Supramolecular approach to chiral photochemistry becomes more popular in recent years. Supramolecular photochirogenesis utilizes the noncovalent interactions both in the ground and excited states to photochemically transfer the supramolecular chirality to molecular chirality through the photoreaction occurring in chiral supramolecular environment. Supramolecular photochirogenesis with biomolecules is particularly attractive in view of their inherently chiral and well-defined 3D structures.

Serum albumins (SA) possess inherently chiral binding sites for endogenous and exogenous organic compounds, which can be exploited for supramolecular photochirogenesis. In this study, we chose 2-anthracenecarboxylate (AC) as guest substrate, and first examined spectroscopically the binding behavior of AC toward various mammalian SA in aqueous buffer solution at pH 7 to characterize the available binding sites for AC. Then, the enantiodifferentiating photocyclodimerization of AC was performed in the presence of SA to give four stereoisomeric [4+4]-cyclodimers. We found that (1) mammalian SA possess 3-5 binding sites for AC of different affinities, stoichiometries, and chiral environment for the photoreaction, (2) the head-to-tail/head-to-head ratio critically depends on the SA used, and (3) SA-mediated photodimerization of AC affords optically active cyclodimers in excellent ee's.

In conclusion, the supramolecular photochirogenesis with SA is a promising strategy for asymmetric synthesis that is not only an attractive alternative to the thermal counterpart but also a unique methodology for obtaining chiral compounds through the electronically excited state in chiral low-entropy environment.