An Efficient Gram‐Scale Chemical Synthesis of UNA‐Nucleoside‐5′‐O‐Triphosphates

Abstract This unit describes a facile, reliable, and efficient method for the gram‐scale chemical synthesis of unlocked nucleic acid‐ (UNA) nucleoside‐5′‐ O ‐triphosphates such as UNA‐guanosine‐5′‐ O ‐triphosphate (UNA‐GTP), UNA‐adenosine‐5′‐ O ‐triphosphate (UNA‐ATP), UNA‐cytidine‐5′‐ O ‐triphosphate (UNA‐CTP), and UNA‐uridine‐5′‐ O ‐triphosphate (UNA‐UTP), starting from the commercially available corresponding nucleoside‐5′‐ O ‐triphosphate. The present process involves a “one‐pot, two‐step” strategy that utilizes green chemistry principles. The overall reaction involves the oxidation of nucleoside‐5′‐ O ‐triphosphate using sodium periodate under aqueous conditions, followed by reduction using sodium borohydride to furnish the corresponding UNA‐nucleoside‐5′‐ O ‐triphosphate in good yields with high purity (>99.5%). © 2023 Wiley Periodicals LLC. Basic Protocol : Synthesis of UNA‐nucleoside‐5′‐ O ‐triphosphates