biostudies-literatureWojtczak BAFundacja na rzecz Nauki PolskiejNarodowe Centrum NaukiEuropean Regional Development Fund6827-6846https://www.ebi.ac.uk/biostudies/studies/S-EPMC10242767biostudies-literatureUnknown88(11)Chemical modifications of the mRNA cap structure can enhance the stability, translational properties, and half-life of mRNAs, thereby altering the therapeutic properties of synthetic mRNA. However, cap structure modification is challenging because of the instability of the 5'-5'-triphosphate bridge and N7-methylguanosine. The Suzuki-Miyaura cross-coupling reaction between boronic acid and halogen compound is a mild, convenient, and potentially applicable approach for modifying biomolecules. Herein, we describe two methods to synthesize C8-modified cap structures using the Suzuki-Miyaura cross-coupling reaction. Both methods employed phosphorimidazolide chemistry to form the 5',5'-triphosphate bridge. However, in the first method, the introduction of the modification <i>via</i> the Suzuki-MThe Journal of organic chemistrySynthesis and Evaluation of Diguanosine Cap Analogs Modified at the C8-Position by Suzuki-Miyaura Cross-Coupling: Discovery of 7-Methylguanosine-Based Molecular Rotors.PMC10242767POIR.04.04.00-00-20A2/16UMO-2016/21/N/ST4/03750POIR.04.04.00-00- 20A2/16UMO-2017/26/D/ST5/00901Surynt PWojtczak ABednarczyk MWojtczak BASikorski PJJemielity JKowalska JfalseSynthesis and Evaluation of Diguanosine Cap Analogs Modified at the C8-Position by Suzuki-Miyaura Cross-Coupling: Discovery of 7-Methylguanosine-Based Molecular Rotors.Chemical modifications of the mRNA cap structure can enhance the stability, translational properties, and half-life of mRNAs, thereby altering the therapeutic properties of synthetic mRNA. However, cap structure modification is challenging because of the instability of the 5'-5'-triphosphate bridge and N7-methylguanosine. The Suzuki-Miyaura cross-coupling reaction between boronic acid and halogen compound is a mild, convenient, and potentially applicable approach for modifying biomolecules. Herein, we describe two methods to synthesize C8-modified cap structures using the Suzuki-Miyaura cross-coupling reaction. Both methods employed phosphorimidazolide chemistry to form the 5',5'-triphosphate bridge. However, in the first method, the introduction of the modification <i>via</i> the Suzuki-M2023-01-01T00:00:00Z2023 Jun2025-05-29T20:24:16.239Z2025-05-29T20:24:16.239ZS-EPMC102427673720910210.1021/acs.joc.3c00126