Preparation of 5-benzyluracil and 5-benzylcytosine nucleosides as potential inhibitors of uridine phosphorylase

Article abstract of DOI:10.1135/cccc19960627

Reaction of 3,4,6-tri-O-acetyl-2-deoxyglucopyranosyl bromide (1) with silylated 5-benzyluracil and subsequent ammonolysis afforded α- and β-anomers of 5-benzyl-1-(2-deoxy-D-glucopyranosyl)uracil (2 and 3). Under catalysis with tin tetrachloride, silylated 5-benzyluracil reacted with 1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose to give 2′,3′,5′-tri-O-benzoyl-5-benzyluridine (10), which was converted into the 4-thio derivative 11 by reaction with Lawesson reagent. Debenzoylation of compound 11 afforded 5-benzyl-4-thiouridine (12), whereas its reaction with methyl iodide and deblocking gave 4-methylthiopyrimidine nucleoside 14. Amonolysis of derivative 12 at elevated temperature afforded 5-benzylcytidine (15). This reacted with thionyl chloride at room temperature to give cyclic sulfite 16 which on heating at 100°C in dimethylformamide was converted into 5-benzyl-2, 2′-cyclocytidine (17). Mild alkaline hydrolysis of compound 17 afforded 1-(β-D-arabinofuranosyl)-5-benzyl-cytosine (18). With boiling thionyl chloride, compound 15 formed 2′,3′-cyclic sulfite 19 which on alkaline hydrolysis gave 5-benzyl-5′-chloro-5′-deoxycytidine (20). Compound 20 was reduced with tributylstannane to 5-benzyl-5′-deoxycytidine (21). Reaction of silylated 5-benzyluracil with 2-deoxy-3,5-bis(O-p-toluoyl)-D-ribofuranosyl chloride, catalyzed with mercury(II) bromide, afforded 5-benzyl-2′-deoxy-3′,5′-bis(O-p-toluoyl)uridine (22) and its α-anomer 23. With Lawesson reagent, compound 22 gave 5-benzyl-4-thiouracil derivative 24 which was ammonolyzed to give 5-benzyl-2′-deoxycytidine (25). Analogously, compound 23 was converted into 5-benzyl-2-deoxy-α-cytidine (27). 5′-O-Benzoyl-5-benzyluridine (29) was converted into the 2, 2′-anhydro derivative 30 which on reaction with hydrogen chloride afforded 3′-chloro-3′-deoxynucleoside 31. This compound was reduced with tributylstannane and the obtained 2′-deoxynucleoside 32 on treatment with thionyl chloride gave a mixture of erythro- and threo-3′-chloro-2′,3′-dideoxynucleosides (33 and 34, respectively) which were reduced to 5′-O-benzoyl-5-benzyl-2′,3′-dideoxyuridine (35). Compound 35 reacted with Lawesson reagent under formation of 4-thiouracil derivative 36 and this was deblocked to 5-benzyl-4-thio-2′,3′-dideoxyuridine (37). On heating with ammonia, compound 37 was converted into 5-benzyl-2′,3′-dideoxycytidine (38). Reaction of 4-thiouracil derivative with methyl iodide and subsequent hydrazinolysis afforded 4-hydrazino derivative 40 which was heated with silver oxide in ethanol to give a mixture of anomeric 5-benzyl-1-(2,3-dideoxyribofuranosyl)-2(1H)-pyrimidinones (42).

Full text of DOI:10.1135/cccc19960627

5-Benzyluracil and 5-Benzylcytosine Nucleosides
627
PREPARATION OF 5-BENZYLURACIL AND 5-BENZYLCYTOSINE
NUCLEOSIDES AS POTENTIAL INHIBITORS OF URIDINE
PHOSPHORYLASE
Marcela KRECMEROVA, Hubert HREBABECKY 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 November 18, 1995
Reaction of 3,4,6-tri-O-acetyl-2-deoxyglucopyranosyl bromide (1) with silylated 5-benzyluracil and
subsequent ammonolysis afforded α- and β-anomers of 5-benzyl-1-(2-deoxy-D-glucopyranosyl)uracil
(2 and 3). Under catalysis with tin tetrachloride, silylated 5-benzyluracil reacted with 1-O-acetyl-
2,3,5-tri-O-benzoyl-D-ribofuranose to give 2′,3′,5′-tri-O-benzoyl-5-benzyluridine (10), which was
converted into the 4-thio derivative 11 by reaction with Lawesson reagent. Debenzoylation of com-
pound 11 afforded 5-benzyl-4-thiouridine (12), whereas its reaction with methyl iodide and deblock-
ing gave 4-methylthiopyrimidine nucleoside 14. Amonolysis of derivative 12 at elevated temperature
afforded 5-benzylcytidine (15). This reacted with thionyl chloride at room temperature to give cyclic
sulfite 16 which on heating at 100 °C in dimethylformamide was converted into 5-benzyl-2, 2′-cyclo-
cytidine (17). Mild alkaline hydrolysis of compound 17 afforded 1-(β-D-arabinofuranosyl)-5-benzyl-
cytosine (18). With boiling thionyl chloride, compound 15 formed 2′,3′-cyclic sulfite 19 which on
alkaline hydrolysis gave 5-benzyl-5′-chloro-5′-deoxycytidine (20). Compound 20 was reduced with
tributylstannane to 5-benzyl-5′-deoxycytidine (21). Reaction of silylated 5-benzyluracil with 2-deoxy-
3,5-bis(O-p-toluoyl)-D-ribofuranosyl chloride, catalyzed with mercury(II) bromide, afforded 5-benzyl-
2′-deoxy-3′,5′-bis(O-p-toluoyl)uridine (22) and its α-anomer 23. With Lawesson reagent, compound
22 gave 5-benzyl-4-thiouracil derivative 24 which was ammonolyzed to give 5-benzyl-2′-deoxy-
cytidine (25). Analogously, compound 23 was converted into 5-benzyl-2-deoxy-α-cytidine (27). 5′-O-
Benzoyl-5-benzyluridine (29) was converted into the 2, 2′-anhydro derivative 30 which on reaction
with hydrogen chloride afforded 3′-chloro-3′-deoxynucleoside 31. This compound was reduced with
tributylstannane and the obtained 2′-deoxynucleoside 32 on treatment with thionyl chloride gave a
mixture of erythro- and threo-3′-chloro-2′,3′-dideoxynucleosides (33 and 34, respectively) which
were reduced to 5′-O-benzoyl-5-benzyl-2′,3′-dideoxyuridine (35). Compound 35 reacted with Lawesson
reagent under formation of 4-thiouracil derivative 36 and this was deblocked to 5-benzyl-4-thio-2′,3′-
dideoxyuridine (37). On heating with ammonia, compound 37 was converted into 5-benzyl-2′,3′-
dideoxycytidine (38). Reaction of 4-thiouracil derivative with methyl iodide and subsequent
hydrazinolysis afforded 4-hydrazino derivative 40 which was heated with silver oxide in ethanol to
give a mixture of anomeric 5-benzyl-1-(2,3-dideoxyribofuranosyl)-2(1H)-pyrimidinones (42).
Key words: 5-Benzyluracil; Pyrimidine; Nucleosides; Uridine phosphorylase.
In connection with our studies of uridine phosphorylase inhibitors we focused our attention
on the preparation of some hitherto undescribed nucleosides derived from 5-benzyl-
Collect. Czech. Chem. Commun. (Vol. 61) (1996)

628
Krecmerova, Hrebabecky, Holy:
uracil and 5-benzylcytosine. As shown by previous investigations in other laboratories,
potent inhibitors have been found particularly among acyclic derivatives of 5-benzyl-
uracil or 5-(3-benzyloxy)benzyluracil and also the 2,2′-anhydro derivatives of nucleo-
side analogs1–5. On the other hand, some 5-benzyluracil nucleosides (riboside,
arabinoside, 2′-deoxyriboside amd 2′-bromo-2′-deoxyriboside) proved to be inactive5.
Recently, a series of 5-benzyluracil nucleosides was prepared (e.g. 2′,3′-dideoxy-,
3′-azido-2′,3′-dideoxy- and 2′-deoxy-2′-fluoroarabinosyl derivatives6,7) which were stu-
died as cytostatics or antivirals; however, their effect on uridine phosphorylase was not
described. Save for several exceptions, no 5-benzylcytosine nucleosides have been pre-
pared so far.
We considered it interesting to prepare particularly the 2′-deoxyglucopyranose deri-
vative of 5-benzyluracil as a compound analogous to the so-called TdG, i.e. 1-(2-
deoxy-β-D-glucopyranosyl)thymine1,8 which represents one of the most effective
CH OAc
2
O
Br
OAc
AcO
1
O
N
O
N
HN
HN
O
O
RO
RO
O
O
OR
RO
RO
R
R
Ac
H
2
6
Ac
H
4
8
RO
RO
O
O
OR
RO
RO
N
O
O
N
O
O
NH
NH
R
R
Ac
H
3
7
Ac
H
5
9
Collect. Czech. Chem. Commun. (Vol. 61) (1996)

