Versatile synthesis of amino acid functionalized nucleosides via a domino carboxamidation reaction

Abstract

SummaryFunctionalized oligonucleotides have recently gained increased attention for incorporation in modified nucleic acid structures both for the design of aptamers with enhanced binding properties as well as the construction of catalytic DNA and RNA. As a shortcut alternative to the incorporation of multiple modified residues, each bearing one extra functional group, we present here a straightforward method for direct linking of functionalized amino acids to the nucleoside base, thus equipping the nucleoside with two extra functionalities at once. As a proof of principle, we have introduced three amino acids with functional groups frequently used as key-intermediates in DNA- and RNAzymes via an efficient and straightforward domino carboxamidation reaction.

One-pot construction of carbohydrate scaffolds mediated by metal catalysts

“…55 Synthesis of amino acid functionalised uracil nucleosides (127) was reported by Gheerardijn et al by a Pd(0)-catalysed domino carboxamidation reaction of uracil nucleosides (126) using amino acid esters and carbon monoxide under pressure at 70 C (Scheme 39). 56 Pd 2 (dba) 3 was utilised by Grigg et al to catalyse 3C reactions of purine/thymidine/uridine-based allene, aryl/heteroaryl iodide and adamantyl amine or other amines for generation of trisubstituted Z-alkenes bearing the corresponding nucleoside skeleton. They further developed a Pd(0)mediated MC-reaction protocol based on a 1,3,5,7-tetrakis(4iodophenyl)adamantane, purine derived allene and different amines for generation of a tetrakis adamantane skeleton.…”