Highly efficient solid phase synthesis of oligonucleotide analogs containing phosphorodithioate linkages.
A triester method for the synthesis of deoxynucleoside phosphorodithioate dimers is described. The phosphorodithioate linkage is introduced using a new dithiophosphorylating reagent DPSE-SP(S)Cl(2)where DPSE = 2-diphenylmethylsilylethyl. This group is removed quickly using tetra-butylammonium fluoride leading to the quantitative formation of phosphorodithioate diesters uncontaminated with the corresponding phosphorothioates. The utility of this group is demonstrated by the synthesis of a penta-decathymidylic acid, [T(PS(2))T(PO(2))](7)T, which contains alternating phosphorodithioate/phosphate diester internucleotide linkages.
Capaldi
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DC
Isis Pharmaceuticals, 2292 Faraday Avenue, Carlsbad, CA 92008, USA.
Cole
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DL
Ravikumar
V T
VT
D004952:Esters / Q000737:chemistry; D007202:Indicators and Reagents; D019906:Nuclear Magnetic Resonance, Biomolecular; D009841:Oligonucleotides / Q000138:chemical synthesis*; D009946:Organothiophosphorus Compounds / Q000737:chemistry; D010710:Phosphates / Q000138:chemical synthesis*
C406743:2-diphenylmethylsilylethyldithiophosphorodichloridate; D004952:Esters; D007202:Indicators and Reagents; D009841:Oligonucleotides; D009946:Organothiophosphorus Compounds; D010710:Phosphates; C406744:pentadecathymidylic acid; C083120:phosphorodithioic acid