Synthesis of 5-phenyl-2(1H)-pyrimidinone nucleosides

Article abstract of DOI:10.1135/cccc19960458

Reaction of 2-phenyltrimethinium salt 1 with thiourea and subsequent reaction with chloroacetic acid afforded 5-phenyl-2(1H)-pyrimidinone (3). Its silyl derivative 4 was condensed with 1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose under catalysis with tin tetrachloride or trimethylsilyl trifluoromethanesulfonate to give protected nucleoside 5 together with 5′,O ⁶-cyclo-5-phenyl-1,3-bis-(β-D-ribofuranosyl)-6-hydroxy-5,6- dihydro-2(1H,3H)-pyrimidinone (7). The greatest amounts of 7 were formed with the latter catalyst. Nucleosidation of the silyl derivative 4 with protected methyl 2-deoxy-D-ribofuranoside 8 or 2-deoxy-D-ribofuranosyl chloride 9 afforded 1-(2-deoxy-3,5-di-O-p-to-luoyl-β-D-ribofuranosyl)-5-phenyl-2(1H)- pyrimidinone (10) and its α-anomer 11. Reaction of 10 and 11 with methanolic ammonia gave free 2′-deoxynucleosides 12 and 13. Compound 13 was converted into 5′-O-tert-butyldiphenylsilyl-3′-O-mesyl derivative 14 which on heating with 1,8-diazabicydo[5.4.0]undec-7-ene (DBU) and subsequent cleavage with tetrabutylammonium fluoride afforded 2′,3′-dideoxy-2′,3′-didehydronucleoside 15. Reaction of the silyl derivative 4 with 1,2-di-O-acetyl-3,5-di-O-benzoylxylofuranose (18), catalyzed with tin tetrachloride, furnished 1-(2-O-acetyl-3,5-di-O-benzoyl-β-D-xylofuranosyl)-2(1H)-pyrimidinone (19) which was deprotected to give the β-D-xylofuranosyl derivative 22. As a side product, the nucleosidation afforded the β-D-xylopyranosyl derivative 23. Deacetylation of compound 19 gave 1-(3,5-di-O-benzoyl-β-D-xylofuranosyl)-5-phenyl-2(1H)-pyrimidinone (24) which on reaction with thionyl chloride afforded 2′-chloro-2′-deoxynucleoside 25 and 2′,O⁶-cyclonucleoside 26. Heating of compound 25 with DBU in dimethylformamide furnished the lyxo-epoxide 27 which on reaction with methanolic ammonia was converted into free 1-(2,3-anhydro-β-D-lyxofuranosyl)-5-phenyl-2(1H)-pyrimidinone (28). Reaction of 1,2-di-O-acetyl-5-O-benzoyl-3-O-methanesulfonyl-D-xylofuranose (30) with silyl derivative 4 gave the nucleoside 31 which by treatment with DBU was converted into an equilibrium mixture of 5′-benzoylated arabinofuranoside 33a and its 2′,6-anhydro derivative 33b.

Full text of DOI:10.1135/cccc19960458

458
Krecmerova, Hrebabecky, Masojidkova, Holy:
SYNTHESIS OF 5-PHENYL-2(1H)-PYRIMIDINONE NUCLEOSIDES
Marcela KRECMEROVA, Hubert HREBABECKY, Milena MASOJIDKOVA and Antonin HOLY
Institute of Organic Chemistry and Biochemistry,
Academy of Sciences of the Czech Republic, 166 10 Prague 6, Czech Republic
Received October 11, 1995
Accepted January 13, 1996
Reaction of 2-phenyltrimethinium salt 1 with thiourea and subsequent reaction with chloroacetic acid
afforded 5-phenyl-2(1H)-pyrimidinone (3). Its silyl derivative 4 was condensed with 1-O-acetyl-
2,3,5-tri-O-benzoyl-D-ribofuranose under catalysis with tin tetrachloride or trimethylsilyl trifluoro-
methanesulfonate to give protected nucleoside 5 together with 5′,O6-cyclo-5-phenyl-1,3-bis-
(β-D-ribofuranosyl)-6-hydroxy-5,6-dihydro-2(1H,3H)-pyrimidinone (7). The greatest amounts of 7
were formed with the latter catalyst. Nucleosidation of the silyl derivative 4 with protected methyl
2-deoxy-D-ribofuranoside 8 or 2-deoxy-D-ribofuranosyl chloride 9 afforded 1-(2-deoxy-3,5-di-O-p-to-
luoyl-β-D-ribofuranosyl)-5-phenyl-2(1H)-pyrimidinone (10) and its α-anomer 11. Reaction of 10 and
11 with methanolic ammonia gave free 2′-deoxynucleosides 12 and 13. Compound 13 was converted
into 5′-O-tert-butyldiphenylsilyl-3′-O-mesyl derivative 14 which on heating with 1,8-diazabicy-
clo[5.4.0]undec-7-ene (DBU) and subsequent cleavage with tetrabutylammonium fluoride afforded
2′,3′-dideoxy-2′,3′-didehydronucleoside 15. Reaction of the silyl derivative 4 with 1,2-di-O-acetyl-
3,5-di-O-benzoylxylofuranose (18), catalyzed with tin tetrachloride, furnished 1-(2-O-acetyl-3,5-di-O-ben-
zoyl-β-D-xylofuranosyl)-2(1H)-pyrimidinone (19) which was deprotected to give the β-D-xylofuranosyl
derivative 22. As a side product, the nucleosidation afforded the β-D-xylopyranosyl derivative 23.
Deacetylation of compound 19 gave 1-(3,5-di-O-benzoyl-β-D-xylofuranosyl)-5-phenyl-2(1H)-pyrimidi-
none (24) which on reaction with thionyl chloride afforded 2′-chloro-2′-deoxynucleoside 25 and
2′,O6-cyclonucleoside 26. Heating of compound 25 with DBU in dimethylformamide furnished the
lyxo-epoxide 27 which on reaction with methanolic ammonia was converted into free 1-(2,3-anhydro-
β-D-lyxofuranosyl)-5-phenyl-2(1H)-pyrimidinone (28). Reaction of 1,2-di-O-acetyl-5-O-benzoyl-3-O-
methanesulfonyl-D-xylofuranose (30) with silyl derivative 4 gave the nucleoside 31 which by
treatment with DBU was converted into an equilibrium mixture of 5′-benzoylated arabinofurano-
side 33a and its 2′,6-anhydro derivative 33b.
Key words: Nucleosides; Deoxynucleosides; 5-Phenyl-2(1H)-pyrimidinone base-modified; Pyrimidines.
Nucleosides of 2(1H)-pyrimidinone and its 5-substituted derivatives play an important
role among biologically active analogs of natural pyrimidine nucleosides. 1-(β-D-Ribo-
furanosyl)-2(1H)-pyrimidinone (zebularin) exhibits an antibacterial activity connected
with its in vivo transformation into 1-(2-deoxy-β-D-ribofuranosyl)-2(1H)-pyrimidinone
5′-phosphate, a strong inhibitor of thymidylate synthetase1. Zebularin is also an effec-
tive cytidine deaminase inhibitor and can be therefore combined with some antitumor
compounds of the cytosine nucleoside group that undergo in vitro deamination, e.g.
Collect. Czech. Chem. Commun. (Vol. 61) (1996)

5-Phenyl-2(1H)-pyrimidinone Nucleosides
459
with araC (refs2,3). Moreover, zebularin itself, similarly as its 5-fluoro derivative, has
antitumor effects (ref.4 and references therein).
In connection with investigation of antiviral effects of 5-substituted 2-deoxyuridine
derivatives, a series of 2′-deoxynucleosides with 5-substituted pyrimidinone ring has
been prepared. Derivatives, substituted in the position 5 with a halogen atom (Br, I), an
SCH3 group5,6 or an alkynyl (ethynyl, 1-propynyl) group7 are active especially against
herpesviruses. Other nucleosides, particularly with modified sugar moieties, were pre-
pared by us already earlier8.
This communication concerns the preparation of pyrimidinone nucleosides sub-
stituted in position 5 with a phenyl group and is connected with investigations of
uridine phosphorylase inhibitors9. The most effective inhibitors of this enzyme are pyri-
midine nucleosides with a hydrophobic group (e.g. benzyl) in the position 5. It is also
known that many C-5 alkylated pyrimidine nucleosides are potent antivirals or cyto-
statics.
All the compounds described in this study were prepared by nucleosidation reaction
of silylated 2(1H)-pyrimidinone with the corresponding sugar derivative8 and, where
needed, by further transformations of the obtained nucleoside. The starting 5-phenyl-
2(1H)-pyrimidinone (3) was prepared from 2-phenyltrimethinium salt (1-dimethyl-
amino-3-dimethylimonio-2-phenyl perchlorate) (1) (ref.10) by cyclization with thiourea
and subsequent conversion of the obtained 5-phenyl-2-mercaptopyrimidine (2) into 5-phenyl-
2(1H)-pyrimidinone (3) by reaction with chloroacetic acid (Scheme 1). This pathway
has been described by us already for the preparation of 5-substituted (5-ethyl-, 5-methyl-
and 5-alkoxy-) 2(1H)-pyrimidinones10,*.
Condensation of 5-phenyl-2(1H)-pyrimidinone (3) with 1-O-acetyl-2,3,5-tri-O-ben-
zoyl-D-ribofuranose was performed after conversion of the base into the silyl derivative 3
by reaction with hexamethyldisilazane. Nucleosidation in 1,2-dichloroethane or aceto-
nitrile, catalyzed with tin tetrachloride, or in acetonitrile with trimethylsilyl trifluoro-
methanesulfonate as catalyst, afforded invariably the protected nucleoside 5 in low
yield (about 40%). As a side product we isolated a compound containing further sugar
unit in the molecule. After debenzoylation, the NMR spectrum has shown that the side
product was 5′,O6-anhydro-5-phenyl-1,3-bis(β-D-ribofuranosyl)-5,6-dihydro-6-hydroxy-
2(1H,3H)-pyrimidinone (7). The highest ratio of the mono- to the bis(ribofuranosyl) deri-
vative was achieved in the nucleosidation in acetonitrile with tin tetrachloride as cata-
lyst. On the other hand, relatively the highest proportion of the side product 7 was
obtained in reactions catalyzed with trimethylsilyl triflate. We did not find conditions
suppressing entirely the formation of the compound 7.
* Abbreviations: Ac, acetyl; Bz, benzoyl; tert-BuPh2Si, tert-butyldiphenylsilyl; Ms, methanesulfonyl;
TMS, trimethylsilyl; Tol, p-toluoyl.
Collect. Czech. Chem. Commun. (Vol. 61) (1996)

