The final deprotection step in oligonucleotide synthesis is reduced to a mild and rapid ammonia treatment by using labile base-protecting groups

Abstract

Phenoxyacetyl (pac) and methoxyacetyl (mac) for adenine and guanine, isobutyryl for cytosine, were successfully applied as amino protecting group: both in phosphotriester and phosphoramidite approaches. As shown by N.M.R. and H.P.L.C. analysis, they are completely deblocked in less than four hours in 29% ammonia at room temperature allowing the preparation of modified DNA containing alkali labile bases such as saturated pyrimidines. The stability of N6-phenoxyacetyl-deoxyadenosine versus depurination in acidic conditions used in the detritylation step was favorably compared with that of the classic N6-benzoyl protected adenine.