| Summary: | 碩士 === 國防醫學院 === 藥學研究所 === 83 === A mimicry analog of anti conformation acyclic pyrimidine
nucleosides,8-amino-2,2-bis(hydroxymethyl)-9-methyl-1H,2H, 4H-
pyrimido[1,6-c][1,3]oxazin-6-one,was synthesized in our
laboratory and showed a slight activity against HIV(IC50=35mM).
In order to optimizee the anti-HIV activity and gain a broad
spectrum of structure-activity relationship of these anti
conformation acyclic pyrimidine nucleosides , halogenation on
the C-9 position and deletion of one of bishydroxylmethyl group
of the reported active compound have been accomplished. The
synthesis was performed by treating 6-mdthyl-2,4-dimethoxy-
pyrimidine with 1,3-bis(benzyloxy)-2-propanone or
benzyloxyacet- aldehyde to give 6-[2-(1,3-dibenzyyloxy)-2-
hydroxy)propyl]methyl- 2,4-dimethoxypyrimidine and 6-[2-(1-
benzyloxy-2-hydroxy)ethyl]- methyl-2,4-dimethoxypyrimidine,
respecticely.The hydroxyl group of these two intermediates was
converted to methylthiomethyl ether derivative by reacting with
acetic anhydride in DMSO. Treatment of the ether derivatives
with iodine in dry tetra- hydrofuran at room temperature
furnished the cyclized product, 2,2-bis(bebzyloxymethyl-8-
methoxyl-1H,2H,4H-pyrimido[1,6-c] [1,3]oxazin-6-one, and
2-benzyloxymethyl-8-methoxyl-1H,2H,4H- pyrimido[1,6-c][1,3
]oxazin-6-one, respectively. The 8-methoxyl group was converted
to an amino group by using methanolic ammonia under high
pressure, followed by debenzylation with boron trichloride to
give 8-amino-2,2- bis(hydroxylmethyl)-1H,2H,4H- pyrimido[1,6-
c][1,3]oxazin-6-one,and 8-amino-2-hydroxylmethyl- 1H,2H,4H-
pyrimido[1,6-c][1,3]oxazin-6-one, respective. Halogen- ation of
8-amino-2,2-bis(hydroxylmethyl)-1H,2H,4H-pyrimido[1,6-c] [1,3
]oxazin-6-one and 8-amino-2-hydroxyl-methyl-1H,2H,4H-pyrimido
[1,6-c][1,3]oxazin-6-one provided the target compounds.All the
target compounds will send for anti-HIV and anti-cancer
activity.
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