460
Krecmerova, Hrebabecky, Masojidkova, Holy:
The reactivity in position 6 of the pyrimidinone ring is generally known and the
formation of 5′,O6-cyclo derivatives was observed also with other 5-substituted pyri-
midinone nucleosides. The cyclization may take place e.g. during treatment with am-
monia in removal of alkali-labile protecting groups. Such situation has been described
ClO
4
(CH ) N
3 2
N
N
HS
N
O
N
H
(CH ) N
3 2
2
1
3
N
Me SiO
N
3
4
SCHEME 1
recently for 5-halogeno-2′,3′-dideoxy-3′-azidopyrimidinone nucleosides12 and 2′-deoxy-
nucleosides of 5-alkynylpyrimidinones7. The action of strong nucleophiles such as OH
or F leads to complete destruction of the pyrimidinone ring, the attack by the nucleo-
philic anion taking place again in the position 6 (refs4,7). However, none of the cited
papers has described such complications of the nucleosidation reaction that would lead
N
N
OH
OH
O
N
O
O
N
H
O
B
RO
O
A
O
OH
OH
OH
OR
OR
R
7
5
6
Bz
H
Collect. Czech. Chem. Commun. (Vol. 61) (1996)

5-Phenyl-2(1H)-pyrimidinone Nucleosides
461
to products analogous to the bis(ribofuranosyl) derivative 7 isolated by us. On the con-
trary, most of the 5-phenylpyrimidinone nucleosides protected with acyl groups (ribo-
furanosyl derivative 5 and the 2′-deoxyribofuranosyl and xylofuranosyl derivatives
described in this communication) were quantitatively deblocked with ammonia to give
the free nucleosides (e.g. 6) without any undesired cyclization to 5′,O6-cyclo deriva-
tives.
N
O
N
TolO
RO
O
O
X
OTol
OR
X
R
10 Tol
12
8
9
OCH3
Cl
H
R1O
RO
O
O
OR2
N
O
N
O
N
N
R1
R2
R
t-BuPh2Si
H
11 Tol
Tol
H
16
17
13
14
H
H
t-BuPh2Si
15 t-BuPh2Si Ms
Collect. Czech. Chem. Commun. (Vol. 61) (1996)

462
Krecmerova, Hrebabecky, Masojidkova, Holy:
Nucleosidation of compound 4 with protected methyl 2-deoxy-D-ribofuranoside (8)
or 2-deoxy-D-ribofuranosyl chloride (9) afforded 1-(2-deoxy-3,5-bis(O-p-toluoyl)-β-D-
ribofuranosyl)-5-phenyl-2(1H)-pyrimidinone (10) together with its α-anomer 11. The
dependence of the anomer ratio on the reaction conditions is given in Table I. For the
preparation of the β-anomer, the reaction with methyl glycoside 8 at low temperature in
acetonitrile with trimethylsilyl triflate as catalyst is the method of choice. Treatment of
bis(O-toluoyl) derivatives 10 and 11 with methanolic ammonia gave the free 2′-deoxy-
nucleosides 12 and 13. Both these nucleosides were utilized for the preparation of further
5-phenylpyrimidinone derivatives modified in the sugar part of the molecule.
The free α-anomer 13 reacted with tert-butyldiphenylsilyl chloride in dimethylform-
amide in the presence of imidazole as base, affording in quantitative yield the 5′-O-tert-
butyldiphenylsilyl derivative 14 which was converted into the mesyl derivative 15.
Heating of compound 15 with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in acetonitrile
gave 2′,3′-didehydronucleoside 16. The 5′-silyl group was removed with tetrabutyl-
ammonium fluoride under neutral conditions (the reaction mixture was rendered at pH 7 by
addition of acetic acid during the reaction) to suppress the nucleophilic attack in posi-
tion 6 and opening the pyrimidinone ring. This procedure led to the free 2′,3′-dideoxy-
2′,3′-didehydronucleoside 17.
Preparation of the corresponding didehydro derivative from the β-anomer 10 using
an analogous reaction pathway was not practical because the protection of the starting
nucleoside was difficult. The silylation of compound 7 was not quantitative and afforded a
mixture of the 5′-O-tert-butyldiphenylsilyl and 3′-O-tert-butyldiphenylsilyl derivatives,
together with the 3′,5′-O-bis(tert-butyldiphenylsilyl) derivative, which arose in about
the same ratios from the beginning of the reaction.
For the preparation of another group of modified nucleosides we carried out the
nucleosidation of compound 4 with 1,2-di-O-acetyl-3,5-di-O-benzoylxylofuranose13 in
acetonitrile under catalysis with tin tetrachloride. The desired 1-(2-O-acetyl-3,5-di-O-
benzoyl-β-D-xylofuranosyl)-2(1H)-pyrimidinone (19) was obtained in 36% yield;
TABLE I
Nucleosidation reaction of 5-phenyl-2-trimethylsilyloxypyrimidine (4) with methyl 2-deoxy-3,5-di-O-
p-toluoyl-D-ribofuranoside (8) and 2-deoxy-3,5-di-O-p-toluoyl-D-ribofuranosyl chloride (9)
Sugar
Solvent
Catalyst
Time
Temperature
Yield
β : α
8
8
9
9
acetonitrile
acetonitrile
chloroform
TMS-triflate
TMS-triflate
–
10 min
20 min
22
–20
22
58
58
86
56
3 : 2
2 : 1
1 : 3
1 : 3
overnight
overnight
chloroform p-nitrophenol
22
Collect. Czech. Chem. Commun. (Vol. 61) (1996)

5-Phenyl-2(1H)-pyrimidinone Nucleosides
463
N
O
N
1
R O
BzO
O
O
OAc
OBz
2
OR
3
OAc
OR
1
2
3
R
R
R
18
19
20
22
24
29
Bz Bz Ac
Bz Bz Bz
H
H
H
H
Bz Bz
Bz Bz Ms
N
N
O
N
O
N
BzO
O
O
OR
OBz
RO
Cl
OR
25
R
21 Bz
23
H
N
NH
O
N
RO
O
N
O
O
BzO
O
O
OBz
R
27 Bz
28
26
H
Collect. Czech. Chem. Commun. (Vol. 61) (1996)

464
Krecmerova, Hrebabecky, Masojidkova, Holy:
together with this product we isolated a small amount of 2,3,5-tri-O-benzoyl-β-D-xylo-
furanosyl derivative 20 and 2,3,4-tri-O-benzoyl-β-D-xylopyranosyl derivative 21. The
protected nucleosides 19 and 20 were converted into the free β-D-xylofuranosyl deriva-
tive 22 by reaction with methanolic ammonia. In the same way we also prepared free
β-D-xylopyranosyl derivative 23 from tri-O-benzoyl derivative 21. Deacetylation of
compound 19 with hydrogen chloride in dioxane gave 1-(3,5-di-O-benzoyl-β-D-xylo-
furanosyl)-5-phenyl-2(1H)-pyrimidinone (24) in high yield. This compound was reacted
with thionyl chloride in acetonitrile at 75 °C to give the desired 2′-chloro-2′-deoxy-
nucleoside 25. The reaction apparently proceeds via the 2′-O-chlorosulfinate which on
nucleophilic attack by the carbonyl oxygen of the base gives rise to non-isolable pyri-
midinium intermediate A (Scheme 2); analogously as in pyrimidine anhydronucleo-
sides, the 2′,O2 bond in the intermediate is cleaved with hydrogen chloride under
formation of chloro derivative 25. During the workup of the reaction mixture the pyri-
midine base is attacked in the position 2 with water or hydroxyl anion to give the lyxo
derivative. The cleavage of the anhydro bond in pyrimidine cyclonucleosides by alkali
metal hydroxides proceeds in the same manner, however, the pyrimidinium derivative
is much more reactive. Also in this case, there is a marked propensity of 2-pyrimidine
analogs to add hydroxyl in the position “up” of the pentafuranose ring to the 5,6-double
bond of the base. The reaction mixture afforded no lyxo derivative but only compound
26. When the reaction was carried out at room temperature and for a relatively short
time (6–7 h) in hexamethylphosphoramide, the cyclo derivative 26 was the principal
product.
Heating of chloro derivative 25 with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in
dimethylformamide in the presence of a catalytic amount of methanol afforded the
lyxo-epoxide 27 which by reaction with methanolic ammonia was converted into free
1-(2,3-anhydro-β-D-lyxofuranosyl)-5-phenyl-2(1H)-pyrimidinone (28). An alternative
24
25
N
N
O
N
N
O
BzO
BzO
O
O
OBz
OBz
OSOCl
A
SCHEME 2
Collect. Czech. Chem. Commun. (Vol. 61) (1996)

5-Phenyl-2(1H)-pyrimidinone Nucleosides
465
preparation of this epoxide started from the 3′-O-mesyl derivative 29, prepared by reac-
tion of compound 24 with mesyl chloride in pyridine; the closure of the epoxide ring
was realized by reaction with methanolic ammonia under simultaneous removal of the
benzoyl group. The epoxide 28 was thus prepared from the mesylate 29 in one step and
in high yield (higher than 80%).
Nucleosidation reaction of silyl derivative 3 with 1,2-di-O-acetyl-5-O-benzoyl-3-O-
methanesulfonyl-D-xylofuranose (30) afforded the nucleoside 31. The starting sugar
was prepared from 5-O-benzoyl-1,2-O-isopropylidene-α-D-xylofuranose14 by mesylation
and subsequent acetolysis in a mixture of acetic anhydride, acetic acid and sulfuric
acid. Originally, we intended to utilize 3′-O-mesylxylofuranoside 31 for the synthesis
of 3′-substituted 2′,3′-dideoxy derivatives because the mesyl functionality in position 3′
can be easily substituted with inversion of configuration. It appeared, however, that
such syntheses encounter deoxygenation in position 2′. Introduction of a halogen atom
into position 2′ and its subsequent reduction invariably proceeds with simultaneous
attack of the pyrimidinone ring. The easy reduction of this system under conditions of
catalytic hydrogenation as well as radical deoxygenations with tributylstannane15 is
known. On the other hand, some mild reducing agents, such as tris(trimethylsilyl)silane
with azobis(isobutyronitrile) (AIBN), do not reduce the pyrimidinone system16. We
tried to reduce compound 25 with dimethyl phosphite under catalysis with AIBN or
dibenzoyl peroxide17; however, in both cases the base was also reduced.
N
O
N
BzO
BzO
O
O
OAc
OMs
OMs
OAc
OAc
30
31
Reaction of the 3′-O-mesyl derivative 31 with DBU under conditions similar to those
used for the preparation of epoxide 28 afforded, instead of the expected ribo-epoxide 32, an
equilibrium mixture of 5′-O-benzoylated arabinofuranosyl nucleoside 33a and its 2′,6-
anhydro derivative 33b (Scheme 3). The reaction also gave rise to a chromatographically
more mobile intermediate (probably 32) which, however, could not be isolated. Ob-
viously, the ribo-epoxide 32 also in this case gave the pyrimidinium intermediate. This
was cleaved to the arabino derivative 33a which then gave rise to the tricyclic analogue 33b.
Collect. Czech. Chem. Commun. (Vol. 61) (1996)

466
Krecmerova, Hrebabecky, Masojidkova, Holy:
Attempts to obtain the free arabinofuranosyl derivative 33a by reaction with methanolic
ammonia resulted in total destruction of the pyrimidinone ring and from the complex reac-
tion mixture we were able to isolate and characterize only compounds 34 and 35.
N
O
N
BzO
O
31
O
32
N
NH
O
O
N
H
O
N
BzO
BzO
O
O
HO
OH
OH
33a
33b
SCHEME 3
The structure of the studied compounds was verified by their 1H and 13C NMR spec-
tra. The individual carbon atoms were assigned on the basis of J-modulated spectra
(“attached proton test pulse sequence”, ref.18), enabling discrimination of the C, CH,
NH
N
H
N
NH
O
N
HO
O
NH
O
HO
OH
OH
OH
35
34
Collect. Czech. Chem. Commun. (Vol. 61) (1996)