5-Benzyluracil and 5-Benzylcytosine Nucleosides
629
uridine phosphorylase inhibitors. As the starting compound we have chosen 3,4,6-tri-
O-acetyl-2-deoxyglucopyranosyl bromide (1), prepared by addition of hydrogen bro-
mide to tri-O-acetyl-D-glucal9. The nucleosidation reaction of the 1-bromohexose 1
with silylated 5-benzyluracil was performed in acetonitrile under catalysis with tri-
methylsilyl triflate. As expected, the reaction gave both anomers of 5-benzyl-1-
(2-deoxy-D-glucopyranosyl)uracil (2 and 3), the α-anomer predominating in the ratio of
about 2 : 1, and didehydro derivatives 4 and 5. Both anomers of the desired 2′-deoxy-
nucleosides, as well as both the didehydro derivatives, differed only slightly in their
chromatographic mobilities. In the case of acetylated nucleosides, the only pure product
obtained was the α-anomer 3 which was deacetylated to give the free 2′-deoxygluco-
pyranosyl derivative 7. To some extent, the nucleosidation was also accompanied by
elimination leading to two 2′,3′-didehydro derivatives 4 and 5 which contaminated the
acetylated β-anomer 2. Only after deacetylation of this mixture of acetyl derivatives 2, 4
and 5 with methanolic ammonia it was possible to separate chromatographically the
individual products and to obtain 5-benzyl-1-(2-deoxy-β-D-glucopyranosyl)uracil (6)
along with small amounts of the free didehydro derivatives 8 and 9.
Nucleosidation reaction of silylated 5-benzyluracil with 1-O-acetyl-2,3,5-tri-O-ben-
zoyl-D-ribofuranose in 1, 2-dichloroethane, catalyzed with tin tetrachloride, afforded
2′,3′,5′-tri-O-benzoyl-5-benzyluridine (10) which was subsequently converted into
2′,3′,5′-tri-O-benzoyl-5-benzyl-4-thiouridine (11) by reaction with Lawesson reagent.
The 4-thio derivative 11 was debenzoylated with methanolic ammonia to give free
5-benzyl-4-thiouridine (12). It was also converted into the protected 4-methylthio deri-
vative 13 by reaction with methyl iodide in dimethylformamide. Compound 13 was
methanolyzed to give free 1-(β-D-ribofuranosyl)-5-benzyl-4-methylthiopyrimidin-2-one
(14). Reaction of the free 4-thiouridine derivative 12 with ammonia at elevated temperature
in an autoclave gave 5-benzylcytidine (15) (Scheme 1).
5-Benzylcytidine was converted into other 5-benzylcytosine nucleosides as described
below. Its reaction with thionyl chloride at ambient temperature gave cyclic sulfite 16
which on heating in dimethylformamide at 100 °C was quantitatively converted into
5-benzyl-2,2′-cyclocytidine (17). In an aqueous medium, treatment with an alkaline
reagent such as potassium carbonate or Dowex 1 in the carbonate form resulted in
fission of the anhydro bond in compound 17 under formation of 1-(β-D-arabinofurano-
syl)-5-benzylcytosine (18), an analog of the known cytostatic araC. When the reaction
of 5-benzylcytidine with thionyl chloride was performed at reflux, we isolated 2′,3′-cyclic
sulfite 19 containing a chlorine atom in position 5′. This compound was hydrolyzed
with a solution of potassium carbonate to give 5-benzyl-5′-chloro-5′-deoxycytidine (20)
which was reduced with tributylstannane in a mixture of dimethyl sulfoxide and dioxane to
5-benzyl-5′-deoxycytidine (21). A similar sequence of reactions was used already earlier in
the preparation of some analogs of unsubstituted cytosine nucleosides10 (Scheme 2).
Collect. Czech. Chem. Commun. (Vol. 61) (1996)

630
Krecmerova, Hrebabecky, Holy:
The preparation of 2′-deoxyribosides of 5-benzylcytosine consisted in the transfor-
mation of the corresponding uracil nucleosides via the 4-thiouracil derivatives. The
nucleosidation reaction of silylated 5-benzyluracil with 2-deoxy-3,5-bis(O-p-toluoyl)-
D-ribofuranosyl chloride was performed in acetonitrile in the presence of molecular
sieves, with mercury(II) bromide as catalyst. This method is described11 as very advan-
tageous particularly for the preparation of 5-alkyl-2′-deoxyuridines because it gives
S
O
HN
O
HN
N
O
N
BzO
BzO
O
O
OBz
OBz
OBz
10
OBz
11
SCH
N
S
3
N
HN
O
O
N
RO
HO
O
O
OR
OR
OH
OH
12
R
Bz
H
13
14
NH
2
N
O
N
HO
O
OH
OH
SCHEME 1
15
Collect. Czech. Chem. Commun. (Vol. 61) (1996)

5-Benzyluracil and 5-Benzylcytosine Nucleosides
631
predominantly the β-anomers which, moreover, are easily isolable from the reaction
mixture by crystallization. In our case, the β : α ratio (22 : 23) was 2 : 1, with high total
yield of the nucleosidation reaction (88%). The obtained 5-benzyl-2′-deoxy-3′,5′-bis(O-
p-toluoyl)uridine (22) was treated with Lawesson reagent in 1,2-dichloroethane to give
5-benzyl-4-thiouracil derivative 24 which, without purification, was deblocked with
ammonia at room temperature and then further heated with ammonia in an autoclave
under formation of 5-benzyl-2′-deoxycytidine (25). The same reaction course was used
in the conversion of the protected α-anomer 23 into the 4-thio derivative 26 and then
NH
N
NH . HCl
2
N
N
O
N
O
R
HO
O
O
O
O
OH
S
17
O
R
OH
Cl
16
19
NH
2
N
N
O
HO
O
HO
OH
18
NH
NH
2
2
N
N
N
N
O
O
Cl
CH
3
O
O
OH
OH
OH
OH
20
21
SCHEME 2
Collect. Czech. Chem. Commun. (Vol. 61) (1996)

632
Krecmerova, Hrebabecky, Holy:
into 5-benzyl-1-(2-deoxy-α-D-ribofuranosyl)cytosine (5-benzyl-2-deoxy-α-cytidine)
(27).
Another synthesized group of 5-benzylpyrimidine nucleoside derivatives prepared in
this context were 2′,3′-dideoxynucleosides. So far, only one representative, 5-benzyl-
2′,3′-dideoxyuridine, has been described6. Our synthesis started from 5′-O-benzoyl-5-
benzyluridine (29) which was converted into 2′-chloro-2′-deoxynucleoside 31 via
2,2′-anhydronucleoside 30. Compound 31 was reduced with tributylstannane and the
obtained 2′-deoxyribonucleoside 32 was treated with thionyl chloride to give a mixture
of erythro- and threo-3′-chloro-3′-deoxy derivatives 33 and 34, respectively. Reductive
dehalogenation with tributylstannane converted both the compounds 33 and 34 into
5′-O-benzoyl-5-benzyl-2′,3′-dideoxyuridine (35). This on reaction with Lawesson rea-
gent afforded the 4-thiouracil derivative 36 which was deblocked to free 5-benzyl-4-thio-
2′,3′-dideoxyuridine (37). Compound 37 on heating with ammonia gave 5-benzyl-
2′,3′-dideoxycytidine (38). Using reactions generally used for transformation of uracil
nucleosides into pyrimidinone derivatives12, we converted the 4-thiouracil derivative
36 into 2′,3′-dideoxynucleosides derived from 5-benzyl-2-pyrimidinone: reaction with
X
TolO
HN
O
O
N
TolO
N
X
O
O
OTol
NH
OTol
X
X
22
24
23
26
O
S
O
S
NH2
HO
N
O
O
N
HO
N
O
O
OH
N
OH
NH2
25
27
Collect. Czech. Chem. Commun. (Vol. 61) (1996)

5-Benzyluracil and 5-Benzylcytosine Nucleosides
633
O
NH
N
HN
N
O
N
O
RO
BzO
O
O
OH
OH
OH
30
R
28
H
29 Bz
O
S
N
HN
HN
O
N
O
BzO
RO
O
O
R1
R2
R1 R2 R3
R3
R
36
37
Bz
H
H
H
H
Cl
H
OH Cl
31
32
33
34
35
OH
Cl
H
H
H
H
H
H
X
N
O
N
RO
RO
O
O
N
O
N
X
R
R
H
38 NH2
41 Bz
42
SCH3
NHNH2
Bz
Bz
Bz
H
39
40
43
44
H
NHN C(CH3)2
NHN C(CH3)2
Collect. Czech. Chem. Commun. (Vol. 61) (1996)

