%0 Journal Article
%T An expanded framework toward improving the detritylation reaction in solid-phase oligonucleotide syntheses - filling the gap.
%A Li Q
%A Sanghvi YS
%A Yan H
%J Nucleosides Nucleotides Nucleic Acids
%V 0
%N 0
%D 2024 Aug 9
%M 39120431
%F 1.449
%R 10.1080/15257770.2024.2388789
%X A few interactions should be considered during the detritylation reaction of solid-phase oligonucleotide synthesis (SPOS): (i) interaction of solvent with acid; (ii) interaction (or reaction) of solvent with trityl cation, and (iii) interaction of scavenger with acid, with the last one as the focus of this work. Using a stopped-flow setup, commonly used trityl cation scavengers (methanol, thioanisole, 1-dodecanethiol, triisopropylsilane, triethylsilane, and trihexylsilane) were evaluated for their reactivity toward tritylium hexafluorophosphate. Among the scavengers screened, methanol and thioanisole were found to be the most and least reactive, respectively; however, methanol does interact and react with trichloroacetic acid, thus it should not be pre-mixed and stored with acid as deblock solutions. Overall, all aspects of interactions must be taken into consideration while optimizing the detritylation reaction, especially for large scale SPOS.