Diastereomeric process control in the synthesis of 2'-O-(2-methoxyethyl) oligoribonucleotide phosphorothioates as antisense drugs.
Coupling of 2'-O-methoxyethylsubstituted nucleoside phosphoramidites to 5'-hydroxyl group of a nucleoside or nucleotide on solid support is under stereochemical process control and is independent of scale, concentration, synthesizer, ratio of amidite diastereomers, solid support etc. However, activators and phosphate protecting groups do play a role in influencing the ratio of phosphorothioate diesters obtained by sulfurization of phosphite triesters.
Ravikumar
Vasulinga T
VT
Isis Pharmaceuticals, Carlsbad, California 92008, USA. vravikumar@isisph.com
Cole
Douglas L
DL
D001483:Base Sequence; D015195:Drug Design; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D009943:Organophosphorus Compounds; D010710:Phosphates; D016372:RNA, Antisense / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use*; D013237:Stereoisomerism
D007202:Indicators and Reagents; D009841:Oligonucleotides; D009943:Organophosphorus Compounds; D010710:Phosphates; D016372:RNA, Antisense; C434331:phosphoramidite