634
Krecmerova, Hrebabecky, Holy:
methyl iodide in dimethylformamide gave 4-methylthiopyrimidine 39 which on heating
with hydrazine afforded 4-hydrazino derivative 40. This was treated with silver oxide
in ethanol12 and the obtained intermediate 41 was deprotected to give 5-benzyl-1-(2,3-
dideoxyribofuranosyl)-2(1H)-pyrimidinone (42).
The reaction with silver oxide was accompanied with anomerization of the nucleo-
side bond and both the compound 41 and the free pyrimidinone derivative 42 were
obtained only as chromatographically inseparable mixture of anomers with the β : α
anomer ratio of about 3 : 1. On the other hand, the dimethylhydrazone 43 (prepared by
reaction of hydrazino derivative 40 with acetone) and the free nucleoside 44 (prepared
from 43 by methanolysis) were pure β-anomers. Consequently, the mentioned anomeri-
zation took place only in the reaction with silver oxide and not already during the
preparation of the hydrazino derivative 40.
All the described free 5-benzyl derivatives were tested on cell cultures L1210, HeLa
and L929 for cytostatic activity. Neither of them exhibited marked inhibitory effect on
the cell growth. On the other hand, some of the compounds are effective inhibitors of
uridine phosphorylase and their study will be described elsewhere13.
EXPERIMENTAL
Unless stated otherwise, the solutions were evaporated at 40 °C/2 kPa and the compounds were dried
over phosphorus pentoxide at 13 Pa. Thin-layer chromatography was performed on Silufol UV 254
foils (Kavalier, Czech Republic) in the systems S1, toluene–acetone 4 : 1; S2, toluene–acetone 3 : 1;
S3, toluene–acetone 3 : 2; S4, toluene–ethyl acetate 6 : 1; S5, toluene–ethyl acetate 1 : 1; S6, ethyl
acetate; S7, ethyl acetate–acetone–ethanol–water 18 : 3 : 1 : 1; S8, ethyl acetate–acetone–ethanol–water
18 : 3 : 2 : 2 . Spots were detected by UV light at 254 nm. Preparative column chromatography was
carried out on silica gel (30–60 µm, Service Laboratory of the Institute) or Silpearl (Kavalier, Czech
1
Republic). H NMR spectra (δ, ppm; J, Hz) were measured on Varian UNITY 200 (200.01 MHz) or
Varian UNITY 500 (499.8 MHz) spectrometers in hexadeuteriodimethyl sulfoxide with tetramethyl-
silane as internal standard. Mass spectra were obtained with a ZAB-EQ spectrometer (VG Analytical)
using the FAB method (Xe, 8 kV, glycerol (G) or thioglycerol (TG) as matrices).
Reaction of 3,4,6-Tri-O-acetyl-2-deoxy-D-arabino-hexopyranosyl Bromide (1)
with Silylated 5-Benzyluracil
Tri-O-acetyl-D-glucal (2.45 g, 9 mmol) was codistilled with toluene (2 × 20 ml) and then again dis-
solved in toluene (10 ml). The solution was saturated with gaseous hydrogen bromide at 0 °C for 45 min,
the solvent was evaporated, the residue (compound 1) was codistilled with toluene (3 × 20 ml) and
dried in vacuo at room temperature for 1 h.
A mixture of 5-benzyluracil (2.02 g, 10 mmol), hexamethyldisilazane (30 ml) and a catalytic
amount of ammonium sulfate was heated at 150 °C for 4 h (after 1 h the silylated base dissolved).
After cooling, the solution was concentrated, the residue was codistilled with xylene (3 × 30 ml) and
then dissolved in acetonitrile (20 ml). This solution was added to the 1-bromohexose 1 prepared
above. The mixture was cooled to 0 °C, trimethylsilyl trifluoromethanesulfonate (2.2 ml, 12 mmol)
was added and the solution was stirred at 0 °C for 30 min and at room temperature for 15 min. The
mixture was poured into saturated solution of sodium hydrogen carbonate (250 ml) and the products
Collect. Czech. Chem. Commun. (Vol. 61) (1996)

5-Benzyluracil and 5-Benzylcytosine Nucleosides
635
were extracted with ethyl acetate. The organic phase was dried over magnesium sulfate and the sol-
vent evaporated. Chromatography of the residue on silica gel (500 ml) in system S2 afforded 1.4 g
of a mixture containing compounds 2, 4 and 5 (RF 0.24). Further elution gave 1-(3,4,6-tri-O-acetyl-
2-deoxy-α-D-arabino-hexopyranosyl)-5-benzyluracil (3), yield 1.60 g (38%), amorphous compound.
For C23H26N2O9 (474.5) calculated: 58.22% C, 5.52% H, 5.90% N; found: 58.47% C, 5.51% H,
1
5.81% N. Mass spectrum (FAB; T + G, chloroform): 475.2 (M + H). H NMR spectrum: 1.995 s, 3 H,
2.075 s, 3 H and 2.08 s, 3 H (3 × acetyl); 2.00 dt, 1 H, J(2′a,1′) ≈ J(2′a,3′) = 3.9, J(gem) = 14.2 (H-2′a);
2.48 ddd, 1 H, J(2′b,3′) = 3.9, J(2′b,1′) = 10.0 (H-2′b); 3.58 s, 2 H (CH2); 4.20–4.26 m, 2 H (H-5′ and H-6′a);
4.36 dd, 1 H, J(6′b,5′) = 6.1, J(gem) = 11.5 (H-6′b); 4.76 t, 1 H, J(4′,3′) = 4.1, J(4′,5′) = 3.9 (H-4′);
5.16 br q, 1 H, (H-3′); 5.96 dd, 1 H, J(1′,2′a) = 3.7, J(1′,2′b) = 10.0 (H-1′); 7.10–7.30 m, 5 H (H arom);
7.61 s, 1 H (H-6); 11.44 s, 1 H (NH).
5-Benzyl-1-(2-deoxy-β-D-arabino-hexopyranosyl)uracil (6)
The mixture of acetates 2, 4 and 5 (1.4 g), obtained in the above experiment, was stirred with methanolic
ammonia at room temperature for 2 days. Evaporation of the solvent and chromatography of the
residue on silica gel (200 ml) in system S7 gave as principal product 2′-deoxynucleoside 6 (RF 0.30).
The amorphous residue of the product 6 was dissolved in ethyl acetate–ether (1 : 1) and set aside in
a refrigerator overnight. The deposited compound was collected and dried in vacuo, yield 650 mg
1
(21% from compound 1). Mass spectrum (FAB, G + dimethyl sulfoxide): 349.2 (M + H). H NMR spec-
trum: 1.75 dt, 1 H, J(2′a,1′) ≈ J(2′a,3′) ≈ 11.4, J(gem) = 12.4 (H-2′a); 1.96 ddd, 1 H, J(2′b,1′) = 2.2,
J(2′b,3′) = 4.9 (H-2′b); 3.08 td, 1 H, J(4′,3′) = 9.0, J(4′,OH) = 5.4, J(4′,5′) = 9.5 (H-4′); 3.25 ddd, 1 H,
J(5′, 6′b) = 2.0, J(5′,6′a) = 5.9 (H-5′); 3.47 br pent, 1 H, J(6′a,OH) = 6.0, J(gem) = 12.0 (H-6′a); 3.56 br s,
2 H (CH2); 3.52–3.60 m, 1 H (H-3′); 3.70 ddd, 1 H, J(6′b,OH) = 5.4 (H-6′b); 4.56 br t, 1 H (6′-OH); 5.05 d,
1 H (4′-OH); 5.13 d, 1 H, J(OH,3′) = 4.4 (3′-OH); 5.61 dd, 1 H, J(1′,2′a) = 11.2, J(1′,2′b) = 2.2
(H-1′); 7.15–7.30 m, 5 H (H arom.); 7.78 s, 1 H (H-6); 11.40 br, 1 H (NH).
Further chromatography afforded:
5-Benzyl-1-(2,3-dideoxy-β-D-erythro-hex-2-enopyranosyl)uracil (8); yield 120 mg (4% from com-
1
pound 1), amorphous compound, RF 0.50 (S7). H NMR spectrum: 3.45–3.50 m, 2 H and 3.65–3.69 m,
1 H (H-5′ and H-6′); 3.55 s, 2 H (CH2); 3.96 m, 1 H, J(4′,5′) = 8.3 (H-4′); 4.77 t, 1 H, J(OH,6′) = 5.6
(6′-OH); 5.34 d, 1 H, J(OH,4′) = 6.8 (4′-OH); 5.66 dt, 1 H, J = 1.7, 2.0 and J(3′,2′) = 10.2 (H-3′);
6.08 dt, 1 H, J = 2.0, 2.0 and J(2′,3′) = 10.2 (H-2′); 6.26 br q, 1 H, J = 2.1 (H-1′); 7.15–7.30 m, 6 H
(H arom. and H-6); 11.42 br s, 1 H (NH).
5-Benzyl-1-(2,3-dideoxy-α-D-erythro-hex-2-enopyranosyl)uracil (9); yield 130 mg (4.4% from
compound 1), amorphous compound, RF 0.45 (S7). 1H NMR spectrum: 3.34 ddd, 1 H, J = 2.2, 5.8
and 8.0 (H-5′); 3.47 pent, 1 H, J = 5.8, 5.8 and 12.0 (H-6′a); 3.52 s, 2 H (CH2); 3.62 ddd, 1 H, J = 2.2,
5.4 and 12.0 (H-6′b); 3.90 q, 1 H (H-4′); 4.17 t, 1 H, J(OH,6′) = 5.8 (6′-OH); 5.20 d, 1 H, J(OH,4′) =
7.6 (4′-OH); 5.77 ddd, 1 H, J(3′,4′) = 2.0, J(3′,2′) = 10.2 (H-3′); 6.18 dt, 1 H, J(1′,2′) = J(1′,4′) =
2.2, J(1′,3′) = 3.0 (H-1′); 6.23 dt, 1 H, J(2′,4′) = 2.0 (H-2′); 7.17 t, 1 H, 7.21 d, 2 H and 7.26 t, 2 H
(H arom.); 7.63 s, 1 H (H-6); 11.45 br s, 1 H (NH).
5-Benzyl-1-(2-deoxy-α-D-arabino-hexopyranosyl)uracil (7)
A solution of compound 3 (1.4 g, 2.95 mmol) in methanolic ammonia (100 ml) was stirred at room
temperature for 2 days. Evaporation of the solvent, followed by chromatography on silica gel (100 ml)
in system S7, afforded 700 mg (68%) of colorless amorphous compound 7 (RF 0.30). Mass spectrum
1
(FAB; T + G, methanol): 349.2 (M + H). H NMR spectrum: 1.65 dt, 1 H, J(2′a,1′) = J(2′a,3′) = 3.6,
J(gem) = 13.4 (H-2′a); 2.21 ddd, 1 H, J(2′b,3′) = 3.4, J(2′b,1′) = 10.0 (H-2′b); 3.38 m, 1 H (H-4′); 3.57 s,
2 H (CH2); 3.54–3.60 m, 1 H (H-6′a); 3.74–3.79 m, 2 H (H-6′b and H-5′); 3.86 br pent, 1 H (H-3′); 4.61 t,
Collect. Czech. Chem. Commun. (Vol. 61) (1996)

