Studies on The Application of The Paternò-Büchi Reaction to The Synthesis of Novel Fluorinated Scaffolds.

In the context of new scaffolds obtained by photochemical reactions, Paternò-Büchi reactions between heteroaromatic, trifluoromethylphenyl ketone and electron rich alkenes to give oxetanes are described. A comprehensive study has then been carried out on the reaction of aromatic ketones with fluorinated alkenes. Depending on the substitution pattern at the oxetane ring, a metathesis reaction is described as a minor side process to give mono fluorinated alkenes.

A machine learning-based chemoproteomic approach to identify drug targets and binding sites in complex proteomes.

Chemoproteomics is a key technology to characterize the mode of action of drugs, as it directly identifies the protein targets of bioactive compounds and aids in the development of optimized small-molecule compounds. Current approaches cannot identify the protein targets of a compound and also detect the interaction surfaces between ligands and protein targets without prior labeling or modification. To address this limitation, we here develop LiP-Quant, a drug target deconvolution pipeline based on limited proteolysis coupled with mass spectrometry that works across species, including in human cells.

Modulation of voltage-gated Na+ and K+ channels by pumiliotoxin 251D: a "joint venture" alkaloid from arthropods and amphibians.

Certain amphibians provide themselves with a chemical defense by accumulating lipophilic alkaloids into skin glands from dietary arthropods. Examples of such alkaloids are pumiliotoxins (PTXs). In general, PTXs are known as positive modulators of voltage-gated sodium channels (VGSCs).

Planar chirality: cycloaddition and transannular reactions of optically active azoninones that contain (E)-olefins.

Unsaturated nine-membered ring lactams that contain (E)-olefins within the ring are characterized by planar chiral properties. Thus, selective conversions of the double bond allowed a complete transfer of the planar chiral information into new stereogenic centers The basis of the transformations was the high activation barrier that prevented efficient flipping of the double bond at room temperature (epimerization pR <=> pS) with respect to the ring. Cycloadditions led diastereoselectively to cyclopropano, epimino, epoxy, and dihydroxy azonanones under mild conditions with moderately high yields.

Planar Chirality: Synthesis and Transannular Reactions of Unsaturated Optically Active Azoninones Bearing E-Olefins.

The zwitterionic aza-Claisen rearrangement of optically active trans 4-silyloxy-2-vinylpyrrolidines and carboxylic acid fluoride generated nine-membered ring lactams with high yields. The reaction proceeded with an almost complete 1,4-chirality transfer and the exclusive generation of the E-double bond in the medium sized rings to cause additional planar chiral information. The initially formed azoninones were characterized by a pS-arrangement of the olefin with respect to the ring.