Post-synthetic modification of oligonucleotides containing 5-trifluoromethylpyrimidine bases

• Published in: Tetrahedron Vol. 74; no. 47; pp. 6854 - 6860
• Main Authors: Ito, Yuta, Matsuo, Misaki, Yamamoto, Kazuki, Yamashita, Wakana, Osawa, Takashi, Hari, Yoshiyuki
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 22.11.2018; Elsevier
• Subjects: 5-Substituted pyrimidine nucleobase; 5-Trifluoromethylpyrimidine nucleobase; Chemistry; Chemistry, Organic; Nucleoside; Oligonucleotide; Physical Sciences; Post-synthetic modification; Science & Technology; 5-Trifluoromethylpyrimidine nucleobase; Nucleoside; Oligonucleotide; 5-Substituted pyrimidine nucleobase; Post-synthetic modification; THERMAL-STABILITY; NUCLEASE-RESISTANCE PROPERTIES; DIELS-ALDER REACTIONS; NUCLEOSIDES; CROSS-LINKING; LINKED NUCLEOTIDES; OLIGODEOXYRIBONUCLEOTIDES; MEDICINAL CHEMISTRY; BIOORTHOGONAL REACTIONS; DNA
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2018.10.006

A practical and operationally simple post-synthetic modification of oligonucleotides containing 5-trifluoromethylpyrimidine bases is described. Trifluoromethyl group was used as a post-synthetic precursor and 5-trifluoromethylpyrimidine bases within oligonucleotides were converted into the corresponding 5-carboxy-, 5-cyano-, 5-amidinyl-, and 5-carbamoyl derivatives by treatment with an alkaline solution and amines. Moreover, post-synthetic treatment of fully protected and controlled pore glass (CPG)-attached oligonucleotides proceeded successfully with the simultaneous removal of all protecting groups, cleavage from CPG, and conversion of the trifluoromethyl group to afford the corresponding modified oligonucleotides. [Display omitted]