Solution-phase synthesis of phosphorothioate oligodeoxynucleosides by the phosphotriester method.
A "phosphorothioate triester method" was investigated for the solution-phase synthesis of phosphorothioate oligonucleosides. Using fully protected 3'-phosphorothiolate thymidine bearing O-cyanoethyl and S-2,4-dichlorobenzyl groups as phosphorothioate protecting groups, decathymidine nonaphosphorothioate was efficiently assembled through a blockwise procedure. Two side reactions occurred during the deprotection steps: breakage of internucleoside linkages (1.8% per linkage) and formation of phosphate diester linkages (0.9%). Substitution of the dichlorobenzyl group by the more labile 4-nitrobenzyl S-protecting group reduced the extent of internucleoside bond breakage by one-half.
Barber
I
I
Laboratoire de Chimie BIo-organique, Université de Montpellier II, France.
Imbach
J L
JL
Rayner
B
B
D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis* / Q000302:isolation & purification; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013873:Thionucleotides / Q000138:chemical synthesis* / Q000302:isolation & purification
D007202:Indicators and Reagents; D009838:Oligodeoxyribonucleotides; D013873:Thionucleotides; C094634:decathymidine nonaphosphorothioate