Nucleic acid component analogues: Synthesis of 2′-deoxynucleosides from 5-substituted-4-hydroxy-6(1H)-pyrimidinones

Article abstract of DOI:10.1081/NCN-120018626

Condensation of the silylated pyrimidines 5a-c with methyl 2-deoxy-3, 5-di-O-toluoyl-D-pentofuranoside 6, using trimethylsilyltriflate as catalyst gave anomeric mixtures of 2′-deoxynucleosides 7a-c, the pure α- and β-anomers were separated and deprotected with sodium methoxide in methanol to give 1-(2′-deoxy-α-D-pentafuranosyl)-4-hydroxy-5-substituted-6 (1H)-pyrimidinones 10a,b and 13a and their corresponding β-anomers 11a,b and 13b.

Full text of DOI:10.1081/NCN-120018626

NUCLEOSIDES, NUCLEOTIDES & NUCLEIC ACIDS
Vol. 22, No. 1, pp. 99–107, 2003
Nucleic Acid Component Analogues: Synthesis of
20-Deoxynucleosides from 5-Substituted-4-
hydroxy-6(1H)-pyrimidinones
1
2
Ahmed F. Khattab,1, Ahmed E.-S. Abdel Megied, and Erik B. Pedersen
*
1Chemistry Department, Faculty of Science, Monoufiya University,
Shebien El-Koam, A. R. Egypt
2Chemistry Department, Syddansk University, Odense M, Denmark
ABSTRACT
Condensation of the silylated pyrimidines 5a–c with methyl 2-deoxy-3,5-di-O-
toluoyl-D-pentofuranoside 6, using trimethylsilyltriflate as catalyst gave anomeric
mixtures of 20-deoxynucleosides 7a–c, the pure a- and b-anomers were separated
and deprotected with sodium methoxide in methanol to give 1-(20-deoxy-a-D-
pentafuranosyl)-4-hydroxy-5-substituted-6(1H)-pyrimidinones 10a,b and 13a
and their corresponding b-anomers 11a,b and 13b.
Key Words: 20-Deoxynucleosides; 1-Chloromethyl naphalene; Pyrimidinones.
INTRODUCTION
Prystaꢀs[1,2] reported on the synthesis of 1-glycosyl-4-alkoxy-5-(un)substituted-
6(1H)-pyrimidinones by ribosylation or deoxyribosylation of 2,6-dialkoxypyri-
midines. Transformation of these nucleosides to the corresponding 4-hydroxy
*Correspondence: Ahmed F. Khattab, Chemistry Department, Faculty of Science, Monoufiya
University, Shebien El-Koam, A. R. Egypt; E-mail: khattab2000@yahoo.com.
99
DOI: 10.1081/NCN-120018626
Copyright # 2003 by Marcel Dekker, Inc.
1525-7770 (Print); 1532-2335 (Online)
www.dekker.com

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Khattab, Abdel Megied, and Pedersen
derivatives was accomplished only with difficulty by hydrogenolysis, which was
accompanied by hydrogenation of the ring at position 2 and 3.[1,2] On the other
hand, carcinogenic polycyclic aromatic hydrocarbons are known to undergo meta-
bolic activation to reactive diol epoxide intermediates that bind covalently to
DNA in vivo.[3] Thus, in this report, as a continuation of our interest in the synthesis
of nucleosides and acyclonucleosides.[4–8] We describe a practical synthesis of 1-(20-
Deoxy-D-ribofuranosyl)-4-hydroxy-6(1H)-pyrimidinones, 10a,b; 11a,b and 13a,b,
bearing an aromatic fragment at position 5.
RESULTS AND DISCUSSION
The commercial 1-chloromethyl naphthalene (1) reacts with sodium salt of
dimethylmalonate to afford the new ester 2, which has been shown to be a versatile
synthon for further functionalizations and ring closure reactions to several hetero-
cyclic compounds. The ester 2 was converted into the corresponding malondiamide
3, that can be cyclised by reaction with formamide, in presence of sodium ethoxide,
to give 4-hydroxy-5-(1-naphthylmethyl)-6(1H)-pyrimidinone 4a (Sch. 1).
