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Synthesis of (2′ S )‐ and (2′ R )‐2′‐Deoxy‐2′‐[(2‐methoxyethoxy)amino] Pyrimidine Nucleosides and Oligonucleotides
Author(s) -
Zatsepin Timofei S.,
Ivanova Yulia M.,
Oretskaya Tatiana S.
Publication year - 2004
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.200490114
Subject(s) - chemistry , oligonucleotide , pyrimidine , nucleotide , nuclease , stereochemistry , dna , nucleic acid , rna , nucleophile , duplex (building) , deoxyribonucleotide , intramolecular force , oligonucleotide synthesis , combinatorial chemistry , biochemistry , catalysis , gene
Syntheses of specified 2′‐modified nucleosides were achieved: a ) via oximation of the 5′,3′‐blocked 2′‐oxocytidine, followed by reduction, or b ) by intramolecular nucleophilic addition of 3′‐(2‐methoxyethoxy)carbamate to the 2′‐position with opening of O 2 ,2′‐anhydrouridine. For the first time, 3′‐phosphoroamidites of these 2′‐modified nucleosides were successfully incorporated into oligonucleotides by solid‐phase synthesis. Incorporation of 2′‐modified nucleotides into oligodeoxyribonucleotides had a negative effect on the duplex T m values with the DNA or RNA complements. Nevertheless, modified nucleotides have shown good target recognition; the ( S )‐isomer binds preferably to RNA and the ( R )‐isomer to DNA. Both modified nucleosides significantly increased nuclease resistance of the oligodeoxyribonucleotides.