Stereoselective Synthesis of trans-threo-trans-Oligopyrrolidines: Potential Agents for RNA Cleavage

The 2,5‐trans‐substituted oligopyrrolidines constitute a promising class of novel RNA‐binding agents as well as potential building blocks for artificial anion channels. A convergent synthesis of terpyrrolidine 1 and pyrrolidino‐THF‐pyrrolidine 2 is reported, relying upon convergent coupling of 2,5‐trans‐pyrrolidinecarboxaldehydes through bridging alkyne units under Felkin–Anh control and subsequent closure of the central ring. After complete deprotection, the free polyamine products were isolated in excellent yield and purity. Crystal structure analyses of a terpyrrolidine and a pyrrolidino‐THF‐pyrrolidine documented their helical privileged conformations. The compounds were then screened for RNA cleavage activity. Unlike the only weakly active simple polyamines, p‐nitrosulfonamide 33 was found to induce cleavage at mM concentrations under physiologically relevant conditions. A promising class of novel RNA‐binding agents has been developed by using bis‐ and terpyrrolidines with 2,5′‐threo‐trans configurations. The compounds such as depicted were synthesized stereoselectively and tested for RNA cleavage.