Chemical Synthesis of a Locked Nucleic Acid–Substituted Dinucleotide Cap Analog

This article describes a reliable and efficient method for synthesis of the dinucleotide cap analog m 7(LNA) G[5′]ppp[5′]G containing a locked nucleic acid moiety. The required LNA intermediate for the final coupling reaction, m 7(LNA) GDP, is prepared in six steps starting from 5′‐DMTr‐ N ‐DMF LNA guanosine. The overall reaction involves removal of DMTr and DMF groups, 5′ monophosphorylation, imidazolide formation, diphosphorylation, and regioselective m 7 methylation. The final coupling reaction of m 7(LNA) GDP with ImGMP in the presence of zinc chloride as a catalyst affords m 7(LNA) G[5′]ppp[5′]G in 59% yield. © 2021 Wiley Periodicals LLC. This article was corrected on 18 July 2022. See the end of the full text for details. Basic Protocol : Synthesis of an LNA‐substituted dinucleotide cap analog Support Protocol : Preparation of the tris(tributylammonium) phosphate linker