论文信息 - Synthesis of Oligodeoxynucleoside Phosphoro-Monothioates and Phosphorodithioates by a Phosphotriester Method

Synthesis of Oligodeoxynucleoside Phosphoro-Monothioates and Phosphorodithioates by a Phosphotriester Method

Abstract A phosphotriester method for the synthesis of dithymidine phosphoromonothoates and phosphorodithioates with new S-protecting groups has been investigated. Four of the S-protecting groups possesed catalytic activity, however side reactions occurred during deprotection. The best S-protecting group was 4-chloro-2-nitlobenzyl which could be removed with a minimum of side reactions (0.3 %). The coupling reagent PyFNOP (14) gave protected dithymidine phosphoromonothioate in 96 % yield after 15 min coupling. Furthermore PyFNOP chemoselectively activates oxygen in nucleoside phosphorodithioate monomers 9 and can be used for the synthesis of oligodeoxynucleoside phosphorodithioates with mixed base sequences.

J. Kehler | O. Dahl | A. Püschl

[1] J. H. Boom,et al. CF3-NO2-PyBOP1: A new and highly efficient coupling reagent for N-methyl amino acids , 1995 .

[2] J. C. Martin,et al. Current concepts in antisense drug design. , 1993, Journal of medicinal chemistry.

[3] M. Caruthers,et al. Phosphorodithioate DNA as a potential therapeutic drug. , 1993, Science.

[4] J. Tonkinson,et al. Phosphorothioate oligodeoxynucleotides--anti-sense inhibitors of gene expression? , 1991, Pharmacology & therapeutics.

[5] K. Miura,et al. Nucleosides and nucleotides. VI. Preparation of diribonucleoside monophosphates containing 4-thiouridine. , 1973, Journal of biochemistry.