biostudies-literatureFeatherston ALTakeda Pharmaceuticals International Co.National Institute of General Medical SciencesNIGMS NIH HHS702-707https://www.ebi.ac.uk/biostudies/studies/S-EPMC7961808biostudies-literatureUnknown371(6530)We report the catalytic stereocontrolled synthesis of dinucleotides. We have demonstrated, for the first time to our knowledge, that chiral phosphoric acid (CPA) catalysts control the formation of stereogenic phosphorous centers during phosphoramidite transfer. Unprecedented levels of diastereodivergence have also been demonstrated, enabling access to either phosphite diastereomer. Two different CPA scaffolds have proven to be essential for achieving stereodivergence: peptide-embedded phosphothreonine-derived CPAs, which reinforce and amplify the inherent substrate preference, and C2-symmetric BINOL-derived CPAs, which completely overturn this stereochemical preference. The presently reported catalytic method does not require stoichiometric activators or chiral auxiliaries and enables asymScience (New York, N.Y.)Catalytic asymmetric and stereodivergent oligonucleotide synthesis.PMC7961808R35 GM132092Engl ODFeatherston ALKwon YPompeo MMLeahy DKMiller SJfalseCatalytic asymmetric and stereodivergent oligonucleotide synthesis.We report the catalytic stereocontrolled synthesis of dinucleotides. We have demonstrated, for the first time to our knowledge, that chiral phosphoric acid (CPA) catalysts control the formation of stereogenic phosphorous centers during phosphoramidite transfer. Unprecedented levels of diastereodivergence have also been demonstrated, enabling access to either phosphite diastereomer. Two different CPA scaffolds have proven to be essential for achieving stereodivergence: peptide-embedded phosphothreonine-derived CPAs, which reinforce and amplify the inherent substrate preference, and C2-symmetric BINOL-derived CPAs, which completely overturn this stereochemical preference. The presently reported catalytic method does not require stoichiometric activators or chiral auxiliaries and enables asym2021-01-01T00:00:00Z2021 Feb2025-04-04T19:54:01.122Z2025-04-04T19:54:01.122ZS-EPMC79618083357420810.1126/science.abf4359