5-Phenyl-2(1H)-pyrimidinone Nucleosides
467
CH2 and CH3 type signals. The observed values of the NMR parameters are in accord
with the literature data19–22 for pentofuranose and pentopyranose derivatives.
1
In accord with the suggested structure of compound 7, its H NMR spectrum ex-
hibited signals of two furanose rings one of which (sugar moiety A) does not contain
the 5′-OH group and is characterized by small coupling constants J(1′,2′) and J(5′,4′)
and in the 13C NMR spectrum by a downfield shift (about 9 ppm) of the C-5′ signal.
Due to the different structure of the base there are marked upfield shifts of the H-4 and
H-6 proton signals (about 2.0 and 3.0 ppm, respectively) as well as C-4 and C-6 carbon
signals (about 40 and 60 ppm, respectively). These differences correspond to the 5′,O6-cyclo
derivative structure7. Analogous results were obtained with the 2′,O6-cyclonucleosides
26 and 33b, where we confirmed identical structure of the base and found a downfield
shift of the C-2′ carbon signal. The above structural conclusions were also confirmed
1
by H,13C-heterocorrelated 2D NMR experiments.
The cytostatic activity of the free nucleoside analogs was tested on L1210, L929 and
HeLa cell cultures. None of the studied compounds was active in these systems23.
EXPERIMENTAL
Unless stated otherwise, solutions were evaporated at 40 °C/2 kPa and compounds were dried over
phosphorus pentoxide at 13 Pa. Thin-layer chromatography was carried out on Silufol UV 254 sheets
(Kavalier, Czech Republic). Compounds were detected by UV light at 254 nm. Preparative column
chromatography was performed on silica gel (30–60 µm, Service Laboratories of the Institute). NMR
spectra were measured on Varian UNITY-200 (1H at 200 MHz) and Varian UNITY-500 (1H at 500 MHz
and 13C at 125.7 MHz) in hexadeuteriodimethyl sulfoxide. Chemical shifts of protons were refer-
enced to tetramethylsilane as internal standard whereas the carbon shifts to the solvent signal
(δ(CD3SOCD3) = 39.7 ppm). Mass spectra were measured on a ZAB-EQ (VG Analytical) spectro-
meter by the FAB method (Xe, 8 kV) using glycerol (G) or thioglycerol (TG) as matrix.
5-Phenyl-2(1H)-pyrimidinone (3)
Methanolic sodium methoxide (1 M, 480 ml) was added to a suspension of 2-phenyltrimethinium per-
chlorate (1; 60.55 g, 200 mmol) and dry thiourea (20 g, 264 mmol) in absolute ethanol (400 ml). The
mixture was stirred at room temperature for 30 min and then refluxed for 2 h. After cooling, the
obtained solution was neutralized with acetic acid (precipitate formation) and the solvent was evapo-
rated. Water (800 ml) was added, the solid was collected, washed with water and air-dried. Yield 37 g
(98%) of 5-phenyl-2-mercaptopyrimidine (2).
This product (37 g, 197 mmol) was slurried in water (150 ml) and chloroacetic acid (20.8 g, 220 mmol)
was added. After reflux for 2 h, 36% hydrochloric acid (60 ml) was added and reflux was continued for
another 5 h. Azeotropic (20.2%) hydrochloric acid (1.15 l) was then added and the mixture was refluxed
for 1 h. After cooling, the mixture was taken down and the residue codistilled with water (2 × 250 ml).
Water (300 ml) was added to the residue, the mixture was neutralized with aqueous ammonia to pH 6
and the suspension was set aside in a refrigerator overnight. The deposited product was collected,
washed with water, dissolved in hot ethanol and treated with charcoal. After filtration, the filtrate was
concentrated and the residue crystallized from ethanol to give 20.2 g of compound 3 (60% from 2). For
C10H8N2O (172.2) calculated: 69.76% C, 4.68% H, 16.27% N; found: 69.49% C, 4.72% H, 16.07% N.
1H NMR spectrum: 7.28–7.50 m, 3 H and 7.56–7.69 m, 2 H (H-arom.); 8.61 s, 2 H (H-4, H-6); 12.24
Collect. Czech. Chem. Commun. (Vol. 61) (1996)

468
Krecmerova, Hrebabecky, Masojidkova, Holy:
br s, 1 H (NH). 13C NMR spectrum: 116.66 (C-5); 125.58, 2 C, 127.47, 129.19, 2 C and 133.67
(C-arom.); 155.0 br, 2 C (C-4 and C-6); 156.40 (C-2).
1-(2,3,5-Tri-O-benzoyl-β-D-ribofuranosyl)-5-phenyl-2(1H)pyrimidinone (5)
A. A catalytic amount of ammonium sulfate was added to a suspension of compound 3 (1 g, 5.81 mmol)
in hexamethyldisilazane and the mixture was heated at 150 °C to dissolution and then for another
hour. After cooling, the solution was taken down and the residue was codistilled with xylene (2 × 25 ml).
The obtained 5-phenyl-2-trimethylsilyloxypyrimidine (4) was added to a solution of 1-O-acetyl-2,3,5-
tri-O-benzoyl-D-ribose (2.93 g, 5.81 mmol) in 1,2-dichloroethane (30 ml). Tin tetrachloride (1 ml, 8.5 mmol)
was added and the reaction mixture was stirred at room temperature for 4 h under exclusion of moisture.
The reaction mixture was diluted with chloroform (100 ml) and poured into saturated solution of
sodium hydrogen carbonate (250 ml). The formed emulsion was filtered through Celite, the organic
layer was separated and washed with saturated solution of sodium hydrogen carbonate (3 × 150 ml).
The combined organic extracts were dried over magnesium sulfate, the solvent was evaporated and
the residue was chromatographed on silica gel (500 ml) in toluene–ethyl acetate (2 : 1). A side product
(RF 0.80) was eluted first, followed by the product 5 (RF 0.35); yield 1.53 g (43%), m.p. 189.5 °C
(toluene–ether). For C36H28N2O8 (616.6) calculated: 70.12% C, 4.58% H, 4.54% N; found: 69.54% C,
1
4.62% H, 4.15% N. H NMR spectrum: 4.72 dd, 1 H, J(5′a,4′) = 5.4, J(gem) = 12.2 (H-5′a); 4.79 dd,
1 H, J(5′b,4′) = 3.4 (H-5′b); 4.89 td, 1 H (H-4′); 6.09 t, 1 H, J(3′,2′) = J(3′,4′) = 6.3 (H-3′); 6.11 dd,
1 H, J(2′,1′) = 3.0 (H-2′); 6.33 d, 1 H (H-1′); 7.30–7.50 m, 9 H, 7.55–7.70 m, 5 H, 7.90–8.00 m, 6 H
(H-arom.); 8.60 d, 1 H and 9.07 d, 1 H, J(4,6) = 3.4 (H-6 and H-4). 13C NMR spectrum: 63.75
(C-5′); 70.69 (C-3′); 74.12 (C-2′); 79.78 (C-4′); 92.66 (C-1′); 117.33 (C-5); 125.77, 2 C, 127.82 and
128.74–134.11, 21 C (C-arom.); 143.32 (C-6); 154.18 (C-2); 164.78, 2 C and 165.72 (C=O); 166.46
(C-4).
B. Tin tetrachloride (1 ml, 8.5 mmol) was added to a mixture of silyl derivative 4 (prepared from
1 g of compound 3 according to procedure A), 1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribose (2.93 g, 5.81 mmol)
and acetonitrile (30 ml) and the resulting solution was stirred at ambient temperature for 12 h. The
workup was the same as described in procedure A. Yield 1.54 g (43%) of compound 5.
C. To a mixture of silyl derivative 4, 1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribose (same amounts as in
procedure A) and acetonitrile (50 ml) was added trimethylsilyl trifluoromethanesulfonate (1.6 ml, 8.5 mmol).
The reaction mixture was stirred at room temperature for 12 h and worked up as described for pro-
cedure A. Yield 1.25 g (35%) of compound 5.
5-Phenyl-1-(β-D-ribofuranosyl)-2(1H)-pyrimidinone (6)
Benzoyl derivative 5 (2.25 g, 3.65 mmol) was stirred with methanolic ammonia (100 ml) for 65 h at
room temperature. After evaporation, the residue was mixed with light petroleum–ether (1 : 1, 100 ml),
the mixture was set aside for 1 h and then decanted. The solid product was crystallized from methanol–ethanol
(1 : 1) to give crystalline product 6 (626 mg, 56%), m.p. 188–191 °C. Further portion was obtained
from the mother liquors by evaporation and chromatography on silica gel in ethyl acetate–acetone–
ethanol–water (18 : 3 : 2 : 2), RF 0.50. This afforded another 100 mg (9%) of compound 6. For
C15H16N2O5 (304.3) calculated: 59.20% C, 5.30% H, 9.21% N; found: 58.55% C, 5.35% H, 8.44% N.
Mass spectrum (FAB, G + dimethyl sulfoxide): 305 (M+ + H). 1H NMR spectrum: 3.68 ddd, 1 H,
J(5′a,4′) = 2.0, J(5′a,OH) = 4.4, J(gem) = 12.2 (H-5′a); 3.88 ddd, 1 H, J(5′b,4′) = 2.4, J(5′b,OH) = 4.6
(H-5′b); 4.00 dt, 1 H, J(4′,3′) = 7.6 (H-4′); 4.06 td, 1 H, J(2′,1′) = 1.7, J(2′,OH) = J(2′,3′) = 4.6 (H-2′);
4.10 ddd, 1 H (H-3′); 5.04 d, 1 H, J(OH,3′) = 6.6 (3′-OH); 5.50 t, 1 H, J(OH,5′) = 4.5 (5′-OH); 5.69 d,
1 H, J(OH,2′) = 4.6 (2′-OH); 5.80 d, 1 H (H-1′); 7.34 t, 1 H, 7.43 t, 2 H, 7.62 d, 2 H (H-arom.); 8.99 d,
1 H and 9.14 d, 1 H, J(4,6) = 3.4 (H-6 and H-4). 13C NMR spectrum: 59.03 (C-5′); 67.72 (C-3′); 74.94
Collect. Czech. Chem. Commun. (Vol. 61) (1996)

