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Stereoselective Synthesis of trans ‐ threo ‐ trans ‐Oligopyrrolidines: Potential Agents for RNA Cleavage
Author(s) -
Arndt HansDieter,
Welz Rüdiger,
Müller Sabine,
Ziemer Burkhart,
Koert Ulrich
Publication year - 2004
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200400181
Subject(s) - pyrrolidine , cleavage (geology) , chemistry , stereochemistry , rna , polyamine , convergent synthesis , stereoselectivity , biochemistry , biology , catalysis , paleontology , fracture (geology) , gene
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 m M concentrations under physiologically relevant conditions.