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.
Institut für Chemie der Humboldt-Universität zu Berlin, Brook-Taylor-Strasse 2, 12489 Berlin, Germany.
Hans-Dieter
HD
Arndt
Rüdiger
R
Welz
Sabine
S
Müller
Burkhart
B
Ziemer
Ulrich
U
Koert
D003460:Crystallization; D018360:Crystallography, X-Ray; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D008968:Molecular Conformation; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D012313:RNA / Q000737:chemistry* / Q000187:drug effects* / Q000502:physiology; D016337:RNA, Catalytic / Q000737:chemistry; D013237:Stereoisomerism; D013696:Temperature
D011759:Pyrrolidines; D016337:RNA, Catalytic; D012313:RNA