with ammonia to afford the product ( 82 ) from replacement of fluorine.
Reaction of this intermediate with ammonia under more strenuous
conditions replaces chlorine ( 83 ). Treatment 83 with fluoride ion
removes the silyl protecting group to afford the reverse transcriptase inhibi-
toramdoxovir( 84 ).^12
The surrogate sugar moiety in the antiviralomaciclovir( 90 ) like that in
acyclovir, consists of an open-chain alcohol. The presence of two hydroxyl
groups more closely mimics the structure of a sugar than does the side
chain in the latter. This agent shows good activity against varicela
zoster, the cause of chicken pox and shingles. The scheme for preparing
this compound differs from the preceding example in that the pendant
group is attached via a Michael reaction. Thus reaction of the purine
( 85 ) with exomethylene glutarate ( 86 ) in the presence of base leads to
conjugate addition of purine nitrogen to the double bond ( 87 ). The carbox-
ylates are next reduced to the corresponding alcohols by means of boro-
hydride to afford 88 as a mixture of enatiomers. Reaction with ammonia
then replaces chlorine on the purine by nitrogen to afford the diamine
( 89 ). This intermediate is then treated with the enzyme adenosine deami-
nase immobilized on a solid support. The enzyme preferentially reacts
with the isomer in which the stereochemistry of the secondary hydroxyl
group more closely resembles that in the furanoside in a natural nucleoside
converting the amine at the 4 position to a hydroxyl group. Separation of
that from unreacted starting material affords 90.^13
N
N NHNClH 2 N+85CO 2 HCH 3 O 2 C86NaOH N
N NNClH 2 NCO 2 HCH 3 O 2 C
87LiBH 4 N
N NNClH 2 NOHHO
88N
N NNNH 2H 2 NOHHO89EnzymeN
N NNOHH 2 NOHHO
90- COMPOUNDS WITH FIVE-MEMBERED RINGS FUSED TO SIX-MEMBERED RINGS 199