Polymethylene derivatives of nucleic bases bearing ω-functional groups. VIII.1 ω-oxo-ω-phenylalkylpyrimidines and - Purines

Article abstract of DOI:10.1134/S1068162010040060

Novel polymethylene derivatives of nucleic bases containing a phenylketo functional group at the ω-position were synthesized by the alkylation of uracil, thymine, cytosine, hypoxanthine, adenine, and N-isobutyrylguanine with ω-chloro-l-phenylalkan-1-ones and their physicochemical properties were studied. Pleiades Publishing, Ltd., 2010.

Full text of DOI:10.1134/S1068162010040060

ISSN 1068ꢀ1620, Russian Journal of Bioorganic Chemistry, 2010, Vol. 36, No. 4, pp. 477–487. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © V.V. Komissarov, A.M. Kritzyn, 2010, published in Bioorganicheskaya Khimiya, 2010, Vol. 36, No. 4, pp. 514–525.
Polymethylene Derivatives of Nucleic Bases Bearing ωꢀFunctional
Groups. VIII.1
ω
ꢀOxoꢀ ꢀPhenylalkylpyrimidines and ꢀPurines
ω
V. V. Komissarov and A. M. Kritzyn2
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, ul. Vavilova 32, Moscow, 119991 Russia
Received November 11, 2009; in final form, February 15, 2010
Abstract—Novel polymethylene derivatives of nucleic bases containing a phenylketo functional group at
the
and
studied.
ω
ꢀposition were synthesized by the alkylation of uracil, thymine, cytosine, hypoxanthine, adenine,
N
ꢀisobutyrylguanine with
ω
ꢀchloroꢀlꢀphenylalkanꢀ1ꢀones and their physicochemical properties were
Key words: alkylation, nucleosides, polymethylene analogues
DOI: 10.1134/S1068162010040060
3 2 1
INTRODUCTION
hydrolysis with lipoproteinꢀassociated phospholipase
А2 provoke inflammatory processes and are involved in
atherosclerosis pathology. Thus, this enzyme is an
attractive target in the search for agents for atheroscleꢀ
rosis treatment.
Among highly active neuroleptic drugs, there is a
group of antipsychotic agents that effectively inhibit
dopamine receptors, lack hypnosedative activity, and
stimulate the central nervous system.3 This group
includes haloperidol, trifluperidol, droperidol, and
others [2]. These compounds bear a piperidine heteroꢀ
cycle, which is linked at the nitrogen atom to a pꢀfluoꢀ
robutyrophenone. These drugs received the group
name of “butyrophenones.”
Polymethylene derivatives of nucleic bases with ꢀ
ω
functional groups proved to be convenient tools for the
regulation of various biochemical processes. For
example, compounds bearing carboxy, alkoxycarboꢀ
nyl, or hydroxyl groups at the
DNA topoisomerase I [5]. Among polymethylene
ꢀdiketo derivatives of the pyrimidine series, comꢀ
ωꢀposition can inhibit
A large number of medicines displaying a wide
spectrum of physiological activity contain an arylketo
fragment similar to a butyrophenone one. Antiarꢀ
rhythmic (propafenone and amiodarone), ganglion
blocking (lobeline), nonsteroidal antiꢀinflammatory
(ketoprofen) drugs, etc., can be given as examples [2].
A recently described nucleoside analogue, 1ꢀ(3ꢀcycloꢀ
pentenꢀ1ꢀyl)ꢀ6ꢀ(3,5ꢀdimethylbenzoyl)ꢀ5ꢀethylꢀ2,4ꢀ
pyrimidinedione [3], bearing an arylketo fragment
manifested high antiviral activity towards both HIVꢀ2
and HIVꢀ1.
β
pounds were found that inhibited the activity of E. coli
thymidineꢀ and uridine phosphorylase with an effiꢀ
cacy close to that for known inhibitors [6]. Similar
adenine and hypoxanthine derivatives display antiproꢀ
liferative properties and can be regarded as potential
antitumor agents [1].
Earlier, we reported the preparation and properties
of purine and pyrimidine
polymethylene nucleoside analogues bearing an
arylketo function at the ꢀposition of the hydrocarbon
γꢀbutyrophenones, new
γ
O
backbone [7]. These derivatives are structurally similar
to drugs of the butyrophenone group and, therefore,
can be expected to possess neuroleptic activity.
Indeed, when studying the behavior reactions in rats
and mice s following the administration of 1ꢀ(4ꢀoxoꢀ
4ꢀphenylbutyl)thymine, N.A. Bondarenko (Zakusov
Research Institute of Pharmacology, Russian Acadꢀ
emy of Medical Sciences) demonstrated that this
compound reduced the intensity of stereotypical reacꢀ
Cl
N
N
S
N
N
O
Smith et al. have found a compound with an
arylketo fragment that can inhibit phospholipase А2
(IC50 54 nM) [4]. It is known that the products of oxiꢀ
dized lowꢀdensity lipoproteins formed upon the
tions in rats administered with LꢀDOPA (Lꢀ3,4ꢀdihyꢀ
droxyphenylalanine), which supports its neuroleptic
potential [8]. The administration of this compound in
mice did not cause catalepsy but, on the contrary,
stimulated the motor activity of the animals. This
1
For communication VII, see [1].
Corresponding author; fax: + 7 (499) 135ꢀ1405; eꢀmail:
amk@eimb.ru.
2
3
Abbreviations: DBU, 1,8ꢀdiazabicycle[5.4.0.]undecꢀ7ꢀene.
477

478
KOMISSAROV, KRITZYN
allowed for the assumption that this compound was a purine (adenine, hypoxanthine, and guanine) nucleic
neuroleptic agent with D2 blocker properties.
Based on the above observations, it seems rational
to obtain similar compounds with longer polymethylꢀ
ene chains bearing a phenylcarbonyl residue at the ꢀ
position of the hydrophobic hydrocarbon backbone.
bases with the corresponding
nephenones.
ω
ꢀchloropolymethyleꢀ
Alkylating agents (IIa)–(IIc) were prepared in high
yields under Friedel–Crafts reaction conditions by the
ω
acylation of benzene with
ω
ꢀchloroacyl chlorides
(Scheme 1). The reactions were carried out at reduced
temperature with aluminum trichloride being added
to the reaction mixture in small portions to avoid the
RESULTS AND DISCUSSION
Target compounds were synthesized by the alkylaꢀ
tion of pyrimidine (uracil, thymine, and cytosine) and formation of alkylation products.
O
a
:
n
n
n
= 2, yield 82%
= 4, yield 95%
= 6, yield 82%
Cl
n
O
b
:
i
Cl
n
c:
Cl
(
I
)
(II)
O
R
HN
O
O
(
(
(
(
(
(
IIIa):
IVa):
IIIb):
IVb):
IIIc):
IVc):
n
n
n
n
= 2, R = H, yield 33%
= 2, R = CH3, yield 39%
= 4, R = H, yield 59%
= 4, R = CH3, yield 46%
= 6, R = H, yield 29%
n = 6, R = CH3, yield 27%
R
N
ii
NH
+ (II
)
O
a
:
n
n
n
= 2
= 4
= 6
n
N
H
O
b
:
n
c
:
NH2
N
N
NH2
N
(
Va):
Vb):
Vc):
n
= 2, yield 33%
= 4, yield 38%
n = 6, yield 56%
O
iii
(
n
+ (II
)
O
(
a
:
n
n
n
= 2
= 4
= 6
n
N
H
O
b
:
c
:
i – AlCl3/C6H6, ii – DBU/DMF, 90
°
C (method
А
); iii – NaH/DMF, 90°C (method B).
Scheme 1.
Compounds (IIa)–(IIc) became accessible after earlier described synthesis of polymethylene derivaꢀ
Nesmeyanov et al. had published classical works on tives with terminal phenylketo groups separated from
the synthesis and study of the properties of telomeres, the nucleic base residues by a threeꢀunit methylene
the products of ethylene radical telomerization with chain, where such protection was absolutely necessary
carbon tetrachloride [9]. In our experiments, we used [7]. The reaction was completed at 80–100 C in 20 h
°
telomeres of C5 (1,1,1,5ꢀtetrachloropentane), C7 to give the target monoalkyl uracil and thymine derivꢀ
(1,1,1,7ꢀtetrachloroheptane), and C9 (1,1,1,9ꢀtetraꢀ atives (IIIa)–(IIIc) and (IVa)–(IVc) in good yields. In
chlorononane). They were hydrolyzed to
ω
ꢀchloroꢀ addition, the reaction yielded significant amounts of
carboxylic acids [10], which were transformed into the bisalkylated products, which were also isolated and
corresponding acyl chlorides (Ia)–(Ic).
characterized. Derivatives (Va )–(Vc) were obtained by
the alkylation of cytosine sodium salt, because the
alkylation of cytosine in the presence of DBU led to a
complex mixture of side reaction products with only
traces of the target compound [11] (Scheme 1).
The alkylation of the nucleic bases of the pyrimiꢀ
dine series (IIa)–(IIc) was carried out in DMF in the
presence of DBU similar to [5] (method
А)
(Scheme 1). It was found in the preliminary experiꢀ
ments that the carbonyl groups of compounds (IIa)–
The corresponding polymethylene derivatives of
(
IIc) do not need to be protected, in contrast to the purine nucleic bases were prepared, for the most part,
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POLYMETHYLENE DERIVATIVES OF NUCLEIC BASES
479
by alkylation in the presence of DBU (Scheme 2) alkylation effects” [12] and provided an unambiguous
except compounds (VIIb) and (VIIIb), which were
obtained by the alkylation of adenine sodium salt with
reagent (IIb). The only products of hypoxanthine
alkylation with reagents (IIa)–(IIc) were its 9ꢀsubstiꢀ
tuted derivatives (VIa)–(VIc). The alkylation of adeꢀ
nine using either method resulted in a major product
alkylated at position 9 of the purine heterocycle and
minor 3ꢀsubstituted isomer. Isomeric pairs (VIIa)–
assignment of the side chain position at the purine
nucleus (Tables 1, 2; see Experimental section). For 3ꢀ
substituted isomers (VIIIa)–(VIIIb), the C2 signal was
shifted upfield by 9 ppm and the C2 signal, by about
11.6 ppm downfield if compared with 9ꢀsubstituted
isomers (VIIa)–(VIIb). In addition, the C1' signales of
the side chain also considerably differed: the signal of
the 3ꢀsubstituted derivatives was shifted by about 6ꢀ
ppm upfield relative to the corresponding signales of
(
VIIIa), (VIIb)–(VIIIb), and (VIIc)–(VIIIc) were
characterized by significant differences in the 13C
NMR spectra, which A. Holy called “characteristic the 9ꢀsubstituted derivatives.