636
Krecmerova, Hrebabecky, Holy:
1 H, J(OH,6′) = 5.3 (6′-OH); 5.06 d, 1 H, J(OH,4′) = 5.4 (4′-OH); 5.22 d, 1 H, J(OH,3′) = 3.6 (3′-OH);
5.98 dd, 1 H (H-1′); 7.15–7.30 m, 5 H (H arom.); 7.70 s, 1 H (H-6); 11.25 br s, 1 H (NH).
2′,3′,5′-Tri-O-benzoyl-5-benzyluridine (10)
5-Benzyluracil (3.03 g, 15 mmol) was silylated as described for the preparation of compound 2.
A solution of 1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribose (6.56 g, 13 mmol) in 1, 2-dichloroethane (50 ml) was
added to the silylated base, followed by tin tetrachloride (3.5 ml, 30 mmol). After stirring for 2 h at room
temperature, the reaction mixture was diluted with chloroform (1 000 ml) and poured into saturated
solution of sodium hydrogen carbonate (500 ml). The mixture was shaken and filtered through Celite.
The organic layer was separated, again washed with sodium hydrogen carbonate (3 × 250 ml) and
dried over magnesium sulfate. Evaporation of the solvent afforded compound 10 (8.4 g, 100%) as
white foam, chromatographically homogeneous (RF 0.34, S1). To obtain an analytically pure sample,
a part (200 mg) of the product was chromatographed on silica gel in system S1. For C37H30N209
(646.7) calculated: 68.72% C, 4.68% H, 4.33% N; found: 68.51% C, 4.76% H, 4.37% N.
2′,3′,5′-Tri-O-benzoyl-5-benzyl-4-thiouridine (11)
Lawesson reagent (3.24 g, 8.0 mmol) was added to a solution of compound 10 (8.2 g, 12.7 mmol) in
1,2-dichloroethane (150 ml) and the mixture was refluxed under argon for 8 h. After cooling, the
solution was chromatographed on a column of silica gel (750 ml) in system S4 (RF: 11, 0.42; 10, 0.11).
Yield 6.82 g (81%) of yellow foam. For C37H30N2O8S (662.7) calculated: 67.06% C, 4.56% H,
4.23% N, 4.84% S; found: 66.78% C, 4.59% H, 3.81% N, 5.27% S. 1H NMR spectrum: 3.71 d, 1 H and
3.82 d, 1 H, J(gem) = 14.9 (CH2); 4.63 dd, 1 H, J(5′a,4′) = 5.6, J(gem) = 12.0 (H- 5′a); 4.68 dd, 1 H,
J(5′b,4′) = 3.8 (H-5′b); 4.78 td, 1 H, J(4′,3′) = 5.6 (H-4′); 5.97 br t, 1 H (H-3′); 6.03 dd, 1 H, J(2′,1′) = 4.2,
J(2′,3′) = 6.3 (H-2′); 6.20 d, 1 H (H-1′); 7.10–7.30 m, 5 H, 7.42–7.50 m, 6 H, 7.64 t, 3 H, 7.90 2 × d,
4 H and 8.03 d, 2 H (H arom.); 7.84 s, 1 H (H-6); 12.93 br s, 1 H (NH).
5-Benzyl-4-thiouridine (12)
Benzoyl derivative 11 (6.6 g, 9.96 mmol) in methanolic ammonia (100 ml) was stirred at room tem-
perature for 72 h. Evaporation of the solvent and chromatography on silica gel in ethyl acetate affor-
ded 2.99 g (86%) of yellow foam (RF 0.33, S6). For C16H18N2O5S (350.4) calculated: 54.85% C,
5.18% H, 7.99% N, 9.15% S; found: 54.58% C, 5.26% H, 7.88% N, 9.00% S. 1H NMR spectrum:
3.51 br ddd, 1 H, J = 3.7, 3.9 and 12.2, decoupling OH: dd, J(5′a,4′) = 3.2 (H-5′a); 3.64 br ddd,
1 H, J = 3.6, 4.2 and 12.2, decoupling OH: dd, J(5′b,4′) = 3.2, J(gem) = 12.2 (H-5′b); 3.79 d, 1 H
and 3.83 d, 1 H, J(gem) = 14.9 (CH2); 3.87 dt, 1 H, J(4′,5′a) = J(4′,5′b) = 3.2, J(4′,3′) = 4.9 (H-4′);
3.96 br q, 1 H, decoupling OH: J(3′,4′) = 4.9 (H-3′); 4.04 br q, 1 H, decoupling OH: J(2′,3′) = 4.6
(H-2′); 5.10 d, 1 H, J(OH,3′) = 5.4 (3′-OH); 5.16 t, 1 H, J(OH,5′) = 5.0 (5′-OH); 5.48 d, 1 H,
J(OH,2′) = 5.4 (2′-OH); 5.74 d, 1 H, J(1′,2′) = 4.4 (H-1′); 7.18 m, 1 H, 7.25 s, 2 H and 7.26 s, 2 H
(H arom.); 8.03 s, 1 H (H-6); 12.30 br, 1 H (NH).
2′,3′,5′-Tri-O-benzoyl-5-benzyl-4-methylthiopyrimidine (13)
Finely ground potassium carbonate (100 mg) and methyl iodide (0.5 ml, 8 mmol) were added to a
solution of the 4-thio derivative 11 (1.56 g, 2.35 mmol) in dimethylformamide (4 ml). The mixture
was stirred at room temperature for 2 h, filtered and the filtrate was concentrated. The residue was
partitioned between water and ethyl acetate (150 ml each), the organic layer was dried over magne-
sium sulfate and the solvent evaporated. The residue was chromatographed on silica gel (220 ml) in
Collect. Czech. Chem. Commun. (Vol. 61) (1996)