5-Phenyl-2(1H)-pyrimidinone Nucleosides
469
(C-2′); 83.98 (C-4′); 91.44 (C-1′); 116.72 (C-5); 125.43, 2 C, 127.52, 129.26, 2 C and 133.62 (C-arom.);
141.56 (C-6); 154.41 (C-2); 164.59 (C-4).
5′,O6-Cyclo-5-phenyl-1,3-bis(β-D-ribofuranosyl)-2(1H,3H)-5,6-dihydropyrimidinone (7)
The chromatographically more mobile side product (2.06 g) from the preparation of compound 5 was
stirred with methanolic ammonia (100 ml) for 72 h at room temperature. After evaporation of the
solvent, the residue was mixed with ether (100 ml) and the mixture was set aside for 1 h. The
ethereal layer was discarded and the solid residue was crystallized from ethanol. Yield 610 mg of
pure crystalline compound 7. For C20H24N2O9 (436.4) calculated: 55.04% C, 5.54% H, 6.42% N;
1
found: 54.77% C, 5.52% H, 6.26% N. Mass spectrum (FAB, G + methanol): 437 (M+ + H). H NMR
spectrum, sugar part A: 3.69 br d, 1 H, J(5′a,4′) ≥ 0, J(gem) = 12.4 (H-5′a); 3.75 dd, 1 H, J(5′b,4′) =
2.2 (H-5′b); 4.10 td, 1 H, J(3′,2′) = 6.1, J(3′,4′) = 2.2 (H-3′); 4.135 br t, 1 H (H-2′); 4.31 br t, 1 H
(H-4′); 5.02 d, 1 H, J(OH,3′) = 5.9 (3′-OH); 5.25 d, 1 H, J(OH,2′) = 5.1 (2′-OH); 5.51 br s, 1 H,
J(1′,2′) ≥ 0 (H-1′); sugar part B: 3.56 ddd, 1 H, J(5′a,4) = 3.4, J(5′a,OH) = 5.0, J(gem) = 11.7 (H-5′a);
3.64 ddd, 1 H, J(5′b,4′) = 3.2 (H-5′b); 3.79 br q, 1 H (H-4′); 3.97 dt, 1 H, J(3′,2′) = 5.0, J(3′,4′) = 3.6
(H-3′); 4.05 q, 1 H (H-2′); 5.00 d, 1 H, J(OH,3′) = 4.6 (3′-OH); 5.12 t, 1 H, J(OH,5′) = 5.0 (5′-OH); 5.16 d,
1 H, J(OH,2′) = 6.1 (2′-OH); 5.82 d, 1 H, J(1′,2′) = 6.1 (H-1′); base: 7.23 d, 1 H, J(4,6) = 1.4 (H-4);
7.20–7.40 m, 5 H (H-arom.); 5.99 d, 1 H (H-6). 13C NMR spectrum: 61.48 (C-5′B); 70.34 (C-5′A);
70.49 (C-3′B); 71.13 (C-3′A); 72.54 (C-2′B); 76.62 (C-2′A); 83.07 (C-6); 84.41 (C-4′B); 87.50 (C-1′B);
89.54 (C-4′A); 94.42 (C-1′A); 109.94 (C-5); 123.05 (C-4), 124.78, 2 C, 126.45, 128.74, 2 C and
136.36 (C-arom.); 148.64 (C-2).
1-(2-Deoxy-3,5-di-O-p-toluoyl-β-D-ribofuranosyl)-5-phenyl-2(1H)-pyrimidinone (10)
and 1-(2-Deoxy-3,5-di-O-p-toluoyl-α-D-ribofuranosyl)-5-phenyl-2(1H)-pyrimidinone (11)
Trimethylsilyl trifluoromethanesulfonate (1.6 ml, 8.5 mmol) was added at –20 °C to a mixture of
silyl derivative 4 (prepared from compound 3; 1 g, 5.81 mmol), methyl 2-deoxy-3,5-di-O-p-toluoyl-
D-ribofuranoside (8; 2.23 g, 5.81 mmol) and acetonitrile (50 ml). The solution was stirred at –20 °C
for 20 min and then poured into saturated solution of sodium hydrogen carbonate (300 ml). The pro-
duct was taken up in chloroform (200 ml), the organic phase was dried over magnesium sulfate and
the solvent was evaporated. Chromatography on silica gel (750 ml) in ethyl acetate–toluene (2 : 1)
afforded the β-anomer 10 (RF 0.49) as the first fraction (1.22 g, 40%); white foam. For C31H28N2O6
(524.6) calculated: 70.98% C, 5.38% H, 5.34% N; found: 70.20% C, 5.23% H, 5.09% N. 1H NMR
spectrum: 2.40 s, 3 H and 2.34 s, 3 H (CH3); 2.66 dt, 1 H, J(2′a,3′) = 6.8, J(gem) = 14.4 (H-2′a);
2.86 ddd, 1 H, J(2′b,3′) = 2.4, J(2′b,1′) = 6.3 (H-2′b); 4.64 dd, 1 H, J(5′a,4′) = 6.6, J(gem) = 12.7
(H-5′a); 4.71 dd, 1 H, J(5′b,4′) = 3.4 (H-5′b); 4.72 br pent, 1 H (H-4′); 5.65 dt, 1 H, J(3′,2′b) =
J(3′,4′) = 2.4 (H-3′); 6.31 dd, 1 H, J(1′,2′a) = 7.3, J(1′,2′b) = 6.3 (H-1′); 7.21 d, 2 H, 7.32 m, 3 H,
7.37 d, 2 H, 7.47 d, 2 H, 7.78 d, 2 H and 7.94 d, 2 H (H-arom.); 8.38 d, 1 H and 8.97 d, 1 H, J(4,6) = 3.4
(H-6 and H-4). 13C NMR spectrum: 21.32 and 21.40 (CH3); 38.08 (C-2′); 64.37 (C-5′); 75.10 (C-3′);
83.01 (C-1′); 88.32 (C-4′); 117.15 (C-5); 125.65–129.65, 15 C and 133.31 (C-arom.); 140.58 (C-6);
144.01 and 144.28 (C-arom.); 154.15 (C-2); 165.36 (C-4); 165.46 and 165.71 (C=O).
Further chromatography afforded 0.56 g (18%) of amorphous α-anomer 11 (RF 0.40). For C31H28N2O6
(524.6) calculated: 70.98% C, 5.38% H, 5.34% N; found: 69.89% C, 5.42% H, 5.26% N. 1H NMR
spectrum: 2.24 s, 3 H and 2.40 s, 3 H (CH3); 2.55 dt, 1 H, J(2′a,1′) = J(2′a,3′) = 1.0, J(gem) = 14.4
(H-2′a); 3.05 dt, 1 H (H-2′b); 4.51 d, 2 H, J(5′,4′) = 4.9 (2 × H-5′); 5.37 br t, 1 H (H-4′); 5.59 br d,
1 H, J(3′,2′b) = 5.9, J(3′,4′) = 1.0 (H-3′); 6.26 dd, 1 H, J(1′,2′a) = 1.0, J(1′,2′b) = 6.8 (H-1′); 6.96 d, 2 H,
7.30–7.40 m, 5 H, 7.50 d, 2 H, 7.56 d, 2 H, 7.94 d, 2 H (H-arom.); 8.50 d, 1 H and 8.98 d, 1 H, J(4,6) = 3.4
(H-6 and H-4). 13C NMR spectrum: 21.24 and 21.37 (CH3); 38.19 (C-2′); 64.15 (C-5′); 74.87 (C-3′);
Collect. Czech. Chem. Commun. (Vol. 61) (1996)

470
Krecmerova, Hrebabecky, Masojidkova, Holy:
85.11 (C-1′); 89.46 (C- 4′); 116.98 (C-5); 125.97–129.60, 15 C and 133.42 (C-arom.); 140.60 (C-6);
143.92 and 144.14 (C-arom.); 154.35 (C-2); 164.94 (C-4); 164.99 and 165.66 (C=O).
5-Phenyl-1-(2-deoxy-β-D-ribofuranosyl)-2(1H)-pyrimidinone (12)
A solution of compound 10 (2.2 g, 4.19 mmol) in methanolic ammonia (100 ml) was stirred at room
temperature for 24 h. After evaporation of the solvent, the residue was crystallized from ethanol,
yield 884 mg (73%) of compound 12, m.p. 176–178 °C. For C15H16N2O4 (288.3) calculated: 62.49% C,
1
5.59% H, 9.72% N; found: 62.26% C, 5.58% H, 9.71% N. H NMR spectrum: 2.20 dt, 1 H, J(2′a,1′) =
J(2′a,3′) = 5.8, J(gem) = 13.4 (H-2′a); 2.42 ddd, 1 H, J(2′b,1′) = 6.1, J(2′b,3′) = 5.4 (H-2′b); 3.65 ddd,
1 H, J(5′a,4′) = 3.2, J(5′a,OH) = 4.9, J(gem) = 12.0 (H-5′a); 3.76 ddd, 1 H, J(5′b,4′) = 3.2, J(5′b,OH) = 4.9,
J(gem) = 12.0 (H-5′b); 3.93 br q, 1 H (H-4′); 4.30 pent, 1 H (H-3′); 5.32 t, 1 H, J(OH,5′) = 4.9
(5′-OH); 5.32 d, 1 H, J(OH,3′) = 4.6 (3′- OH); 6.14 t, 1 H, J(1′,2′a) = J(1′,2′b) = 5.9 (H-1′); 7.34 t,
1 H, 7.44 t, 2 H and 7.61 d, 2 H (H-arom.); 8.94 d, 1 H and 8.98 d, 1 H, J(4,6) = 3.4 (H-6 and H-4).
13C NMR spectrum: 41.35 (C-2′); 60.35 (C-5′); 69.10 (C-3′); 87.23 (C-1′); 88.19 (C-4′); 116.71 (C-5);
125.47, 2 C, 127.55, 129.28, 2 C and 133.69 (C-arom.); 141.25 (C-6); 154.30 (C-2); 164.48 (C-4).
5-Phenyl-1-(2-deoxy-α-D-ribofuranosyl)-2(1H)-pyrimidinone (13)
A solution of compound 11 (3.4 g, 6.48 mmol) in methanolic ammonia (100 ml) was stirred at room
temperature for 24 h. After evaporation, the residue was crystallized from ethyl acetate–acetone–ethanol–water
(18 : 3 : 1 : 1) mixture. Yield 1.4 g (73%), m.p. 103–105 °C. For C15H16N2O4 . 1/2 H2O (297.3)
calculated: 60.06% C, 5.76% H, 9.42% N; found: 59.99% C, 5.77% H, 9.12% N. 1H NMR spectrum:
2.07 dt, 1 H, J(2′a,1′) = J(2′a,3′) = 1.5, J(gem) = 12.7 (H-2′a); 2.63 ddd, 1 H, J(2′b,1′) = 7.3,
J(2′b,3′) = 5.4 (H-2′b); 3.43 dd, 1 H, J(5′a,4′) = 5.4, J(gem) = 11.7 (H-5′a); 3.47 dd, 1 H, J(5′b,4′) = 4.4
(H-5′b); 4.27 dt, 1 H, J(3′,2′a) = J(3′,4′) = 1.0, J(3′,2′b) = 5.4 (H-3′); 4.44 br t, 1 H, J(4′,3′) ≤ 1.0,
J(4′,5′a) ≈ J(4′,5′b) = 4.8 (H-4′); 4.90 br, 1 H and 5.20 br, 1 H (OH); 6.11 dd, 1 H, J(1′,2′a) = 1.5,
J(1′,2′b) = 7.3 (H-1′); 7.36 t, 1 H, 7.46 t, 2 H and 7.58 d, 2 H (H-arom.); 8.45 d, 1 H and 8.95 d, 1 H,
J(4,6) = 3.4 (H-6 and H-4). 13C NMR spectrum: 40.67 (C-2′); 61.92 (C-5′); 70.96 (C-3′); 89.15 (C-1′);
91.07 (C-4′); 116.24 (C-5); 125.58, 2 C, 127.61, 129.36, 2 C and 133.88 (C-arom.); 141.91 (C-6);
154.44 (C-2); 164.40 (C-4).
1-(5-O-tert-Butyldiphenylsilyl-2-deoxy-α-D-ribofuranosyl)-5-phenyl-2(1H)-pyrimidinone (14)
Prior to the reaction, compound 13 (1.82 g, 6.31 mmol) was codistilled with dry pyridine (30 ml).
The residue was dissolved in dimethylformamide (30 ml), and imidazole (859 mg, 12.6 mmol), fol-
lowed by tert-butyldiphenylsilyl chloride (1.64 ml, 6.31 mmol), was added. The reaction mixture was
stirred at room temperature for 24 h, mixed with ethanol (1 ml) and the solvent was evaporated. The
residue was twice codistilled with xylene. The deposited crystalline imidazole hydrochloride was
removed by filtration, the filtrate was concentrated and the residue purified by chromatography on
silica gel (400 ml) in toluene–acetone (1 : 1), RF 0.33. Yield 3.04 g (92%) of white amorphous com-
pound 14. For C31H34N2O4Si (526.7) calculated: 70.69% C, 6.51% H, 5.32% N; found: 70.33% C,
6.54% H, 5.23% N. 1H NMR spectrum: 1.01 s, 9 H (CH3); 2.12 br d, 1 H, J(gem) = 14.0 (H-2′a);
2.69 m, 1 H (H-2′b); 3.71 d, 2 H, J(5′,4′) = 4.0 (H-5′); 4.39 m, 1 H (H-4′); 4.58 t, 1 H, J(3′,4′) = 2.4
(H-3′); 5.31 d, 1 H, J(OH,3′) = 2.4 (OH); 6.15 d, 1 H, J(1′,2′b) = 6.3 (H-1′); 7.28–7.75 m, 15 H
(H-arom.); 8.45 d, 1 H and 8.96 d, 1 H, J(4,6) = 3.4 (H-6 and H-4).
Collect. Czech. Chem. Commun. (Vol. 61) (1996)