Similarly, condensation of benzyl malondiamide with fomamide afforded 4-
hydroxy-5-benzyl-6(1H)-pyrimidinone 4b, whereas, 4-hydroxy-5-phenyl-6(1H)-pyri-
midinone 4c was prepared, according to the procedure of Hull.[9] Silylation of 4a–c
with 1,1,1,3,3,3-hexamethyldisilizane (HMDS) in the presence of a catalytic amount
of ammonium sulfate was performed according to Wittenburg[10] to give the silylated
derivatives 5a–c that were reacted with methyl 2-deoxy-3,5-di-O-toluoyl-D-pentofur-
anoside (6)[11] using trimethylsilyl trifluoromethanesulfonate (TMS triflate) as the
catalyst according to the method of Vorbrugen et al.[12] in anhydrous acetonitrile
¨
to give anomeric mixtures of nucleosides 7a–c in 60–86% yield with the a=b
ratio 2:1. Stirring of the protected nucleosides 7a,b, after their chromatographic
purification, in dry diethylether at room temperature for 1 h followed by filtration
resulted in complete separation of the anomeric mixture. The a anomers 8a,b were
obtained in 40–51% yields and the b anomers 9a,b in 20–35% yield. Deprotection
of the nucleosides with sodium methoxide in methanol afforded the deprotected a
anomers 10a–b (90–92%) and the b anomers 11a,b (86–94%). The mixture of a
and b anomers 7c was deprotected using sodium methoxide in methanol to give
the unprotected anomers 12 which could be separated by use of preparative HPLC
to afford the a anomer 13a in 38% yield and the b anomer 13b in 48% yield (Sch. 2).
Scheme 1.

Synthesis of 20-Deoxynucleosides
101
Scheme 2.
In agreement with the reported data,[4–6,13,14] the 40-H protons of the a anomers
10a,b and 13a appear downfield from those observed for the b anomers 11a,b
and 13b.
EXPERIMENTAL
Mps are uncorrected. Elemental analyses were carried out in the Microanalytical
1
Laboratories of the Faculty of Science, Cairo University. H and 13C NMR spectra
1
were recorded on a Bruker AC 250 FT-nmr spectrometer at 250 MHz for H NMR
and 62.9 MHz for 13C NMR. Mass spectra (MS) were recorded using fast atom
bombardment (FAB) on a Kratos MS 50-spectrometer. Analytical TLC plates

102
Khattab, Abdel Megied, and Pedersen
60 F254 and silica gel (0.040–0.063 mm) was purchased from Merck. Anhydrous
CH3CN was distilled from P2O5 followed by distillation from CaH. All other
solvents were used after distillation and drying.
Dimethyl (1-naphthylmethyl) malonate (2). To methanol (300 mL) and sodium
(19.3 g, 0.84 mol), dimethylmalonate (113 mL, 0.98 mol) was added dropwise with
stirring then 1-chloromethylnaphthalene 1 (154 mL, 0.87 mol) was added. The reac-
tion mixture was refluxed with stirring for 5 h. The excess alcohol was evaporated
under reduced pressure and the residue dissolved in water, extracted with diethyl
ether (3 ꢀ 100), dried (Na2SO4). Fractional distillation yielded 2 (62%; bp150–
1
155ꢁC, 20 mbar); H-NMR (DMSO-d6) d 3.60 (m, 8H, CH2 and 2 ꢀ CH3), 3.92
(t, 1H, J ¼ 7.6 Hz, CH), 7.32–7.58 (m, 4H, arom.), 7.82 (d, 1H, J ¼ 8.0 Hz, arom.),
7.94 (d, 1H, J ¼ 7.3 Hz, arom.), 8.1 (d, 1H, J ¼ 7.7 Hz, arom.). 13C-NMR
(DMSO-d6) d 31.03 (CH2), 51.87 (CH), 52.1 (2 ꢀ CH3), 123.10, 125.24, 125.62,
126.28, 126.63, 127.28, 128.59, 130.96, 133.25 and 133.31 (C-arom.), 168.66 (2
CO). MS FAB (CHCl3 þ 3-nitrobenzyl alcohol) m=z: 353 (Mþ þ 1).