OH
N
N
OH
N
N
N
i
N
+ (II
)
O
a
:
n
= 2
= 4
= 6
n
(
VIa):
VIb):
VIc):
n
= 2, yield 48%
= 4, yield 35%
n = 6, yield 31%
N
H
b: n
N
(
n
c: n
(
NH2
NH2
N
N
N
N
N
n
N
NH2
N
N
N
N
i
or ii
+ (II
)
+
O
O
a
:
n
= 2
= 4
= 6
n
N
H
b
:
n
n
N
(
VIIa):
VIIb):
VIIc):
n
n
n
= 2, iꢀyield 38%
= 4, iiꢀyield 61%
= 6, iꢀyield 56%
(
VIIIa):
VIIIb):
VIIIc):
n
n
n
= 2, iꢀyield 10%
= 4, iiꢀyield 8.4%
= 6, iꢀyield 3.7%
c
:
(
(
(
(
iꢀPr
O
O
HN
N
O
O
N
N
N
N
N
NH
O
N
HN
iꢀPr
NH
i
N
N
H
+ (II
)
+
N
H
O
NH
a
:
n
= 2
= 4
= 6
O
n
O
b: n
n
c: n
(
IXa):
IXb):
IXc):
n
n
n
= 2, yield 24%
= 4, yield 18%
= 6, yield 26%
(
Xa):
Xb):
Xc):
n
n
n
= 2, yield 28%
= 4, yield 15%
= 6, yield 37%
(
(
(
(
iii
iii
O
H2N
N
O
N
N
N
NH
HN
N
N
NH2
O
O
n
n
(
XIa):
XIb):
XIc):
n
n
n
= 2, yield 92%
= 4, yield 94%
= 6, yield 82%
(
XIIa):
XIIb):
XIIc):
n
n
n
= 2, yield 52%
= 4, yield 56%
= 6, yield 50%
(
(
(
(
i—DBU/DMF (method
А
), 90oC; ii—NaH/DMF (method
B
), 90oC, iii—NEt3/EtOH/H2O,
Δ
(method C).
Scheme 2.
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480
KOMISSAROV, KRITZYN
1
Table 1. H NMR spectral data of synthesized compounds (IIIa)–(VIIa), (XIa), and (XIIa)
8'
B
=
9'
7'
6'
(
(
(
(
IIIa): uracilꢀ1ꢀyl; (IVa): thymineꢀ1ꢀyl;
B
2'
4'
10'
Va ): cytosineꢀ1ꢀyl; (VIa): hypoxantineꢀ9ꢀyl
VIIa): adenineꢀ9ꢀyl; (VIIIa): adenineꢀ3ꢀyl
XIa): guanineꢀ7ꢀyl; (XIIa): guanineꢀ7ꢀyl
;
;
1'
3'
5'
11'
O
.
Compound, δ, ppm
VIa VIIa
12.21, s
Protons
(
III
a
)
(
IVa
)
*
(
Va
)
(
)
(
)
(
VIIIa
)
(
XIa
)
(XIIa)
1 H, H1 or H3
1 H, H2 or H5
1 H, H6 or H8
11.24, s
11.22, s
–
–
–
8.13, s
8.16, s
7.2, s
–
10.52, s
–
10.67, s
–
5.55,d**
5.64, d*** 7.85, s
7.58, d*** 8.18, s
7.76, s
8.35, s
7.84, s
7.66,d** 7.52, s
7.65, s
6.71, s
7.87, s
6.34, s
2 H, 2ꢀNH2 or
–
–
7.00, s
–
4ꢀNH2, or 6ꢀNH2
2 H,
J
7.16, H1
and H3
6.88, H4
7.48, H7
and H10
7.16, H9
'
3.69, t
1.59, m
3.06, t
7.95, d
7.51, m
7.62, t
3.66, t
3.65, t
4.18, t
4.19, t
4.35, t
3.96, t
4.20, t
4 H, H2
'
'
1.61, m 1.59, m
1.6–1.9,m 1.5–1.9,m 1.5–1.9,m 1.5–1.8,m 1.4–1.9,m
2 H,
2 H,
J
J
'
3.05, t
7.94, d
3.05, t
7.95, d
3.05, t
7.91, d
7.48, m
7.59, t
3.07, t
7.92, d
7.50, m
7.61, t
3.09, t
7.95, d
7.50, m
7.62, t
3.05, t
7.93, d
7.50, m
7.61, t
3.04, t
7.92, d
7.49, m
7.61, t
'
and H11'
2 H, H8
'
'
7.49, m 7.51, m
7.61, t 7.62, t
1 H,
J
'
Notes: * For compound (IVa), the 5ꢀCH signal was observed at 1.73 ppm (s, 3H);
3
** J 7.8;
*** J 7.16.
1
Since the alkylation of guanine in the presence of confirmed by H and 13C NMR spectra (Tables 1, 2;
DBU did not result in satisfactory yields because of the see the Experimental section).
low solubility, we used 2ꢀisobutyrylguanine. The reacꢀ
tion yielded a mixture of 9ꢀsubstituted (IXa)–(IXc
and 7ꢀsubstituted (Xa)–(Xc) derivatives with close Rf
values. The isolation of homogeneous isomers
required multifold column chromatography. Target
The carbonyl group of the synthesized compounds
can easily be reduced to a hydroxyl group in the presꢀ
ence of sodium borohydride, which was exemplified
by the reduction of pyrimidine and purine derivatives
)
(
IIIb)–(VIIb) (Scheme 3, Table 3).
guanine derivatives (XIa)–(XIc) and (XIIa)–(XIIc
)
B
B
B
B
were obtained by the hydrolysis of 2ꢀisobutyrylguanine
derivatives (IXa)–(IXc) and (Xa)–(Xc) under mild
basic conditions (Scheme 2).
O
HO
4
4
i
The differences in the 13C NMR spectra of 9ꢀsubꢀ
(
IIIb)–(VIIb
)
(IIId)–(VIId)
stituted (XIa)–(XIc) and 7ꢀsubstituted (XIIa)–(XIIc
)
isomers were also essential: for 7ꢀsubstituted isomers
in comparison with 9ꢀsubstituted an upfield shift
(about 8.5 ppm) of the C5 signal, a downfield shift
(about 6 ppm) of the C8 signal, and a downfield shift
of the side chain C1' signal (about 3 ppm) were
observed [13]. These results allow for the NMR idenꢀ
tification of isomeric products. The UV spectroscopy
generally used for this purpose is inapplicable in
this case because the absorption band resulting
from the electron transfer from the carbonyl group
to the phenyl radical is located at around 245 nm
i – NaBH4/EtOH/H2O (method D).
Scheme 3.
EXPERIMENTAL
Uracil, thymine, cytosine, adenine, hypoxanthine,
and guanosine were purchased from Sigma (United
States); sodium hydride as an 80% suspension in minꢀ
eral oil, and aluminum trichloride were from Fluka
(Switzerland); 1,8ꢀdiazabicycle[5.4.0]undecꢀ7ꢀene
(
13000 M–1 cm–1) and overlaps with that of the (DBU) was from Aldrich (United States); and sodium
ε
nucleic base. Thus, the UV spectra give little informaꢀ borohydride was from Acros (Belgium). Solvents were
tion. The structures of the synthesized compounds are purified using routine procedures [14]. Mass spectra
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POLYMETHYLENE DERIVATIVES OF NUCLEIC BASES
481
Table 2. 13C NMR spectral data of synthesized compounds (IIIa)–(VIIa), (XIa), and (XIIa)
8'
B
=
9'
7'
6'
(
(
(
(
IIIa): uracilꢀ1ꢀyl; (IVa): thymineꢀ1ꢀyl;
B
2'
4'
10'
Va ): cytosineꢀ1ꢀyl; (VIa): hypoxantineꢀ9ꢀyl
VIIa): adenineꢀ9ꢀyl; (VIIIa): adenineꢀ3ꢀyl
XIa): guanineꢀ9ꢀyl; (XIIa): guanineꢀ7ꢀyl
;
;
1'
3'
5'
11'
O
.
Compound, δ, ppm
VIa VIIa
Carbon
atoms
(III
a)
(IVa)*
(
Va )
(
)
(
)
(
VIIIa
)
(
XIa
)
(XIIa)
C2
C4
C5
C6
C8
C1
C2
C3
C4
C5
C6
C7
C8
C9
150.9
163.7
100.8
145.6
–
150.9
164.2
108.4
141.3
–
155.8
165.9
93.1
147.2
148.0
114.3
153.6
140.7
46.1
152.3
149.6
118.8
155.9
140.8
42.7
143.3
149.8
120.5
154.9
152.4
49.1
154.8
151.4
116.7
156.8
137.1
42.4
156.3
152.7
108.2
159.5
142.5
45.6
146.0
–
'
'
'
'
'
'
47.2
46.9
48.2
28.0
28.0
28.2
28.7
28.9
28.2
29.0
30.0
20.4
21.1
20.6
20.5
20.7
20.5
20.7
20.3
37.3
37.4
37.4
37.3
37.1
37.2
37.2
37.2
199.7
136.7
128.7
127.8
133.0
199.7
136.7
128.6
127.8
133.0
199.8
136.7
128.7
127.8
133.0
199.6
136.6
128.6
127.8
133.0
199.7
136.7
128.6
127.8
133.0
199.7
136.7
128.6
127.8
133.0
199.8
136.6
128.7
127.9
133.1
199.8
136.7
128.6
127.8
133.0
'
'
'
and C11
'
'
and C10
* For compound (IVa), the 5ꢀCH signal was observed at 11.2 ppm.
