Synthesis and Biological Evaluation of Acyclic Neplanocin Analogues

Acyclic neplanocin analogues were prepared by condensation of adenine or N²-acetylguanine with (E)-l,4-dichlorobut-2-ene and subsequent hydrolysis. The N-9-substituted product 9- [E)-4-hydroxybut-2-enyl]adenine (5) was obtained when adenine was employed as the starting purine, while N²-acetylguanine yielded both the N-7 and N-9 isomers. Cell-culture studies revealed that only the chloro-substituted intermediate 9-[E)-4-chlorobut-2-enyl]adenine (4) exhibited significant cytotoxicity against P-388 mouse lymphoid leukemia cells, while the N-9-substituted guanine analogue 9-[E)-4-hydroxybut-2-enyl]guanine (10) inhibited replication of herpes simplex viruses type 1 and type 2.