Some observations relating to the oximate ion promoted unblocking of oligonucleotide aryl esters

The action of the N1, N1, N3, N3-tetramethylguanidinium salts of a number of oximes on 5'-O-methoxytetrahydropyranylthymidylyl-(3' leads to 5')-3'-O-methoxytetrahydropyranylthmidine aryl esters (7a-c) in dioxan-water (1:1 v/v) has been investigated. The O-chlorophenyl ester (7a) was unblocked by 4-nitrobenzaldoximate ion ca. 2.5 times as rapidly as the p-chlorophenyl ester (7b) and ca. 25 times as rapidly as the phenyl ester (7c). syn-2-Nitrobenzaldoxime (15a) is the unblocking agent of choice; its conjugate base reacts with 7a and 7b ca. 4 and 2.5 times, respectively, as rapidly as does the conjugate base of its 4-isomer (1). Internucleotide cleavage cannot be detected in the reaction between 2-nitrobenzaldoximate ion and 7a; its extent has been estimated to be no greater than 0.1%. Experiments with the corresponding fully-protected tetranucleoside triphosphate (14a) confirm the greater reactivity of 2- and 4-nitrobenzaldoximate ion and suggest that, if the molecular concentrations both of protected oligonucleotide and oximate ions are maintained, rates of unblocking may not decrease significantly with increasing oligonucleotide chain lengths.