Tang Shengzhuang, Cannon Jayme, Yang Kelly, Krummel Matthew F, Baker James R, Choi Seok Ki
Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan Medical School, Ann Arbor, Michigan 48109, United States.
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109, United States.
J Org Chem. 2020 Mar 6;85(5):2945-2955. doi: 10.1021/acs.joc.9b02617. Epub 2020 Feb 5.
Despite its importance in the design of photocaged molecules, less attention is focused on linker chemistry than the cage itself. Here, we describe unique uncaging properties displayed by two coumarin-caged thymidine compounds, each conjugated with () or without () an extended, self-immolative spacer. Photolysis of using long-wavelength UVA (365 nm) or visible (420, 455 nm) light led to the release of free thymidine along with the competitive generation of a thymidine-bearing recombination product. The occurrence of this undesired side reaction, which is previously unreported, was not present with the photolysis of , which released thymidine exclusively with higher quantum efficiency. We propose that the spatial separation between the cage and the substrate molecule conferred by the extended linker can play a critical role in circumventing this unproductive reaction. This report reinforces the importance of linker selection in the design of coumarin-caged oligonucleosides and other conjugates.
尽管连接子化学在光笼分子设计中很重要，但与笼本身相比，它受到的关注较少。在这里，我们描述了两种香豆素笼化胸苷化合物所展现出的独特解笼特性，每种化合物都（有或没有）与一个延长的、自牺牲性间隔基共轭。使用长波长紫外光A（365纳米）或可见光（420、455纳米）对[具体化合物1]进行光解，会导致游离胸苷的释放，同时竞争性地生成一种含胸苷的重组产物。这种之前未被报道的不期望的副反应在[具体化合物2]的光解过程中并未出现，[具体化合物2]以更高的量子效率专一性地释放胸苷。我们认为，延长的连接子赋予笼与底物分子之间的空间分离在规避这种非生产性反应中可能起关键作用。本报告强化了连接子选择在香豆素笼化寡核苷及其他共轭物设计中的重要性。
