2, CH2) ppm. 13C NMR (DMF-d7, δ), 162.2 (adenine-C),
161.8 (adenine-C), 156.7 (adenine-C), 156.6 (adenine-C), 152.9
(adenine-C), 152.8 (adenine-C), 141.2 (adenine-C), 141.1 (adenine-
C), 119.1 (adenine-C), 119.0 (adenine-C), 61.6 (OCH2), 45.2
(SeCH2), 44.1 (SeCH2), 33.2 (CH2), 31.3 (CH2), 30.9 (CH2), 29.9
(CH2), 29.8 (CH2), 29.7 (CH2), 29.6 (CH2), 29.3 (CH2), 29.1 (CH2),
26.1 (CH2), 23.5 (CH2), 22.3 (CH2) ppm. 77Se NMR (DMF-d7, δ),
297.9, 140.0 ppm. Mass spectrum [CI+, m/z]: 414 [M+H]+. Accurate
mass measurement [CI+, m/z]: 414.1759 [M+H]+, calculated mass
for C18H31N5OSeH: 414.1767.
A mixture of 1-(naphthalen-2-yl)-2-selenocyanatoethanone (0.275
g, 1.0 mmol) and NaBH4 (0.041 g, 1.1 mmol) in dry THF (30 mL)
and dry EtOH (5 mL) was stirred at room temperature until a pale
yellow solution was formed, then 9-(2-bromoethyl)adenine (0.241 g,
1.0 mmol) was added. The mixture was stirred at room temperature
for 20 h. Upon evaporating to remove solvent the residue was
purified by silica gel column (1 : 4 methanol/dichloromethane as
eluent) to give 0.350 g of the titled compound 8 as a pal purple solid
in 85% yield. M.p. 178-180°C. Selected IR (KBr, cm-1): 1672(vs),
1600(vs), 1575(s), 1478(m), 1418(m), 1327(m), 1306(s), 1228(m),
3.2.8. Synthesis of 2-(6-Amino-9H-purin-9-yl)ethyl diselane (10).
1
1070(m), 1011(m), 662(s), 598(m), 542(m). H NMR (DMF-d7, δ),
To a suspension of 9-(2-bromoethyl)adenine (0.723 g, 3.0 mmol)
in dry ethanol (50 mL) was added potassium selenocyanate (0.541 g,
3.75 mmol) at 20°C. The mixture was stirred at that temperature for
4 h. Then, an aqueous solution of NaOH (0.24 g, 6.0 mmol in 10 mL
of water) was added to the mixture and stirring was continued for
another 2 h. After extraction with dichloromethane (30 mL x 3) and
washing with water (20 mL x 3), the organic layer was dried over
MgSO4. The organic residue was further purified by silica gel
chromatography (1 : 5 ethyl acetate / dichloromethane as eluent) to
give 0.420 g of the titled compound 10 as a off-white solid in 87%
isolated yield. M.p. 159-161°C. Selected IR (KBr, cm-1): 1688(s),
1648(s), 1603(s), 1570(m), 1513(m), 1477(m), 1419(m), 1370(m),
1332(m), 1296(s), 1248(m), 1219(m), 1079(m), 998(m), 970(m),
887(m), 793(m), 712(s), 641(s), 592(m), 344(m). 1H NMR (DMF-d7,
δ), 8.57 (s, 2H, adenine-H), 8.30 (s, 2H, adenine-H), 7.54 (s, 4H,
adenine-NH2), 6.22 (t, J(H,H) = 6.9 Hz, 4H, NCH2), 3.67 (s, 4H,
SeCH2) ppm. 13C NMR (DMF-d7, δ), 162.7 (adenine-C), 156.8
(adenine-C), 153.6 (adenine-C), 139.0 (adenine-C), 119.9 (adenine-
C), 45.3 (NCH2), 31.4 (SeCH2) ppm. 77Se NMR (DMF-d7, δ), 282.8
ppm. Mass spectrum [CI+, m/z]: 485 [M+H]+. Accurate mass
measurement [CI+, m/z]: 484.9979 [M+H]+, calculated mass for
C14H16N10SeH: 484.9965.
