A (4 + 1)-annulation of arylidene heterocyclic-N-fused imidazolones with α-carbonyl sulfoxonium ylides has been developed. The reaction enabled efficient access to a range of N-heterocycle-fused furans, such as secondary hydroxyl and the structural parts of drug/bioactive compounds. A unique triplerole of α-carbonyl sulfoxonium ylides and a characteristic stereo-electronic functional behavior of the arylidene N-fused imidazolones have been explored.

image The CH activation‐based late‐stage functionalization (LSF) has emerged as a powerful strategy in the synthetic organic chemistry. The strategy has definitely transformed the way synthetic chemists think for CC and C–Heteroatom bond‐forming structural diversification. It has made significant advances in functionalization of a diverse range of structurally complex molecules, including drugs, natural products, peptides, nucleosides, nucleic acids, and polysaccharides, which provides highly efficient access to chemical space of biologically/functionally important derivatives or analogs with functionalization at previously inaccessible and otherwise inert CH bonds. These LSF chemistry facets reported in recent years have been illustrated in this article. They have been categorized into classes of molecules and subdivided into aspects of the mechanistic pathway combining with molecular properties. This pool of information will be useful for designing a new strategy of CH activation and application toward the rapid exploration of extended space of complex molecular architectures that are inaccessible by conventional synthesis.

Stereoselective total synthesis of Ligraminol E has been achieved in 8 steps in 23.9 % overall yield by employing an imidazolidinone based chiral auxiliary. The key steps involved in the synthesis are the asymmetric glycolate alkylation of (R)-3-(2-(benzyloxy)acetyl)-4-isopropyl-1-((S)-1-phenylethyl)imidazo-lidin-2-one with substituted benzyl bromide and the Mitsonobu reaction of a secondary alcohol and phenolic group.

A Core‐Linker‐Polyamine (CLP) strategy has been exploited to develop new antileishmanial agents. It involves the linker‐based assembly of alkyl‐polyamine side chain as a potential pharmacophore motif with a privileged heterocyclic motif, 4‐arylquinoline. A series of aminoalkyl 4‐arylquinoline‐2‐carboxamides and their analogs were synthesized and tested against L. donovani promastigotes. Among all synthesized derivatives, 10 compounds showed significant antipromastigote activities with more efficacy (IC50: 4.75–8 μM) than an antileishmanial oral drug Miltefosine (IC50: 8.9±1.55 μM). Most active aminoalkyl‐quinoline‐carboxamides 9 a and 9 b, displayed negligible cytotoxicity towards human monocytic (THP‐1) macrophages. The compounds show antileishmanial activity by generating mitochondrial superoxide radicals. However, they did not show interference with trypanothione reductase, a redox enzyme of Leishmania. Significant change in the morphology of the L. donovani promastigote by the compounds was observed. The Structure‐activity relationship analysis suggest the pharmacophoric importance of alkylpolyamine and carboxamide motifs. In silico evaluation indicated that the investigated active molecules 9 a and 9 b possess important drug‐likeness, physicochemical and pharmacokinetic‐relevant properties.