Synthesis and Anti-HIV Activity of 5-Fluorocytallene: N-Dimethylaminomethylene as a Facilitating Group in Acetylene → Allene Isomerization

The synthesis and biological activity of 5-fluorocytallene (3a) is described. 5-Fluorocytosine (4) was alkylated with 1-benzoyloxy-4-bromo-2-butyne (5) to give N1-(4-benzoyloxy-2-butyn-1-yl)-5-fluorocytosine (6). Debenzoylation led to N1-(4-hydroxy-2-butyn-1-yl)-5-fluorocytosine (7a). The latter compound was transformed to the N4-dimethylaminomethylene derivative 8 which was isomerized in situ to the corresponding allene 9. Deprotection afforded 5-fluorocytallene (3a). Compound 3a suppressed the infectivity and replication of both laboratory and primary HIV-1 strains in vitro at nontoxic concentrations.