Premium
Nucleotides, Part LXII , Pyridinium Salts – An Effective Class of Catalysts for Oligonucleotide Synthesis
Author(s) -
Beier Markus,
Pfleiderer Wolfgang
Publication year - 1999
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/(sici)1522-2675(19990609)82:6<879::aid-hlca879>3.0.co;2-5
Subject(s) - pyridinium , chemistry , phosphoramidite , pyridine , nucleophile , combinatorial chemistry , catalysis , bromide , chloride , organic chemistry , medicinal chemistry , polymer chemistry , oligonucleotide , dna , biochemistry
Various pyridinium salts (see 1 – 9 ) have been tested as catalysts for the condensation step in the phosphoramidite approach of oligonucleotide synthesis. Pyridinium chloride ( 1 ) turned out to be the most effective activator, speeding up the condensation tremendously. Pyridinium bromide ( 2 ) and 4‐methylbenzenesulfonate ( 4 ) can also be regarded as powerful substitutes for the commonly used 1 H ‐tetrazole. The acidic p K a of the pyridinium cation provides an optimal range for phosphoramidite activation, which is followed by a nucleophilic attack of the pyridine ring to give the P ‐pyridinio intermediate 11 as the most likely precursor of phosphite ester formation ( Scheme ). 31 P‐NMR Studies support this proposal indirectly.