5-Benzyluracil and 5-Benzylcytosine Nucleosides
637
system S1 (RF: 13, 0.15; 11, 0.60) to give 1.0 g (63%) of white foam. For C38H32N2O8S (676.8)
calculated: 67.44% C, 4.77% H, 4.14% N, 4.74% S; found: 67.45% C, 4.69% H, 4.11% N, 4.68% S.
1H NMR spectrum: 2.40 s, 3 H (CH3); 3.65 and 3.69 2 × d, 2 H, J(gem) = 14.1 (CH2); 4.65 dd, 1 H,
J(5′a,4′) = 5.4, J(gem) = 12.2 (H-5′a); 4.72 dd, 1 H, J(5′b,4′) = 3.7 (H-5′b); 4.82 td, 1 H, J(4′,3′) = 6.1
(H-4′); 6.00 br t, 1 H, J(3′,2′) = 6.3 (H-3′); 6.03 dd, 1 H, J(2′,1′) = 3.8 (H-2′); 6.24 d, 1 H (H-1′);
7.16–7.28 m, 5 H, 7.42–7.48 m, 6 H, 7.60–7.67 m, 3 H, 7.88–7.92 m, 4 H and 7.99 m, 2 H (H arom.);
7.97 s, 1 H (H-6).
5-Benzyl-4-methylthiouridine (14)
A solution of benzoyl derivative 13 (760 mg, 1.12 mmol) in methanolic 0.1 M sodium methoxide (35 ml)
was allowed to stand at room temperature for 4 h. The solution was neutralized with Dowex 50 (H+ form),
filtered and the filtrate was taken down. Crystallization of the residue from system S7 afforded com-
pound 14 (100 mg), m.p. 155.5–157 °C. Another portion of the product was obtained by chromato-
graphy of the mother liquors on silica gel in system S7 (RF 0.42); total yield 260 mg (64%). For
C17H20N2O5S (364.4) calculated: 56.03% C, 5.53% H, 7.69% N, 8.80% S; found: 56.23% C, 5.47% H,
1
7.71% N, 8.69% S. H NMR spectrum: 2.36 s, 3 H (CH3); 3.56 ddd, 1 H, J(5′a,4′) = 2.9, J(5′a,OH) = 4.9,
J(gem) = 12.2 (H-5′a); 3.69 d, 1 H and 3.73 d, 1 H, J(gem) = 15.9 (CH2); 3.75 ddd, 1 H, J(5′b,4′) = 2.9,
J(5′b,OH) = 4.9 (H-5′b); 3.91 dt, 1 H, J(4′,3′) = 6.1 (H-4′); 3.97 br q, 1 H (H-3′); 3.995 m, 1 H
(H-2′); 5.07 d, 1 H, J(OH,3′) = 5.9 (3′-OH); 5.22 t, 1 H, J(OH,5′) = 4.9 (5′-OH); 5.56 d, 1 H, J(OH, 2′) = 4.6
(2′-OH); 5.74 d, 1 H, J(1′,2′) = 2.7 (H-1′); 7.16–7.22 m, 3 H and 7.26–7.32 m, 2 H (H arom.); 8.29 s,
1 H (H-6).
5-Benzylcytidine (15)
5-Benzyl-4-thiouridine (12; 3.2 g, 9.1 mmol) was heated with methanolic ammonia (200 ml) at 120 °C
for 1 h in an autoclave. After cooling, the solvent was evaporated, the residue was chromatographed
on silica gel (500 ml) in system S8 (RF 0.25) and the product was crystallized from the same solvent
mixture. Yield 2.54 g (77%) of compound 15, m.p. 211 °C. For C16H19N3O5 (333.3) calculated:
57.65% C, 5.74% H, 12.61% N; found: 57.58% C, 5.64% H, 12.66% N. 1H NMR spectrum: 3.48 ddd, 1 H,
J = 3.9, 5.1 and 12.0 (H-5′a); 3.63 ddd, 1 H, J = 3.2, 5.1 and 12.0 (H-5′b); 3.63 s, 2 H (CH2); 3.83 dt,
1 H, J = 3.4, 3.4 and 5.1 (H-4′); 3.92 q, 1 H (H-3′); 3.96 q, 1 H (H-2′); 5.03 d, 1 H, J(OH,3′) = 5.6
(3′-OH); 5.07 t, 1 H, J(OH,5′) = 5.2 (5′-OH); 5.36 d, 1 H, J(OH,2′) = 5.4 (2′-OH); 5.77 d, 1 H,
J(1′,2′) = 4.4 (H-1′); 7.20 t, 1 H, 7.24 d, 2 H and 7.29 t, 2 H (H arom.); 6.75 br s, 1 H and 7.43 br s,
1 H (NH2); 7.60 s, 1 H (H-6).
2,2′-Anhydro-1-(β-D-arabinofuranosyl)-5-benzylcytosine Hydrochloride (17)
Thionyl chloride (0.15 ml, 2.06 mmol) was added to a suspension of 5-benzylcytidine (530 mg, 1.59 mmol)
in acetonitrile (5 ml) and the mixture was stirred at room temperature for 1 h. After dilution with dry
ether, the mixture was set aside in a refrigerator for 1 h, the crystalline material was collected on
filter under exclusion of moisture, washed with ether and dried in vacuo. The obtained intermediate 16
(655 mg, 99%) was heated in dimethylformamide (15 ml) at 100 °C for 1 h. The solvent was evapo-
rated and the residue codistilled with toluene (2 × 20 ml) and ethanol (20 ml). Precipitation with
ether from methanolic solution afforded 537 mg (96%) of hygroscopic 2,2′-anhydro derivative 17.
1H NMR spectrum: 3.27 dd, 1 H, J(5′a,4′) = 3.7, J(gem) = 12.0 (H-5′a); 3.41 dd, 1 H, J(5′b,4′) = 3.2
(H-5′b); 3.85 d, 1 H and 3.89 d, 1 H, J(gem) = 16.1 (CH2); 4.21 br td, 1 H, J(4′,3′) = 1.2, J(4′,5′) = 3.5
(H-4′); 4.48 br s, 1 H (H-3′); 5.06 br, 1 H (OH); 5.39 d, 1 H, J(2′,1′) = 5.9, J(2′, 3′) < 1 (H-2′); 6.18 br,
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638
Krecmerova, Hrebabecky, Holy:
1 H (OH); 6.66 d, 1 H, J(1′,2′) = 5.9 (H-1′); 7.20–7.40 m, 5 H (H arom.); 8.14 s, 1 H (H-6); 8.86 s,
1 H, 9.01 br, 2 H and 9.44 s, 1 H (NH).
1-(β-D-Arabinofuranosyl)-5-benzylcytosine (18)
Dowex 1 (CO23− form, 10 ml) was added to a solution of 2, 2′-anhydro derivative 17 (300 mg, 0.85 mmol)
in water (10 ml) and the mixture was stirred at ambient temperature for 2 h. The ion exchanger was
filtered off, the filtrate was taken down and the residue crystallized from methanol (with several
drops of water) to give 216 mg (74%) of crystalline product, m.p. 215–217 °C. For C16H19N3O5 . 0.5 H2O
(342.3) calculated: 56.13% C, 5.89% H, 12.27% N; found: 56.23% C, 5.89% H, 12.25% N. Mass
1
spectrum (FAB; T + G, CH3OH): 334.1 (M + H, C16H20N3O5). H NMR spectrum: 3.42 dt, 1 H, J =
5.1, 5.1 and 11.5 (H-5′a); 3.50 dt, 1 H, J = 5.1, 5,1 and 11.5 (H-5′b); 3.61 s, 2 H (CH2); 3.70 m, 1 H
(H-4′); 3.86 m, 1 H (H-3′); 3.96 m, 1 H (H-2′); 4.97 t, 1 H, J(OH,5′) = 4.9 (5′-OH); 5.39 d, 2 H, J = 4.4
(2′-OH and 3′-OH); 6.04 d, 1 H, J(1′,2′) = 3.2 (H-1′); 6.64 br, 2 H (NH2); 7.21 m, 3 H and 7.29 m, 2 H (H
arom.); 7.37 s, 1 H (H-6).
5-Benzyl-5′-chloro-5′-deoxycytidine (20)
Thionyl chloride (0.55 ml, 7.5 mmol) was added to a suspension of 5-benzylcytidine (1.11 g, 3.33 mmol) in
acetonitrile (25 ml) and the mixture was refluxed for 1.5 h. The solution of the formed sulfite 19 was
cooled, concentrated to a half and added dropwise with stirring to ether (75 ml). The suspension
formed was stirred for 15 min, filtered under exclusion of moisture and the product was washed with
ether to neutral reaction. The thus-obtained intermediate 19 was dried in vacuo and dissolved in
methanol (25 ml). A solution of potassium carbonate (10%, 20 ml) was added dropwise with stirring
and the reaction mixture was stirred for 20 min. The deposited product was collected, washed with
water to neutral reaction and then boiled with water. The suspension was allowed to stand overnight,
filtered and the product was air-dried to give crystalline 5′-chloro derivative 20 (1.04 g, 89%), m.p.
223.5–226 °C. For C16H18ClN3O4 (351.8) calculated: 54.63% C, 5.16% H, 10.08% Cl, 11.94% N;
1
found: 53.99% C, 5.11% H, 9.83% Cl, 12.22% N. H NMR spectrum: 3.62 s, 2 H (CH2); 3.63 dd, 1 H,
J(5′a,4′) = 5.9, J(gem) = 12.2 (H-5′a); 3.81 dd, 1 H, J(5′b,4′) = 3.7 (H-5′b); 3.82 m, 1 H (H-3′);
3.93–3.99 m, 2 H (H-2′and H-4′); 5.26 d, 1 H, J(OH, 3′) = 4.2 (3′-OH); 5.44 d, 1 H, J(OH,2′) = 4.6
(2′-OH); 5.82 d, 1 H, J(1′,2′) = 4.4 (H-1′); 6.86 br, 1 H (NH); 7.19–7.33 m, 6 H (H arom. and H-6);
7.45 br, 1 H (NH).
5-Benzyl-5′-deoxycytidine (21)
A solution of tributylstannane in toluene (1 mol l–1, 5 ml), followed by azobis(isobutyronitrile) (250 mg),
was added at 130 °C to a solution of 5′-chloro derivative 20 (820 mg, 2.33 mmol) in dioxane–dimethyl
sulfoxide (1 : 1, 10 ml). The reaction mixture was heated at 130 °C for 1 h, cooled and the solvent
was evaporated. The residue was codistilled with xylene (4 × 20 ml) and chromatographed on silica
gel (200 ml) in system S7 (RF: 21, 0.27; 20, 0.34). Yield 400 mg (54%) of compound 21, m.p. 224–226 °C
(aqueous 2-propanol). For C16H19N3O4 (317.3) calculated: 60.56% C, 6.03% H, 13.24% N; found:
60.30% C, 5.98% H, 13.01% N. 1H NMR spectrum: 1.01 d, 3 H, J(5′,4′) = 6.3 (H-5′); 3.41 td, 1 H,
J(3′,2′) = 5.1, J(3′,4′) = J(3′,OH) = 6.3 (H-3′); 3.60 s, 2 H (CH2); 3.78 pent, 1 H, J = 6.3 (H-4′); 3.83 td,
1 H, J(2′,1′) = 3.2, J(2′,3′) = J(2′,OH) = 5.0 (H-2′); 4.95 d, 1 H, J(OH,3′) = 6.1 (3′-OH); 5.30 d, 1 H,
J(OH,2′) = 4.9 (2′-OH); 5.67 d, 1 H, J(1′,2′) = 3.2 (H-1′); 6.84 br, 1 H (NH); 7.01 s, 1 H (H-6); 7.24 m,
3 H and 7.33 m, 2 H (H arom.); 7.39 br, 1 H (NH).
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5-Benzyluracil and 5-Benzylcytosine Nucleosides
639
5-Benzyl-2′-deoxy-3′,5′-bis(O-p-toluoyl)uridine (22) and 5-Benzyl-1-(2-deoxy-3,5-bis(O-p-toluoyl)-
α-D-ribofuranosyl)uracil (23)
5-Benzyluracil (910 mg, 4.5 mmol) was silylated in the same manner as described for preparation of
compound 2. To the silylated base in acetonitrile (25 ml) was added 2-deoxy-3,5-bis(O-p-toluoyl)-
D-ribofuranosyl chloride (1.36 g, 3.5 mmol) and molecular sieve 3Å (2 g), preheated at 200 °C in
vacuo. Mercury(II) bromide (613 mg, 1.7 mmol) was added, the suspension was stirred at room tem-
perature overnight, filtered, the solid was washed with a small amount of acetonitrile and then with
chloroform. The chloroform filtrate was washed with 30% potassium iodide solution (3 × 75 ml) and
water (100 ml) and dried over magnesium sulfate. Evaporation of the solvent and crystallization from
ethanol afforded 715 mg (37%) of the product 22.
The acetonitrile filtrate was taken down and the obtained mixture of anomers 22 and 23 was separated
on silica gel in system S1. RF: 22, 0.34; 23, 0.29. Total yield of the β-anomer 22 was 1.135 g (59%).
Mass spectrum (FAB; G + DMSO): 555 (M + H). 1H NMR spectrum and other physical constants
were identical with those described in the literature6. The α-anomer 23 was obtained in the yield 600
mg (31%). Mass spectrum (FAB; G + DMSO): 555 (M + H). 1H NMR spectrum and other physical
constants were identical with those described in the literature6.
5-Benzyl-2′-deoxycytidine (25)
Lawesson reagent (360 mg, 0.89 mmol) was added under argon to a solution of compound 22 (982 mg,
1.77 mmol) in 1,2-dichloroethane (20 ml) and the mixture was refluxed for 1 h. Another portion of
the reagent (90 mg) was added and the refluxing continued for another 4 h. After cooling, the reaction
mixture was applied onto a column of silica gel (300 ml) and chromatographed in toluene–acetone (8 : 1)
to give 960 mg (95%) of derivative 24 (RF 0.40, S1) as a yellow foam. The derivative 24 in methanolic
ammonia was stirred at room temperature for 48 h. The solvent was evaporated, the residue was
again dissolved in freshly made methanolic ammonia (70 ml) and heated at 120 °C for 1 h in an
autoclave. After cooling, the solvent was evaporated and the residue chromatographed on silica gel
(150 ml) in system S8 (RF 0.29). Crystallization from 2-propanol–ethanol (1 : 1) afforded 364 mg
(65%) of compound 25, m.p. 192–194 °C. For C16H19N3O4 (317.3) calculated: 60.56% C, 6.03% H,
13.24% N; found: 60.30% C, 6.08% H, 13.40% N. 1H NMR spectrum: 1.90 pent, 1 H, J(2′a,1′) =
J(2′a,3′) = 6.1, J(gem) = 13.1 (H-2′a); 2.11 ddd, 1 H, J(2′b,1′) = 5.8, J(2′b,3′) = 3.4 (H-2′b); 3.44 m,
2 H (H-5′); 3.62 s, 2 H (CH2); 3.74 br q, 1 H (H-4′); 4.16 m, 1 H (H-3′); 4.94 t, 1 H, J(OH,5′) = 5.2
(5′-OH); 5.19 d, 1 H, J(OH,3′) = 4.0 (3′-OH); 6.15 t, 1 H (H-1′); 6.73 br, 1 H (NH); 7.17–7.40 m, 6 H
(H arom. and NH); 7.59 s, 1 H (H-6).
5-Benzyl-1-(2-deoxy-α-D-ribofuranosyl)cytosine (27)
The title compound was prepared from derivative 23 (428 mg, 0.77 mmol) in the same manner as
described for the β-anomer 25. Chromatography on silica gel in system S8 gave 181 mg (74%) of the
1
α-anomer 27, RF 0.25. Mass spectrum (FAB; TG + G, methanol): 318 (M + H). H NMR spectrum:
1.85 br dt, 1 H, J(gem) = 14.0 (H-2′a); 2.40–2.60 m, 1 H (H-2′b); 3.37 m, 2 H (H-5′); 3.63 s, 2 H
(CH2); 4.08 m, 1 H (H-4′); 4.18 m, 1 H (H-3′); 4.81 t, 1 H, J(OH,5′) = 4.6 (5′-OH); 5.15 d, 1 H,
J(OH,3′) = 2.8 (3′-OH); 6.02 dd, 1 H, J(1′,2′a) = 2.4, J(1′,2′b) = 7.0 (H-1′); 6.60–6.90 br, 1 H (NH);
7.12–7.33 m, 6 H (H arom. and NH); 7.60 s, 1 H (H-6).
5-Benzyluridine (28)
A suspension of tribenzoyl derivative 10 (13 g, 20 mmol) in methanolic ammonia was stirred to ho-
mogeneity, the solution was set aside at room temperature for 3 days and the solvent was evaporated.
Collect. Czech. Chem. Commun. (Vol. 61) (1996)

