Ali Moazzam

This paper describes the development of 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylate compound as a heterocyclic enols containing a Michael acceptor so that it participates in an Ugi-type multicomponent condensation through a Smiles rearrangement in replacement of acid components. The new four-component containing 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylate, aldehyde derivatives, amine derivatives and isocyanides process leads readily and efficiently to heterocyclic enamines. This report is an outstanding strategy for the preparation of new biologically structures containing peptidic or pseudo-peptidic with quinolin-2(1H)-one scaffolds. Graphical abstract

The β‐hairpin is a structural element of native proteins, but it is also a useful artificial scaffold for finding lead compounds to convert into peptidomimetics or non‐peptide structures for drug discovery. Since linear peptides are synthetically more easily accessible than cyclic ones, but are structurally less well‐defined, we propose XWXWXpPXK(/R)X(R) as an acyclic but still rigid β‐hairpin scaffold that is robust enough to accommodate different types of side chains, regardless of the secondary‐structure propensity of the X residues. The high conformational stability of the scaffold results from tight contacts between cross‐strand cationic and aromatic side chains, combined with the strong tendency of the d‐Pro‐l‐Pro dipeptide to induce a type II′ β‐turn. To demonstrate the robustness of the scaffold, we elucidated the NMR structures and performed molecular dynamics (MD) simulations of a series of peptides displaying mainly non‐β‐branched, poorly β‐sheet‐prone residues at the X positions. Both the NMR and MD data confirm that our acyclic β‐hairpin scaffold is highly versatile as regards the amino‐acid composition of the β‐sheet face opposite to the cationic−aromatic one.