8.73 (s, 1H, Nap-H), 8.26 (s, 1H, adenine-H), 8.24 (s, 1H, adenine-
H), 8.05-8.03 (m, 4H, Nap-H), 7.70-7.61 (m, 2H, Nap-H), 7.38 (s,
2H, NH2), 3.58 (s, 2H, SeCH2), 2.92 (t, J(H,H) = 6.1 Hz, 2H, NCH2),
2.75 (t, J(H,H) = 6.1 Hz, 2H, SeCH2), ppm. 13C NMR (CD2Cl2, δ),
193.2 (C=O), 162.7 (adenine-C), 162.2 (adenine-C), 161.8 (adenine-
C), 156.6 (adenine-C), 152.9 (adenine-C), 141.6 (Nap-C), 141.3
(Nap-C), 130.6 (Nap-C), 129.8 (Nap-C), 128.7 (Nap-C), 128.5 (Nap-
C), 127.9 (Nap-C), 127.1 (Nap-C), 123.7 (Nap-C), 119.5 (Nap-C),
97.6 (C≡N), 66.5 (Se-C), 45.2 (N-C), 31.3 (Se-C) ppm. 77Se NMR
(DMF-d7, δ), 197.2 ppm. Mass spectrum [CI+, m/z]: 412 [M+H]+.
Accurate mass measurement [CI+, m/z]: 412.0670 [M+H]+,
calculated mass for C19H17N5OSeH: 412.0671.
3.2.7.
Synthesis
of
1-((2-(6-Amino-9H-purin-9-
yl)ethyl)selanyl)undecan-1-ol (9).
A mixture of potassium selenocyanate (2.88 g, 20 mmol) in dry
acetone (50 mL) was heated to 60 °C, and 2-bromo-11undecanol
(5.04 g, 20 mmol) in acetone (20 mL) was added dropwise to the
mixture. The resulting mixture was stirred at 60 °C for another 5 h.
Upon cooling to room temperature the mixture was hydrolysed by
adding water (30 mL) and extracted with diethyl ether (2 x 50 mL).
The ethereal layers were combined and dried over MgSO4 overnight.
The solvent was evaporated in vacuo and the residue was purified by
silica gel column chromatography (dichloromethane as eluent) to
give 5.50 g of 11-selenocyanatoundecan-1-ol as a pale yellow oil in
99% yield. Selected IR (KBr, cm-1): 2927(s), 2854(s), 2151(m),
3.2.9. 9-(2-((2-Bromobenzyl)selanyl)ethyl)adenine (11).
Method 1: 1,2-Bis(2-bromobenzyl)diselane was prepared by a
modified literature method.26
A
suspension of 1,2-bis(2-
1
1463(m), 1056(m), 722(m), 628(m), 519(w). H NMR (CD2Cl2, δ),
bromobenzyl)diselane (0.250 g, 0.5 mmol) and NaBH4 (0.041 g, 1.1
mmol) in dry THF (30 mL) and dry EtOH (5 mL) was stirred at
room temperature until a pale yellow solution was formed, then 9-(2-
5.30 (s, 1H, OH), 3.53 (t, J(H,H) = 7.4 Hz, 2H, OCH2), 3.02 (t,
J(H,H) = 7.4 Hz, 2H, SeCH2), 1.91-1.79 (m, 4H, CH2), 1.55-1.28 (m,

6
Tetrahedron
bromoethyl)adenine (0.241 g, 1.0 mmol) was added. The mixture
0.740 g as white solid in 78% yield. M.p. 157-159°C. Selected IR
ACCEPTED MANUSCRIPT
was stirred at room temperature for 20 h. Upon evaporating to
remove solvent the residue was purified by silica gel column (1 : 4
methanol/dichloromethane as eluent) to give 0.354 g of the titled