5-Phenyl-2(1H)-pyrimidinone Nucleosides
471
1-(5-O-tert-Butyldiphenylsilyl-2-deoxy-3-O-methanesulfonyl-α-D-ribofuranosyl)-
5-phenyl-2(1H)-pyrimidinone (15)
Methanesulfonyl chloride (0.21 ml, 2.78 mmol) was added at 0 °C to a solution of compound 14 (1.2 g,
2.28 mmol) in pyridine (15 ml) and the mixture was stirred overnight (about 16 h) at room tempera-
ture. The reaction was quenched with methanol (2 ml) and water (2 ml) and the solvent was evaporated.
The residue was codistilled successively with ethanol (30 ml) and toluene (30 ml) and then parti-
tioned between ethyl acetate (150 ml) and 1% hydrochloric acid (50 ml). The organic layer was
washed with water (2 × 100 ml), dried over magnesium sulfate and taken down. The residue was
chromatographed on silica gel (350 ml) in toluene–acetone (3 : 2), RF 0.40. Yield 1.12 g (81%) of
mesyl derivative 15, white foam. For C32H36N2O6SSi (604.8) calculated: 63.55% C, 6.00% H, 4.63% N,
5.30% S; found: 63.71% C, 6.05% H, 4.83% N, 5.09% S. 1H NMR spectrum: 1.03 s, 9 H (CH3); 2.53 br d,
1 H, J(gem) = 16.0 (H-2′a); 3.00 ddd, 1 H (H-2′b); 3.19 s, 3 H (CH3); 3.80 d, 2 H, J(5′,4′) = 3.7 (H-5′);
5.06 t, 1 H (H-4′); 5.42 d, 1 H, J(3′,2′b) = 5.2 (H-3′); 6.20 d, 1 H, J(1′,2′b) = 5.8 (H-1′); 7.33–7.74 m,
15 H (H-arom.); 8.34 d, 1 H and 8.99 d, 1 H, J(4,6) = 3.4 (H-6 and H-4).
1-(5-O-tert-Butyldiphenylsilyl-2,3-dideoxy-α-D-glycero-pent-2-enofuranosyl)-
5-phenyl-2(1H)-pyrimidinone (16)
To a solution of compound 15 (605 mg, 1 mmol) in acetonitrile was added DBU (0.22 ml, 1.5 mmol)
and the solution was heated at 70 °C for 12 h. The reaction mixture was neutralized with acetic acid
and taken down. The residue was partitioned between ethyl acetate and water (100 ml each) and the
organic layer was dried over magnesium sulfate. After evaporation of the solvent, the residue was
chromatographed on silica gel (100 ml) in toluene–acetone–triethylamine (25 : 8 : 1), RF 0.45, to give
460 mg (90%) of pure amorphous compound 16. For C31H32N2O3Si (508.7) calculated: 73.20% C,
6.34% H, 5.51% N; found: 73.11% C, 6.38% H, 5.42% N. 1H NMR spectrum: 1.00 s, 9 H (CH3);
3.77 dd, 1 H, J(5′a,4′) = 4.0, J(gem) = 11.0 (H-5′a); 3.86 dd, 1 H, J(5′b,4′) = 3.7 (H-5′b); 5.47 m, 1 H
(H-4′); 6.17 dt, 1 H J(3′,4′) = 1.8, J(3′,2′) = 6.1 (H-3′); 6.50 dt, 1 H, J(2′,3′) = 6.1, J(2′,4′) = 1.5
(H-2′); 6.99 dt, 1 H, J(1′,4′) = 5.2, J(1′,2′) = J(1′,3′) = 1.5 (H-1′); 7.30–7.73 m, 15 H (H-arom.); 8.07 d,
1 H and 8.99 d, 1 H, J(4,6) = 3.4 (H-6 and H-4).
1-(2,3-Dideoxy-α-D-glycero-pent-2-enofuranosyl)-5-phenyl-2(1H)pyrimidinone (17)
To a solution of compound 16 (440 mg, 0.86 mmol) in tetrahydrofuran (50 ml) was added 1 M tetra-
butylammonium fluoride in tetrahydrofuran (0.86 ml) and the solution was stirred for 2 h at room
temperature. During the reaction the mixture was kept neutral by dropwise addition of acetic acid.
After evaporation of the solvent, the residue was chromatographed on silica gel in ethyl acetate–ethanol–
triethylamine (25 : 2 : 1), RF 0.33. Yield 147 mg (63%) of white foam. 1H NMR spectrum: 3.55 m,
2 H (H-5′); 4.90 t, 1 H, J(OH,5′) = 6.0 (OH); 5.33 m, 1 H (H-4′); 6.11 d, 1 H, J(3′,2′) = 6.1 (H-3′);
6.46 d, 1 H, J(2′,3′) = 6.1 (H-2′); 6.93 d, 1 H, J(1′,4′) = 4.9 (H-1′); 7.26–7.72 m, 5 H (H-arom.); 8.04 d,
1 H and 8.97 d, 1 H, J(4,6) = 3.4 (H-6 and H-4).
Reaction of Compound 12 with tert-Butyldiphenylsilyl Chloride
Nucleoside 12 (100 mg, 0.35 mmol) was codistilled with pyridine (20 ml) and then dissolved in di-
methylformamide (1.6 ml). Imidazole (48 mg, 0.7 mmol) and tert-butyldiphenylsilyl chloride (0.1 ml,
0.38 mmol) were added and the solution was stirred at room temperature overnight. After addition of
ethanol (0.2 ml), the solution was taken down, the residue was codistilled with xylene and partitioned
between ethyl acetate and water (50 ml each). The organic phase was dried over magnesium sulfate,
the solvent was evaporated and the residue was chromatographed on silica gel (40 ml) in toluene–
Collect. Czech. Chem. Commun. (Vol. 61) (1996)

