Referenced in: none

Automatically associated channels: Kv12.1

Title: Stereoselective synthesis of trans-threo-trans-oligopyrrolidines: potential agents for RNA cleavage.

Authors: Hans-Dieter Arndt, Rüdiger Welz, Sabine Müller, Burkhart Ziemer, Ulrich Koert

Journal, date & volume: , 2004 Aug 20 , 10, 3945-62

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/15317060

Abstract
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.