[Reactive derivatives of oligonucleotide phosphorothioate analogs. I. Selective activation of terminal phosphates and preparation of phosphamide derivatives of oligonucleotide phosphorothioate analogs].
Selective activation of the terminal phosphates of oligonucleotide analogs containing internucleotide phosphorothioate groups was carried out using the triphenylphosphine-dipyridyldisulfide reducing-oxidizing pair. This formed the basis for a new method of synthesizing various derivatives of phosphorothioate oligonucleotide analogs. Using this method, zwitterionic 3'-phosphamide derivatives of di- and trinucleotide phosphorothioates TpsTp and TpsTpsTp containing the 4-dimethylaminopyridine or N-methylimidazole residues were synthesized. The derivatives reacted almost quantitatively with amines to form, within 5-10 min, the corresponding 3'-phosphamides without cleavage of the internucleotide phosphorothioate groups. Alkylating derivatives of phosphorothioates TpsTp(N(CH3)CH2RCl) and TpsTpsTp(N(CH3)CH2RCl) (RCl = -C6H4N(CH3)CH2CH2Cl) were also synthesized by the proposed method. The internucleotide phosphorothioate residues of the oligonucleotide analogs were stable during the synthesis in DMF. The activity of the alkylating RCl groups in the synthesized compounds was maintained at 85-90%.
Amirkhanov
N V
NV
Zarytova
V F
VF
D004117:Dimethoate / Q000737:chemistry*; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy; D009943:Organophosphorus Compounds / Q000737:chemistry*; D010084:Oxidation-Reduction; D013873:Thionucleotides / Q000138:chemical synthesis / Q000737:chemistry*
D009943:Organophosphorus Compounds; D013873:Thionucleotides; D004117:Dimethoate
Reaktsionnosposobnye proizvodnye fosfotioatnykh analogov oligonukleotidov. I. Selektivnaia aktivatsiia kontsevykh fosfatov i poluchenie fosfamnykh proizvodnykh fosfotioatnykh analogov oligonukleotidov.