Synthesis of oligonucleotides containing thiazole and thiazole N-oxide nucleobases

(equation presented) The thiazole C-nucleoside analogue was synthesized by the Hantzsch cyclization method to form the thiazole ring and was then converted to the thiazole N-oxide C-nucleoside analogue by peracid oxidation of the heterocycle nitrogen. Incorporation of the thiazole and thiazole N-oxide phosphoramidites into DNA was successful though significant deoxygenation of the N-oxide occurred during DNA assembly. The mechanism proposed for the reduction of the thiazole N-oxide to thiazole involves the formation of an N-oxide phosphite ester.