3
were registered on an MSꢀ30 mass spectrometer (Kraꢀ give 19.45 g (82.4%); mp 50–51°C; Mass:
m
/
z
196.7
196.7 (C11H13ClO). 1H NMR (CDCl3):
.75–1.9 (4 H, m, 2C 2CH2Cl); 2.95 (2 H, t, 6.8,
2); 3.52 (2 H, t, 6.2, C 2Cl); 7.41 (2 H, m,
H, Ph); 7.51 (1 H, t, 7.5 ꢀH, Ph); 7.91 (2 H, d,
7.5, CDCl3): 21.31
H2CH2CO); 31.86 ( H2CH2Cl); 37.32 (CO H2);
44.51 ( H2Cl); [127.78 (2 C); 128.41 (2 C); 132.83;
136.71] ( 6H5); 199.29 ( ). Published data [15]: mp
[
1
M M
+]. Calc.
tos, Japan); electron impact was used as an ionization
method. NMR spectra ( , ppm, , Hz) were registered
δ
J
C
H
H
J
on a Bruker AMXIIIꢀ400 (Germany) with a working
COC
H
J
J
H
p
mꢀ
1
frequency of 400 MHz for H and 100 MHz for 13C
,
NMR at 300 K in CDCl3 and DMSOꢀd6. TLC was
J
o
ꢀH, Ph). 13C NMR
(
carried out on Kieselgel 60 F254 plates (Merck, Gerꢀ
many) in chloroform–ethanol systems: 19 : 1 (A);
19.7 : 0.3 (B); 19.5 : 0.5 (C); 18 : 2 (D); 18.5 : 1.5 (E);
17 : 3 (F); 17.5 : 2.5 (G); 16 : 4 (H); and 15 : 5 (I). Colꢀ
umn chromatography was performed on Kieselgel 60
(0.040–0.063 mm, Merck, Germany).
(C
C
C
C
С
CO
48–50°C, bp 128–130°C/1 mmHg.
Table 3. Reaction yields of the reduction of compounds
(IIIb)–(VIIb)
5ꢀChloroꢀ1ꢀphenylpentanoneꢀ1 (IIa). Anhydrous
aluminum trichloride (17.3 g, 0.13 mol) was added by
small portions under stirring for 25 min to a cooled to
0°C solution of 5ꢀchloropentanoate chloride (18.6 g,
0.12 mol) (Ia) in absolute benzene (30 ml). The resultꢀ
ing solution was stirred for 1 h at 0°C and then for 1 h
at 20°C and then poured out onto ice (200 g). The
organic layer was separated, and the aqueous layer was
Starting compound/reaction
Nucleic base
,
B
Yield, %
product
IIIb)/(IIId
IVb)/ IVd
Vb)/(Vd
VIb)/(VId
VIIb)/(VIId
(
(
(
(
(
)
Ura
Thy
Cyt
Hyp
Ade
89
95
97
80
81
(
)
)
extracted with benzene (2 30 ml). The extracts were
combined, dried with anhydrous sodium sulfate, and
the solvent was evaporated and distilled in a vacuum to
×
)
)
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482
KOMISSAROV, KRITZYN
7ꢀChloroꢀ1ꢀphenylheptanoneꢀ1 (IIb) was syntheꢀ
Removal of an isobutyryl group from isobutyrylguaꢀ
sized similar to (IIa) from 7ꢀchloroheptanoate chloꢀ nine derivatives (IXa)–(IXc) and (Xa)–(Xc), the prepꢀ
ride (Ib) (33.7 g, 0.18 mol). Yield 38.5 g (95%); bp aration of guanine derivatives (XIa)–(XIc) and
152–154
°
С/4 mmHg. Mass:
m
/
z
224.7 [M+
]
. Calc.
M
(XIIa)⎯(XIIc) (method C). Triethylamine (0.28 ml,
1
224.7 (C13H17ClO). H NMR (CDCl3): 1.25–1.61 2 mmol) was added to a solution of the corresponding
(8 H, m,
COC 2); 3.488 (2 H, t,
ꢀH, Ph); 7.50 (1 H, t,
7.2,
H2CH2CO); 26.53
H2CH2Cl); 32.24 (
(CO H2); 44.78 (
132.71; 136.91] (
C
H
2C
H
2C
H
2C
H
J
J
2CH2Cl); 2.92 (2 H, t,
J
7.16, isobutyrylguanine derivative (1 mmol) in ethanol
H
6.52, C 2Cl); 7.40 (2 H, m, (10 ml) and water (2 ml). The solution was refluxed
7.5 ꢀH, Ph); 7.91 (2 H, d, and the reaction course was monitored by TLC in the
CDCl3): 23.89 proper eluting system. After 16 h, the solvents and triꢀ
H2CH2CH2Cl); 28.36 ethylamine were evaporated in a vacuum and the resiꢀ
H2CH2CH2CH2Cl); 38.15 due was chromatographed on a silica gel column (30 g,
H2Cl); [127.83 (2 C); 128.38 (2 C); 10 cm) eluting in a gradient of ethanol in chloroꢀ
6H5) 199.98 ( O). Published data form ( 30%). Target fractions were evaporated and
[9]: bp 147–148°C/1.5 mmHg.
H
m
J
, p
o
ꢀH, Ph). 13C NMR
(
(
C
(C
(C
C
C
C
С
5
×
,
C
0
→
the residue was recrystallized from a 1 : 1 water–ethaꢀ
nol mixture.
9ꢀChloroꢀ1ꢀphenylnonanoneꢀ1 (IIc) was syntheꢀ
sized similar to (IIa) from 9ꢀchlorononanoate chloꢀ
ride (Ic) (28.55 g, 0.135 mol). Yield 28 g (82%). Mass:
1ꢀ(5ꢀOxoꢀ5ꢀphenylpentyl)uracil
obtained by method A in a yield of 33%, Rf 0.49 (A),
mp 146–147 (propanolꢀ2). Mass: m/z 272.3 [
+],
273.3 [ 272.3 (C15H16N2O3). NMR
+ H+]. Calc.
spectra: see Tables 1 and 2.
(IIIa)
was
m/z
252.78 [M+
]
. Calc.
1H NMR (CDCl3):
.24–1.9 (12 H, m,
2C 2C 2C 2C 2C 2CH2Cl); 2.92 (2 H, t, 7.16,
COC 2); 3.47 (2 H, t, 6.85, C 2Cl); 7.41 (2 H, m,
H, Ph); 7.50 (1 H, t, 7.5 ꢀH, Ph); 7.93 (2 H, d,
7.2, CDCl3): 23.80
ꢀH, Ph). 13C NMR
H2CH2CO); 26.39 ( H2CH2CH2CH2Cl); 28.29
H2CH2CH2Cl); 28.78 (COCH2CH2 H2); 28.87
H2Cl); 32.19 ( H2CH2CH2CH2CH2Cl); 38.00
(CO H2); 44.56 ( H2Cl); [127.56 (2 C); 128.08 (2 C);
132.34; 136.70] ( 6H5); 199.55 ( ).
M 252.78 (C15H21ClO).
°
С
M
M
M
1
CH
H
H
H
H
H
J
H
J
J
H
mꢀ
1,3ꢀBis(5ꢀoxoꢀ5ꢀphenylpentyl)uracil was obtained
as a side product in the synthesis of (IIIa), method A,
, p
J
o
(
in a yield of 31%;
R
f 0.41 (B), oil. Mass:
m/z ]
432.5 [M+
432.5 (C26H28N2O4). H
1
+ H+]. Calc.
M
(C
C
433.5 [M
C
C
NMR (CDCl3): 1.74 (8 H, m, H2', H2'', and H3',
H3''), 2.95–3.05 (4 H, m, H4' and H4''); 3.75 (2 H, t,
C
C
C
С
J
6.2, H1''); 3.95 (2 H, t,
H5); 7.13 (1 H, d, 7.8, H6); 7.40 (4 H, m,
7.50 (2 H, t, 7.8 ꢀH, Ph); 7.90 (4 H, d,
J
7.5, H1'); 5.68 (1 H, d,
ꢀH, Ph);
8.1, ꢀH,
J 7.8,
CO
J
m
J
J
,
p
o
Alkylation of nucleic bases in the presence of DBU
(method A). The corresponding alkylating agent
(15 mmol) and DBU (2.2 ml, 15 mmol) were added to
a suspension of a nucleic base or its protected derivaꢀ
tive (10 mmol) in absolute DMF (25 ml), and the mixꢀ
Ph). 13C NMR (CDCl3): 20.67 (C3'); 21.27 (3''); 26.98
(C2'); 28.40 (C2''); 37.51 (C4'); 37.90 (C4''); 40.59
(C1'); 49.45 (C1''); 101.51 (C5); [127.85 (2 C); 127.92
(2 C); 128.41 (2 C); 128.52 (2 C); 132.79; 133.05;
136.60; 136.81] (Ph); 142.12 (C6); 151.31 (C2);
162.92 (C4); 199.36 (C5'); 199.35 (C5'').
ture was heated for 20 h at 80–100 С (TLC control),
°
cooled, and evaporated in a vacuum. The residue was
suspended in a minimal volume of chloroform and
1ꢀ(5ꢀOxoꢀ5ꢀphenylpentyl)thymine
obtained by method A in a yield of 39%; Rf 0.28 (C),
mp.156–157 (propanolꢀ2). Mass: 286.3 [
+],
287.3 [ 286.3 (C16H18N2O3). NMR
+ H+]. Calc.
spectra: see Tables 1 and 2.
(IVa)
was
chromatographed on a silica gel (200 g) column (
28 cm) eluting in a gradient of ethanol in chloroform
20%). The target fractions were evaporated and
5
×
°
С
m
/z
M
M
M
(
0
→
the residue was recrystallized.
1,3ꢀBis(5ꢀoxoꢀ5ꢀphenylpentyl)thymine was obtaiꢀ
Alkylation of adenine and cytosine sodium salts
(method B). Sodium hydride (80% suspension in minꢀ
eral oil, 0.33 g, 11 mmol) was added to a suspension of
adenine or cytosine (10 mmol) in absolute DMF
ned as a side product in the synthesis of (IVa), method
A, in a yield of 36%; Rf 0.72 (C), oil. Mass:
m
/
z
446.5
446.5 (C27H30N2O4). H NMR
(CDCl3): 1.69 (8 H, m, H2', H2'' and H3', H3''); 1.83
(3 H, s, 5ꢀC 3); 2.94 (4 H, m, H4' and H4''); 3.68 (2 H,
t, 6.2, H1''); 3.92 (2 H, t, 6.5, H1'), 6.96 (1 H, s,
H6); 7.36 (4 H, m, ꢀH, Ph); 7.44 (2 H, t, 7.8 ꢀH,
Ph); 7.86 (4 H, d, 7.8,
ꢀH, Ph). 13C NMR (CDCl3):
12.75 (5ꢀ H3); 20.58 (C3'); 21.18 (C3''); 26.90 (C2');
1
1
[M M
+]. H. Calc.