(1-Naphthylmethyl)-malondiamide (3). A solution of 2 (14 g, 48 mmol) in a 1:1
mixture (100 mL) of methanol and conc. ammonia (25%) was stirred at room tem-
perature for 24 h. The solid product which formed was collected by filtration, dried
and recrystallized from methanol to give 3 as white prisms (78%): mp. 268–70ꢁC. 1H-
NMR (DMSO-d6) d 3.37–3.60 (m, 3H, CH and CH2), 7.10 (s, 2H, NH2), 7.28 (s, 2H,
NH2), 7.34–7.70 (m, 4H, arom.), 7.78 (d, 1H, J ¼ 7.3 Hz, arom.), 7.92 (d, 1H,
J ¼ 7.6 Hz, arom.), 8.11 (d, 1H, J ¼ 8.0 Hz, arom.). 13C-NMR (DMSO-d6) d 31.98
(CH2), 53.84 (CH), 123.53, 125.34, 125.47, 126.01, 126.47, 126.76, 128.55, 131.35,
133.34 and 135.19 (C-arom.), 170.84 (2 ꢀ CO). Anal. Calcd for C14H14N2O2
(242.37): C, 69.37; H, 5.82; N, 11.60. Found: C, 69.50; H, 5.70; N, 11.60.
4-Hydroxy-5-(1-naphthylmethyl)-6(1H)-pyrimidinone (4a).
A mixture of 3
(7.2 g, 30 mmol), formamide (5 mL) and sodium ethoxide [prepared by dissolving
(2.8 g, 120 mmol) of sodium metal in 100 mL ethanol] was refluxed for 12 h. The resi-
due obtained after removal of ethanol in vacuo was dissolved in warm water
(100 mL) and acidified with 4M HCl. The solid product, which formed, was filtered
off, dried and recrystallized from water to afford 4a (92%) as white prisms, mp 334–
336 ꢁC. 1H-NMR (DMSO-d6) d 4.06 (s, 2H, CH2), 7.25 (d, 1H, J ¼ 7.1, arom.), 7.37
(t, 2H, J ¼ 7.5 Hz, arom.), 7.51 (m, 2H, arom.), 7.73 (d, 1H, J ¼ 8.0 Hz, arom.), 7.87
(d, 1H, J ¼ 8.3 Hz, arom.), 8.03 (s, 1H, C2-H), 8.37 (d, 1H, J ¼ 7.3 Hz, arom.); 11.85
(s. br., 1H, NH). 13C-NMR (DMSO-d6) d 25.26 (CH2), 100.64 (C-5) 124.05, 125.34,
125.64, 126.04, 128.28, 131.83, 133.24, and 135.96 (C-arom.), 147.45 (C-2). 164.51
(C-4 and CO). Anal. Calcd for C15H12N2O2 (252.37): C, 71.38; H, 4.79; N, 11.14.
Found: C, 71.60; H, 4.90; N, 11.30.
4-Hydroxy-5-benzyl-6(1H)-pyrimidinone (4b). This compound was obtained
from benzyl malondiamide (5.37 g, 30 mmol), formamide (5 mL) and sodium ethox-
ide (2.8 g, sodium metal in 100 mL ethanol) according to the procedure described for
4a to afford 4b as white prisms (86%), mp 326–326ꢁC (DMF). 1H-NMR (DMSO-d6)
d 3.61 (s, 2H, CH2), 7.09–7.26 (m, 5H, arom.), 7.97 (s, 1H, C2-H), 11.78 (s. br, 1H,

Synthesis of 20-Deoxynucleosides
103
NH). 13C-NMR (DMSO-d6) d 27.89 (CH2), 102.02 (C-5), 125.45, 127.91 and 128.29
(C-arom.), 140.99 (C-2), 147.21 (C-4), 164.24 (CO). Anal. calcd for C11H10N2O2
(202.31): C, 65.30; H, 4.98; N, 13.89. Found: C, 65.20; H, 4.70; N, 13.60.
General Procedure for the Preparation of 7a–c. Pyrimidine derivatives 4a–c
(5 mmol) was treated with 1,1,1,3,3,3-hexamethyldisilazane (HMDS) (30 mL) and
ammonium sulfate (30 mg) at reflux temperature for 6 h (clear solution after 2 h),
and the solvent was removed in vacuo. The residue 5a–c was dissolved in dry MeCN
(20 mL), and the sugar 6 (3 mmol) in dry MeCN (50 mL) was added. The mixture
was cooled to ꢂ35ꢁC under magnetic stirring. A solution of CF3SO3SiMe3
(1.1 mL, 6 mmol) in dry MeCN (5 mL) was then added dropwise with stirring over
a period of 10 min. The reaction mixture was stirred at ꢂ25ꢁC for 1 h and then at
room temperature for 1 h. The reaction mixture was diluted with 200 mL of CH2Cl2
and washed ice-cold sat. aq. NaHCO3 (3 ꢀ 100 mL). The organic phase was sepa-
rated, washed with cold H2O (3 ꢀ 100 mL), dried over Na2SO4, and evaporated to
obtain the crude products which were chromatographed on a silica gel column using
petroleum ether=diethyl ether (40–0%) as eluent.