compound 11 as an yellowish white solid in 86% yield. Method 2: A
mixture of 1-bromo-2-(selenocyanatomethyl)benzene (0.275 g, 1.0
mmol) and NaBH4 (0.041 g, 1.1 mmol) in dry THF (30 mL) and dry
EtOH (5 mL) was stirred at room temperature until a pale yellow
solution was formed, then 9-(2-bromoethyl)adenine (0.241 g, 1.0
mmol) was added. The mixture was allowed to stir at room
temperature for 20 h. Upon evaporating to remove solvent the
(KBr, cm-1): 3333.9(m), 3147(m), 1649(vs), 1596(vs), 1576(s),
1483(s), 1437(m), 1416(m), 1354(m), 1326(m), 1309(m), 1223(s),
1105(m), 1015(s), 943(s), 796(m), 740(m), 685(m), 645(m), 601(m),
1
549(s), 493(s). H NMR (DMF-d7, δ), 8.05 (s, 1H, adenine-H), 7.94
(s, 1H, adenine-H), 7.87-7.76 (m, 2H, Ar-H), 7.50-7.46 (m, 3H, Ar-
H), 7.15 (s, 2H, NH2), 4.35 (dt, J(H,H) = 6.6 Hz, J(P,H) = 1.7 Hz,
2H, NCH2), 4.14-3.90 (m, 2H, OCH2), 3.27-3.18 (m, 2H, SeCH2),
1.22 (t, J(H,H) = 7.0 Hz, 3H, CH3) ppm. 13C NMR (DMF-d7, δ),
156.9 (adenine-C), 153.2 (adenine-C), 150.4 (adenine-C), 141.2
(adenine-C), 137.5 (Ar-C), 133.2 (Ar-C), 130.6 (Ar-C), 129.2 (Ar-
C), 119.8 (adenine-C), 63.6 (OCH2), 43.4 (NCH2), 31.7 (SeCH2),
15.6 (CH3) ppm. 31P NMR (DMF-d7, δ), 79.3 (s, J(P,Se) = 436 Hz,
J(P,Se) = 826 Hz) ppm. 77Se NMR (DMF-d7, δ), 319.7 (d, J(P,Se) =
434 Hz), -97.9 (d, J(P,Se) = 825 Hz) ppm. Mass spectrum [APCI+,
m/z]: 476 [M+H]+. Accurate mass measurement [APCI+, m/z]:
475.9652 [M+NH4]+, calculated mass for C15H18N5OPSe2H:
475.9655.
residue was purified by silica gel column (1
:
4
methanol/dichloromethane as eluent) to give 0.250 g of the titled
compound 11 as an yellowish white solid in 61% yield. M.p. 118-
119°C. Selected IR (KBr, cm-1): 1669(s), 1599(vs), 1477(s), 1416(s),
1325(m), 1306(s), 1230(m), 1069(m), 1021(m), 797(m), 759(m),
657(m). 1H NMR (DMF-d7, δ), 8.26 (s, 1H, adenine-H), 8.23 (s, 1H,
adenine-H), 7.65-7.33 (m, 4H, Ar-H), 7.54 (s, 2H, NH2), 4.70 (t,
J(H,H) = 6.9 Hz, 2H, CH2), 4.05 (t, J(H,H) = 6.9 Hz, 2H, CH2), 3.59
(s, 2H, CH2) ppm. 13C NMR (DMF-d7, δ), 162.3 (adenine-C), 161.8
(adenine-C), 156.6 (adenine-C), 152.8 (adenine-C), 141.3 (Ar-C),
139.4 (Ar-C), 133.2 (Ar-C), 131.2 (Ar-C), 129.0 (Ar-C), 124.0 (Ar-
C), 119.5 (adenine-C), 45.2 (NCH2), 31.3 (SeCH2), 26.9 (SeCH2)
ppm. 77Se NMR (DMF-d7, δ), 225.4 ppm. Mass spectrum [CI+, m/z]:
409 [M+H]+. Accurate mass measurement [CI+, m/z]: 408.9705
[M+NH4]+, calculated mass for C14H14BrN5SeH: 408.9708.