(25 ml). The mixture was stirred for 30 min at 20 С
°
H
and the corresponding alkylating agent (12 mmol) was
added. The reaction mixture was heated at 80–100°C
for 20 h (TLC control). The solvent was evaporated in
a vacuum and the residue was dissolved in chloroform
(50 ml). Water (20 ml) was added and the mixture was
poured into a funnel. The organic layer was separated
and the aqueous phase was extracted with chloroform
J
J
m
J
J
, p
o
C
28.28 (C2''); 37.41 (C4'); 37.78 (C4''); 40.62 (C1');
48.90 (C1''); 109.40 (C5); [127.70 (2 C); 127.76 (2 C);
128.26 (2 C); 128.36 (2 C); 132,64; 132.87; 136.48;
136.65] (Ph); 138.26 (C6); 151.12 (C2); 163.48 (C4);
199.29 (C5'); 199.73 (C5'').
(
5 30 ml). The extracts were combined, dried with
×
sodium sulfate, the solvent was evaporated, and the
residue was purified by column chromatography (for
conditions, see method A). The target fractions were
1ꢀ(5ꢀOxoꢀ5ꢀphenylpentyl)cytosine (Va) was obtaiꢀ
evaporated, and the residue was recrystallized from the ned by method B in a yield of 33%;
Rf 0.22 (D),
proper solvent.
mp.199–200°С dec. (propanolꢀ2–water). Mass: m/z
RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY Vol. 36
No. 4
2010

POLYMETHYLENE DERIVATIVES OF NUCLEIC BASES
483
271.3 [
M
+], 272.3 [
M
+ H+]. Calc.
M
271.3 Mass:
C16H17N5O2). NMR spectra: see Tables 1 and 2.
1ꢀ(7ꢀOxoꢀ7ꢀphenylheptyl)uracil (IIIb)
obtained by method A in a yield of 59%,
153–154 (ethanol). Mass: 300.3 [
+ H+]. Calc.
300.3 (C17H20N2O3). H NMR
(CDCl3): 1.30–1.80 (8 H, m, H2'–H5'); 2.95 (2 H, t,
7.2, H6'); 3.70 (2 H, t, 7.2, H1'); 5.67 (1 H, d, 7.8
H5); 7.14 (1 H, d, 7.8, H6); 7.44 (2 H, m, ꢀH, Ph);
7.53 (1 H, t, 7.2 ꢀH, Ph); 7.93 (2 H, d, 7.5, ꢀH,
m
/
z
311.3 [
M
+], 312.3 [
M
+ H+]. Calc.
M
311.3
(C15H17N3O2). NMR spectra: see Tables 1 and 2.
(
was
9ꢀ(5ꢀOxoꢀ5ꢀphenylpentyl)hypoxantine (VIa) was
obtained by method A in a yield of 48%; Rf 0.79 (D),
mp 114–115
R
f 0.2 (B), mp
°
С
m
/z
M
+], 301.3
°
С
dec. (EtOAc–heptane). Mass:
m/z
296.3
1
+], 297.3 [
M
+ H+]. Calc.
M
[M
M
296.3 [M
(C16H16N4O2). NMR spectra: see Tables 1 and 2.
J
J
J
,
9ꢀ(5ꢀOxoꢀ5ꢀphenylpentyl)adenine (VIIa) was
obtained by method A in a yield of 38%, Rf 0.51 (D),
J
p
m
J
J
,
о
mp 207–208
295.3 [
+], 296.3 [
(C16H17N5O). NMR spectra: see Tables 1 and 2.
°
С
dec. (EtOAc–heptane). Mass:
m/z
Ph); 9.40 (1 H, s, H3). 13C NMR (CDCl3): 23.85
(C5'); 26.18 (C3'); 28.68 (C2'); 28.77 (C4'); 38.21
(C6'); 48.67 (C1'); 102.07 (C5); [127.96 (2 C); 128.54
(2 C); 132.93; 136.94] (Ph); 144.35 (C6); 150.40 (C2);
163.74 (C4); 200.12 (C7').
M
M
+ H+]. Calc.
M
295.3
3ꢀ(5ꢀOxoꢀ5ꢀphenylpentyl)adenine (VIIIa) was
obtained by method A as a side product in a yield of
10%; Rf 0.26 (D), mp 216–217
Mass: 295.3 [
+], 296.3 [
(C16H17N5O). NMR spectra: see Tables 1 and 2.
°
С
dec. (propanolꢀ2).
1,3ꢀBis(7ꢀoxoꢀ7ꢀphenylheptyl)uracil was obtained
m
/z
M
M
+ H+]. Calc.
M
295.3
by method A as a side product in the synthesis of (IIIb
)
in a yield of 34%, Rf 0.5 (B), oil. Mass: m/z 488.6 [M
+],
489.6 [
M M 488.6 (C30H36N2O4).
+ H+]. Calc.
N2ꢀ(2ꢀMethylpropionyl)ꢀ9ꢀ(5ꢀoxoꢀ5ꢀphenylpenꢀ
tyl)guanine (IXa) was obtained by method A in a yield
of 24%, Rf 0.375 (E), mp 141–142°С (EtOAc–
1H NMR (CDCl3): 1.30–1.85 (16 H, m, H2'–H5',
H2"–H5"); 2.95 (4 H, m, H6' and H6"); 3.72 (2 H, t,
77.2, H1''); 3.93 (2 H, t, 77.2, H'); 5.69 (1 H, d, J 7.8,
octane). Mass:
381.4 (C20H23N5O3). H NMR (DMSOꢀ
(6 H, d, 6.9, COCH(C 3)2); 1.56 (2 H, m, H3'); 1.82
(2 H, m, H2'); 2.78 (1 H, m, COC (CH3)2); 3.04 (2 H,
t, 7.2, H4'); 4.08 (2 H, t, 6.9, H1'); 7.47 (2 H, m,
H, Ph); 7.59 (1 H, t, 7.5 ꢀH, Ph); 7.91 (2 H, d,
7.5, ꢀH, Ph); 8.00 (1 H, s, H8); 11.91 (2 H, br s, H1
and 2ꢀN 6): 18.83 (2 C,
). 13C NMR (DMSOꢀ
COCH( H3)2); 20.57 (C3'); 28.92 (C2'); 34.70
(CO H(CH3)2); 37.07 (C4'); 42.95 (C1'); 119.99 (C5);
m/z 381.4 [M M
+], 382.4 [
+ H+]. Calc.
6): 1.08
1
H5); 7.09 (1 H, d,
J
7.8, H6); 7.45 (4 H, m, ꢀH, Ph);
m
M
d
7.53 (2 H, m, ꢀH, Ph); 7.94 (4 H, d,
p
J
7.2, оꢀH, Ph).
J
H
13C NMR (CDCl3): 23.90 (C5'); 24.18 (C5"); 26.27
(C3'); 26.71 (C3''); 27.39 (C2'); 28.72 (C2''); 28.78
(C4'); 28.96 (C4"); 38.22 (C6'); 38.45 (C6"); 41.08
(C1'); 49.62 (C1''); 101.55 (C5); [127.95 (2 C); 127.98
(2 C); 128.48 (2 C); 128.53 (2 C); 132.74; 132.89;
137.04; 137.15] (Ph); 141.97 (C6); 151.38 (C2);
162.97 (C4); 200.02 (C7'); 200.28 (C7").
H
J
J
mꢀ
J
, p
J
о
H
d
C
C
1ꢀ(7ꢀOxoꢀ7ꢀphenylheptyl)thymine (IVb) was
obtained by method A in a yield of 46%, Rf 0.30 (C),
mp.113–114
+], 315.4 [
1H NMR (CDCl3): 1.30–1.80 (8 H, m, H2'–H5');
1.89 (3 H, s, 5ꢀC 3); 2.95 (2 H, t, 7.2, H6'); 3.67 (2 H,
t, 7.2, H1'); 6.97 (1 H, s, H6); 7.44 (2 H, m, ꢀH,
Ph); 7.53 (1 H, t, 7.2 ꢀH, Ph); 7.93 (2 H, d, 7.5,
ꢀH, Ph); 9.30 (1 H, s, H3). 13C NMR (CDCl3): 12.22
(5ꢀ H3); 23.88 (C5'); 26.20 (C3'); 28.72 (C2'); 28.81
°
С
M
(EtOAc–octane). Mass:
m/z 314.4
[M
+ H+]. Calc.
M
314.4 (C18H22N2O3).
H
J
J
m
J
,
p
J
о
C
(C4'); 38.23 (C6'); 48.33 (C1'); 110.54 (C5); [127.96
(2 C); 128.54 (2 C); 132.91; 137.05] (Ph); 140.34
(C6); 150.88 (C2); 164.26 (C4); 200.14 (C7').
1,3ꢀBis(7ꢀoxoꢀ7ꢀphenylheptyl)thymine
was
obtained by method A as a side product in the syntheꢀ
sis of (IVb) in a yield of 43% in the synthesis of (IVb),
Rf 0.71 (C), oil. Mass:
Calc.
.31–1.85 (16 H, m, H2'–H5 and H2"–H5"); 1.92
(3 H, s, 5ꢀC 3); 2.97 (4 H, m, H6' and H6"); 3.71 (2 H,
t, 7.2, H1''); 3.95 (2 H, t, 7.2, H1'); 6.99 (1 H, s,
H6); 7.46 (4 H, m, ꢀH, Ph); 7.54 (2 H, t, 7.8 ꢀH,
Ph); 7.95 (4 H, d, 7.8,
ꢀH, Ph). 13C NMR (CDCl3):
12.86 (5ꢀ H3); 23.83 (C5'); 24.08 (C5"); 26.19 (C3');
26.65 (C3''); 27.33 (C2'); 28.65 (C2"); 28.75 (C4');
was 28.87 (C4"); 38.15 (C6'); 38.37 (C6"); 41.18 (C1');
obtained by method C from compound (Xa) in a yield 49.17 (C1"); 109.51 (C5); [127.85 (2 C); 127.89 (2 C);
of 52%, f 0.265 (F), mp >250 (1 :1 water–ethanol). 128.38 (2 C); 128.44 (2 C); 132.66; 132.80; 136.92;
m/z 502.6 [M M .