Preparation of 8a,b and 9a,b. A suspension of anomeric mixtures 7a,b (5 mmol)
in dry diethyl ether (20 mL) was stirred at room temperature for 2 h, then filtered,
washed with diethyl ether to afford the pure a anomer 8a,b as a white solid. The
mother liquor was evaporated to dryness to afford b anomer 9a,b as white foam.
Whereas, the anomeric mixtures 7c fails to separate by this method or by using
column chromatograph, using HPLC after deprotection separated these anomers.
1-[20-Deoxy-3, 5-di-O-(4-methylbenzoyl)-a=b-D-pentofuranozyl]-5-phenyl-4-
hydroxy-6(1H)-pyrimidinone (7c). Yield ((89%); (a=b mixture), 1H-NMR(CDCl3)
d 2.19 (s, 3H, CH3), 2.24–2.28 (m, 1H, H-20), 2.32 (s, 3H, CH3), 2.63–2.66 (m, 1H,
H-20), 2.97–3.12 (m, 2H, H-20), 4.51–4.57 (m, 2H, H-50), 4.64–4.66 (m, 1H, H-40),
4.71–4.90 (m, 2H, H-50), 4.95–4.98 (m, 1H, H-40), 5.55 (d, 1H, J ¼ 6.1 Hz, H-30),
5.63 (d, 1H, J ¼ 5.4 Hz, H-30), 6.38 (t, 1H, J ¼ 6.6 Hz, H-10), 6.47 (d, 1H,
J ¼ 6.3 Hz, H-10), 7.01 (d, 2H, J ¼ 8.0 Hz, arom.), 7.10 (d, 2H, J ¼ 8.1 Hz, arom.),
7.23–7.39 (m, 12H, arom.), 7.52–7.56 (m, 4H, arom.), 7.67 (d, 2H, J ¼ 8.1 Hz,
arom.), 7.81 (d, 2H, J ¼ 8.1 Hz, arom.), 7.93 (d, 2H, J ¼ 8.1 Hz, arom.), 8.37 (s,
1H, C2-H), 8.40 (s, 1H, C2-H). 13C-NMR(CDCl3) d 21.55 (CH3), 21.64 (CH3),
39.32 (C-20), 39.81 (C-20), 63.89 (2 C-50), 74.83 (2 C-30), 84.03 (C-40), 85.82 (C-
40), 87.38 (C-10), 89.02 (C-10), 103.81 (C-5), 103.95 (C-5), 125.95–130.68 (Carom.),
144.29–145.15 (Carom.), 160.70 (C-2), 161.10 (C-2), 163.92 (C-4), 164.11 (C-4),
165.29, 165.93, 166.03 and 166.23 (4 CO).
1-[20-Deoxy-3,5-di-O-(4-methybenzoyl)-a-D-pentofuranosyl]-4-hydroxy-5-
(1-naphthylmethyl)-6(1H)-pyrimidinone (8a). (Yield (59%). 1H-NMR (DMSO-d6) d
2.34 (s, 3H, CH3), 2.39 (s, 3H, CH3), 2.53 (d, 1H, J ¼ 14.73 Hz, H-20), 2.92–3.36 (m,
1H, H-20), 4.08 (s, 2H, CH2), 4.50–4.52 (m, 1H, H-50), 5.10–5.13 (m, 1H, H-40), 5.58
(d, 1H, J ¼ 5.3 Hz, H-30), 6.34 (d, 1H, J ¼ 6.0 Hz, H-10), 7.09–7.24 (m, 2H, arom.),
7.36 (d, 2H, J ¼ 8.0 Hz, arom.), 7.46–7.48 (m, 2H, arom.), 7.62 (d, 2H, J ¼ 8.2 Hz,
arom.), 7.61 (d, 1H, J ¼ 8.0 Hz, arom.), 7.70 (d, 1H, J ¼ 7.9 Hz, arom.), 7.86

104
Khattab, Abdel Megied, and Pedersen
(d, 1H, J ¼ 7.3 Hz, arom.), 7.94 (d, 1H, J ¼ 8.1 Hz, arom), 8.43 (d, 1H, J ¼ 8.0 Hz,
1
arom.), 8.49 (s, C2-H, arom.), 11.69 (s., br., 1H, OH). H-NMR (DMSO-d6) d
21.07 (2 ꢀ CH3), 25.30 (CH2), 38.27 (C-20), 63.90 (C-50), 74.72 (C-30), 84.32 (C-40),
88.01 (C-10), 99.51 (C-5), 123.88–143.82 (C-arom.), 145.62 (C-2), 161.90 (C-4),
164.76, 165.38 and 165.66 (3 ꢀ CO). MS FAB (CHCl3 þ 3-nitrobenzyl alcohol)
m=z: 627 (M þ Naþ).
