The mechanism of the chemical synthesis of oligonucleotides and its synthetic consequences.
The data obtained mainly by pulsed NMR spectroscopy on phosphorus nuclei on the mechanism of the internucleotide phosphodiester (PDE) group formation are summarised. With arylsulphonyl chloride as condensing reagent monomeric nucleotide derivative B (nucleoside metaphosphate or its pyridinium adduct) is the highly reactive intermediate. In the presence of PDE groups in nucleoside or nucleotide component the significantly less reactive derivatives with trisubstituted pyrophosphoryl residues are formed both with arylsulphonyl chloride and dicyclohexylcarbodiimide (DCC). The reactive B form of nucleotide component may be obtained using greater excess of arylsulphonyl chloride with simultaneous convertion of PDE groups to tetrasubstituted pyrophosphates amenable to side reactions. The convertion of PDE groups to easily hydrolysable dicyclohexylurea derivatives by reaction with DCC is proposed to reversible blocking of PDE groups of nucleoside component. The B type derivatives of mononucleotides or oligonucleotides with blocked PDE groups seems to be the best nucleotide components.
D001190:Arylsulfonates; D055598:Chemical Phenomena; D002621:Chemistry; D004024:Dicyclohexylcarbodiimide; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008722:Methods; D009711:Nucleotides; D009841:Oligonucleotides / Q000138:chemical synthesis*; D010710:Phosphates
D001190:Arylsulfonates; D009711:Nucleotides; D009841:Oligonucleotides; D010710:Phosphates; D004024:Dicyclohexylcarbodiimide