+], 503.6 [ + H+]
502.6 (C31H38N2O4). H NMR (CDCl3):
1
M
1
H
J
J
m
J
, p
J
о
C
RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY Vol. 36
No. 4
2010

484
KOMISSAROV, KRITZYN
137.01] (Ph); 138.21 (C6); 151.25 (C2); 163.61 (C4);
199.97 (C7'); 200.21 (C7").
M
409.5 (C22H27N5O3). 1H NMR (CDCl3): 1.18 (6 H,
d,
H2'
J
⎯
6.86, COCH(C
H5'); 2.81 (1 H, m, COC
7.16, H1'); 7.43 (2 H, m,
ꢀH, Ph); 7.63 (1 H, s, H8);
ꢀH, Ph); 10.19 (1 H, br s, 2ꢀN );
12.13 (1 H, br s, H1). C NMR (CDCl3): 18.94 (2 C,
COCH( H3)2); 23.69 (C5'); 25.83 (C3'); 28.09 (C2');
29.68 (C4'); 36.10 (CO H(CH3)2); 38.21 (C6'); 43.18
H
3)2); 1.20–1.80 (8 H, m,
H(CH3)2); 2.96 (2 H, t,
1ꢀ(7ꢀOxoꢀ
obtained by method B in a yield of 38%, Rf 0.33 (G),
mp.191–192 (ethanol). Mass: 299.3 [
+], 300.3
+ H+]. Calc.
299.3 (C17H21N3O2). H NMR
(DMSOꢀ 6): 1.22–1.60 (8 H, m, H2'–H5'); 2.98 (2 H,
t, 7.2, H6'); 3.60 (2 H, t, 7.2, H1'); 5.62 (1 H, d,
7.2, H5); 6.89 (2 H, 4ꢀN 2); 7.53 (1 H, d, 7.2, H6);
ꢀH, Ph); 7.61 (1 H, t, 7.2, ꢀH, Ph);
7.5, 6):
ꢀH, Ph). 13C NMR (DMSOꢀ
7ꢀphenylheptyl)cytosine
(Vb)
was
J
7.16, H6'); 3.98 (2 H, t,
H, Ph); 7.54 (1 H, t, 7.5
7.90 (2 H, d, 7.16,
J
, p
mꢀ
J
°
С
m/z
M
1
J
о
H
[M
M
13
d
C
J
J
C
J
H
J
(C1'); 120.69 (C5); [127.95 (2 C); 128.61 (2 C);
133.19; 136.94] (Ph); 138.80 (C8); 147.74 (C4);
148.78 (C2); 155.78 (C6); 179.30 (
7.49 (2 H, m,
7.94 (2 H, d,
m
J
J
p
o
d
COCH(CH3)2);
23.60 (C5'); 25.72 (C3''); 28.16 (C2'); 28.46 (C4');
37.70 (C6'); 48.44 (C1'); 92.86 (C5); [127.72 (2 C);
128.56 (2 C); 132.84; 136.69] (Ph); 145.81 (C6);
155.67 (C2); 165.78 (C4); 199.95 (C7').
201.11 (C7').
N2ꢀ(2ꢀMethylpropionyl)ꢀ7ꢀ(7ꢀoxoꢀ
7
ꢀphenylhepꢀ
tyl)guanine (Xb) was obtained by method A in a yield of
15.5%, Rf 0.76 (D), oil. Mass: 409.5 [
+], 410.5
+ H+]. Calc.
409.5 (C22H27N5O3). H NMR
(CDCl3): 1.18 (6 H, d, 6.85, COCH(C 3)2); 1.25–
1.95 (8 H, m, H2'–H5'); 2.90 (2 H, t,
(1 H, m, COC (CH3)2); 4.30 (2 H, t,
(2 H, m, ꢀH, Ph); 7.49 (1 H, t, 7.5
(1 H, s, H8); 7.88 (2 H, d, 7.16, ꢀH, Ph); 10.75 (1 H,
br s, 2ꢀN
); 12.35 (1 H, br s, H1). 13C NMR (CDCl3):
18.94 (2 C, COCH( H3)2); 23.88 (C5'); 26.04 (C3');
28.53 (C2'); 30.82 (C4'); 35.80 (CO H(CH3)2); 38.17
m/z
M
9ꢀ(7ꢀOxoꢀ7ꢀphenylheptyl)hypoxantine (VIb) was
obtained by method A in a yield of 35%, Rf 0.28 (D),
1
[M
M
m/z 324.3 [M
+],
J
H
mp 181–182
325.3 [
+ H+]. Calc.
NMR (DMSOꢀ 6): 1.21–1.80 (8 H, m, H2'–H5');
2.96 (2 H, t, 7.2, H6'); 4.10 (2 H, t, 7.2, H1'); 7.49
(2 H, m, ꢀH, Ph); 7.60 (1 H, t, 7.2 ꢀH, Ph); 7.91
(2 H, d, 7.5, ꢀH, Ph), 8.01 (1 H, H8); 8.08 (1 H, s,
H2); 12.27 (2 H, s, 6ꢀO ). C NMR (DMSOꢀd6):
°
С
dec. (ethanol). Mass:
1
J
7.16, H6'); 2.95
M
M
324.3 (C18H20N4O2). H
H
J 7.16, H1'); 7.40
, pꢀH, Ph); 7.77
d
m
J
J
J
, p
J
о
m
J
H
J
о
13
C
H
C
23.30 (C5'); 25.71 (C3'); 27.90 (C2'); 29.38 (C4');
37.59 (C6'); 43.22 (C1'); [127.36 (2 C); 128.08 (2 C);
132.40; 136.37] (Ph); 123.87 (C5); 139.22 (C8);
145.24 (C2); 154.25 (C4); 156.63 (C6); 199.30 (C7').
9ꢀ(7ꢀOxoꢀ7ꢀphenylheptyl)hypoxantine (VIIb) was
obtained by method B in a yield of 61%, Rf 0.44 (D),
(C6'); 47.23 (C1'); 112.01 (C5); [127.89 (2 C); 128.45
(2 C); 132.80; 136.93] (Ph); 142.88 (C8); 147.74 (C4);
153.25 (C2); 156.93 (C6); 179.79 (
COCH(CH3)2);
200.09 (C7').
9ꢀ(7ꢀOxoꢀ7ꢀphenylheptyl)guanine
(XIb) was
m/z 323.4 [M
+],
obtained from compound (IXb) by method C in a yield
mp 161–162
324.4 [
+ H+]. Calc.
(DMSOꢀ 6): 1.2 1.8 (8 H, m, H2'–H5'); 2.95 (2 H, t,
7.2, H6'); 4.12 (2 H, t, 7.2, H1'); 7.14 (2 H, C,
6ꢀN 2); 7.49 (2 H, m, ꢀH, Ph); 7.59 (1 H, t, 7.2
ꢀH, Ph); 7.91 (2 H, d, 7.5, ꢀH, Ph); 8.12 (1 H, H2);
8.13 (1 H, s, H8). 13C NMR (DMSOꢀ
6): 23.54 (C5');
°
С
dec. (ethanol). Mass:
of 94%, Rf 0.5 (H), mp 192–193oС (1 : 1 water–ethaꢀ
M
M
323.4 (C18H21N5O). 1H NMR
nol). Mass:
339.4 (C18H21N5O2). 1H NMR (DMSOꢀ
(8 H, m, H2'–H5'); 2.97 (2 H, t, 7.16, H6'); 3.90
(2 H, t, 7.16, H1'); 6.45 (2 H, br s, 2ꢀN 2); 7.49 (2 H,
m, ꢀH, Ph); 7.60 (1 H, t, 7.5 ꢀH, Ph); 7.67 (1 H,
s, H8); 7.92 (2 H, d, 7.16, ꢀH, Ph); 10.58 (1 H, br s,
H1). 13C NMR (DMSOꢀ
6): 23.60 (C5'); 25.80 (CÇ');
28.01 (C2'); 29.26 (C4'); 37.69 (C6'); 42.52 (C1');
116.64 (C5); [127.77 (2 C); 128.62 (2 C); 132.93;
136.68] (Ph); 137.37 (C8); 151.11 (C4); 153.41 (C2);
156.79 (C6); 199.99 (C7').
m/z 339.4 [M M M
+], 340.4 [ + H+]. Calc.
d
⎯
d6): 1.20–1.71
J
J
J
H
m
J
,
J
H
p
J
о
m
J
, p
d
J
о
25.78 (C3'); 27.93 (C2'); 29.17 (C4'); 37.67 (C6');
42.77 (C1'); 118.72 (C5); [127.74 (2 C); 128.59 (2 C);
132.88; 136.67] (Ph); 140.76 (C8); 149.52 (C4);
152.27 (C2); 155.89 (C6); 199.94 (C7').
d
3ꢀ(7ꢀOxoꢀ7ꢀphenylheptyl)adenine (VIIIb) was
obtained by method B as a side product in the syntheꢀ
sis of (VIIb) in a yield of 84%; Rf 0.20 (D), mp 195–
7ꢀ(7ꢀOxoꢀ7ꢀphenylheptyl)guanine (XIIb) was
obtained from compound (Xb) by method C in a yield
196
°
С
dec. (propanolꢀ2). Mass:
+ H+]. Calc.
323.4 (C18H21N5O). H NMR
(DMSOꢀ 6): 1.21–1.92 (8 H, m, H2'–H5'); 2.96 (2 H,
t, 7.2, H6'); 4.28 (2 H, t, 7.2, H1'); 7.49 (2 H, m,
H, Ph); 7.60 (1 H, t, 7.2 ꢀH, Ph); 7.76 (1 H, H2);
7.92 (2 H, d, 7.5, ꢀH, Ph); 7.95 (2 H, s, 6ꢀN 2); 8.34
(1 H, s, H8). 13C NMR (DMSOꢀ
6): 23.59 (C5'); 25.71
m/z 323.4 [M
+], 324.4
1
of 56%,
Mass:
C18H21N5O2). 1H NMR (DMSOꢀ
m, H2'–H5'); 2.98 (2 H, t, 7.16, H6'); 4.15 (2 H, t,
7.16, H1'); 6.09 (2 H, br s, 2ꢀN 2); 7.51 (2 H, m,
H, Ph); 7.62 (1 H, t, 7.5 ꢀH, Ph); 7.89 (1 H, s, H8);
7.94 (2 H, d, 7.16, ꢀH, Ph); 10.73 (1 H, br s, H1).
