Scalable Multistep One-Pot Synthesis of Natural and Modified Nucleoside Triphosphates
Year: 2025
Type: article
Abstract: Polymerases are among the most powerful tools in the molecular biology toolbox; however, access to large quantities of chemically modified nucleoside triphosphates for diverse applications remains hindered by the need for purification by high-performance liquid chromatography (HPLC). Here, we describe a scalable approach to modified nucleoside triphosphates that proceeds through a P(III)-P(V) mixed anhydride intermediate obtained from the coupling of a P(III) nucleoside phosphoramidite and a P(V) pyrene pyrophosphate reagent. The synthetic strategy allows the coupling, oxidation, and deprotection steps to proceed as stepwise transformations in a single one-pot reaction. The fully protected nucleoside triphosphates are purified by silica gel chromatography and converted to their desired compounds on scales exceeding those achievable by conventional strategies. The power of this approach is demonstrated through the synthesis of several natural and modified nucleoside triphosphates using protocols that are efficient and straightforward to perform.
Source: The Journal of Organic Chemistry
Authors: Sergei Negria, Yinglong Jia, Noah A. Setterholm, Bhawna Barpuzary, John C. Chaput
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funder: University of California, Irvine
OpenAlex ID: W4409705022