Observation and elimination of N-acetylation of oligonucleotides prepared using fast-deprotecting phosphoramidites and ultra-mild deprotection.
Commercially available 'fast-deprotecting' phosphoramidites are useful for synthesizing oligonucleotides containing alkali-sensitive nucleotides. However, N-acetylated oligonucleotides were observed during solid-phase synthesis using 'fast-deprotecting' phosphoramidites in conjunction with K2CO3/MeOH ('ultra-mild') deprotection. Transamidation was localized at deoxyguanosine, which is protected as its isopropylphenoxyacetyl amide. Substitution of trimethylacetic anhydride for acetic anhydride and appropriate modification of the automated synthesis cycles eliminated this problem.
Zhu
Q
Q
Department of Chemistry, Colorado State University, Fort Collins 80523, USA.
Delaney
M O
MO
Greenberg
M M
MM
D000107:Acetylation; D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry; D002254:Carbonates / Q000737:chemistry; D007202:Indicators and Reagents; D000432:Methanol / Q000737:chemistry; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry*; D009943:Organophosphorus Compounds / Q000737:chemistry*; D011188:Potassium / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization
D000577:Amides; D002254:Carbonates; D007202:Indicators and Reagents; D009841:Oligonucleotides; D009943:Organophosphorus Compounds; C037593:potassium carbonate; D011188:Potassium; D000432:Methanol