1. Optimized Method for the Synthesis of Alkyne-Modified 2′-Deoxynucleoside Triphosphates.
- Author
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Kuznetsova, Viktoriya E., Shershov, Valeriy E., Shtylev, Georgiy F., Shishkin, Ivan Yu., Butvilovskaya, Veronika I., Stomakhin, Andrey A., Grechishnikova, Irina V., Zasedateleva, Olga A., and Chudinov, Alexander V.
- Subjects
NUCLEOSIDE synthesis ,COUPLING reactions (Chemistry) ,DNA polymerases ,DNA primers ,SONOGASHIRA reaction - Abstract
A general approach is presented for synthesizing alkyne-modified nucleoside triphosphates via the Sonogashira cross-coupling reaction of unprotected halogenated 2ʹ-deoxynucleoside, followed by monophosphorylation and the reaction of the corresponding phosphoromorpholidate with tributylammonium pyrophosphate. A highly efficient approach for the milligram-scale synthesis of base-modified nucleoside triphosphates with an amino acid-like side chain was developed. The present chemical method outweighs the other reported methods of a base-modified nucleoside triphosphates synthesis in terms of it being a protection-free strategy, the shortening of reaction steps, and increased yields (about 70%). The resulting 8-alkynylated dATP was tested as a substrate for DNA polymerases in a primer extension reaction. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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