1-[20-Deoxy-3,5-di-O-(4-methylbenzoyl)-b-D-pentofuranosyl]-4-hydroxy-5-
1
(1-naphthylmethyl)-6(1H)-pyrimidinone (9a). Yield (30%); H-NMR (DMSO-d6) d,
2.33 (s, 3H, CH3), 2.39 (s, 3H, CH3), 2.61–2.65 (m, 1H, H-20), 2.93–2.98 (m, 1H, H-
20), 4.11 (s, 2H, CH2), 4.52–4.60 (m, 1H, H-40), 4.65–4.68 (m, 2H, H-50), 5.54–5.59
(m, 1H, H-30), 6.38–6.43 (m, 1H, H-10), 7.13–7.96 (m, 13H, arom.), 8.49 (m, 3H,
C2-H and arom.), 11.74 (s. br., 1H, OH). 13C-NMR (DMSO-d6) d, 21.08 (2 CH3),
25.33 (CH2), 38.31 (C-20), 63.95 (C-50), 74.95 (C-30), 82.10 (C-40), 86.30 (C-10),
99.70 (C-5), 123.89–135.71 (C-arom.), 143.76, 143.82 and 143.93 (C-arom.), 145.95
(C-2), 161.32 (C-4), 165.16, 165.39 and 165.66 (3 ꢀ CO).
5-Benzyl-1-[20-deoxy-3,5-di-O-(4-methylbenzoyl)-a-D-pentofuranosyl)-4-hydroxy-
1
6(1H)pyrimidinone (8b). Yield (63%). H-NMR (DMSO-d6) d 2.36 (s, 3H, CH3),
2.39 (s, 3H, CH3), 2.53 (d, 1H, J ¼ 14.73 Hz, H-20), 3.35 (m, 1H, H-20), 3.65 (s,
2H, CH2), 4.53–4.57 (m, 2H, H-50), 5.15 (m, 1H, H-40), 5.57 (d, J ¼ 5.2 Hz, 1H, H-
30), 6.32 (d, J ¼ 6.0 Hz, 1H, H-10), 7.07–7.27 (m, 7H, arom.), 7.36 (d, 2H, J ¼ 7.8 Hz,
Hz, arom.), 7.63 (d, 2H, J ¼ 7.9 Hz, arom), 7.93 (d, 2H, J ¼ 7.8 Hz, arom.), 8.43 (s,
1H, C2-H), 11.62 (s., br., 1H, OH). 13C-NMR (DMSO-d6) d 21.08 (2 ꢀ CH3), 27.85
(CH2), 38.18 (C-20), 63.85 (C-50), 74.76 (C-30), 84.26 (C-40), 87.79 (C-10), 100.83 (C-5),
125.42–129.29, 140.67 and (C-arom.), 145.46 (C-2), 161.64 (C-4), 164.79 165.20 and
165.38 (3 CO). MS FAB (CHCl3 þ 3-nitrobenzyl alcohol) m=z: 577 (M þ Naþ).
