We report herein a nonbiomimetic strategy for the total synthesis of the plicamine‐type alkaloids zephycarinatines C and D. The key feature of the synthesis is a stereoselective reductive radical ipso‐cyclization using visible‐light‐mediated photoredox catalysis. This cyclization enabled the construction of a 6,6‐spirocyclic core structure through the addition of a carbon‐centered radical onto the aromatic ring. Biological evaluation of zephycarinatines and their derivatives revealed that the synthetic derivative with a keto group displays moderate inhibitory activity against LPS‐induced NO production. This approach could offer future opportunities to expand the chemical diversity of plicamine‐type alkaloids as well as providing useful intermediates for their syntheses.

Synucleinopathies are characterized by the deposition of α-synuclein (α-syn) aggregates before the onset of clinical symptoms. Therefore, in vivo imaging of α-syn may contribute to early diagnosis of these diseases and has attracted much attention in recent years. However, no clinically useful probes have been reported. In the present study, 16 quinoline/​quinoxaline derivatives with different styryl and fluorine groups were evaluated in order to develop α-syn imaging probes. Among them, SQ3, which is a quinoline analogue with a p-(dimethyl­amino)­styryl group and fluoro­ethoxy group at the 2- and 7- positions of the skeleton, displayed moderate selectivity for α-syn aggregates over β-amyloid (Aβ) aggregates (K i = 230 nM), while maintaining high binding affinity for α-syn aggregates (K i = 39.3 nM). In a biodistribution study, [18F]­SQ3 exhibited high uptake (2.08% ID/g at 2 min after intravenous injection) into a normal mouse brain. Taken together, we demonstrate that [18F]­SQ3 has basic properties as a lead compound for the development of a useful α-syn imaging probe.

We report herein a nonbiomimetic strategy for the total synthesis of the plicamine‐type alkaloids zephycarinatines C and D. The key feature of the synthesis is a stereoselective reductive radical ipso‐cyclization using visible‐light‐mediated photoredox catalysis. This cyclization enabled the construction of a 6,6‐spirocyclic core structure through the addition of a carbon‐centered radical onto the aromatic ring. Biological evaluation of zephycarinatines and their derivatives revealed that the synthetic derivative with a keto group displays moderate inhibitory activity against LPS‐induced NO production. This approach could offer future opportunities to expand the chemical diversity of plicamine‐type alkaloids as well as providing useful intermediates for their syntheses.

Bridged polycyclic ring systems constitute the core structures of numerous natural products and biologically active molecules. We found that simple biphenyl substrates derived from amino acids participate in a radical cascade reaction under visible light irradiation in the presence of [Ir{dF(CF 3 )ppy} 2 (dtbpy)]PF 6 to enable the direct construction of bicyclo[2.2.2]octene structures. Isotopic labeling experiments suggested that intramolecular hydrogen atom transfer is involved in the cascade processes.