Nucleotides - Part LXII - Pyridinium salts - An effective class of catalysts for oligonucleotide synthesis

Various pyridinium sails (see 1-9) have been tested as catalysts for the co ndensation step in the phosphoramidite approach of oligonucleotide synthesi s. Pyridinium chloride (1) turned out to be the most effective activator, s peeding up the condensation tremendously Pyridinium bromide (2) and 4-methy lbenzenesulfonate (4) can also be regarded as powerful substitutes for the commonly used 1H-tetrazole. The acidic pK(a) of the pyridinium cation provi des an optimal range for phosphoramidite activation, which is followed by a nucleophilic attack of the pyridine ring to give the P-pyridinio intermedi ate 11 as the most likely precursor of phosphite ester formation (Scheme). P-31-NMR Studies support this proposal indirectly.