Study of the Staudinger Reaction and Reveal of Key Factors Affecting the Efficacy of Automatic Synthesis of Phosphoryl Guanidinic Oligonucleotide Analogs
- Authors: Bazhenov M.A.1, Shernyukov A.V.2,3, Kupryushkin M.S.1, Pyshnyi D.V.1,3
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Affiliations:
- Institute of Chemical Biology and Fundamental Medicine, Russian Academy of Sciences, Siberian Branch
- N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Russian Academy of Sciences, Siberian Branch
- Novosibirsk State University
- Issue: Vol 45, No 6 (2019)
- Pages: 699-708
- Section: Article
- URL: https://journals.rcsi.science/1068-1620/article/view/229304
- DOI: https://doi.org/10.1134/S1068162019060074
- ID: 229304
Cite item
Abstract
In this work, we introduce a novel nuanced analysis of the chemical transformations occurs during the automatic synthesis of phosphoryl guanidine oligonucleotides (PGOs). It was shown on model compounds that the stable form of phosphoryl guanidine afforded by the P(III) atom of the phosphite component oxidation by the corresponding organic azide is the positively charged triester phosphoryl guanidinium fragment. The idea that the presence of such kind of fragments in PGOs, obtained under automatic DNA synthesis conditions, may have an adverse effect on its backbone stability when at the postsynthetic stage PGOs on polymer treated with aqueous basic solutions has been proposed. To overcome this impediment, we suggest before the stage of the desired PGO final deblocking to treat the solid phase with a protected PGO chain fixed with a solution of a strong base in an anhydrous medium. In consequence of this treatment, the transformation of PGO triester form to diester takes place, imparting better stability to the modified chain under deblocking conditions and increasing the yield of the desired oligonucleotide derivatives.
About the authors
M. A. Bazhenov
Institute of Chemical Biology and Fundamental Medicine, Russian Academy of Sciences,Siberian Branch
Email: pyshnyi@niboch.nsc.ru
Russian Federation, Novosibirsk, 630090
A. V. Shernyukov
N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Russian Academy of Sciences, Siberian Branch; Novosibirsk State University
Email: pyshnyi@niboch.nsc.ru
Russian Federation, Novosibirsk, 630090; Novosibirsk, 630090
M. S. Kupryushkin
Institute of Chemical Biology and Fundamental Medicine, Russian Academy of Sciences,Siberian Branch
Email: pyshnyi@niboch.nsc.ru
Russian Federation, Novosibirsk, 630090
D. V. Pyshnyi
Institute of Chemical Biology and Fundamental Medicine, Russian Academy of Sciences,Siberian Branch; Novosibirsk State University
Author for correspondence.
Email: pyshnyi@niboch.nsc.ru
Russian Federation, Novosibirsk, 630090; Novosibirsk, 630090