An Efficient Reagent for the Phosphorylation of Deoxyribonucleosides

ORGANIC LETTERS

An Efficient Reagent for the Phosphorylation of Deoxyribonucleosides, DNA Oligonucleotides, and Their Thermolytic Analogues

2005 Vol. 7, No. 19 4201-4204

Cristina Ausı´n, Andrzej Grajkowski, Jacek Cies´lak, and Serge L. Beaucage* DiVision of Therapeutic Proteins, Center for Drug EValuation and Research, Food and Drug Administration, 8800 RockVille Pike, Bethesda, Maryland 20892 [email protected] Received July 11, 2005

ABSTRACT

The phosphoramidite 11 was prepared in three steps from methyl 2-mercaptoacetate and demonstrated efficiency in the synthesis of conventional 5′-/3′-phosphate/thiophosphate monoester derivatives of 2′-deoxyribonucleosides and DNA oligonucleotides. Moreover, the use of 11 has enabled the preparation of the dinucleoside phosphorothioate analogue 26 in high yields (>95%) with minimal cleavage (