13C NMR (DMSOꢀ
6): 23.60 (C5'), 25.49 (C3'); 27.97
R
/z
f 0.5 (H), mp >250
°
С
(1 : 1 water–ethanol).
+ H+]. Calc.
339.4
6): 1.30–1.80 (8 H,
[M
M
m
339.4 [M
+], 340.4 [
M
M
d
(
d
J
J
, p
mꢀ
J
J
J
H
mꢀ
J
о
H
J
о
, p
d
J
(C3'); 27.96 (C2'); 28.51 (C4'); 37.70 (C6'); 49.32
(C1'); 120.52 (C5); [127.21 (2 C); 128.59 (2 C);
132.73; 136.67] (Ph); 143.21 (C2); 149.83 (C4);
152.51 (C8); 154.89 (C6); 200.03 (C7').
d
(C2'); 29.50 (C4'); 37.70 (C6'); 45.93 (C1'); 107.99
(C5); [127.77 (2 C); 128.63 (2 C); 132.92; 137.44]
(Ph); 142.96 (C8); 152.62 (C4); 154.48 (C2); 159.96
(C6); 200.00 (C7').
N2ꢀ(2ꢀMethylpropionyl)ꢀ9ꢀ(7ꢀoxoꢀ7ꢀphenylhepꢀ
tyl)guanine (IXb) was obtained by method A in a yield
of 18.5%, Rf 0.63(D), mp 140–141 (EtOAc–
°
С
1ꢀ(9ꢀOxoꢀ9ꢀphenylnonyl)uracil (Шc) was obtained
octane). Mass: 409.5 [ M
m/z
M
+], 410.5 [ + H+]. Calc. by method A in a yield of 29%, Rf 0.63 (C), mp 102–
RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY Vol. 36
No. 4
2010

POLYMETHYLENE DERIVATIVES OF NUCLEIC BASES
485
103 С (EtOAc–heptane). Mass: m/z 328.4 [M
+], 329.4 133.69 (2 C); 137.99 (2 C)] (Ph); 140.19 (C6); 152.12
°
1
[
M
+ H+]. Calc.
(CD3CN): 1.23–1.72 (12 H, m, H2'–H7'); 2.97 (2 H,
t, 7.3, H8'); 3.70 (2 H, t, 7.2, H1'); 5.56 (1 H, d,
7.9, H5); 7.35 (1 H, d, 7.8, H6); 7.48 (2 H, m,
H, Ph); 7.58 (1 H, t, 7.2 ꢀH, Ph); 7.93 (2 H, d,
7.5,
ꢀH, Ph); 9.65 (1 H, s, H3). 13C NMR
M
328.4 (C19H24N2O3). H NMR (C2); 164.52 (C4); 201.23 (2 C, C9' and C9").
1ꢀ(9ꢀOxoꢀ9ꢀphenylnonyl)cytosine (Vc)
obtained by method B in a yield of 56%, Rf 0.66 (F),
mp 172–173°C (1 : 1 water–ethanol). Mass: 327.4
+], 328.4 [ + H+]. Calc. 327.4 (C19H25N3O2). 1H
NMR (DMSOꢀ 6): 1.14–1.62 (12 H, m, H2'–H7');
2.97 (2 H, t, 7.3, H8'); 3.58 (2 H, t, 7.2, H1'); 5.62
(1 H, d, 7.16, H5); 7.00 (2 H, br s, 4ꢀN 2); 7.54 (1H,
d, 7.2, H6); 7.49 (2H, m, ꢀH, Ph); 7.60 (1H, t,
7.2, ꢀH, Ph); 7.93 (2H, d, 7.5,
ꢀH, Ph). 13C NMR
(DMSOꢀ 6): 23.87 (C7'); 25.99 (C3'); 28.64 (C2'),
was
J
J
J
J
mꢀ
m/z
J
, p
[
M
M
M
J
о
d
(CD3CN): 24.82 (C7'); 26.75 (C3'); 29.33 (C2'); 29.52
(C6'); 29.62 (C4'); 29.76 (C5'); 39.00 (C8'); 48.93
(C1'); 101.68 (C5); [128.70 (2 C); 129.42 (2 C);
133.69; 138.03] (Ph); 146.42 (C6); 151.91 (C2);
164.93 (C4); 201.49 (C9').
J
J
J
H
J
m
J
J
p
o
d
28.68 (C6'); 28.75 (C4'); 28.89 (C5'); 37.94 (C8');
48.67 (C1'); 93.12 (C5); [127.93 (2 C); 128.77 (2 C);
133.10; 136.77] (Ph); 146.09 (C6); 155.94 (C2);
165.95 (C4); 200.26 (C9').
1,3ꢀBisꢀ(9ꢀoxoꢀ9ꢀphenylnonyl)uracil was obtained by
method A as a side product in the synthesis of (IIIc) in
a yield of 29%; Rf 0.90 (C), oil. Mass:
545.7 [ 544.7 (C34H44N2O4).
+ H+]. Calc.
1H NMR (CD3CN): 1.17–1.70 (24 H, m, H2'–H,
H2"–H7"); 2.93 (4 H, t, 7.32, H8' and H8"); 3.65
(2 H, t, 7.2, H1'');3.80 (2 H, t, 7.5, H'); 5.59 (1 H,
d, 7.8, H5); 7.30 (1 H, d, 7.8, H6); 7.45 (4 H, m,
ꢀH, Ph);7.55 (2 H, m, ꢀH, Ph); 7.92 (4 H, d, 7.3,
ꢀH, Ph). 13C NMR (CD3CN): 24.86 (2 C, C7' and
m/z 544.7 [M
+],
M
M
9ꢀ(9ꢀOxoꢀ9ꢀphenylnonyl)hypoxantine (VIc) was
obtained by method A in a yield of 31%, Rf 0.48 (D),
J
J
J
mp 159–160°C (EtOAc–heptane). Mass:
+], 353.4 [ + H+]. Calc. 352.4 (C20H24N4O2). 1H
NMR (DMSOꢀ 6): 1.1–1.8 (8 H, m, H2'–H7'); 2.94
(2 H, t, 7.3, H8'); 4.27 (2 H, t, 6.8, H1'); 7.47 (2 H,
m, ꢀH, Ph); 7.58 (1 H, t, 7.2, ꢀH, Ph); 7.91 (2 H,
d, 7.5, ꢀH, Ph), 7.95 (1 H, H8); 8.22 (1 H, s, H2);
12.27 (2 H, s, 6ꢀO 6): 23.74
). 13C NMR (DMSOꢀ
m/z 352.4
J
J
[M
M
M
m
p
J
d
о
J
J
C7''); 26.88 (C3'); 27.47 (C3''); 28.14 (C2'); 29.43
(C2"); 29.62 (C4'); 29.73 (C4"); 29.77 (2 C, C6' and
C6"); 29.95 (C5'); 29.91 (C5"); 39.06 (2 C, C8' and
C8"); 41.47 (C1'); 49.96 (C1''), 101.25 (C5); [128.74
(4 C); 129.45 (4 C); 133.70 (2 C); 138.02 (2 C)] (Ph);
144.21 (C6); 152.25 (C2); 163.95 (C4); 201.21 (2 C,
C9' and C9").
m
J
J
p
o
H
d
(C7'); 25.60 (C3'); 28.31 (C2'); 28.50 (C6'); 28.69
(C4'); 30.62 (C5'); 37.82 (C8'); 46.33 (C1'); [127.79 (2
C); 128.61 (2 C); 132.92; 136.70] (Ph); 123.87 (C5);
140.23 (C8); 143.78 (C2); 144.39 (C4); 154.28 (C6);
200.00 (C9').
1ꢀ(9ꢀoxoꢀ9ꢀphenylnonyl)thymine
obtained by method A in a yield of 27%, Rf 0.62 (C),
mp 127°C (EtOAc–heptane). Mass: 342.4 [
+],
345.4 [ 342.4 (C20H26N2O3). H
+ H+]. Calc.
NMR (CD3CN): 1.21–1.70 (12 H, m, H2'–H7); 1.81
(3 H, s, 5ꢀC 3); 2.97 (2 H, t, 7.3, H8'); 3.63 (2 H, t,
7.2, H1'); 7.19 (1 H, s, H6); 7.48 (2 H, m, ꢀH, Ph);
7.58 (1 H, t, 7.2 ꢀH, Ph); 7.94 (2 H, d, 7.5, ꢀH,
Ph); 9.33 (1 H, s, H3). 13C NMR (CD3CN): 12.16 (5ꢀ
H3); 25.06 (C7'); 26.95 (C7'); 29.53 (C2'); 29.68
(IVc)
was
9ꢀ(9ꢀOxoꢀ9ꢀphenylnonyl)adenine
obtained by method A in a yield of 56%, Rf 0.57 (D),
mp 165–166°C (ethanol). Mass: 351.4 [
+], 352.4
+ H+]. Calc.
351.4 (C20H25N5O). H NMR
(DMSOꢀ 6): 1.22–1.83 (12 H, m, H2'–H7'); 2.94 (2
H, t, 7.3, H8'); 4.11 (2 H, t, 7.2, H1'); 7.09 (2 H, s,
6ꢀN 2); 7.48 (2 H, m, ꢀH, Ph); 7.59 (1 H, t, 7.2,
ꢀH, Ph); 7.92 (2 H, d, 7.5, ꢀH, Ph); 8.10 (1 H,
H2); 8.12 (1 H, s, H8). 13C NMR (DMSOꢀ
6):
(VIIc)
was
m/z
M
1
M
M
m/z
M
1
[M
M
H
J
J
d
m
J
J
J
,
p
J
о
H
m
J
J
p
o
C
d
(C6'); 29.81 (C4'); 29.90 (C5'); 39.22 (C8'); 48.80
(C1'); 110.37 (C5); [128.87 (2 C); 129.58 (2 C);
133.79; 138.37] (Ph); 142.31 (C6); 152.06 (C2);
165.45 (C4); 201.65 (C9').
23.67(C7'); 25.81 (C3'); 28.17 (C2'); 28.38 (C6');
28.55 (C4'); 29.19 (C5'); 37.74 (C8'); 42.76 (C1');
118.71 (C5); [127.69 (2 C); 128.52 (2 C); 132.78;
136.71] (Ph); 140.69 (C8); 149.50 (C4); 152.22 (C2);
155.84 (C6); 199.97 (C9').
