Synthesis of marmycin A and investigation into its cellular activity

Anthracyclines such as doxorubicin are used extensively in the treatment of cancers. Anthraquinone-related angucyclines also exhibit antiproliferative properties and have been proposed to operate via similar mechanisms, including direct genome targeting. Here, we report the chemical synthesis of marmycin A and the study of its cellular activity. The aromatic core was constructed by means of a one-pot multistep reaction comprising a regioselective Diels-Alder cycloaddition, and the complex sugar backbone was introduced through a copper-catalysed Ullmann cross-coupling, followed by a challenging Friedel-Crafts cyclization. Remarkably, fluorescence microscopy revealed that marmycin A does not target the nucleus but instead accumulates in lysosomes, thereby promoting cell death independently of genome targeting. Furthermore, a synthetic dimer of marmycin A and the lysosome-targeting agent artesunate exhibited a synergistic activity against the invasive MDA-MB-231 cancer cell line. These findings shed light on the elusive pathways through which anthraquinone derivatives act in cells, pointing towards unanticipated biological and therapeutic applications

Synthesis of heterocycles via aerobic oxidation

\u3cp\u3eResearch in the field of aerobic oxidation has recently gained much attention from both academia and industry. The main reason for this has to be found in the inherent greenness of such methods. Although much investigation has been undertaken to develop new methods and reactions and to elucidate the mechanistic aspects of this chemistry, its applications in the synthesis of heterocycles have been relatively limited. In this review, the recent developments in this field are summarized.\u3c/p\u3

Flow photochemistry:shine some light on those tubes!

\u3cp\u3eContinuous-flow chemistry has recently attracted significant interest from chemists in both academia and industry working in different disciplines and from different backgrounds. Flow methods are now being used in reaction discovery/methodology, in scale-up and production, and for rapid screening and optimization. Photochemical processes are currently an important research field in the scientific community and the recent exploitation of flow methods for these methodologies has made clear the advantages of flow chemistry and its importance in modern chemistry and technology worldwide. This review highlights the most important features of continuous-flow technology applied to photochemical processes and provides a general perspective on this rapidly evolving research field.\u3c/p\u3

Synthesis and coordination chemistry of 1,1,1-tris-(pyrid-2-yl)ethane

A new synthesis of 1,1,1-tris(pyrid-2-yl)ethane (L), and a survey of its coordination chemistry, are reported. The complexes [ML2]n+ (Mn+ = Fe2+, Co2+, Co3+, Cu2+ and Ag+), [PdCl2L] and [CuI(L)] have all been crystallographically characterised. Noteworthy results include an unusual square planar silver(i) complex [Ag(L)2]X (X- = NO3- and SbF6-); the oxidative fixation of aerobic CO2 by [CuI(L)] to yield [Cu2I(L)2(μ-CO3)]2[CuI3] and [Cu(CO3)(L)]; and, water/carbonato tape and water/iodo layer hydrogen bonding networks in hydrate crystals of two of the copper(ii) complexes. Cyclic voltammetric data on [Fe(L)2]2+ and [Co(L)2]2+/3+ imply that the peripheral methyl substituent has a weak influence on the ligand field exerted by L onto a coordinated metal ion

Copper catalysed Ullmann type chemistry: From mechanistic aspects to modern development

Cu-catalysed arylation reactions devoted to the formation of C-C and C-heteroatom bonds (Ullmann-type couplings) have acquired great importance in the last decade. This review discusses the history and development of coupling reactions between aryl halides and various classes of nucleophiles, focusing mostly on the different mechanisms proposed through the years. Selected mechanistic investigations are treated more in depth than others. For example, evidence in favour or against radical mechanisms is discussed. Cu(i) and Cu(III) complexes involved in the Ullmann reaction and N/O selectivity in aminoalcohol arylation are discussed. A separate section has been dedicated to the synthesis of heterocyclic rings through intramolecular couplings. Finally, recent developments in green chemistry for these reactions, such as reactions in aqueous media and heterogeneous catalysis, have also been reviewed

Picolinamides as Effective Ligands for Copper‐Catalysed Aryl Ether Formation: Structure–Activity Relationships, Substrate Scope and Mechanistic Investigations

The use of picolinic acid amide derivatives as an effective family of bidentate ligands for copper-catalysed aryl ether synthesis is reported. A fluorine-substituted ligand gave good results in the synthesis of a wide range of aryl ethers. Even bulky phenols, known to be very challenging substrates, were shown to react with aryl iodides with excellent yields using these ligands. At the end of the reaction, the first examples of end-of-life Cu species were isolated and identified as CuII complexes with several of the anionic ligands tested. A preliminary mechanistic investigation is reported that suggests that the substituents on the ligands might have a crucial role in determining the redox properties of the metal centre and, consequently, its efficacy in the coupling process. An understanding of these effects is important for the development of new efficient and tunable ligands for copper-based chemistry