Spirooxindol-1,3-oxazine Alkaloids: Highly Potent and Selective Antitumor Agents Evolved from Iterative Structure Optimization.

Spirooxindole-1,3-oxazines are a small and structurally unique class of spirooxindole alkaloids. To date, only four of these compounds have been isolated from natural sources, and their biological properties remained unknown thus far. Dioxyreserpine is a synthetic spirooxindole-1,3-oxazine, that can readily be prepared from the Rauvolfia alkaloid (-)-reserpine by catalytic photooxygenation. While dioxyreserpine itself was now identified as a moderately effective antitumoral agent, structurally modified analogs of it emerged as a new class of highly potent and selective growth inhibitors of various human cancers, including pancreatic cancers. Systematic structural optimization ultimately led to an inhibitor displaying low-micromolar IC50 -values against six cancer cell lines as well as selective apoptosis induction in vitro.

Ligand Substitution of RuII -Alkylidenes to Ru(bpy)3 2+ : Sequential Olefin Metathesis/Photoredox Catalysis.

Ruthenium(II) alkylidene complexes such as the Grubbs' 1st and 2nd generation catalysts undergo a ligand substitution with 2,2'-bipyridine, which readily leads to the common photoredox catalyst Ru(bpy)3 2+ . The application of this catalyst transformation in sequential olefin metathesis/photoredox catalysis is demonstrated by way of ring-closing metathesis (RCM)/photoredox ATRA reactions.

A Photoredox-Induced Stereoselective Dearomative Radical (4+2)-Cyclization/1,4-Addition Cascade for the Synthesis of Highly Functionalized Hexahydro-1H-carbazoles.

A stereoselective synthesis of functionalized hexahydrocarbazoles was developed based on an unprecedented photoredox-induced dearomative radical (4+2)-cyclization/1,4-addition cascade between 3-(2-iodoethyl)indoles and acceptor-substituted alkenes. The title reaction simultaneously generates three C-C bonds and one C-H bond, along with three contiguous stereogenic centers. The hexahydro-1H-carbazole products are highly valuable intermediates for the synthesis of novel antibiotics, as well as unnatural ring homologues of polycyclic indoline alkaloids.

Photoassisted oxidation of ruthenium(II)-photocatalysts Ru(bpy)3(2+) and Ru(bpz)3(2+) to RuO4: orthogonal tandem photoredox and oxidation catalysis.

Common photoredox catalysts Ru(bpy)3(2+) and Ru(bpz)3(2+) are rapidly converted into Ruthenium(viii)-oxide through continuous visible light irradiation in the presence of NaIO4 or H5IO6. This hitherto unreported photoassisted catalyst oxidation was utilized in the development of tandem catalytic protocols which combine a photoredox reaction with a subsequent RuO4-mediated oxidation. The new concept was demonstrated through one-pot radical cation Diels-Alder (RCDA)/1,5-diene cyclisation sequences.