TY - JOUR

T1 - Study of the Staudinger Reaction and Reveal of Key Factors Affecting the Efficacy of Automatic Synthesis of Phosphoryl Guanidinic Oligonucleotide Analogs

AU - Bazhenov, M. A.

AU - Shernyukov, A. V.

AU - Kupryushkin, M. S.

AU - Pyshnyi, D. V.

N1 - Publisher Copyright: © 2019, Pleiades Publishing, Ltd.

PY - 2019/11/1

Y1 - 2019/11/1

N2 - 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.

AB - 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.

KW - automated oligonucleotide synthesis

KW - modified oligonucleotides

KW - organic azides

KW - phosphoazides

KW - phosphoryl guanidine oligonucleotides (PGO)

KW - phosphoryl guanidines

KW - Staudinger reaction

UR - http://www.scopus.com/inward/record.url?scp=85077854068&partnerID=8YFLogxK

U2 - 10.1134/S1068162019060074

DO - 10.1134/S1068162019060074

M3 - Article

AN - SCOPUS:85077854068

VL - 45

SP - 699

EP - 708

JO - Russian Journal of Bioorganic Chemistry

JF - Russian Journal of Bioorganic Chemistry

SN - 1068-1620

IS - 6

ER -