472
Krecmerova, Hrebabecky, Masojidkova, Holy:
ethyl acetate (2 : 1). First eluted was the 3′,5′-bis(tert-butyldiphenylsilyl) derivative, RF 0.80 (70 mg,
26%), then the 3′-O-tert-butyldiphenylsilyl derivative, RF 0.45 (20 mg, 11%), and finally the desired
5′-O-tert-butyldiphenylsilyl derivative, RF 0.40 (74 mg, 40%) as a white foam. 1H NMR spectrum:
0.96 s 9 H (CH3); 2.20 ddd, 1 H, J(2′a,3′) = 6.1, J(2′a,1′) = 7.1, J(gem) = 13.2 (H-2′a); 2.51 ddd, 1 H,
J(2′b,3′) = 2.9, J(2′b,1′) = 6.1 (H-2′b); 3.79 dd, 1 H, J(5′a,4′) = 5.1, J(gem) = 11.7 (H-5′a); 3.94 dd,
1 H, J(5′b,4′) = 3.2 (H-5′b); 4.08 dt, 1 H, J(4′,3′) = 3.0 (H-4′); 4.24 m, 1 H (H-3′); 5.37 d, 1 H,
J(OH,3′) = 4.1 (OH); 6.16 br t, 1 H (H-1′); 7.25–7.48 and 7.54 m, 15 H (H-arom.); 8.39 d, 1 H and
8.95 d 1 H, J(4,6) = 3.4 (H-6 and H-4).
1-(2-O-Acetyl-3,5-di-O-benzoyl-β-D-xylofuranosyl)-5-phenyl-2(1H)-pyrimidinone (19)
The silyl derivative 4, prepared from 5-phenyl-2(1H)-pyrimidinone (3; 12.54 g, 72.8 mmol) as described
in the preparation of compound 5, was added to a solution of 1,2-di-O-acetyl-3,5-di-O-benzoyl-D-xylose
(32.23 g, 72.8 mmol) in acetonitrile (500 ml). To this mixture was added tin tetrachloride (13 ml,
111 mmol). The reaction mixture was stirred at room temperature overnight, poured into saturated
solution of sodium hydrogen carbonate (2 l) and shaken with ethyl acetate (2 l). The formed suspen-
sion was filtered through Celite, the organic layer in the filtrate was separated and washed with a
solution of sodium hydrogen carbonate (2 × 750 ml). The organic phase was dried over magnesium
sulfate, the solvent was evaporated and the residue chromatographed on silica gel (2.5 l).
Elution with ethyl acetate–toluene (1 : 1) afforded 1.313 g (3%) of 1-(2,3,4-tri-O-benzoyl-β-D-xy-
lopyranosyl)-5-phenyl-2(1H)-pyrimidinone (21) as a white solid, RF 0.43. For C36H28N2O8 (616.6)
calculated: 70.12% C, 4.58% H, 4.54% N; found: 69.83% C, 4.72% H, 4.66% N. Mass spectrum
(FAB, T + G, dimethyl sulfoxide): 617 (M+ + H). 1H NMR spectrum: 4.22 t, 1 H, J(5′a,4′) = J(gem) = 11.0
(H-5′a); 4.36 dd, 1 H, J(5′b,4′) = 5.8 (H-5′b); 5.81 br td, 1 H, ΣJ = 25.3 (H-4′); 6.20 br t, 1 H,
J(2′,3′) = 9.5 (H-2′); 6.23 br t, 1 H, J(3′,4′) = 8.5 (H-3′); 6.58 d, 1 H, J(1′,2′) = 8.6 (H-1′); 7.40–7.65 m,
12 H and 7.75–7.90 m, 8 H (H-arom.); 9.00 d, 1 H and 9.01 d, 1 H, J(4,6) = 3.35 (H-6 and H-4).
Further elution with ethyl acetate–toluene (1 : 1) afforded 1-(2,3,5-tri-O-benzoyl-β-D-xylofuranosyl)-
5-phenyl-2(1H)-pyrimidinone (20; 820 mg, 2%) as a white foam, RF 0.35. For C36H28N2O8 (616.6)
calculated: 70.12% C, 4.58% H, 4.54% N; found: 69.80% C, 4.85% H, 4.86% N. Mass spectrum
(FAB, T + G, dimethyl sulfoxide): 617 (M+ + H). 1H NMR spectrum: 4.74 dd, 1 H, J(4′,5′a) = 3.7,
J(gem) = 12.2 (H-5′a); 4.96 dd, 1 H, J(4′5′b) = 7.0 (H-5′b); 5.13 m, 1 H (H-4′); 5.85 m, 1 H (H-2′);
5.91 dd, 1 H, J(3′,2′) = 1.2, J(3′,4′) = 3.7 (H-3′); 6.29 d, 1 H, J(1′,2′) = 1.8 (H-1′); 7.12–8.18 m, 20 H
(H-arom.); 8.61 d, 1 H and 9.06 d, 1 H, J(4,6) = 3.4 (H-6 and H-4). 13C NMR spectrum: 64.65
(C-5′); 68.96 (C-4′); 71.10 (C-2′); 73.17 (C-3′); 81.94 (C-1′); 117.51 (C-5); 125.88, 2 C, 128.02,
129.42, 14 C, 132.95, 133.98, 134.05 a 134.16 (C-arom.); 142.43 (C-6); 154.11 (C-2); 164.91, 165.13
and 165.33 (C=O); 166.52 (C-4).
Elution with ethyl acetate–toluene (3 : 1) finally gave 14.6 g (36%) of the product 19, RF 0.35, as
a white foam. For C31H26N2O8 (554.6) calculated: 67.14% C, 4.73% H, 5.05% N; found: 66.94% C,
1
4.87% H, 5.14% N. H NMR spectrum: 2.19 s, 3 H (CH3); 4.69 dd, 1 H, J(5′a,4′) = 3.7, J(gem) = 12.0
(H-5′a); 4.91 dd, 1 H, J(5′b,4′) = 6.8 (H-5′b); 4.97 dt, 1 H (H-4′); 5.78 dd, 1 H, J(3′,2′) = 1.5, J(3′,4′) = 3.7
(H-3′); 5.80 t, 1 H (H-2′); 6.10 d, 1 H, J(1′,2′) = 1.7 (H-1′); 7.18 t, 2 H, 7.40 m, 5 H, 7.55 t, 1 H,
7.60 t, 1 H, 7.62 d, 2 H, 7.70 d, 2 H and 7.88 d, 2 H (H-arom.); 8.55 d, 1 H and 9.04 d, 1 H, J(4,6) = 3.4
(H-6 and H-4). 13C NMR spectrum: 20.74 (CH3); 61.78 (C-5′); 74.74 (C-3′); 79.04 (C-2′); 80.15 (C-4′);
90.67 (C-1′); 117.26 (C-5); 125.80, 2 C, 127.80, 128.40–129.40, 12 C, 133.22, 133.66 and 133.93
(C-arom.); 140.20 (C-6); 154.18 (C-2); 164.24 and 165.67 (C=O); 165.83 (C-4); 168.99 (C=O).
Collect. Czech. Chem. Commun. (Vol. 61) (1996)

5-Phenyl-2(1H)-pyrimidinone Nucleosides
473
5-Phenyl-1-(β-D-xylofuranosyl)-2(1H)-pyrimidinone (22)
Compound 20 (600 mg, 0.97 mmol) was stirred with methanolic ammonia (20 ml) at room tempera-
ture for 48 h. The solvent was evaporated and the residue was crystallized from ethyl acetate–
acetone–ethanol–water (18 : 3 : 2 : 1). Evaporation of the mother liquors and chromatography of the
residue in the mentioned solvent system gave further amount of the product, RF 0.41. Total yield 262 mg
(89%) of crystalline compound 22, m.p. 199.5–202 °C. For C15H16N2O5 (304.3) calculated: 59.20% C,
5.30% H, 9.21% N; found: 58.87% C, 5.26% H, 8.94% N. 1H NMR spectrum: 3.84 t, 2 H J(5′,4′) = 5.8
(H-5′); 3.97 t, 1 H, J(3′,4′) = 3.1 (H-3′); 4.09 br d, 1 H (H-2′); 4.34 m, 1 H (H-4′); 4.91 t, 1 H,
J(OH,5′) = 5.8 (OH); 5.35 d, 1 H, J(OH,3′) = 3.1 (OH); 5.71 s, 1 H (H-1′); 5.98 d, 1 H, J(2′,OH) = 4.3
(OH); 7.30–7.60 m, 5 H (H-arom.); 8.51 d, 1 H and 8.96 d, 1 H, J(4,6) = 3.4 (H-6 and H-4).
5-Phenyl-1-(β-D-xylopyranosyl)-2(1H)-pyrimidinone (23)
A suspension of compound 21 (1.3 g, 2.1 mmol) in methanolic ammonia (150 ml) was stirred at
room temperature for 72 h. After evaporation of the solvent, the residue was adsorbed on silica gel
(25 ml) and chromatographed on a silica gel column (100 ml) in ethyl acetate–acetone–ethanol–water
(18 : 3 : 1 : 1), RF 0.20. The chromatographically pure product 23 was crystallized from ethanol,
yield 475 mg (74%), m.p. 225–227 °C. For C15H16N2O5 (304.3) calculated: 59.20% C, 5.30% H,
9.21% N; found: 58.80% C, 5.26% H, 9.11% N. 1H NMR spectrum: 3.28 dd, 1 H, J(5′a,4′) = 10.4,
J(gem) = 11.3 (H-5′a); 3.33 td, 1 H, J(3′,2′) = J(3′,4′) = 8.9, J(3′,OH) = 4.3 (H-3′); 3.55 ddt, 1 H
(H-4′); 3.79 td, 1 H, J(2′,1′) = 9.4, J(2′,OH) = 5.8 (H-2′); 3.86 dd, 1 H, J(5′b,4′) = 5.5 (H-5′b); 5.14 d,
1 H, J(OH,4′) = 5.2 (4′-OH); 5.31 d, 1 H (3′-OH); 5.39 d, 1 H (2′-OH); 5.57 d, 1 H, J(1′,2′) = 9.4
(H-1′); 7.36 t, 1 H, 7.45 t, 2 H and 7.68 d, 2 H (H-arom.); 8.45 d, 1 H, 9.00 d, 1 H, J(4,6) = 3.4 (H-6
and H-4). 13C NMR spectrum: 69.04 (C-5′); 69.13 (C-4′); 71.20 (C-2′); 77.32 (C-3′); 85.64 (C-1′);
125.94, 2 C, 127.80, 129.16, 2 C and 133.20 (C-arom.); 142.36 (C-6); 154.82 (C-2); 165.69 (C-4).
1-(3,5-Di-O-benzoyl-β-D-xylofuranosyl)-5-phenyl-2(1H)-pyrimidinone (24)
Hydrochloric acid (36%, 0.8 ml) was added to a solution of compound 19 (1.14 g, 2.06 mmol) in
dioxane (12 ml). The reaction mixture was stirred at room temperature for 48 h and then diluted with
methanol to dissolution of the product. The solution was neutralized with triethylamine and the solvent
evaporated. The residue was partitioned between water and ethyl acetate (130 ml each), the organic
layer was dried over magnesium sulfate and the solvent was evaporated to give 878 mg (83%) of
compound 24 as a white foam. 1H NMR spectrum: 4.50 br d, 1 H, J(2′,OH) = 4.6 (H-2′); 4.69 dd, 1 H,
J(5′a,4′) = 2.0, J(gem) = 12.0 (H-5′a); 5.02 m, 1 H (H-4′); 5.04 dd, 1 H, J(5′b, 4′) = 7.6 (H-5′b); 5.47 dd,
1 H, J(3′,2′) = 1.0, J(3′,4′) = 3.2 (H-3′); 5.86 br s, 1 H, J(1′,2′) ≤ 1 (H-1′); 6.68 d, 1 H (2′-OH); 7.05 t,
2 H, 7.40–7.55 m, 6 H, 7.70 m, 5 H and 7.95 d, 2 H (H-arom.); 8.62 d, 1 H and 8.99 d, 1 H, J(4,6) =
3.4 (H-6 and H-4). 13C NMR spectrum: 62.08 (C-5′); 77.43 (C-3′); 78.21 (C-2′); 80.73 (C-4′); 93.79
(C-1′); 116.78 (C-5); 125.60, 2 C, 127.74, 128.56–129.42, 12 C, 133.34, 133.69 and 133.77 (C-arom.);
140.04 (C-6); 154.36 (C-2); 164.42 (C=0); 165.12 (C-4); 165.83 (C=O).
1-(3,5-Di-O-benzoyl-2-chloro-2-deoxy-β-D-xylofuranosyl)-5-phenyl-2(1H)-pyrimidinone (25)
and 2′,6-Anhydro-1-(3,5-di-O-benzoyl-β-D-lyxofuranosyl)-1,6-dihydro-5-phenyl-6-hydroxy-
2(3H)-pyrimidinone (26)
Thionyl chloride (3 ml, 41 mmol) was added to a solution of compound 24 (5 g, 9.76 mmol) in
acetonitrile (30 ml). The reaction mixture was heated at 75 °C for 6 h, cooled to room temperature,
poured into saturated solution of sodium hydrogen carbonate (300 ml) and the product was taken up
in ethyl acetate (500 ml). The organic layer was separated, again washed with a sodium hydrogen
Collect. Czech. Chem. Commun. (Vol. 61) (1996)

