ABSTRACT
Piperazines are found widely in commercially-available compounds and bioactive molecules (including many drugs). However, in the vast majority of these molecules, the piperazine ring is isolated (i.e. not fused to another ring) and is not substituted on any of its carbon atoms. A modular synthetic approach is described in which combinations of cyclic sulfamidate and hydroxy sulfonamide building blocks may be converted into piperazines and related 1,4-diazepine and 1,5-diazocane scaffolds. By variation of the combinations of building blocks used, it was possible to vary the ring size, substitution and configuration of the resulting heterocyclic scaffolds. The approach was exemplified in the synthesis of a range of heterocyclic scaffolds that, on decoration, would target lead-like chemical space. It was demonstrated that lead-like small molecules based on these scaffolds would likely complement those found in large compound collections.
Subject(s)
Azepines/chemical synthesis , Heterocyclic Compounds, 1-Ring/chemical synthesis , Piperazines/chemical synthesis , Azepines/chemistry , Heterocyclic Compounds, 1-Ring/chemistry , Molecular Structure , Piperazine , Piperazines/chemistryABSTRACT
Ring-opening of cyclic sulfamidates with propargylic sulfonamides yielded substrates for a gold-catalyzed cyclization to yield tetrahydropyrazines. Manipulation of the tetrahydropyrazines, by reduction or using multicomponent reactions, yielded piperazine scaffolds in which substitution of the carbon atoms was varied. Such scaffolds may have value in the synthesis of novel screening compounds with lead-like molecular properties.
Subject(s)
Gold/chemistry , Piperazines/chemical synthesis , Sulfonamides/chemistry , Catalysis , Cyclization , Molecular Structure , Piperazines/chemistryABSTRACT
Several Ru-arene and Ir-Cp* complexes have been prepared incorporating (N,N), (N,O) and (O,O) coordinating bidentate ligands and have been found to be active against both HT-29 and MCF-7 cell lines. By incorporating a biologically active ligand into a metal complex the anti-cancer activity is increased.
Subject(s)
Antineoplastic Agents/pharmacology , Iridium/chemistry , Organometallic Compounds/pharmacology , Ruthenium/chemistry , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Survival/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , HT29 Cells , Humans , Ligands , MCF-7 Cells , Models, Molecular , Molecular Structure , Organometallic Compounds/chemical synthesis , Organometallic Compounds/chemistry , Structure-Activity RelationshipABSTRACT
Fused ring heterocycles were synthesised via the rhodium catalysed isomerisation/regio and stereoselective 1,3-dipolar cycloaddition cascades in good yields.
ABSTRACT
2'-Aminoacetophenone was chemoselectively alkylated with a range of substituted benzyl, heteroaryl alcohols to afford either the corresponding C- or N- alkylated products in good yield.
ABSTRACT
A palladium-catalyzed three-component cascade process for the synthesis of isoindolone and phthalazone derivatives is reported. The cascade process involves carbonylation of an aryl iodide/Michael acceptor to give an acylpalladium species which is intercepted by a hydrazine nucleophile. Intramolecular Michael addition follows to give either N-aminoisoindolones or mono- N- and di-N,N'-phthalazones depending on whether a monosubstituted or 1,2-disubstituted hydrazine nucleophile is used.
Subject(s)
Hydrazines/chemistry , Isoindoles/chemical synthesis , Palladium , Phthalazines/chemical synthesis , CatalysisABSTRACT
Microwave assisted indirect functionalization of alcohols with 1,3-dimethylbarbituric acid followed by spirocyclisation employing a sequential one-pot Ir(III)/Pd(0) catalysed process, involving the formation of three new C-C bonds, one spirocyclic ring and one di- or tri-substituted exocyclic alkene, is described.
Subject(s)
Alkadienes/chemistry , Barbiturates/chemical synthesis , Iridium/chemistry , Palladium/chemistry , Alkylation , Barbiturates/chemistry , Benzyl Alcohols/chemistry , Catalysis , Crystallography, X-Ray , Cyclization , Heterocyclic Compounds/chemical synthesis , Heterocyclic Compounds/chemistry , Microwaves , Models, Molecular , Molecular Conformation , Molecular Structure , Spiro Compounds/chemical synthesis , Spiro Compounds/chemistry , StereoisomerismABSTRACT
A one pot, three component palladium catalysed allenation of aryl iodides, in combination with a nitrone cycloaddition, leads to formation of fused isoxazolidines, creating two rings, two stereocentres and one tetrasubstituted carbon centre.
