Department of Chemistry, Washington State University, Pullman, WA, 99164, USA.
Angew Chem Int Ed Engl. 2018 May 14;57(20):5893-5897. doi: 10.1002/anie.201802845. Epub 2018 Apr 19.
Reactive sulfur species (RSS) are biologically important molecules. Among them, H S, hydrogen polysulfides (H S n>1), persulfides (RSSH), and HSNO are believed to play regulatory roles in sulfur-related redox biology. However, these molecules are unstable and difficult to handle. Having access to their reliable and controllable precursors (or donors) is the prerequisite for the study of these sulfur species. Reported in this work is the preparation and evaluation of a series of O-silyl-mercaptan-based sulfur-containing molecules which undergo pH- or F -mediated desilylation to release the corresponding H S, H S , RSSH, and HSNO in a controlled fashion. This O→S relay deprotection serves as a general strategy for the design of pH- or F -triggered RSS donors. Moreover, we have demonstrated that the O-silyl groups in the donors could be changed into other protecting groups like esters. This work should allow the development of RSS donors with other activation mechanisms (such as esterase-activated donors).
活性硫物种 (RSS) 是具有重要生物学意义的分子。其中，H2S、氢多硫化物 (H2Sn>1)、过硫化物 (RSSH) 和 HSNO 被认为在与硫相关的氧化还原生物学中发挥着调节作用。然而，这些分子不稳定且难以处理。获得其可靠且可控的前体 (或供体) 是研究这些硫物种的前提。本工作报道了一系列基于 O-硅基巯基的含硫分子的制备和评价，这些分子可通过 pH 或 F-介导的去硅化反应以可控的方式释放相应的 H2S、H2Sn、RSSH 和 HSNO。这种 O→S 接力脱保护策略可作为设计 pH 或 F-触发 RSS 供体的一般策略。此外，我们已经证明供体中的 O-硅基可以被改变为其他保护基团，如酯。这项工作应该可以开发出具有其他激活机制（如酯酶激活供体）的 RSS 供体。
