Selective Hydrogenation and Transfer Hydrogenation for Post-Functional Synthesis of Trifluoromethylphenyl Diazirine Derivatives for Photoaffinity Labeling

摘要

Elucidation of protein functions on the basis of structure–activity relationships can revealthe mechanisms of homeostasis functions in life and is one of the greatest interests ofscientists. In the human body, many proteins are activated and/or inactivated by ligands tomaintain homeostasis. Understanding the mechanism of molecular interactions betweensmall bioactive ligands and proteins is an important step in rational drug design anddiscovery. !Photoaffinity labeling, which is one of the most familiar approaches for chemical biologyanalysis, was initiated using diazocarbonyl derivatives in 1962 (Singh et al., 1962). Manyresearchers have subsequently tried to establish alternative approaches for the directidentification of target proteins for the bioactive small ligands. These approaches are basedon the affinity between the ligand and the target protein (Figure 1). Several reviews arepublished for the recent applications of photoaffinity labeling (Tomohiro et al., 2005;Hashimoto & Hatanaka, 2008).To archive photoaffinity labeling, researchers have to prepare photoaffinity labeling ligands.The native ligands must be modified by photoreactive compounds (photophores) by organicsynthesis