3.2.10.1.
Se-(2-(6-Amino-9H-purin-9-yl)ethyl)
O-isopropyl
phenylphosphonodiselenoate (17).
0.335 g as white solid in 69% yield. M.p. 141-142°C. Selected IR
(KBr, cm-1): 3319(m), 3141(m), 1649(s), 1589(s), 1574(m),
1480(m), 1416(m), 1327(m), 1305(m), 1246(m), 1225(m), 1098(s),
962(s), 885(m), 795(m), 733(m), 687(m), 644(m), 546(s), 494(m).
1H NMR (DMF-d7, δ), 8.38 (s, 1H, adenine-H), 8.25 (s, 1H, adenine-
H), 8.14-8.06 (m, 2H, Ar-H), 7.81-7.73 (m, 3H, Ar-H), 7.53 (s, 2H,
NH2), 5.16-5.03 (m, 1H, OCH), 4.74-4.58 (m, 2H, NCH2), 3.70-3.47
(m, 2H, SeCH2), 1.54 (dd, J(H,H) = 6.3 Hz, J(P,H) = 1.6 Hz, 6H,
CH3) ppm. 13C NMR (DMF-d7, δ), 157.1 (adenine-C), 153.3
(adenine-C), 150.5 (adenine-C), 141.7 (adenine-C), 138.3 (Ar-C),
137.0 (Ar-C), 130.6 (Ar-C), 129.3 (Ar-C), 119.9 (adenine-C), 73.9
(OCH), 43.5 (NCH2), 32.1 (SeCH2), 23.9 (CH3) ppm. 31P NMR
(DMF-d7, δ), 76.8 (s, J(P,Se) = 434 Hz, J(P,Se) = 825 Hz) ppm. 77Se
NMR (DMF-d7, δ), 338.6 (d, J(P,Se) = 434 Hz), -92.1 (d, J(P,Se) =
825 Hz) ppm. Mass spectrum [ESI+, m/z]: 490 [M+H]+; 512
[M+Na]+. Accurate mass measurement [ESI+, m/z]: 489.9800
[M+H]+, calculated mass for C16H20N5OPSe2H: 489.9814; Accurate
mass measurement [ESI+, m/z]: 511.9615 [M+Na]+, calculated mass
for C16H20N5OPSe2Na: 511.9634.
3.2.10. General procedure for the synthesis of Se-(2-(6-amino-
9H-purin-9-yl)ethyl) O-alkyl phenylphosphonodiselenoates 15 -
17.
Small pieces of sodium (0.046 g, 2.0 mmol) were stirred in
alcohol (30 mL) at room temperature until fully dissolved. To this
solution Woollins’ reagent (0.54 g, 1.0 mmol) was added and heated
at 60 °C for 15 min. The reaction mixture was allowed to cool to
room temperature and the resulting yellow solution was filtered
through a small Celite pad. The filtrate was dried under vacuum and
THF (30 mL) was added. To this solution 9-(2-bromoethyl)adenine
(0.2482 g, 2.0 mmol) was added and the mixture was stirred at room
temperature overnight. The resultant mixture was filtrated to remove
solid and the filtration was dried in vacuo, the residue was purified
by silica gel column (5% methanol/95% DCM) to give the
corresponding products 15 - 17.
Acknowledgments
3.2.10.1.
Se-(2-(6-Amino-9H-purin-9-yl)ethyl)
O-methyl
phenylphosphonodiselenoate (15).
The authors are grateful to the University of St Andrews for
financial support and the EPSRC National Mass Spectrometry
Service Centre (Swansea) for mass spectral measurements.
0.800 g as greyish white solid in 87% yield. M.p. 123-125°C.