5-Benzyl-1-[20-deoxy-3,5-di-O-(4-methybenzoyl)-b-D-pentofuranozyl]-4-hydroxy-
1
6(1H)pyrimidinone (9b). Yield (31%). H-NMR (DMSO-d6) d 2.36 (s, 3H, CH3),
2.39 (s, 3H, CH3), 2.70–2.75 (m, 1H, H-20), 2.91–2.96 (m, 1H, H-20), 3.65 (s, 2H,
CH2), 4.50–4.55 (m, 1H, H-40), 4.61–4.65 (m, 2H, H-50), 5.52–5.56 (m, 1H, H-30),
6.32–6.36 (m, 1H, H-10), 7.24–7.47 (m, 8H, arom.), 7.63 (d, 2H, J ¼ 7.9 Hz, arom.),
7.81–7.83 (m, 3H, arom.), 8.34 (s, 1H, C2-H), 11.63 (s. br., 1H, OH). 13C-NMR
(DMSO-d6) d 21.08 (2 CH3), 27.85 (CH2), 38.18 (C-20), 63.55 (C-50), 74.75 (C-30),
83.01 (C-40), 85.91 (C-10), 100.92 (C-5), 125.42–129.29 (C-arom.), 140.66 and
143.83 (C-arom.), 145.83 (C-2), 161.84 (C-4), 164.79, 165.20 and 165.28 (3 CO).
General Procedure for the Preparation of 10–12. Compounds 8a,b, 9a,b and 7c
(2.5 mmol) were dissolved in MeOH (25 mL) and then MeONa (0.81 g, 15 mmol) was
added. The reaction mixture was stirred at room temperature for 1 h, NH4Cl
(0.8 g, 15 mmol) was added and the stirring was continued for 1 h. The reaction
mixture was evaporated to dryness and purified on silica gel column using
methanol=diethyl ether as eluentted 10a,b, 11a,b and 12, respectively.
1-(20-Deoxy-a-D-pentofuranosyl)-4-hydroxy-5-(1-naphthylmethyl)-6(1H)-pyri-
midinone (10a). Yield (91%). 1H-NMR (DMSO-d6) d 2.00 (d, 1H, J ¼ 13.9 Hz,

Synthesis of 20-Deoxynucleosides
105
H-20), 2.50–2.61 (m, 1H, H-20), 3.35–3.43 (m, 2H, H-50), 4.05 (s, 2H, CH2), 4.25–4.29
(m, 2H, H-30 and H-40), 5.22 (s. br., 1H, OH), 6.20–6.22 (m, 1H, H-10), 7.29–7.88
(m, 6H, C2-H and arom.) 8.34–8.41 (m, 2H, arom.). 13C-NMR (DMSO-d6)
d 25.77 (CH2), 40.78 (C-20), 60.67 (C-50), 70, 76 (C-30), 86.41 (C-40), 89.89 (C-10),
98.15 (C-5), 124.22, 125.22, 125.33, 125.44, 125.54, 125.87, 128.22, 131.90, 133.21
and 136.48 (C-arom.), 146.34 (C-2), 161.68 (C-4), 166.27 (CO). MS FAB
(CHCl3 þ 3-nitrobenzyl alcohol) m=z: 391 (Mþ þ Na).
1-(20-Deoxy-b-D-pentofuranosyl)-4-hydroxy-5-(1-naphthylmethyl)-6(1H)-pyri-
1
midinone (11a). Yield (86%); H-NMR (DMSO-d6) d 2.29 (m, 1H, H-20), 2.35 (m,
1H, H-20), 3.63 (m, 2H, H-50), 3.85–3.87 (m, 1H, H-40), 4.06 (s, 2H, CH2), 4.31 (m,
1H, H-30), 6.25–6.28 (m, 1H, H-10), 7.25–7.90 (m, 6H, C2-H and arom.), 8.39 (d, 1H,
J ¼ 5.3 Hz, arom.), 8.53 (d, 1H, J ¼ 7.6 Hz, arom.). 13C-NMR (DMSO-d6) d 25.74
(CH2), 41.07 (C-20), 60.85 (C-50), 69.94 (C-30), 84.57 (C-40), 87.67 (C-10), 98.51 (C-
5), 124.11, 125.24, 125.36, 125.57, 128.24, 131.84, 133.21 and 136.16 (C-arom.),
146.21 (C-2), 161.52 (C-4), 165.92 (CO). MS FAB (CHCl3 þ 3-nitrobenzyl alcohol)
m=z: 391 (Mþ þ Na).
5-Benzyl-1-(20-deoxy-a-D-pentofuranosyl)-4-hydroxy-6(1H)-pyrimidinone (10b).
