DNA‐Templated Formation and N,O‐Transacetalization of N‐Methoxyoxazolidines

Abstract

DNA-templated formation and N,O-transacetalization of Nmethoxyoxazolidines have been studied. Compared to the reaction without a DNA-catalyst, the hybridization-driven Nmethoxyoxazolidine formation shows a marked rate acceleration, whereas the rate of corresponding N,O-transacetalization is limited by the rate of decay to aldehyde intermediates. In both cases, the equilibrium yield increases markedly on the DNA template. Different hairpin architectures have been studied to evaluate the role and limits of the template effect. Furthermore, an attention has been paid to stereochemical integrity (R/S) of the N-methoxyoxazolidine linkage. The Nmethoxyoxazolidine formation represents a dynamic pH-responsive DNA-templated ligation that occurs readily in slightly acidic conditions (pH 5).

Assembly of split aptamers by dynamic pH-responsive covalent ligation

“…Aldehyde- and 2′-deoxy-2′- N -(methoxyamino)uridine-modified oligonucleotide (ON) fragments of the CBA and of model ONs were first synthesized. As we recently 32 demonstrated with DNA-templated pseudo trans-N , O -acetalization systems, N -methoxyoxazolidine-protected ONs are convenient precursors for aldehyde-modified ONs. Therefore, dinucleosidic phosphoramidite 3 was prepared and used for the automated synthesis of ONs 1–4 , outlined in Scheme 2.…”

“…We also evaluated the applicability of the reaction for dynamic DNA-templated ligation. 32 The DNA-template increased the rate and yield of the N -methoxyoxazolidine formation ca. 570- and 140-fold respectively compared to a non-templated one.…”