Assessment of 4-nitrogenated benzyloxymethyl groups for 2'-hydroxyl protection in solid-phase RNA synthesis.
The search for a 2'-OH protecting group that would impart ribonucleoside phosphoramidites with coupling kinetics and coupling efficiencies comparable to those of deoxyribonucleoside phosphoramidites led to an assessment of 2'-O-(4-nitrogenated benzyloxy)methyl groups through solid-phase RNA synthesis using phosphoramidites 2a-d, 12a, and 14a. These phosphoramidites exhibited rapid and efficient coupling properties. Particularly noteworthy is the cleavage of the 2'-O-[4-(N-methylamino)benzyloxy]methyl groups in 0.1 M AcOH, which led to U19dT within 15 min at 90 degrees C. [reaction: see text]
Cieślak
Jacek
J
Division of Therapeutic Proteins, Center for Drug Evaluation and Research, Food and Drug Administration, 8800 Rockville Pike, Bethesda, Maryland 20892, USA.
Kauffman
Jon S
JS
Kolodziejski
Michelle J
MJ
Lloyd
John R
JR
Beaucage
Serge L
SL
D001593:Benzyl Compounds / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D007202:Indicators and Reagents; D007700:Kinetics; D008745:Methylation; D009574:Nitro Compounds / Q000737:chemistry; D012313:RNA / Q000138:chemical synthesis*; D013936:Thymidine / Q000737:chemistry; D014529:Uridine / Q000737:chemistry
D001593:Benzyl Compounds; D007202:Indicators and Reagents; D009574:Nitro Compounds; D012313:RNA; D013936:Thymidine; D014529:Uridine