Stereoselective synthesis of N-aryl proline amides by biotransformation-Ugi-Smiles sequence

An efficient combination of MAO-N-catalyzed desymmetrization of cyclic meso-amines with Ugi-Smiles multicomponent chemistry produced optically pure N-aryl proline amides. This method represents the first report of a fully asymmetric Ugi-Smiles process.     

Continuum modeling of periodic brickwork

Continuum models of periodic masonry brickwork, viewed at a micro-level as a discrete system, are identified within the frame of linearized elasticity. The accuracy of various identification schemes is investigated for standard and micropolar continua, which are directly compared with the help of some numerical benchmarks, for different loading conditions that induce periodic and non-periodic deformation states. It is shown that periodic deformation states of brickwork are exactly reproduced by both continua, provided that a suitable identification scheme is adopted. For non-periodic states micropolar continuum is shown to better reproduce the discrete solutions, due to its capability to take scale effects into account. Both continua are asymptotically equivalent as the characteristic length of the discrete system tends to zero, while providing an upper and a lower bound of the discrete solution.     

Novel multicomponent reaction for the combinatorial synthesis of 2-imidazolines

[reaction: see text] The three-component condensation between an amine, an aldehyde, and an alpha-acidic isocyanide efficiently provides substituted 2-imidazolines in a one-pot reaction under mild conditions.     

Palladium‐Catalyzed Construction of Amidines from Arylboronic Acids under Oxidative Conditions

A valuable palladium‐catalyzed three‐component coupling reaction for the synthesis of amidines has been developed. Using arylboronic acids, isocyanides, and anilines as the reactants under oxidative conditions, various amidines were isolated in good yields with good functional group tolerances.     

Osteosarcoma Stem Cell Potent Gallium(III)-Polypyridyl Complexes Bearing Diflunisal

We report the anti-osteosarcoma stem cell (OSC) properties of a series of gallium(III)-polypyridyl complexes ( 5 - 7 ) containing diflunisal, a non-steroidal anti-inflammatory drug. The most effective complex within the series, 6 (containing 3,4,7,8-tetramethyl-1,10-phenanthroline), displayed similar potency towards bulk osteosarcoma cells and OSCs, in the nanomolar range. Remarkably, 6 exhibited significantly higher monolayer and sarcosphere OSC potency (up to three orders of magnitude) than clinically approved drugs used in frontline (cisplatin and doxorubicin) and secondary (etoposide, ifosfamide, and carboplatin) osteosarcoma treatments. Mechanistic studies show that 6 downregulates cyclooxygenase-2 (COX-2) and kills osteosarcoma cells in a COX-2 dependent manner. Furthermore, 6 induces genomic DNA damage and caspase-dependent apoptosis. To the best of our knowledge, 6 is the first metal complex to kill osteosarcoma cells by simultaneously inhibiting COX-2 and damaging nuclear DNA.     

Palladium-catalyzed synthesis of 4-aminophthalazin-1(2H)-ones by isocyanide insertion

Palladium-catalyzed cross-coupling of a wide range of substituted o-(pseudo)halobenzoates and hydrazines with isocyanide insertion followed by lactamization efficiently affords 4-aminophthalazin-1(2H)-ones that are difficult to obtain regioselectively by classical methods.     

1-Azadienes in cycloaddition and multicomponent reactions towards N-heterocycles

1-Azadienes are versatile building blocks for the efficient construction of various N-heterocycles. Depending on the substitution pattern and reaction partner, they may participate in a range of different reactions. An overview of recent methods for the generation of 1-azadienes is presented, as well as their application in cycloaddition, electrocyclization, and multicomponent reactions. Considering the broad range of reactivities and resulting heterocyclic scaffold structures, 1-azadienes are very useful reactive intermediates for the development of modular reaction sequences in diversity-oriented synthesis.     

Efficient C2 functionalisation of 2H-2-imidazolines

Alkylation and oxidation of 2H-2-imidazolines, followed by regioselective deprotection, thionation and microwave-assisted Liebeskind-Srogl reaction, efficiently led to 2-aryl-2-imidazolines as new analogues of p53-hdm2 interaction inhibitors (Nutlins).     

A multicomponent synthesis of triazinane diones

An efficient, one-pot synthetic protocol toward triazinane diones, a rather unexplored class of heterocyclic scaffolds combining phosphonates, nitriles, aldehydes, and isocyanates is described. The optimization of the reaction, synthesis of a small library of different triazinane diones, as well as alternative routes toward the triazinane dione scaffold are discussed.