Allyl Protection in the Synthesis of Oligodeoxyribonucleotide Phosphorothioates

Abstract

Allyl and allyloxycarbonyl groups serve as useful protectors for internucleotide linkages and nucleoside bases, respectively, in the synthesis of partially or fully phosphorothioate-modified oligodeoxyribonucleotides.

Potent inhibition of HIV replication by certain oligodeoxyribonucleotide phosphorothioates¹) has motivated chemists to develop efficient syntheses.²) Although mild deprotection conditions are crucial for attaining high synthetic efficiency, existing methods do not satisfy this requirement.^1–3) The procedures usually use acyl protectors for nucleoside bases as the strong basic conditions needed for their removal often causes hydrolytic cleavage of the phosphate and phosphorothioate linkages. We describe here a convenient synthesis of phosphorothioate-incorporated oligodeoxyribonucleotides. The key procedure is the allylic protection aided by organotransition metal chemistry which can be used safely.for sulfur-containing compounds.⁴)