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 m7(LNA) G[5']ppp[5']G containing a locked nucleic acid moiety. The required LNA intermediate for the final coupling reaction, m7(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 m7 methylation. The final coupling reaction of m7(LNA) GDP with ImGMP in the presence of zinc chloride as a catalyst affords m7(LNA) G[5']ppp[5']G in 59% yield. © 2021 Wiley Periodicals LLC. Basic Protocol: Synthesis of an LNA-substituted dinucleotide cap analog Support Protocol: Preparation of the tris(tributylammonium) phosphate linker.