1,3ꢀBisꢀ(9ꢀoxoꢀ9ꢀphenylnonyl)thymine was obtaiꢀ
ned by method A as a side product in the synthesis of
3ꢀ(9ꢀOxoꢀ9ꢀphenylnonyl)adenine (VIIIc) was
obtained by method C in a yield of 3.7%, Rf 0.29 (D),
(IVc) in a yield of 25%, Rf 0.91 (C), oil. Mass:
558.7 [
+], 559.7 [ + H+]. Calc.
(C35H46N2O4). 1H NMR (CD3CN): 1.22–1.70 (24 H,
m, H2'–H7, H2"–H7"); 1.80 (3 H, s, 5ꢀC 3); 2.93 (DMSOꢀ
(4 H, t, 7.32, H8' and H8"); 3.63 (2 H, t, 7.2, H1''); H, t, 7.2, H8'); 4.27 (2 H, t,
3.82 (2 H, t, 7.16, H1'); 7.17 (1 H, s, H6); 7.45 (4 H, m,
ꢀH, Ph); 7.55 (2 H, t, 7.2 ꢀH, Ph); 7.92 (4 H, H2); 7.93 (2 H, d,
7.6,
ꢀH, Ph). 13C NMR (CD3CN): 12.97 (5ꢀ 2); 8.34 (1 H, s, H8). 13C NMR (DMSOꢀ
m/z
M
M
M
558.7 mp 151–152°C (ethanol). Mass:
+ H+]. Calc.
351.4(C20H25N5O). H NMR
6): 1.22–1.91 (12 H, m, H2'–H7'); 2.96 (2
m/z 351.4 [M
+], 352.4
1
[M
M
H
d
J
J
J
J
7.2, H1'); 7.48 (2 H,
ꢀH, Ph); 7.76 (1 H,
J
m
ꢀH, Ph); 7.59 (1 H, t,
J
7.2, p
m,
d,
m
J
J
,
p
J
7.5,
oꢀH, Ph); 7.93 (2 H, s, 6ꢀ
o
NH
d6): 23.74
C
H3); 24.83 (2 C, C7' and C7"); 26.84 (C3'); 27.43 (C7'); 25.77 (C3'); 28.33 (C2'); 28.48 (C6'); 28.58
(C3''); 28.15 (C2'); 29.44 (C2"); 29.60 (C4'); 29.69 (C4'); 28.66 (C5'); 37.81 (C8'); 49.31 (C1'); 120.47
(C4"); 29.73 (2 C, C6' and C6"); 29.87 (C5'); 29.90 (C5); [127.80 (2 C); 128.63 (2 C); 132.93; 136.72]
(C5"); 39.03 (2 C, C8' and C8"); 41.64 (C1'); 49.59 (Ph); 143.26 (C2); 149.68 (C4); 152.45 (C8); 154.92
(C1"); 109.33 (C5); [128.71 (4 C); 129.42 (4 C); (C6); 200.08 (C9').
RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY Vol. 36
No. 4
2010

486
KOMISSAROV, KRITZYN
2
N ꢀ(2ꢀMethylpropionyl)ꢀ9ꢀ(9ꢀoxoꢀ9ꢀphenylꢀ
37.89 (C8'); 46.04 (C1'); 108.46 (C5); [127.91 (2 C);
nonyl)guanine (IXc) was obtained by method A in a 128.72 (2 C); 132.93; 136.71] (Ph); 143.11 (C8);
yield of 26%, Rf 0.25 (B), mp 114–115°C (EtOAc– 152.72 (C4); 153.51 (C2); 159.41 (C6); 200.21 (C7').
octane). Mass: m/z 437.5 [
M
+], 438.5 [
M
+ H+]. Calc.
6): 1.09
, m,
, t,
Reduction of (IIIb)–(VIIb) carbonyl groups
(method D). Sodium borohydride (0.12 g) was added
to a solution of the starting phenone (2 mmol) in a
mixture of ethanol (25 ml) and water (5 ml). The reacꢀ
tion mixture was heated to reflux under stirring and
then cooled to room temperature under stirring. The
procedure was repeated. After the reaction was comꢀ
pleted (TLC control), the solvents were evaporated
1
M
(6
H
J
437.5 (C24H31N5O3). H NMR (DMSOꢀ
, d, 6.9, COCH(C 3)2); 1.20–1.80 (12
2'– ); 2.76 (1 , m, COC (CH3)2); 2.95 (2
7.2, 8'); 4.02 (2 , t, 7.16, H1 ); 7.48 (2 , m,
H, Ph); 7.59 (1 , t, 7.5, , Ph); 7.91 (2 , d,
7.5, ꢀH, Ph); 7.98 (1 , s, 8); 11.63 (1 , s, 2ꢀ
); 12.05 (1 6): 18.79
, s, H1). 13C NMR (DMSOꢀ
(2C, COCH( H3)2); 23.71 ( 7'); 25.87 ( ); 28.31
); 28.45 ( 6'); 28.68 ( 4'); 29.38 ( 5'); 34.62
(CO H(CH3)2); 37.78 ( 8'); 43.17 ( ); 120.05 ( 5);
[127.75 (2 ); 128.59 (2 ); 132.90; 136.69] (Ph);
139.70 ( 8); 147.71 ( 4); 148.55 ( 2); 154.87 ( 6);
180.08 ( OCH(CH3)2); 199.99 ( 9').
d
H
J
H
H
H
H
H
7
'
H
H
H
J
'
H
mꢀ
H
J
p
ꢀ
H
H
H
J
N
o
H
H
d
H
H
C
C
C
C3'
and the residue was reevaporated with ethanol (
3
×
(C
2'
C
C
20 ml). Ethanol (30 ml) was added to the residue, the
mixture was heated to reflux, and silica gel (10 g) was
added. Ethanol was evaporated and the silica gel with
C
C
C1
'
C
C
C
C
C
C
C
absorbed compound (
gel column (50 g,
eluted in a gradient of ethanol in chloroform (
V
) was transferred onto a silica
C
C
5
×
8 cm), chromatographed, and
2
N ꢀ(2ꢀMethylpropionyl)ꢀ7ꢀ(9ꢀoxoꢀ9ꢀphenylꢀ
nonyl)guanine (Xc) was obtained by method A in a
0
→
30%). The target fractions were combined and evapoꢀ
rated.
yield of 37%, Rf 0.44 (B), oil. Mass:
438.5 [ 437.5 (C24H31N5O3). H
+ H+]. Calc.
NMR (DMSOꢀ 6): 1.10 (6 H, d, 6.86,
COCH(C 3)2); 1.22–1.84 (12 H, m, H2'–H7'); 2.73
(1 H, m, COC (CH3)2); 2.98 (2 H, t, 7.16, H8'); 4.24
(2 H, t, 7.16, H1'); 7.49 (2H, m, ꢀH,Ph); 7.60 (l H,
t, 7.16, ꢀH, Ph); 7.93 (2H, d, 7.16, ꢀH, Ph); 7.92
(1 H, s, H8); 11.55 (1 H, s, 2ꢀN ); 12.08 (1 H, s, H1).
13C NMR (DMSOꢀ
6): 18.80 (2 C, COCH( H3)2);
23.71 (C7'); 25.51 (C3'); 28.24 (C2'); 28.44 (C6');
28.62 (C4'); 30.38 (C5'); 34.65 (CO H(CH3)2); 37.78
m/z 437.5 [M
+],
1
M
M
1ꢀ(7ꢀHydroxyꢀ7ꢀphenylheptyl)uracil (IIId) was
obtained by method D in a yield of 89%, Rf 0.58 (E),
d
J
H
oil. Mass:
302.4 (C17H22N2O3). 1H NMR (DMSOꢀ
(10 H, m, H2'–H6'); 3.60 (2 H, t, 7.2, H1'); 4.47
4.4, 7'ꢀO ); 5.51 (1 H,
ꢀH, Ph); 7.28 (4 H, m,
7.8, H6); 11.19
6): 25.15 (C5'); 25.75
m/z 302.4 [M M M
+], 303.4 [ + H+]. Calc.
H
J
d6): 1.14ꢀ1.62
J
m
J
J
p
J
H
o
(1 H, m, H7'); 5.09 (1 H, d,
d, 7.8, H5); 7.18 (1 H, m,
ꢀH, Ph and
(1 H, s, H3). 13C NMR (DMSOꢀ
J
m
H
J
d
C
o
mꢀH, Ph); 7.60 (1 H, d, J
d
C
(C3'); 28.34 (C2'); 28.52 (C4'); 39.16 (C6'); 47.39
(C1'); 72.22 (C7'), 100.69 (C5); [125.74 (2 C); 126.47;
127.85 (2 C); 146.39] (Ph); 145.63 (C6); 150.87 (C2);
163.69 (C4).
(C8'); 46.23 (C1'); 111.25 (C5); [127.77 (2 C); 128.60
(2 C); 132.89; 136.71] (Ph); 144.15 (C8); 147.71 (C4);
146.94 (C2); 152.50 (C6); 179.87 (
COCH(CH3)2);
200.01 (C9').
1ꢀ(7ꢀHydroxyꢀ7ꢀphenylheptyl)thymine (IVd) was
obtained by method D in a yield of 95%, Rf 0.67 (A),
9ꢀ(9ꢀOxoꢀ9ꢀphenylnonyl)guanine
(XIc) was
obtained from compound (IXc) by method C in a yield
oil. Mass:
316.4 (C18H24N2O3). 1H NMR (DMSOꢀ
(10 H, m, H2'–H6'); 1.74 (3 H, s, 5ꢀC 3); 3.58 (2 H, t,
7.2, H1'); 4.03 (1 H, m, H7'); 7.18(1 H, m, ꢀH, Ph);
7.29 (4 H, m, ꢀH, Ph and ꢀH, Ph); 7.51 (1 H, d,
7.8, H6); 11.13 (1 H, s, H3). C NMR (DMSOꢀ
11.75 (5ꢀ H3); 25.06 (C5'); 25.69 (C3'); 28.30 (C2');
m/z 316.4 [M M M
+], 317.4 [ + H+]. Calc.
of 82%, Rf 0.3 (D), mp 202–203
367.4 [
+], 368.4 [ + H+]. Calc.