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Krecmerova, Hrebabecky, Holy:
Crystallization from 2-propanol gave 4.2 g (63%) of 5-benzyluridine, m.p. 181–183 °C (reported5
m.p. 182–183 °C). Chromatography of the mother liquors on a column of silica gel (150 g) in system
S7 (RF 0.51) and subsequent crystallization from 2-propanol gave additional 1.2 g (18%) of the same
compound.
5′-O-Benzoyl-5-benzyluridine (29)
To a suspension of 5-benzyluridine 28 (5 g, 15 mmol) in acetone (75 ml) was added 2,2-dimethoxy-
propane (10 ml) and concentrated sulfuric acid (40 µl). The mixture was stirred at room temperature
for 45 min and neutralized with finely ground sodium hydrogen carbonate. The insoluble portion was
filtered off, washed with acetone, and the combined filtrates were taken down. The residue was dis-
solved in pyridine (80 ml), the solution was cooled in an ice bath, and benzoyl chloride (1.92 ml,
16.5 mmol) was added. The mixture was allowed to stand at 0 °C for 1 h and at room temperature
for 4 h. Water (0.5 ml) was added and the mixture was taken down. The residue was partitioned
between water (50 ml) and ethyl acetate (100 ml), the organic layer was washed successively with
2% hydrochloric acid to acid reaction of the aqueous phase, water (50 ml), and 5% sodium hydrogen
carbonate solution, dried over magnesium sulfate and the solvent was evaporated. The residue was
dissolved in 80% aqueous methanol (100 ml), Dowex 50 (H+ form, 5 ml) was added and the mixture
was refluxed for 7 h. Acetone (500 ml) was added and the mixture was again heated to the boil. The
ion exchanger was filtered off, washed with acetone and the combined filtrates were concentrated to
25 ml. The product was collected and washed with methanol and ether. Yield 5.51 g (84%) of benzoyl
derivative 29, m.p. 206–208 °C. For C23H22N2O7 (438.4) calculated: 63.01% C, 5.06% H, 6.39% N;
1
found: 62.73% C, 5.07% H, 6.41% N. H NMR spectrum: 3.36 d, 1 H, J(gem) = 14.6 and 3.44 d, 1 H
(CH2); 4.07–4.23 m, 3 H (H-2′, H-3′, H-4′); 4.38 dd, 1 H, J(5a′,4′) = 5.2, J(5a′,5b′) = 11.9 (H-5a′);
4.55 dd, 1 H, J(5b′,4′) = 2.75 (H-5b′); 5.37 d, 1 H, J = 4.9 (OH); 5.53 d, 1 H, J = 5.2 (OH); 5.82 d,
1 H, J(1′,2′) = 5.2 (H-1′); 7.15 m, 5 H (H-benzyl); 7.48–8.00 m, 6 H (H-6, H-benzoyl); 11.41 s, 1 H
(H-3).
2,2′-Anhydro-1-(5-O-benzoyl-β-D-arabinofuranosyl)-5-benzyluracil (30)
Thionyl chloride (1.7 ml, 23 mmol) was added to a suspension of benzoyl derivative 29 (5.26 g, 12 mmol)
in acetonitrile (70 ml) and the mixture was stirred at room temperature for 24 h. After concentration
to a half, the mixture was diluted with ethyl acetate (300 ml), washed with ice-cold 5% sodium hy-
drogen carbonate solution, dried over magnesium sulfate and the solvent was evaporated. The residue
was dissolved in dimethylformamide (45 ml), imidazole (0.85 g, 12.5 mmol) was added and the solution
was heated at 150 °C for 1 h. The solvent was evaporated and the residue was chromatographed on
a column of silica gel (200 g) in ethyl acetate–ethanol (10 : 1), RF 0.32. Crystallization from ethanol
afforded 4.0 g (79%) of anhydronucleoside 30, m.p. 179–182 °C. For C23H20N2O6 (420.4) calculated:
1
65.71% C, 4.79% H, 6.66% N; found: 65.67% C, 4.84% H, 6.64% N. H NMR spectrum: 3.51 bs, 2 H
(CH2); 4.08 dd, 1 H, J(5a′,4′) = 8.1, J(5a′,5b′) = 12.1 (H-5a′); 4.27 dd, 1 H, J(5b′,4′) = 4.1 (H-5b′);
4.36–4.49 m, 2 H (H-3′, H-4′); 5.26 dd, 1 H, J(2′,1′) = 6.3, J(2′,3′) = 0.9 (H-2′); 6.10 d, 1 H, J(OH,3′) = 4.5
(3′-OH); 6.35 d, 1 H (H-1′); 7.15 s, 5 H (H-benzyl); 7.64 s, 1 H (H-6); 7.46–7.90 m, 5 H (H-ben-
zoyl).
1-(5-O-benzoyl-2-deoxy-β-D-erythro-pentofuranosyl)-5-benzyluracil (32)
A solution of anhydro nucleoside 30 (3.57 g, 8.5 mmol) in 1 M hydrogen chloride in dimethylform-
amide was heated for 45 min at 100 °C. The solvent was evaporated, the residue was codistilled with
xylene and then partitioned between ethyl acetate (200 ml) and 10% sodium hydrogen carbonate solution
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5-Benzyluracil and 5-Benzylcytosine Nucleosides
641
(100 ml). The organic layer was separated, dried over magnesium sulfate and the solvent was evapo-
rated. The thus-obtained chloro derivative 31 was dissolved in toluene (40 ml), the solution was
heated at 100 °C and a solution of tributylstannane in toluene (1 mol l–1, 17 ml), followed by
azobis(isobutyronitrile) (170 mg), was added. After heating for 20 min, the reaction mixture was con-
centrated to a half and the deposited crystalline material was collected and washed with light petro-
leum. Crystallization from toluene–ethanol afforded 3.34 g (93%) of deoxy derivative 32, m.p.
212–213 °C. For C23H22N2O6 (422.4) calculated: 65.40% C, 5.25% H, 6.63% N; found: 65.36% C,
5.26% H, 6.81% N. 1H NMR spectrum: 2.09–2.14 m, 2 H (2 × H-2′); 3.36 d, 1 H, J(gem) = 14.7 and 3.44 d,
1 H (CH2); 4.03–4.10 m, 1 H (H-4); 4.31–4.52 m, 3 H (H-3′, 2 × H-5′); 5.50 d, 1 H, J(OH,3′) = 3.7
(3′-OH); 6.22 t, 1 H, J(1′,2a′) = J(1′,2b′) = 6.7 (H-1′); 7.14 m, 5 H (H-benzyl); 7.46–7.98 m, 6 H
(H-6, H-benzoyl); 11.36 s, 1 H (H-3).
1-(5-O-Benzoyl-2,3-dideoxy-β-D-glycero-pentofuranosyl)-5-benzyluracil (35)
A solution of deoxy derivative 32 (3.3 g, 7.8 mmol) and thionyl chloride (0.88 ml, 12 mmol) in
hexamethylphosphoric triamide (15 ml) was allowed to stand at room temperature overnight, then
diluted with ethyl acetate (200 ml) and washed with 10% sodium hydrogen carbonate solution (3 × 100 ml).
The organic layer was dried over magnesium sulfate and the solvent was evaporated. The obtained
mixture of chloro derivatives 33 and 34 was dissolved in toluene (40 ml) and the solution was heated
to the boil. A solution of tributylstannane in toluene (1 mol l–1, 15 ml), followed by azobis(isobuty-
ronitrile) (230 mg), was added and the mixture was refluxed for 1 h. Evaporation of the solvent and
chromatography on a column of silica gel (300 g) in ethyl acetate–toluene (2 : 1) afforded 2.98 g
(94%) of dideoxy derivative 35 as solid foam (RF 0.40). For C23H22N2O5 (406.4) calculated: 67.97% C,
5.46% H, 6.89% N; found: 67.66% C, 5.29% H, 6.63% N. 1H NMR spectrum: 1.82–2.43 m, 4 H (2 × H-2′,
2 × H-3′); 3.38 d, 1 H, J(gem) = 14.8 and 3.46 d, 1 H (CH2); 4.26–4.52 m, 3 H (H-4′, 2 × H-5′); 6.03 dd,
1 H, J(1′,2a′) = 6.9, J(1′,2b′) = 4.3 (H-1′); 7.15 m, 5 H (H-benzyl); 7.43–8.00 m, 6 H (H-6, H-benzoyl);
11.35 s, 1 H (H-3).
1-(5-O-Benzoyl-2,3-dideoxy-β-D-glycero-pentofuranosyl)-5-benzyl-4-thiouracil (36)
Lawesson reagent (850 mg, 2.1 mmol) was added to a solution of 5′-O-benzoyl-5-benzyl-2′,3′-
dideoxyuridine (35; 1.38 g, 3.4 mmol) in 1,2-dichloroethane (30 ml) and the mixture was refluxed
under argon for 3 h. After cooling, the solution was applied onto a column of silica gel (400 ml) and
chromatographed in system S2 to give 1.11 g (77%) of compound 36 as yellow foam. RF 0.28
(toluene–ethyl acetate 3 : 1). For C23H22N2O4S (422.5) calculated: 65.38% C, 5.25% H, 6.63% N,
1
7.59% S; found: 64.95% C, 5.35% H, 6.35% N, 7.47% S. H NMR spectrum: 1.78 m, 1 H (H-3′a);
2.09 m, 2 H (H-3′b and H-2′a); 2.38 m, 1 H (H-2′b); 3.63 d, 1 H and 3.79 d, 1 H, J(gem) = 15.1 (CH2);
4.25 dd, 1 H, J(5′a, 4′) = 6.6, J(gem) = 11.7 (H-5′a); 4.35 ddd, 1 H, J(4′,5′a) = 6.6, J(4′,5′b) = 3.2, J(4′,3′) = 5.9
and 8.5 (H-4′); 4.40 dd, 1 H (H-5′b); 5.96 dd, 1 H, J(1′,2′) = 3.4 and 7.1 (H-1′); 7.10–7.20 m, 5 H (H arom.),
7.42 s, 1 H (H-6); 7.50 m, 2 H, 7.66 m, 1 H and 7.95 m, 2 H (H arom.); 12.76 s, 1 H (NH).
5-Benzyl-1-(2,3-dideoxy-β-D-glycero-pentofuranosyl)-4-thiouracil (37)
A mixture of the protected 4-thio derivative 36 (1.11 g, 2.63 mmol) and methanolic ammonia (50 ml)
was stirred for 3 days at room temperature. The solvent was evaporated and the residue was
chromatographed on silica gel (240 ml) in system S3 (RF 0.39) to give pure compound 37 (620 mg,
74%) as solid foam. For C16H18N2O3S (318.4) calculated: 60.36% C, 5.70% H, 8.80% N, 10.07% S;
found: 60.01% C, 5.70% H, 9.08% N, 9.82% S. 1H NMR spectrum: 1.73 dddd, 1 H, J(3′a,2′a) = 7.6;
J(3′a,4′) = 9.3, J(3′a,2′b) = 10.5, J(gem) = 12.5 (H-3′a); 1.86 dddd, 1 H, J(3′b,2′a) = 3.2, J(3′b,4′) = 5.9,
Collect. Czech. Chem. Commun. (Vol. 61) (1996)

