Facile Iterative Synthesis of 2,5-Terpyrimidinylenes as Nonpeptidic α-Helical Mimics

A facile iterative synthesis of 2,5-terpyrimidinylenes that are structurally analogous to α-helix mimics is presented. Condensation of amidines with readily prepared α,β-unsaturated α-cyanoketones gives 5-cyano-substituted pyrimidines. Iterative transformation of the 5-cyano group into an amidine allows synthesis of 2,5-terpyrimidinylenes with variable groups at the 4-, 4′-, and 4′′-positions. These compounds are designed to mimic the i, i + 4, and i + 7 sites of an α-helix.