Preparation of macrocyclic 15N-labelled oligoaminodeoxysaccharides as probes for RNA-binding

Abstract

Two macrocyclic aminoglycosides were prepared from a 1,4-butanediol linked 2-deoxy-L-rhamnal which was O-allylated at the 4- and 4′-positions via the precursor allyl 3,4-di-O-acetyl-2,6-dideoxy-α-L-arabino-hexoside employing olefin metathesis and ring closing metathesis in a sequential manner. The macrocycles were ¹⁵N-labelled at all four amino groups in order to study interactions with regulatory RNA structures in solution by NMR spectroscopy. A key step for the introduction of the ¹⁵N-label was a reductive amination step using commercially available ¹⁵NH₄OAc. The reductive amination proceeds with excellent stereocontrol. As a by-product the unusual acyclic amino nitrile was isolated which originated from intramolecular imine formation followed by cyanide addition to the intermediate CN double bond.