642
Krecmerova, Hrebabecky, Holy:
J(3′b,2′b) = 8.1 (H-3′b); 2.02 ddt, 1 H, J(2′a, 1′) = 2.7, J(gem) = 13.7 (H-2′a); 2.30 dddd, 1 H, J(2′b,1′) = 6.6
(H-2′b); 3.44 ddd, 1 H, J(5′a,4′) = 3.7, J(5′a,OH) = 5.0, J(gem) = 12.0 (H-5′b); 3.61 ddd, 1 H,
J(5′b,4′) = 3.4, J(5′b,OH) = 5.1 (H-5′b); 3.80 s, 2 H (CH2); 4.03 ddt, 1 H (H-4′); 5.10 t, 1 H (5′-OH);
5.90 dd, 1 H (H-1′); 7.18 m, 1 H and 7.26 m, 4 H (H arom.); 7.98 s, 1 H (H-6); 12.63 br, 1 H (NH).
5-Benzyl-1-(2,3-dideoxy-β-D-glycero-pentofuranosyl)cytosine (38)
A solution of 4-thio derivative 37 (450 mg, 1.41 mmol) in methanolic ammonia (50 ml) was heated
at 120 °C for 1 h in an autoclave. After evaporation of the solvent, a mixture of ethyl acetate and
acetone (5 : 1) was added, the mixture was briefly boiled and set aside at room temperature over-
night. The crystalline product was collected, washed with acetone and ether and dried in vacuo; yield
255 mg (60%) of compound 38. Further portion (65 mg, 15%) of the product was obtained from the
mother liquors by chromatography on silica gel (50 ml) in system S8 (RF 0.29) and subsequent
crystallization from ethanol. M.p. 209–211 °C (ethanol–water). For C16H19N3O3 . 0.25 H2O (305.8)
1
calculated: 62.83% C, 6.43% H, 13.74% N; found: 63.10% C, 6.44% H, 13.61% N. H NMR spectrum:
1.65 ddt, 1 H, J(3′a,4′) = 8.5, J(3′a,2′) = 8.5 and 11.0, J(gem) = 12.5 (H-3′a); 1.78–1.87 m, 2 H
(H-2′a and H-3′b); 2.24 dtd, 1 H, J(2′b,1′) = 6.6, J(2′b,3′b) = J(2′b, 3′a) = 9.O, J(gem) = 13.7 (H-2′b);
3.40 dt, 1 H, J(5′a,4′) = J(5′a,OH) = 4.5, J(gem) = 11.7 (H-5′a); 3.52 ddd, 1 H, J(5′b, 4′) = 4.1,
J(5′b,OH) = 5.4 (H-5′b); 3.61 s, 2 H (CH2); 3.97 ddt, 1 H, J(4′,3′) = 6.0 and 8.5 (H-4′); 4.97 t, 1 H
(5′-OH); 5.92 dd, 1 H, J(1′,2′a) = 3.4, J(1′,2′b) = 6.6 (H-1′); 6.66 br, 1 H and 7.24 br, 1 H (NH2);
7.18–7.27 m, 3 H and 7.30 m, 2 H (H arom.); 7.66 s, 1 H (H-6).
1-(5-O-Benzoyl-2,3-dideoxy-β-D-glycero-pentofuranosyl)-5-benzyl-4-methylthiopyrimidine (39)
Finely ground potassium carbonate (200 mg) and methyl iodide (1 ml) were added to a solution of
4-thio derivative 36 (770 mg, 1.82 mmol) in dimethylformamide (5 ml). The mixture was stirred at
room temperature for 30 min, the solid was filtered off and washed with ethyl acetate. The combined
filtrates were taken down, the residue was codistilled with xylene (20 ml) and then partitioned between
water (50 ml) and ethyl acetate (100 ml). The organic layer was dried over magnesium sulfate, the
solvent evaporated and the residue chromatographed on silica gel (100 ml) in ethyl acetate (RF in S6:
39, 0.34; 36, 0.82). Yield 702 mg (88%) of colorless foam, m.p. 122–124 °C (methanol). For
C24H24N2O4S (436.5) calculated: 66.04% C, 5.54% H, 6.42% N, 7.35% S; found: 65.79% C, 5.58% H,
1
6.42% N, 7.09% S. Mass spectrum (FAB; G + methanol): 437.1 (M + H). H NMR spectrum: 1.75–1.83 m,
1 H, 2.03–2.12 m, 2 H and 2.37–2.50 m, 1 H (H-2′ and H-3′); 2.39 s, 3 H (SCH3); 3.58 d, 1 H and 3.63 d,
1 H, J = 16.1 (CH2); 4.36 dd, 1 H, J(5′a,4′) = 6.1, J(gem) = 11.7 (H-5′a); 4.42 dtd, 1 H, J = 2.7, 6.1,
6.1 and 8.7 (H-4′); 4.48 dd, 1 H, J(5′b,4′) = 2.9 (H-5′b); 5.96 dd, 1 H, J(1′,2′) = 3.4 and 6.8 (H-1′); 7.66 s,
1 H (H-6); 7.12 t, 2 H, 7.22 d, 2 H, 7.23 t, 1 H, 7.47 t, 2 H, 7.64 t, 1 H and 7.93 d, 2 H (H arom.).
1-(5-O-Benzoyl-2,3-dideoxy-D-glycero-pentofuranosyl)-5-benzyl-2(1H)-pyrimidinone (41)
Hydrazine hydrate (80%, 1 ml) was added to a solution of compound 39 (2.17 g, 4.97 mmol) in
dioxane (30 ml) and the solution was refluxed for 2 h. After evaporation, the remaining hydrazino
derivative 40 was codistilled with toluene (2 × 30 ml) and dissolved in ethanol (100 ml). Freshly
prepared silver oxide (1.74 g, 7.5 mmol) was added and the stirred mixture was refluxed for 2.5 h.
After standing overnight at room temperature, the suspension was filtered through Celite and the fil-
trate was taken down. The residue was dissolved in chloroform–methanol and the solution was mixed
with silica gel (15 ml) and evaporated. This material was applied onto a column of silica gel (300 ml,
ethyl acetate). The column was first washed with ethyl acetate and then the product 41 was eluted
with system S6 (RF 0.33, fluorescence in UV light). Yield 860 mg (43%) of amorphous material.
Collect. Czech. Chem. Commun. (Vol. 61) (1996)

