Abstract:
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.
摘要:
在固相寡核苷酸合成(SPOS)的脱三苯甲基反应过程中应考虑一些相互作用:(i)溶剂与酸的相互作用;(ii)溶剂与三苯甲基阳离子的相互作用(或反应),和(iii)清除剂与酸的相互作用,最后一个作为这项工作的重点。使用停止流设置,常用的三苯甲基阳离子清除剂(甲醇,茴香硫醚,1-十二硫醇,三异丙基硅烷,三乙基硅烷,和三己基硅烷)对六氟磷酸三锂的反应性进行了评估。在筛选的食腐动物中,甲醇和苯甲硫醚被发现是反应性最高和最低的,分别;然而,甲醇与三氯乙酸相互作用和反应,因此,它不应该预混合和储存与酸作为解块溶液。总的来说,在优化脱三苯甲基反应时,必须考虑相互作用的所有方面,特别是对于大规模的SPOS。