474
Krecmerova, Hrebabecky, Masojidkova, Holy:
carbonate solution (3 × 200 ml), dried over magnesium sulfate and the solvent was evaporated. Chro-
matography on silica gel (750 ml) in toluene–acetone (5 : 2) gave 3.3 g (64%) of the product 25, RF
0.37, as a yellowish foam. For C29H23ClN2O6 (531.0) calculated: 65.60% C, 4.37% H, 5.28% N,
6.68% Cl; found: 65.89% C, 4.56% H, 5.27% N, 6.73% Cl. Mass spectrum (FAB, T + G, dimethyl
sulfoxide): 531 (M+ + H). 1H NMR spectrum: 4.74 dd, 1 H, J(5′a,4′) = 3.4, J(gem) = 12.0 (H-5′a);
5.06 br t, 1 H (H-2′); 5.08 dd, 1 H, J(5′b,4′) = 7.6 (H-5′b); 5.16 dt, 1 H (H-4′); 5.75 dd, 1 H, J(3′,2′) = 1.0,
J(3′,4′) = 3.4 (H-3′); 6.19 d, 1 H, J(1′,2′) = 1.4 (H-1′); 7.11 t, 2 H, 7.40–7.55 m, 6 H, 7.60–7.70 m,
5 H and 7.98 d, 2 H (H-arom.); 8.57 d, 1 H and 9.02 d, 1 H, J(6,4) = 3.4 (H-6 and H-4). 13C NMR
spectrum: 61.89 (C-5′); 61.97 (C-2′); 77.41 (C-3′); 80.34 (C-4′); 93.48 (C-1′); 117.02 (C-5); 125.69,
2 C, 127.82, 128.56–129.46, 12 C, 133.24, 133.73 and 133.85 (C-arom.); 139.47 (C-6); 154.25 (C-2);
164.14 (C=0); 165.60 (C-4); 165.79 (C=O).
Further elution afforded 2′,6-anhydro-1-(3,5-di-O-benzoyl-β-D-lyxofuranosyl)-1,6-dihydro-5-phenyl-6-
hydroxy-2(3H)-pyrimidinone (26), RF 0.36 (ethyl acetate–toluene, 3 : 1). Yield 1.25 g (25%) of white
solid. Mass spectrum (FAB, T + G, methanol): 513 (M+ + H). 1H NMR spectrum: 4.48 dt, 1 H,
J(4′,3′) = J(4′,5′b) = 4.4, J(4′,5′a) = 7.1 (H-4′); 4.72 dd, 1 H, J(5′a,4′) = 7.1, J(gem) = 11.7 (H-5′a);
4.77 dd, 1 H, J(5′b,4′) = 4.4 (H-5′b); 4.80 dd, 1 H, J(2′,1′) = 5.4, J(2′,3′) = 6.3 (H-2′); 5.67 dd, 1 H,
J(3′,4′) = 4.4 (H-3′); 5.79 s, 1 H (H-6); 6.27 d, 1 H, J(1′,2′) = 5.4 (H-1′); 6.89 d, 1 H, J(NH,4) = 5.4
(H-4); 6.89–8.23 m, 15 H (H-arom.); 9.70 d, 1 H (NH). 13C NMR spectrum: 62.57 (C-5′); 73.17
(C-3′); 76.00 (C-2′); 76.34 (C-4′); 86.54 (C-6); 90.16 (C-1′); 106.67 (C-5); 123.97, 2 C (C-arom.);
124.36 (C-4); 126.05, 127.96, 2 C, 128.97–129.80, 10 C, 133.69, 133.93 and 134.50 (C-arom.);
148.95 (C-2); 164.66 and 165.63 (C=O).
1-(2,3-Anhydro-β-D-lyxofuranosyl)-5-phenyl-2(1H)-pyrimidinone (28)
A. DBU (1 ml) and methanol (0.3 ml) were added at 80 °C to a solution of compound 25 (2.35 g,
4.4 mmol) in dimethylformamide (30 ml). The reaction mixture was heated at 80 °C for 2 h, cooled,
neutralized with acetic acid and the solvent was evaporated. The residue was codistilled with toluene
(100 ml) and partitioned between ethyl acetate (200 ml) and water (150 ml). The organic layer was
dried over magnesium sulfate, the solvent was evaporated and the remaining compound 27 was
stirred with methanolic ammonia (100 ml) for 48 h at room temperature. After evaporation of the
solvent, the product was chromatographed on silica gel (400 ml) in ethyl acetate–acetone–ethanol–water
(36 : 6 : 1 : 1), RF 0.20, to give 600 mg (48%) of compound 28 as a white foam. Mass spectrum
(FAB): 287 (M+ + H). 1H NMR spectrum: 3.71 t, 2 H, J(5′,4′) = J(5′,OH) = 5.8 (H-5′); 4.11 dd, 1 H,
J(3′,2′) = 3.2, J(3′,4′) = 1.0 (H-3′); 4.23 td, 1 H (H-4′); 4.27 dd, 1 H, J(2′,1′) = 1.O (H-2′); 5.14 t, 1 H
(5′-OH); 6.20 d, 1 H (H-1′); 7.38 t, 1 H, 7.48 t, 2 H and 7.56 d, 2 H (H-arom.); 8.29 d, 1 H and
9.025 d, 1 H, J(4,6) = 3.4 (H-6 and H-4). 13C NMR spectrum: 56.30 (C-2′); 57.41 (C-3′); 59.84
(C-5′); 79.13 (C-4′); 84.03 (C-1′); 116.86 (C-5); 125.60, 2 C, 127.84, 129.45, 2 C and 133.39 (C-arom.);
141.52 (C-6); 154.28 (C-2); 165.53 (C-4).
B. Mesyl derivative 29 (750 mg, 1.27 mmol) was stirred with methanolic ammonia (60 ml) for 30 h
at room temperature. Evaporation of the solvent and chromatography on silica gel (120 ml) in ethyl
acetate–acetone–ethanol–water (36 : 6 : 1 : 1) gave 300 mg (83%) of compound 28.
1-(3,5-Di-O-benzoyl-2-O-methanesulfonyl-β-D-xylofuranosyl)-5-phenyl-2(1H)-pyrimidinone (29)
Methanesulfonyl chloride (0.18 ml, 2.34 mmol) was added at 0 °C to a solution of compound 24 (1 g,
1.95 mmol) in pyridine (10 ml) and the mixture was stirred at 0 °C for 30 min and then at room
temperature overnight. The reaction was quenched with methanol (1 ml) and the solvent was evapo-
rated. The residue was partitioned between ethyl acetate and 1% hydrochloric acid (150 ml each), the
organic layer was washed several times with water to neutral reaction and dried over magnesium
Collect. Czech. Chem. Commun. (Vol. 61) (1996)

5-Phenyl-2(1H)-pyrimidinone Nucleosides
475
sulfate. Evaporation of the solvent and chromatography on silica gel (200 ml) in toluene–acetone (2 : 1,
RF 0.34) gave 867 mg (75%) of compound 29 as a white foam. For C30H26N2O9S (590.6) calculated:
61.01% C, 4.44% H, 4.74% N, 5.43% S; found: 60.82% C, 4.59% H, 4.44% N, 4.99% S. Mass spectrum
1
(FAB, TG + dimethyl sulfoxide): 591 (M+ + H). H NMR spectrum: 3.51 s, 3 H (CH3); 4.74 dd, 1 H,
J(5′a,4′) = 7.1, J(gem) = 14.7 (H-5′a); 4.97–5.02 m, 2 H (H-4′and H-5′b); 5.67 br t, 1 H, J = 1.5
(H-2′); 5.85 dd, 1 H, J(3′,2′) = 1.5, J(3′,4′) = 3.0 (H-3′); 6.20 d, 1 H, J(1′,2′) = 1.5 (H-1′); 7.13 t, 2 H,
7.40–7.50 m, 5 H, 7.53 t, 1 H, 7.62 t, 1 H, 7.64 t, 2 H, 7.68 d, 2 H and 7.89 d, 2 H (H-arom.); 8.56 d,
1 H and 9.05 d, 1 H, J(4,6) = 3.4 (H-6 and H-4). 13C NMR spectrum: 38.22 (CH3); 61.66 (C-5′);
75.04 (C-3′); 80.32 (C-2′); 83.88 (C-4′); 90.78 (C-1′); 117.38 (C-5); 125.79, 2 C, 127.86, 128.50–129.47,
12 C, 133.20, 133.70 and 133.88 (C-arom.); 140.11 (C-6); 154.25 (C-2); 165.12 and 165.74 (C=O);
165.78 (C-4).
1-(2-O-Acetyl-5-O-benzoyl-3-O-methanesulfonyl-β-D-xylofuranosyl)-5-phenyl-2(1H)-pyrimidinone (31)
Silyl derivative 4, prepared from 5-phenyl-2(1H)-pyrimidinone (3; 1.72 g, 10 mmol) as described for
compound 5, was added to a solution of 1,2-di-O-acetyl-5-O-benzoyl-3-O-methanesulfonyl-D-xylo-
furanose (18; 3.37 g, 9 mmol) in acetonitrile (50 ml). Tin tetrachloride (1.5 ml) was added and the
reaction mixture was stirred at room temperature overnight, poured into saturated solution of sodium
hydrogen carbonate (1 l) and the product was taken up in ethyl acetate (1 l). The organic layer was
filtered through Celite and washed with a solution of sodium hydrogen carbonate (3 × 300 ml). After
drying over magnesium sulfate, the solvent was evaporated to give 4.22 g (89%) of chromatographically
pure product 31 as a foam. To obtain an analytically pure sample, a part of the product (200 ml) was
chromatographed on silica gel in toluene–acetone (1 : 1), RF 0.40. For C25H24N2O9S (528.5) calcu-
lated: 56.81% C, 4.58% H, 5.30% N, 6.07% S; found: 56.61% C, 4.62% H, 5.54% N, 5.94% S. Mass
spectrum (FAB, TG + dimethyl sulfoxide): 529 (M+ + H). 1H NMR spectrum: 2.19 s, 3 H (acetyl);
3.33 s, 3 H (CH3); 4.67 dd, 1 H, J(5′a,4′) = 7.1, J(gem) = 14.7 (H-5′a); 4.83–4.88 m, 2 H (H-5′b and
H-4′); 5.52 dd, 1 H, J(3′,2′) = 1.5, J(3′,4′) = 3.2 (H-3′); 5.58 br t, 1 H, (H-2′); 6.08 d, 1 H, J(1′,2′) = 1.7
(H-1′); 7.37 t, 1 H, 7.44 t, 2 H, 7.49 t, 2 H, 7.60 d, 2 H, 7.65 t, 1 H and 8.00 d, 2 H (H-arom.); 8.33 d,
1 H and 9.03 d, 1 H, J(4,6) = 3.4 (H-6 and H-4). 13C NMR spectrum: 20.79 and 37.63 (CH3); 61.73
(C-5′); 78.91 (C-3′); 79.78 and 79.79 (C-4′ and C-2′); 90.01 (C-1′); 117.32 (C-5); 125.86, 2 C;
127.84; 128.90, 2 C, 129.27, 129.30, 2 C, 129.55, 2 C, 133.38 and 133.78 (C-arom.); 140.08 (C-6);
154.19 (C-2); 165.64 (C=O); 165.83 (C-4); 169.39 (C=O).
1-(5-O-Benzoyl-β-D-arabinofuranosyl)-5-phenyl-2(1H)-pyrimidinone (33a)
and 2′,6-Anhydro-1-(5-O-benzoyl-β-D-arabinofuranosyl)-1,6-dihydro-
5-phenyl-6-hydroxy-2(3H)-pyrimidinone (33b)
Methanol (0.2 ml) and DBU (0.2 ml) were added to a solution of compound 31 (500 mg, 0.946 mmol)
in dimethylformamide (7 ml) and the reaction mixture was stirred at room temperature for 90 min.
The solution was diluted with ethyl acetate (35 ml), neutralized with acetic acid and washed with
water (15 ml). The organic layer was dried over magnesium sulfate, the solvent was evaporated and
the residue chromatographed on silica gel (100 ml), first in toluene–acetone (3 : 2) to remove nonpolar
impurities and then in acetone–toluene (2 : 1). The product fractions (RF 0.23) were evaporated and
the residue was crystallized from methanol to give 116 mg (30%) of the product. According to NMR
spectrum, the product was an equilibrium mixture of compounds 33a and 33b in which the cyclic
form 33b predominated in the ratio 5 : 2.
1H NMR spectrum: Compound 33a: 4.13 m, 1 H (H-3′); 4.24 td, 1 H, J(2′,3′) = 1.5, (H-2′); 4.35 ddd,
J(4′,3′) = 1.5 (H-4′); 4.48 dd, 1 H, J(5′a,4′) = 3.4, J(gem) = 12.0 (H-5′a); 4.81 dd, 1 H, J(5′b,4′) = 8.3
(H-5′b); 5.79 d, 1 H, J(OH,3′) = 3.7 (3′-OH); 5.83 d, 1 H, J(OH,2′) = 4.6 (2′-OH); 6.18 d, 1 H,
Collect. Czech. Chem. Commun. (Vol. 61) (1996)