5-Benzyluracil and 5-Benzylcytosine Nucleosides
643
According to NMR, the compound was an inseparable mixture of anomers (β : α = 3 : 1). For
C23H22N2O4 (390.4) calculated: 70.75% C, 5.68% H, 7.17% N; found: 69.53% C, 5.84% H, 7.11% N.
Mass spectrum (FAB; bis(hydroxyethyl)disulfide + dimethyl sulfoxide): 391.1 (M + H). 1H NMR
spectrum (β-anomer): 1.79–1.87 m, 2.02–2.11 m and 2.50–2.56 m, 4 H (H-2′ and H- 3′); 3.57 d, 1 H
and 3.65 d, 1 H, J = 15.2 (CH2); 4.48 m, 1 H (H-4′); 4.49 dd, 1 H, J(5′a,4′) = 3.9, J(gem) = 13.9 (H-5′a);
4.57 dd, 1 H, J(5′b,4′) = 5.6 (H-5′b); 5.95 dd, 1 H, J = 3.4 and 6.6 (H-1′); 7.10–7.30 m, 5 H, 7.50–7.60 m,
2 H, 7.65 m, 1 H and 7.98 m, 2 H (H arom.); 7.99 d, 1 H and 8.47 d, 1 H, J(4,6) = 3.4 (H-4 and
1
H-6). H NMR spectrum (α-anomer): 1.91–1.98 m and 2.10–2.14 m, 4 H (H-2′and H-3′); 3.81 s, 2 H
(CH2); 4.35 dd, 1 H, J(5′a,4′) = 5.6, J(gem) = 11.7 (H-5′a); 4.41 dd, 1 H, J(5′b,4′) = 3.7 (H-5′b); 4.95 m, 1 H
(H-4′); 6.04 dd, 1 H, J = 2.9 and 6.3 (H-1′); 7.10–7.30 m, 5 H, 7.50–7.60 m, 2 H, 7.65 m, 1 H and 7.98 m,
2 H (H arom.); 8.03 d, 1 H and 8.49 d, 1 H, J(4,6) = 3.4 (H-4 and H-6).
5-Benzyl-1-(2,3-dideoxy-D-glycero-pentofuranosyl)- 2(1H)-pyrimidinone (42)
A solution of benzoyl derivative 41 (850 mg, 2.18 mmol) in methanolic ammonia (20 ml) was
allowed to stand at room temperature for 24 h. After evaporation, the residue was chromatographed
on silica gel (200 ml) in system S7 (RF 0.26) to give 500 mg (80%) of amorphous product, m.p.
168–174 °C (ethyl acetate–2-propanol). According to NMR, the product was a mixture of β and α
anomers (about 5 : 2). 1H NMR spectrum (signals common to both anomers): 1.70–2.10 m, 3 H and
2.35–2.45 m, 1 H (H-2′ and H-3′); 3.72 s, 2 H (CH2); 5.23 t, 1 H, J = 4.9 (OH); 7.20–7.35 m, 5 H (H arom.).
Exchange with CD3COOD (β-anomer): 3.55 dd, 1 H, J(5′a,4′) = 3.2, J(gem) = 12.2 (H-5′a); 3.77 dd, 1 H,
J(5′b,4′) = 2.9 (H-5′b); 4.12 m, 1 H (H-4′); 5.88 dd, 1 H, J = 2.9 and 6.6 (H-1′); 8.11 br s, 1 H and 8.44 br s,
1 H (H-4 and H-6). Exchange with CD3COOD (α-anomer): 3.40 dd, 1 H, J(5′a,4′) = 4.9, J(gem) = 11.7
(H-5′a); 3.45 dd, 1 H, J(5′b,4′) = 4.6 (H-5′b); 4.48 m, 1 H (H-4′); 5.94 dd, 1 H, J = 2.9 and 6.3 (H-1′);
8.44 br s, 1 H and 8.58 br s, 1 H (H-4 and H-6).
1-(5-O-Benzoyl-2,3-dideoxy-β-D-glycero-pentofuranosyl)-5-benzyl-4-(isopropylidenehydrazino)-
2(1H)-pyrimidinone (43)
Hydrazine hydrate (80%, 0.1 ml) was added to a solution of compound 36 (643 mg, 1.47 mmol) in
dioxane (20 ml) and the stirred mixture was refluxed for 1 h. The refluxing was continued for another
6 h during which further portions of hydrazine hydrate (total 0.6 ml) were added. After cooling to
room temperature, acetone (1 ml) was added, the solution was stirred for 30 min and the solvent was
evaporated. Chromatography on silica gel (250 ml) in system S5 (RF: 43, 0.33; 36, 0.12) gave 494 mg
(73%) of sirupy product. For C26H28N4O4 (460.5) calculated: 67.81% C, 6.13% H, 12.17% N; found:
67.77% C, 6.14% H, 11.82% N. Mass spectrum (EI): 460.2 (M+), 256.1 (base + H). 1H NMR spec-
trum: 1.87 s, 3 H and 1.95 s, 3 H (CH3); 1.91 m, 1 H (H-3′a); 2.00 m, 1 H (H-2′a); 2.11 m, 1 H
(H-3′b); 2.30 m, 1 H (H-2′b); 3.44 d, 1 H and 3.50 d, 1 H, J(gem) = 14.4 (CH2); 4.29 m, 1 H (H-4′);
4.35 dd, 1 H, J(5′a,4′) = 6.3, J(gem) = 11.7 (H-5′a); 4.45 dd, 1 H, J(5′b,4′) = 2.9 (H-5′b); 6.06 dd,
1 H, J = 5.1 and 7.1 (H-1′); 7.04 s, 1 H (H-6); 7.12 m, 1 H, 7.19 m, 4 H, 7.51 t, 2 H, 7.65 t, 1 H and
7.99 d, 2 H (H arom.); 9.40 br s, 1 H (NH).
5-Benzyl-1-(2,3-dideoxy-β-D-glycero-pentofuranosyl)-4-(isopropylidenehydrazino)-2(1H)-pyrimidin-
one (44)
A solution of benzoyl derivative 43 (450 mg, 0.98 mmol) in methanolic ammonia (15 ml) was set
aside at room temperature for 24 h. After evaporation, the residue was chromatographed on silica gel
(100 ml) in ethyl acetate (RF 0.28). Yield 285 mg (82%) of yellow sirup. Mass spectrum (FAB; G +
1
methanol): 357.3 (M + H). H NMR spectrum: 1.75–1.84 m, 1 H, 1.87–1.94 m, 2 H and 2.18–2.26 m,
Collect. Czech. Chem. Commun. (Vol. 61) (1996)

644
Krecmerova, Hrebabecky, Holy:
1 H (H-2′ and H-3′); 1.91 s, 3 H and 1.97 s, 3 H (CH3); 3.46 dt, 1 H, J(5′a,4′) = J(5′a,OH) = 4.5,
J(gem) = 11.7 (H-5′a); 3.58 dt, 1 H, J(5′b,4′) = J(5′b,OH) = 4.6 (H-5′b); 3.58 s, 2 H (CH2); 3.97 m,
1 H (H-4′); 4.99 t, 1 H (5′-OH); 5.98 dd, 1 H, J = 3.9 and 7.3 (H-1′); 7.17 m, 1 H and 7.24–7.32 m, 4 H
(H arom.); 7.35 s, 1 H (H-6); 9.38 br, 1 H (NH).
The authors are indebted to the staff of the Analytical Laboratory of this Institute (Dr V. Pechanec,
Head) for the elemental analyses, Dr J. Kohoutova for measurement of mass spectra and Dr I. Votruba
for the cytostatic activity assays. The technical assistance of Dr J. Sterecova is gratefully acknowledged.
This study was supported by a Rhone-Poulenc Rorer (France) research grant.
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Collect. Czech. Chem. Commun. (Vol. 61) (1996)