(C20H25N5O2). H NMR (DMSOꢀ 6): 1.20–1.81
(12 H, m, H2'–H7'); 2.97 (2 H, t, 7.16, H8'); 3.89
(2 H, t, 7.16, H1'); 6.44 (2 H, br s, 2ꢀN 2); 7.49 (2 H,
m, ꢀH, Ph); 7.60 (1 H, t, 7.5, ꢀH, Ph); 7.67 (1 H,
s, H8); 7.93 (2 H, d, 7.16, ꢀH, Ph); 10.52 (1 H, br s,
H1). 13C NMR (DMSOꢀ
6): 23.74 (C7'); 25.90 (C3');
°
С
(ethanol). Mass:
d6): 1.15–1.60
m/
z
M
M
M
367.4
1
H
d
J
p
J
o
m
J
6):
J
H
13
d
m
J
o
p
C
J
28.45 (C4'); 39.66 (C6'); 47.01 (C1'); 72.10 (C7');
108.24 (C5); [125.68 (2 C); 126.38; 127.77 (2 C);
146.36] (Ph); 141.35 (C6); 150.76 (C2); 164.16 (C4).
d
28.34 (C2'); 28.48 (C6'); 28.70 (C4'); 29.34 (C5');
37.81 (C8'); 42.58 (C1'); 116.56 (C5); [127.79 (2 C);
128.63 (2 C); 132.93; 136.71] (Ph); 137.40 (C8);
151.11 (C4); 153.41 (C2); 156.81 (C6); 200.08 (C7').
1ꢀ(7ꢀHydroxyꢀ7ꢀphenylheptyl)cytosine (Vd) was
obtained by method D in a yield of 97%, Rf 0.36 (I),
7ꢀ(9ꢀOxoꢀ9ꢀphenylnonyl)guanine (XIIc) was oil. Mass:
obtained from compound (Xc) by method C in a yield 301.4 (C17H23N3O2). 1H NMR (DMSOꢀ
of 50%, Rf 0.35 (D), mp >250 (ethanol). Mass: (10 H, m, H2'–H6'); 3.70 (2 H, t, 6.6, H1'); 4.46
367.4 [ 367.4 (1 H, m, H7'); 5.09 (1 H, d, 4.4, 7'ꢀO ); 5.51 (1 H, d,
+], 368.4 [ + H+]. Calc.
C20H25N5O2). 1H NMR (DMSOꢀ
6): 1.23–1.81 7.8, H5); 5.64 (1 H, d, 7.2, H5); 6.93 (2 H, s, 4ꢀ
(12 H, m, H2'–H7'); 2.98 (2 H, t, 7.16, H8'); 4.13 2); 7.17 (1 H, m, ꢀH, Ph); 7.28 (4 H, m, ꢀH, Ph
(2 H, t, 7.16, H1'); 6.11 (2 H, br s, 2ꢀN 2); 7.50 (2 H, and ꢀH, Ph); 7.54 (1 H, d,
7.2, H6). 13C NMR
m, ꢀH, Ph); 7.61 (1 H, t, 7.5, ꢀH, Ph); 7.88 (1 H, (DMSOꢀ 6): 25.08 (C5'); 25.60 (C3'); 27.96 (C2');
s, H8); 7.94 (2 H, d, 7.16, ꢀH, Ph); 10.73 (1 H, br s, 28.48 (C4'); 39.12 (C6'); 48.78 (C1'); 72.12 (C7');
H1). 13C NMR (DMSOꢀ
6): 23.74 (C7'); 25.62 (C3'); 93.04 (C5); [125.72 (2 C); 126.43; 127.81 (2 C);
28.41 (C2'); 28.52 (C6'); 28.84(C4'); 30.37 (C5'); 146.36] (Ph); 147.26 (C6); 149.63 (C2); 159.93 (C4).
m/z 301.4 [M M M
+], 302.4 [ + H+]. Calc.
d6): 1.14–1.60
°
С
m/z
J
M
M
M
J
H
(
d
J
J
J
NH
p
o
J
H
m
J
m
J
o
p
d
J
d
RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY Vol. 36
No. 4
2010

POLYMETHYLENE DERIVATIVES OF NUCLEIC BASES
487
3. Buckheit, R.W., Watson, K., FliakasꢀBoltz, V.,
Russel, J., Loftus, T.L., Osterling, M.C., Turpin, J.A.,
Pallansch, L.A., White, E.L., Lee, J.ꢀW., Lee, S.ꢀH.,
Oh, J.ꢀW., Kwon, H.ꢀS., Chung, S.ꢀG., and
Cho, E. H., Antimicrob. Agents Chemther., 2001,
9ꢀ(7ꢀHydroxyꢀ7ꢀphenylheptyl)hypoxanthine (VId)
was obtained by method D in a yield of 80%, Rf 0.57
(D), oil. Mass:
326.4 (C18H22N4O2). H NMR (DMSOꢀ
1.77 (10 H, m, H2'–H6'); 4.10 (2 H, t,
m/z 326.4 [M M
+], 327.4 [ + H+]. Calc.
1
M
d
6): 1.16–
7.2, H1');
3.7, 7'ꢀO ); 7.18
ꢀH, Ph and ꢀH,
J
vol. 45, pp. 393⎯400.
4.44 (1 H, m, H7'); 5.08 (1 H, d,
(1 H, m, ꢀH, Ph); 7.26 (4 H, m,
J
o
H
4. Boyd, H.F., Fell, S.C.M., Flynn, S.T., Hickey, D.M.B.,
Ife, R.J., Leach, C.A., Macphee, C.H., Milliner, K.J.,
Moores, K.E., Pinto, I.L., Porter, R.A., Rawlings, D.A.,
Smith, S.A., Stansfield, I.G., Tew, D.G., Theobald, C.J.,
and Whittaker, C.M., Bioorg. Med. Chem. Lett., 2000,
vol. 10, pp. 2557⎯2561.
5. Makinsky, A.A., Kritzyn, A.M., Uljanova, E.A.,
p
m
Ph); 8.00 (1 H, H8); 8.06 (1 H, s, H2); 12.22 (2 H, s,
6ꢀO 6): 25.03 (C5'); 25.81
H
). 13C NMR (DMSOꢀ
d
(C3'); 28.23 (C2'); 29.38 (C4'); 39.05 (C6'); 43.19
(C1'); 72.15 (C7'); 123.88 (C5); [125.68 (2 C); 126.43;
127.80 (2 C); 146.33] (Ph); 140.18 (C8); 145.25 (C2);
154.20 (C4); 156.58 (C6).
Zakharova, O.D., and Nevinsky, G.A., Bioorg. Khim.
9ꢀ(7ꢀHydroxyꢀ7ꢀphenylheptyl)adenine (VIId) was
obtained by method D in a yield of 81%, Rf 0.46 (F),
2000, vol. 26, pp. 735
Transl.), 2000, vol. 26, pp. 662
6. Komissarov, V.V., Panova, N.G., and Kritzyn, A.M.,
Bioorg. Khim. 2008, vol. 34, pp. 75 82[Russ. J. Bioorg.
Chem. (Eng. Transl.), 2008, vol. 34, pp. 67 73].
7. Kritzyn, A.M. and Komissarov, V.V., Bioorg. Khim.
2005, vol. 31, pp. 609 615 [Russ. J. Bioorg. Chem. (Eng.
Transl.), 2005, vol. 31, pp. 549 555].
8. Komissarov, V.V., Polymethylene Derivatives of
Nucleic Bases Bearing ꢀFunctional Groups: Syntheꢀ
⎯
742 [Russ. J. Bioorg. Chem. (Eng.
⎯
668].
oil. Mass:
325.4 C18H23N5O
(10 H, m, H2'–H6'); 3.80 (1 H, br s, 7'ꢀO
4.07 (2 H, t, 7.2, H1'); 4.61 (1 H, m, H7'); 6.39 (2 H,
s, 6ꢀN 2); 7.20 (1 H, m, ꢀH, Ph); 7.28 (4 H, m, ꢀH,
Ph and
m/z
325.4 [
1H NMR (CDCl3): 1.19–1.82
);
M M M
+], 326.4 [ + H+]. Calc.
.
⎯
⎯
H
J
⎯
H
p
o
⎯
m
ꢀH, Ph); 7.63 (1 H, H2); 8.22 (1 H, s, H8).
13C NMR (CDCl3): 25.46 (C5'); 26.38 (C3'); 28.77
(C2'); 29.79 (C4'); 38.87 (C6'); 43.76 (C1'); 74.03
(C7'); 119.35 (C5); [125.84 (2 C); 127.25; 128.27 (2
C); 145.13] (Ph); 140.14 (C8); 149.84 (C4); 152.72
(C2); 155.58 (C6).
ω
sis and Properties, Cand. Sci. (Chem.) Dissertation
,
Moscow: Inst. Mol. Biol. Ros. Akad. Nauk, 2005.
9. Nesmeyanov, A.N. and Zakharkin, L.I., Izv. Akad.
Nauk SSSR, Otd. Khim. Nauk, 1955, pp. 224 238.
10. Joyce, R.M., Hanford, W.E., and Harmon, J., . Am.
Chem. Soc., 1948, vol. 70, pp. 2529 2532.
⎯
J
ACKNOWLEDGMENTS
⎯
This work was supported by the Russian Foundaꢀ 11. Kritzyn, A.M. and Komissarov, V.V., Bioorg. Khim.
2004, vol. 30, pp. 487
Transl.), 2004, vol. 30, pp. 436
12. Meszarosova, K., Holy, A., and Masojidkova, M., Colꢀ
lect. Czech. Chem. Commun., 2000, vol. 65, pp. 1109
1125.
13. Kritzun, A.M., Vepsalainen, J., and Komissarov, V.V.,
Bioorg. Khim. 2005, vol. 31, pp. 288 294 [Russ. J.
Bioorg. Chem. (Eng. Transl.), 2005. V. 31. R. 256 262].
⎯
492 [Russ. J. Bioorg. Chem. (Eng.
tion for Basic Research, project no. 09ꢀ04ꢀ00364ꢀa,
and the Federal Program “Studies in Priority Direcꢀ
tions of the Development of the Research and Techniꢀ
cal Complex of Russia for 2007–2012, contract
no. 02.512.11.2237.”
⎯440].
⎯
⎯
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RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY Vol. 36
No. 4
2010