Selected IR (KBr, cm-1): 3323(s), 3138(s), 1648(s), 1598(s),
1481(m), 1415(m), 1301(m), 1251(m), 1105(m), 1019(m), 744(m),
1
Supplementary data
710(m), 687(m), 549(s), 499(s). H NMR (DMF-d7, δ), 8.26 (s, 1H,
adenine-H), 8.22 (s, 1H, adenine-H), 7.69-7.58 (m, 2H, Ar-H), 7.47-
7.37 (m, 3H, Ar-H), 7.32 (s, 2H, NH2), 5.14 (d, J(P,H) = 12.0 Hz,
3H, OCH3), 4.54-4.49 (m, 2H, NCH2), 3.42-3.29 (m, 2H, SeCH2)
ppm. 13C NMR (DMF-d7, δ), 157.0 (adenine-C), 153.8 (adenine-C),
153.0 (adenine-C), 141.5 (adenine-C), 139.3 (Ar-C), 133.3 (Ar-C),
130.7 (Ar-C), 128.0 (Ar-C), 119.7 (adenine-C), 53.1 (OCH2), 43.5
(NCH2), 31.7 (SeCH2) ppm. 31P NMR (DMF-d7, δ), 83.6 (s, J(P,Se)
= 439 Hz, J(P,Se) = 831 Hz) ppm. 77Se NMR (DMF-d7, δ), 307.8 (d,
J(P,Se) = 439 Hz), -105.9 (d, J(P,Se) = 830 Hz) ppm. Mass spectrum
[APCI+, m/z]: 462 [M+H]+. Accurate mass measurement [APCI+,
m/z]: 461.9493 [M+NH4]+, calculated mass for C14H16N5OPSe2H:
461.9498.
Supplementary data associated with this article can be found in
the online version, at xxxx
References and Notes
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2006, 136, 1311-1317.
3.2.10.1.
Se-(2-(6-Amino-9H-purin-9-yl)ethyl)
O-ethyl
phenylphosphonodiselenoate (16).

7
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27. Gray, I. P.; Slawin, A. M. Z.; Woollins, J. D. Dalton 2005,
ACCEPTED MANUSCRIPT
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2188-2194.
28. Crystal structure of 16: colorless chip crystal 0.12 x 0.06 x 0.06
mm, C15H18N5OPSe2, M = 473.23, triclinic, space group P-1, a
= 6.8270(5), b = 7.5233(5), c = 18.5628(13) Å, α = 81.694(9)°,
β = 87.199(10)o, γ = 75.331(9), V = 912.59(12) Å3, Z = 2, ρcalcd
= 1.722 gcm-3, ꢀ = 41.526 cm-1, 6728 reflections collected, 3187
unique [R(int) = 0.0470], R1 = 0.1145, wR2 = 0.3620. CCDC
1037362. Crystal structure of 17: colorless chip crystal 0.13 x
0.10 x 0.04 mm, C16H20N5OPSe2, M = 487.26, triclinic, space
group P-1, a = 8.7661(11), b = 11.9430(14), c = 18.963(2) Å, α
= 97.052(9)°, β = 94.508(3)o, γ = 98.497(3), V = 1939.2(4) Å3,
Z = 4, ρcalcd = 1.669 gcm-3, ꢀ = 39.111 cm-1, 23876 reflections
collected, 7077 unique [R(int) = 0.0556], R1 = 0.0743, wR2 =
0.2430. CCDC 1037363.
29. Hua, G.; Du, J.; Slawin, A. M. Z.; Woollins. J. D. J. Org. Chem.
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Supporting Information
Efficient Synthesis of Novel Chalcogen-Containing Derivatives of DNA Nucleobases
Guoxiong Hua, Junyi Du, David B. Cordes, Alexandra M. Z. Slawin, J. Derek Woollins*
EaStCHEM School of Chemistry, University of St Andrews, Fife, KY16 9ST, UK
*Corresponding author. Tel.: (+44)-1334-463384; email: jdw3@st-and.ac.uk
1. 1H and 13C NMR spectra of compounds 3 - 11 and 15 - 17
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