476
Krecmerova, Hrebabecky, Masojidkova, Holy:
J(1′,2′) = 3.2 (H-1′); 7.34 m, 3 H, 7.50 m, 4 H, 7.65 t, 1 H and 8.01 d, 2 H (H-arom.); 8.26 d, 1 H
and 8.98 d, 1 H, J(6,4) = 3.4 (H-6 and H-4). 13C NMR spectrum: 64.28 (C-5′); 74.15 (C-2′); 76.97
(C-3′); 84.13 (C-4′); 88.86 (C-1′); 116.03 (C-5); 125.36, 2 C, 127.59, 128.97, 2 C, 129.24, 2 C,
129.46, 2 C, 129.60, 133.50 and 133.73 (C-arom.); 142.11 (C-6); 154.18 (C-2); 164.68 (C-4); 165.92
(C=O).
Compound 33b: 3.84 ddd, 1 H, J(4′,3′) = 8.3 (H-4′); 4.44 dd, 1 H, J(5′a,4′) = 6.4, J(gem) = 12.2
(H-5′a); 4.22 br pent, 1 H (H-3′); 4.40 dd, 1 H, J(2′,3′) = 4.2 (H-2′); 4.63 dd, 1 H, J(5′b,4′) = 2.2 (H-
5′b); 5.82 s, 1 H (H-6); 5.86 d, 1 H, J(OH,3′) = 5.4 (3′-OH); 6.16 d, 1 H, J(1′,2′) = 5.5 (H-1′); 6.90 d,
1 H, J(4,NH) = 5.4 (H-4); 7.22 t, 7.35 m, 7.40–7.55 m, 7.62 t and 7.96 d, 10 H (H-arom.); 9.61 d, 1 H
(NH). 13C NMR spectrum: 64.20 (C-5′); 73.91 (C-3′); 78.52 (C-4′); 83.88 (C-6); 83.98 (C-2′); 88.05
(C-1′); 106.53 (C-5); 124.39, 2 C (C-arom.); 124.49 (C-4); 126.49, 128.65, 2 C, 128.93, 2 C, 129.30,
2 C, 129.60, 133.62 and 135.13 (C-arom.); 149.06 (C-2); 165.67 (C=O).
Reaction of Compound 31 with DBU and Methanolic Ammonia
Methanol (0.5 ml) and DBU (0.5 ml) were added to a solution of compound 31 (1.25 g, 2.35 mmol)
in dimethylformamide (15 ml). After stirring for 6 h at room temperature, a further amount of methanol
(0.5 ml) was added and stirring was continued for 30 min. The solution was neutralized with acetic
acid, diluted with ethyl acetate (80 ml) and washed with water (35 ml). The organic layer was dried
over magnesium sulfate, the solvent was evaporated and the residue was stirred with methanolic am-
monia (40 ml) at room temperature for 40 h. After evaporation, the residue was chromatographed on
silica gel in ethyl acetate–acetone–ethanol–water (36 : 6 : 1 : 1). The chromatography afforded:
6-Amino-2′,N6-anhydro-1-(β-D-arabinofuranosyl)-1,6-dihydro-5-phenyl-2(3H)-pyrimidinone (35) as white
crystalline solid (80 mg), m.p. 227–229.5 °C (methanol), RF 0.15. Mass spectrum (FAB, T + G,
methanol + trifluoroacetic acid): 304 (M+ + H). 1H NMR spectrum: 3.25 dd, 1 H, J(NH,2′) = 7.3,
J(NH,6) = 13.2 (NH); 3.39 ddd, 1 H, J(4′,5′b) = 2.2, J(4′,5′a) = 5.4, J(4′,3′) = 8.0 (H-4′); 3.44 br
pent, 1 H, J(5′a,4′) = J(5′a,OH) = 5.9, J(gem) = 11.7 (H-5′a); 3.52 dt, 1 H (H-2′); 3.63 ddd, 1 H,
J(5′b,4′) = 2.2, J(5′b,OH) = 5.4 (H-5′b); 3.77 dt, 1 H, J(3′,OH) = 5.9, J(3′,2′) = 5.6, J(3′,4′) = 8.0
(H-3′); 4.67 brt, 1 H, J = 5.9 (5′-OH); 5.10 d, 1 H, J(6,NH) = 13.2 (H-6); 5.34 d, 1 H, J = 5.9
(3′-OH); 5.85 d, 1 H, J(1′,2′) = 6.4 (H-1′); 6.73 d, 1 H, J(4,NH) = 5.4 (H-4); 7.16 t, 1 H, 7.29 t, 2 H
and 7.57 d, 2 H (H-arom.); 9.04 d, 1 H (NH). 13C NMR spectrum: 61.15 (C-5′); 67.21 (C-2′); 71.37
(C-6); 74.36 (C-3′); 82.13 (C-4′); 88.52 (C-1′); 108.13 (C-5); 123.45 (C-4); 124.90, 2 C, 126.43, 128.70,
2 C and 136.21 (C-arom.); 149.91 (C-2).
5-Phenyl-2-[(β-D-ribopyranosyl)amino]pyrimidine (34; 60 mg), white crystalline compound, RF 0.13.
Mass spectrum (FAB, T + G, methanol): 304 (M+ + H). 1H NMR spectrum: 3.44 br d, 1 H (H-5′a); 3.50 m,
1 H (H-3′); 3.63 m, 1 H (H-2′); 3.65 br dd, 1 H, J(5′b,4′) = 3.6, J(gem) = 12.2 (H-5′b); 3.72 m, 1 H
(H-4′); 4.57 br d, 1 H, J = 4.0 (OH); 4.85 d, 1 H, J = 4.6 (OH); 4.95 d, 1 H, J = 4.4 (OH); 5.04 br t,
1 H, J = 8.2 (H-1′); 7.34 t, 1 H, 7.45 t, 2 H and 7.64 d, 2 H (H-arom.); 7.66 d, 1 H (NH); 8.68 s, 2 H
(H-4 and H-6). 13C NMR spectrum: 66.50 (C-5′); 68.24 (C-3′); 70.35 (C-2′); 73.87 (C-4′); 82.93 (C-1′);
124.58 (C-5); 126.31, 2 C, 127.92, 129.71, 2 C and 135.70 (C-arom.); 156.56, 2 C (C-4 and C-6);
161.74 (C-2).
The authors are indebted to the staff of the Analytical Laboratory of this Institute (Dr V. Pechanec,
Head) for the elemental analyses, Mrs J. Kohoutova for measurement of the mass spectra, and Dr I.
Votruba for the cytostatic activity assays. The technical assistance of Mrs Sterecova is gratefully ac-
knowledged. This study was supported by Rhone-Poulenc Rorer (France).
Collect. Czech. Chem. Commun. (Vol. 61) (1996)

5-Phenyl-2(1H)-pyrimidinone Nucleosides
477
REFERENCES
1. Votruba I., Holy A., Wightman R. H.: Biochim. Biophys. Acta 14, 324 (1973).
2. McCormack J. J., Marquez V. E., Liu P. S., Vistica D. T., Driscoll J. S.: Biochem. Pharmacol.
29, 830 (1980).
3. Holy A., Ludzisa A., Votruba I., Sediva K., Pischel H.: Collect. Czech. Chem. Commun. 50, 393
(1985).
4. Barchi J. J., Musser S., Marquez V. E.: J. Org. Chem. 57, 536 (1992).
5. Schroeder A. C., Bardos T. J.: J. Med. Chem. 24, 109 (1981).
6. Efange S. M. N., Alessi E. M., Shih H. C., Cheng Y.-Ch., Bardos T. J.: J. Med. Chem. 28, 904
(1985).
7. Efange S. M. N., Cheng Y.-Ch., Bardos T. J.: Nucleosides Nucleotides 4, 545 (1985).
8. Holy A.: Collect. Czech. Chem. Commun. 42, 902 (1977).
9. Dvorakova H., Holy A.: Chem. Listy 85, 171 (1991).
10. Jutz Ch., Kirchlechner R., Seidel H.- J.: Chem. Ber. 102, 2301 (1969).
11. Holy A., Arnold Z.: Collect. Czech. Chem. Commun. 38, 1371 (1973).
12. Efange S. M. N., Dutta A. K.: Nucleosides Nucleotides 10, 1451 (1991).
13. Gosselin G., Bergogne M. C., Imbach J. L. in: Nucleic Acid Chemistry (L. B. Townsend and R.
S. Tipson, Eds), Vol. 4, p. 41. Wiley Interscience, New York 1991.
14. Levene P. A., Raymond A. L.: J. Biol. Chem. 102, 317 (1933).
15. Wightman R., Holy A.: Collect. Czech. Chem. Commun. 38, 1381 (1973).
16. Barchi J. J., Haces A., Marquez V. E., McCormack J. J.: Nucleosides Nucleotides 11, 1781
(1992).
17. Barton D. H. R., Jang D. O., Jaszberenyi J. C.: Tetrahedron Lett. 33, 2311 (1992).
18. Le Cocq C., Lallemand J.-Y.: J. Chem. Soc., Chem. Commun. 1981, 150.
19. Breitmaier E., Voelter W.: Carbon-13 NMR Spectroscopy. Verlag Chemie, Weinheim 1990.
20. Haasnoot C. A. G., de Leeuw F. A. A. M., de Leeuw H. P. M., Altona C.: Org. Magn. Reson.
15, 43 (1981).
21. Stevens J. D., Fletcher H. G., jr.: J. Org. Chem. 33, 1799 (1968).
22. Maury G., Daiboun T., Elalaoni A., Genu-Dellac C., Perigaud C., Begogne C., Gosselin G.,
Imbach J.-L.: Nucleosides Nucleotides 10, 1677 (1991).
23. Votruba I.: Unpublished results.
Collect. Czech. Chem. Commun. (Vol. 61) (1996)