Study of the Staudinger Reaction and Reveal of Key Factors Affecting the Efficacy of Automatic Synthesis of Phosphoryl Guanidinic Oligonucleotide Analogs

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 compone...

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Bibliographic Details
Published in:Russian journal of bioorganic chemistry 2019-11, Vol.45 (6), p.699-708
Main Authors: Bazhenov, M. A., Shernyukov, A. V., Kupryushkin, M. S., Pyshnyi, D. V.
Format: Article
Language:English
Subjects:
Biochemistry
Biomedical and Life Sciences
Biomedicine
Bioorganic Chemistry
Chemical synthesis
Life Sciences
Oligonucleotides
Organic Chemistry
Oxidation
Solid phases
Stability
Transformations
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Summary: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.
ISSN:1068-1620
1608-330X
DOI:10.1134/S1068162019060074