Herein, we report a method for the generation of vinylallenes via cobalt/photoredox dual-catalysis-enabled formal 1,8-acyloxy migration of 1,6-diynyl esters. We demonstrated a 1,8acyloxy migration/6π-electrocyclization cascade using (hetero)arylsubstituted 1,6-diynyl esters as substrates, leading to the formation of arenol derivatives. Several control experiments suggested that the β-oxygen elimination of a cobaltacyclopentadiene intermediate enabled formal 1,8-acyloxy migration to generate the vinylallene. We also applied this method to cascade cyclizations involving [2 + 2] or [4 + 2] cycloadditions to furnish various polycyclic molecules.

Herein, we report dual cobalt and photoredox catalysis enabled [2+2+2] cycloaddition of enediynes to produce tricyclic cyclohexadienes bearing a quaternary bridgehead carbon. A variety of enediynes were used, and the corresponding cyclohexadienes were obtained in good to high yields. The use of a chiral ligand, (S)-Segphos, enabled a highly enantioselective reaction allowing access to highly enantio-enriched cyclohexadienes.

GPR85 is a member of the G protein-coupled receptor and is a super-conserved receptor expressed in the brain sub-family (Super Conserved Receptor Expressed in Brain; SREB) with GPR27 and GPR173. These three receptors are "orphan receptors"; however, their endogenous ligands have not been identified. SREB has garnered the interest of many scientists because it is expressed in the central nervous system and is evolutionarily conserved. In particular, brain mass is reported to be increased and learning and memory are improved in GPR85 knockout mice (Matsumoto et al. 2008). In this study, we characterized newly synthesized compounds using a GPR85-Gsα fusion protein and the [ 35 S]GTPγS binding assay and identified novel GPR85 inverse-agonists with

GPR85 is a member of the G protein-coupled receptor and is a super-conserved receptor expressed in the brain sub-family (SREB) with GPR27 and GPR173. These three receptors are orphan receptors; however, their endogenous ligands have not been identified. SREB has garnered the interest of many scientists because it is expressed in the central nervous system and is evolutionarily conserved. In particular, brain mass is reported to be increased and learning and memory are improved in GPR85 knockout mice (Matsumoto et al., 2008). In this study, we characterized newly synthesized compounds using a GPR85-Gsα fusion protein and the [35S]GTPδS binding assay and identified novel GPR85 inverse-agonists with IC50 values of approximately 1 μM. To analyze the neurochemical character of the compounds and investigate the physiological significance of GPR85, we used cerebellar Purkinje cells expressing GPR85 and an electrophysiological technique. Based on the results, the inverse-agonist compound for GPR85 modulated potassium channel opening. Together with the results of previous gene analysis of GPR85, we expect that the development of the GPR85 ligand will provide new insights into a few types of neurological disorders.