Synthesis of Hydrophilic Caged DAG-lactone for Chemical Biology Applications
Synthesis of Hydrophilic Caged DAG-lactone for Chemical Biology Applications
复制标题
用于化学生物学应用的亲水性笼状 DAG-内酯的合成
DOI：
10.1039/d0ob00807a
复制
发表时间：
2020
影响因子：
3.2
通讯作者：
Hirokazu Tamamura
中科院分区：
文献类型：
--
作者：
Takuya Kobayakawa;Hikaru Takano;Takahiro Ishii;Kohei Tsuji;Nami Ohashi;Wataru Nomura;Toshiaki Furuta;Hirokazu Tamamura
6-溴-7-羟基-香豆素-4-基甲基（Bhc）基团因其高摩尔吸光率和光解效率而在笼化学中得到广泛应用。然而，香豆素的缺点之一是它们的低水溶性。水溶性对于笼状化合物的行为很重要，因为疏水性笼状化合物可能在生理条件下聚集，从而损害光裂解。本实验室先前开发的带有溴（8-aza-Bhc）或碘（8-aza-Ihc）的8-氮杂香豆素-4-基甲基衍生物具有比相关香豆素更高的水溶性。在这里，为了改善笼状二酰基甘油内酯（DAG-内酯）的亲水性和管理性，将8-aza-Bhc和8-aza-Ihc引入到DAG-内酯结构中。与母体 Bhc 笼状 DAG-内酯相比，合成的笼状化合物表现出高亲水性，并且 8-aza-Ihc 笼状 DAG-内酯 (2) 显示出优异的光解效率，可通过短暂的光照射快速释放 DAG-内酯 (1)。 8-氮杂-7-羟基-6-碘-香豆素-4-基甲基可能可用于捕获生物活性化合物，特别是疏水性化合物。
The 6-bromo-7-hydroxy-coumarin-4-ylmethyl (Bhc) group has been used widely in cage chemistry because of its high molar absorptivity and photolytic efficiency. One of the drawbacks of coumarins however is their low aqueous solubility. Aqueous solubility is important in the behavior of caged compounds because hydrophobic caged compounds might be aggregated in physiological conditions and consequently the photocleavage would be impaired. The 8-azacoumarin-4-ylmethyl derivatives with bromine (8-aza-Bhc) or iodine (8-aza-Ihc), which were previously developed in this laboratory, have aqueous solubilities that are higher than those of related coumarins. Here, to improve the hydrophilicity and management of caged diacylglycerol lactones (DAG-lactones), 8-aza-Bhc and 8-aza-Ihc were introduced into the DAG-lactone structure. The synthesized caged compounds showed high hydrophilicity compared with the parent Bhc-caged DAG-lactone, and the 8-aza-Ihc-caged DAG-lactone (2) showed excellent photolytic efficiency, which allows rapid release of the DAG-lactone (1) by brief photoirradiation. The 8-aza-7-hydroxy-6-iodo-coumarin-4-ylmethyl group might be useful for caging of bioactive compounds, especially hydrophobic compounds.