Ethynyl Side Chain Hydration during Synthesis and Workup of “Clickable” Oligonucleotides: Bypassing Acetyl Group Formation by Triisopropylsilyl Protection

• Published in: Journal of organic chemistry Vol. 78; no. 22; pp. 11271 - 11282
• Main Authors: Ingale, Sachin A, Mei, Hui, Leonard, Peter, Seela, Frank
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 15.11.2013; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Cross-Linking Reagents - chemical synthesis; Cross-Linking Reagents - chemistry; Guanine - analogs & derivatives; Guanine - chemistry; Hydrolysis; Molecular Conformation; Oligonucleotides - chemical synthesis; Oligonucleotides - chemistry; Physical Sciences; Pyrimidines - chemistry; Science & Technology; Silanes - chemistry; Water - chemistry; MAJOR GROOVE; FUNCTIONALIZATION; CYCLOADDITION; DUPLEX STABILITY; NUCLEOSIDES; IN-VIVO; TERMINAL ALKYNES; DNA-SYNTHESIS; AZIDE; NUCLEIC-ACIDS
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo401780u

Clickable oligonucleotides with ethynyl residues in the 5-position of pyrimidines (ethdC and ethdU) or the 7-position of 7-deazaguanine (ethc7Gd) are hydrated during solid-phase oligonucleotide synthesis and workup conditions. The side products were identified as acetyl derivatives by MALDI-TOF mass spectra of oligonucleotides and by detection of modified nucleosides after enzymatic phosphodiester hydrolysis. Ethynyl → acetyl group conversion was also studied on ethynylated nucleosides under acidic and basic conditions. It could be shown that side chain conversion depends on the nucleobase structure. Triisopropylsilyl residues were introduced to protect ethynyl residues from hydration. Pure, acetyl group free oligonucleotides were isolated after desilylation in all cases.