Preparation of oligodeoxyribonucleoside phosphorodithioates by a triester method.
A method to prepare thymidine phosphorodithioate dimers (ref. 1) has been extended to allow the preparation of oligo-2'-deoxyribonucleotide phosphorodithioates containing all four bases. The method is suitable for large-scale synthesis and gives phosphorodithioates without phosphorothioate impurities (31P nmr, detection limit 0.5 to 1%). Oligonucleotides up to octamers which contain -0-(PS2-)-0- linkages at all positions have been prepared by block synthesis in solution. The phosphorodithioate linkage is introduced by the reaction of a 5'-O, N-protected nucleoside (or oligonucleotide) with a dithiophosphorylating agent RSP(S)(ODhbt)2, R = 2,4-dichlorobenzyl, Dhbt = 3,4-dihydro-4-oxo-benzotriazin-3-yl, followed by coupling of the product to a 3'-O,N-protected nucleoside (or oligonucleotide). This method gives pure protected oligodeoxyribonucleoside phosphorodithioates, and phosphorothioate linkages are only introduced if contact with conc. aqueous ammonia during or after deblocking is unduly prolonged.
Eldrup
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Institute of Chemistry, H.C. Orsted Institute, University of Copenhagen, Denmark.
Bjergårde
K
K
Felding
J
J
Kehler
J
J
Dahl
O
O
D003432:Cross-Linking Reagents; D003853:Deoxyribonucleosides / Q000737:chemistry*; D004952:Esters / Q000737:chemistry; D009838:Oligodeoxyribonucleotides / Q000737:chemistry* / Q000302:isolation & purification; D009946:Organothiophosphorus Compounds / Q000138:chemical synthesis* / Q000302:isolation & purification; D013873:Thionucleotides / Q000138:chemical synthesis* / Q000302:isolation & purification
D003432:Cross-Linking Reagents; D003853:Deoxyribonucleosides; D004952:Esters; D009838:Oligodeoxyribonucleotides; D009946:Organothiophosphorus Compounds; D013873:Thionucleotides