Photolabile protecting groups (PPGs), whose deprotection is performed by photoirradiation alone, are used in various fields such as organic synthesis and cell biology. In particular, PPGs are suitable for spatiotemporal dynamic analysis of bioactive molecules by virtue of the fact that the inherent bioactivity in physiological processes can be controlled by photoinduced deprotection of PPGs caging a functional group important for activity. However, the insolubility of caged molecules would induce irregular aggregation, leading to a significant decrease in the photolytic efficiency. In addition, photoirradiation time should be shortened because light causes potentially harmful damage to cells or tissues, therefore the development of novel PPGs with water solubility and highly photolytic efficiency is still required. We focused a 6-bromo-7-hydroxycoumarin-4-ylmethy (Bhc) group, which has highly photolytic efficiency and the capability of the two-photon photolysis, leading to the amide-alkene isosterism-based design: 8-azacoumarin-4-ylmethyl-type PPGs. The saturated concentration of the synthesized 8-aza-6-bromo-7-hydroxycoumarin-4-ylmethyl acetate (8-aza-Bhc) was 18-fold higher than that of Bhc, indicating that 8-azacoumarin-4-ylmethyl-type PPGs are promising as excellent water soluble PPGs for caging chemistry.1,2 Furthermore we investigated the functionalization of the 8-azacoumarin chromophore. Taking the heavy atom effect into consideration for improving the photolytic efficiency, we synthesized the 8-aza-7-hydroxy-6-iodocoumarin-4-ylmethyl acetate (8-aza-Ihc), which showed sufficient water solubility and dramatically faster photoreaction when irradiated at 365 nm and its photolytic efficiency (ε365Φ) was significantly higher than those of Bhc and 8-aza-Bhc. In addition, this group has also favorable reactivity for two-photon excitation that is useful for biological applications. In this presentation, we will report the details of novel 8-azacoumarin-4-ylmethyl-type PPGs.

Development of water-soluble and highly photosensitive 8-azacoumarin-4-ylmethyl-type photolabile-protecting groups for dynamic analysis of bioactive molecules

251st National Meeting (2016)

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