Synthesis of a novel cyclopropyl phosphonate nucleotide as a phosphate mimic. Issue 55 (18th June 2021)

• Record Type: Journal Article
• Authors: Altenhofer, Erich F.; Lawler, Michael J.; Kumar, Pankaj; Joyce, Leo A.; Fowler-Watters, Matthew; Pei, Tao; Li, Zhen
• Is Part Of: Chemical communications. Volume 57:Issue 55(2021)
• Page Start: 6808
• Page End: 6811
• Publication Date: 2021-06-18
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1039/d1cc02328d
• Languages: English
• ISSNs: 1359-7345

Abstract

Abstract : A novel cyclopropanation has been demonstrated by tuning the electronics of the substrate, allowing for conversion of the highly stable 1, 4-adduct to the desired cyclopropane. Abstract : The inherent in vivo instability of oligonucleotides presents one of many challenges in the development of RNAi-based therapeutics. Chemical modification to the 5′-terminus serves as an existing paradigm which can make phosphorylated antisense strands less prone to degradation by endogenous enzymes. It has been recently shown that installation of 5′-cyclopropyl phosphonate on the terminus of an oligonucleotide results in greater knockdown of a targeted protein when compared to its unmodified phosphate derivative. In this paper we report the synthesis of a 5′-modified uridine.