Yield (91%). 1H-NMR (DMSO-d6) d 1.96 (d, 1H, J ¼ 13Hz, H-20), 2.54 (m, 1H, H-20),
3.55–3.59 (m, 2H, H-50), 3.60–3.64 (m, 2H, CH2), 4.24–4.28 (m, 2H, H-30 and H-40),
5.35 (s. br., 2H, 2 OH), 6.23–6.27 (m, 1H, H-10), 7.06–7.26 (m, 5H, arom.), 8.27 (s,
13
1H, C2-H). C-NMR (DMSO-d6) d 28.52 (CH2), 41.11 (C-20), 61.67 (C-50), 70.76
(C-30), 86.12 (C-40), 89.70 (C-10), 99.22 (C-5), 125.19, 127.74, 128.30, 129.22 and
141.81 (C-arom.), 146.11 (C-2), 161.62 (C-4), 166.62 (CO). MS FAB (CHCl3 þ 3-nitro-
benzyl alcohol) m=z: 341 (MþþNa).
5-Benzyl-1-(20-deoxy-b-D-pentofuranosyl)-4-hydroxy-6(1H)-pyrimidinone (11b).
1
Yield (88%). H-NMR (DMSO-d6) d 2.00–2.13 (m, 1H, H-20), 2.21–2.25 (m, 1H,
H-20), 3.43–3.61 (m, 4H, CH2 and H-50), 3.85–3.91 (m, 1H, H-40), 4.28–4.31 (m,
1H, H-30), 5.26–5.36 (m, 2H, 2 OH), 6.23–6.28 (m, 1H, H-10), 7.10–7.23 (m, 5H,
13
arom.), 8.43 (s, 1H, 1H, C2-H). C-NMR (DMSO-d6) d 28.53 (CH2), 41.04 (C-20),
60.98, (C-50), 70.10 (C-30), 84.39 (C-40), 87.63 (C-10), 99.58 (C-5), 125.33, 127.83,
128.29 and 141.51 (C-arom.), 145.99 (C-2), 161.51 (C-4), 166.25 (CO). MS FAB
(CHCl3 þ 3-nitrobenzyl alcohol) m=z: 341 (Mþ þ Na).
1-(20-Deoxy-a-D-pentofuranosyl)-4-hydroxy-5-phenyl-6(1H)-pyrimidinone (13a).
1
Yield (54%). H-NMR (DMSO-d6) d, 2.09 (d, 1H, J ¼ 14.2 Hz, H-20), 2.59 (m, 1H,
H-20), 3.38–3.54 (m, 2H, H-50), 4.25–4.35 (m, 2H, H-30 and H-40), 6.19 (d, 1H,
J ¼ 6.6 Hz, H-10), 7.15–7.51 (m, 5H, arom.), 8.37 (s, 1H, C2-H). 13C-NMR
(DMSO-d6) d 40.72 (C-20), 61.69 (C-50), 70.76 (C-30), 87.08 (C-40), 90.18 (C-10),
100.63 (C-5), 125.85, 127.05, 130.36 and 133.20 (C-arom.), 146.58 (C-2), 160.49
(C-4), 165.50 (CO). MS FAB (CHCl3 þ 3-nitrobenzyl alcohol) m=z: 327 (M þ Naþ).
1-(20-Deoxy-b-D-pentofuranosyl)-4-hydroxy-5-phenyl-6(1H)-pyrimidinone (13b).
1
Yield (26%). H-NMR (DMSO-d6) d, 2.15–2.28 (m, 1H, H-20), 2.30–2.35 (m, 1H,
H-20), 3.55–3.70 (m, 2H, H-50), 3.87–3.90 (m, 1H, H-40), 4.28 (m, 1H, H-30), 6.25

106
Khattab, Abdel Megied, and Pedersen
(t, 1H, J ¼ 6.2 Hz, H-10), 7.16–7.50 (m, 5H, arom.), 8.59 (s, 1H, C2-H). 13C-NMR
(DMSO-d6) d 41.13 (C-20), 60.77 (C-50), 69.83 (C-30), 85.04 (C-40), 87.80 (C-10),
100.85 (C-5), 125.99, 127.10, 130.01, 133.01 (C-arom.), 146.56 (C-2), 160.34 (C-4),
163.86 (CO). MS FAB (CHCl3 þ 3-nitrobenzyl alcohol) m=z: 305 (M þ Hþ).
ACKNOWLEDGMENTS
DANIDA and the Danish Ministry of Foreign Affairs are gratefully acknowl-
edged for financial support through the project ‘‘Development of New Drugs
Against Hepatitis’’ at Monoufiya University.
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Received May 7, 2002
Accepted November 13, 2002