Alkylation of 9-substituted guanine derivatives with [alpha],[omega]-dihaloalkanes

Reactions of 9-substituted guanine derivatives with NaH/1,2-dibromoethane, 1,3-dibromopropane, or 1,4-dibromobutane at room temperature resulted in the isolation of tricyclic 1,N2-(1,2-ethano)guanine, 1,N2-(1,3-propano)guanine, or 1,N2-(1,4-butano)guanine products, respectively. O6-Haloalkyl and N1-haloalkyl products were obtained following the use of NaH/1,4-dibromobutane, higher [alpha],[omega]-dibromoalkanes, or [alpha]-bromo-[omega]-fluoroalkanes. Raising the reaction temperature opened the synthetic way toward O6-guanine-alkylene-O6-guanine and N1-guanine-alkylene-O6-guanine symmetric and unsymmetric dimers. Protection of the substrate amine group to form N,N-dialkylformamidine provided the access to N1-guanine-alkylene-N1-guanine dimers.