202
M.-H. Choi et al.
dine bases with the bromide
6. The bromide 6 was
ACKNOWLEDGEMENTS
prepared from ketone
sequence in a good overall yield, as shown in Scheme 1.
1,3-Dibenzyloxy-2-propanone ( ) was prepared as Women's University Research Grants 2007.
2 via an efficient six-step
This research was supported by the Sookmyung
2
per the literature method previously reported by us in
literature (Choi and Kim, 2003). 1,2-Nucleophilic addi-
REFERENCES
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generated from ethyl acetate by LDA, gave the
hydroxy ester in an 84% yield. The fluorination of
the -hydroxy ester was successively achieved with
(diethylamino)sulfur trifluoride (DAST) at -78oC in 58%
yield. Fluorinated ester was then directly subjected
2 with the enolate,
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β-
3
β
3
4
to reduction with lithium aluminium hydride in
tetrahydrofuran to give the desired fluorinated alcohol
5
in excellent yield (93%). Unexpectedly, fluorine
atom, positioned to the carbonyl group, was found to
be quite stable to this basic reduction condition. Due
to the possibility of dehydrofluorination of under
basic condition, we had initially adopted an indirect
and lengthy route bypassing the fluorinated ester
Conversion of primary alcohol to the bromide was
accomplished by treatment with -bromosuccinimide
(NBS) and triphenylphosphine in 82% yield. The
β
4
4.
5
6
N
coupling of the bromide
6 with adenine in the pre-
sence of cesium carbonate provided the desired N9-
alkylated adenine 7a in a 70% yield. Deprotection of
the benzyl groups using boron trichloride in DCM
gave 9-[3-fluoro-4-hydroxy-3-hydroxymethyl butyl]
adenine (1a) in 68% yield. The pyrimidine compounds
were prepared in the same lines as used with adenine.
Direct alkylation of pyrimidines to bromide
6 in DMF
with cesium carbonate as a basic catalyst gave the
desired N1-alkylated products. Deprotection of the
benzyl protecting groups using boron trichloride gave
the pyrimidines analogues of 3’-fluoropenciclovir (1b
-
1f). Finally, 5-iodouracil derivative 1g was prepared
from uracil analogue 1d by oxidative iodination. The
structures of final products 1a
-
g
were confirmed by
UV, mass, IR, and H-NMR spectra. The synthesized
nucleosides 1a were evaluated for their antiviral
1
Pankiewicz, K. W., Fluorinated nucleoside. Carbohydr. Res.,
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-g
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to the internal hydrogen bonding formation between
fluorine and hydroxyl group, resulting in the unfavorable
conformation for phosphorylation by kinase.
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purine and pyrimidine bases, and evaluated their anti-
viral activity against poliovirus, HSV-1, HSV-2 and HIV.
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by 1H-NMR spectroscopy. Nucleosides Nucleotides, 18,
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It is also notable that direct reduction of
β-fluoroester to
the corresponding 3-fluoroalcohol provided the easy and
new synthetic entry to 3’-fluoropenciclovir analogues.