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The reactivity of functionalized ynamides and arylynamines with tetracyanoethylene at room temperature was evaluated. In most cases, the corresponding 1,1,4,4-tetracyanobutadienes (TCBDs) were obtained in good to excellent yields through a [2+2]-cycloaddition/[2+2]-retro-electrocyclization sequence. The influence of diverse functional groups on the yield of the reaction was investigated, in particular concerning multiple ynamides. These TCBDs were characterized by various spectroscopic techniques and electrochemistry and X-ray diffraction in some cases. [ABSTRACT FROM AUTHOR]

The synthesis of multi-ynamides according to the copper-catalyzed Evano’s and Hsung’s methods is described. In these new compounds, the ynamide functions are conjugated to each other with a phenyl, a biphenyl, a thienyl, or a triphenylamine spacer. [ABSTRACT FROM AUTHOR]

A high-yielding sequence of [2+2] cycloaddition-retroelectrocyclization of ynamides with tetracyanoethylene (TCNE) is described. The reaction provided tetracyanobutadiene (TCBD) species, which were characterized by various techniques. DFT and TD-DFT calculations were also performed to complement experimental findings. [ABSTRACT FROM AUTHOR]

In an approach to the biologically important 6-azabicyclo[3.2.1]octane ring system, the scope of the tandem 4- exo-trig carbamoyl radical cyclization-dithiocarbamate group transfer reaction to ring-fused β-lactams is evaluated. β-Lactams fused to five-, six-, and seven-membered rings are prepared in good to excellent yield, and with moderate to complete control at the newly formed dithiocarbamate stereocentre. No cyclization is observed with an additional methyl substituent on the terminus of the double bond. Elimination of the dithiocarbamate group gives α,β- or β,γ-unsaturated lactams depending on both the methodology employed (base-mediated or thermal) and the nature of the carbocycle fused to the β-lactam. Fused β-lactam diols, obtained from catalytic OsO4-mediated dihydroxylation of α,β-unsaturated β-lactams, undergo semipinacol rearrangement via the corresponding cyclic sulfite or phosphorane to give keto-bridged bicyclic amides by exclusive N-acyl group migration. A monocyclic β-lactam diol undergoes Appel reaction at a primary alcohol in preference to semipinacol rearrangement. Preliminary investigations into the chemo- and stereoselective manipulation of the two carbonyl groups present in a representative 7,8-dioxo-6-azabicyclo[3.2.1]octane rearrangement product are also reported. [ABSTRACT FROM AUTHOR]

13 examples [ABSTRACT FROM AUTHOR]

In an approach to the biologically important 6-azabicyclo[3.2.1]octane ring system, the scope of tandem 4-exo-trig carbamoyl radical cyclization-dithiocarbamate group transfer reaction to ring-fused β-lactams is evaluated. [ABSTRACT FROM AUTHOR]

The synthesis and characterization of four new tetracyanobutadiene (TCBD) derivatives (1-3 and 2') incorporating 2- or 2,7-fluorenyl and diphenylamino moieties are reported. The electroactivity of 1-3 and 2' was studied by cyclic voltammetry (CV), while the linear optical and (thirdorder) nonlinear optical (NLO) properties were investigated by electronic spectroscopy and Z-scan studies, respectively. All experimental investigations were rationalized by DFT computations, providing an insight into the electronic structure of these derivatives and on their application potential. We show that these derivatives are nonluminescent in solution at ambient temperatures, but become fluorescent in solvent glasses. This finding constitutes an unprecedented observation for TCBD derivatives. Also, we show by Z-scan studies that these derivatives behave as two-photon absorbers in the near-IR range (800-1050 nm). These third-order NLO properties are discussed and compared with those of their alkynyl precursors (4-6), which have been investigated by two-photon excited fluorescence (TPEF). [ABSTRACT FROM AUTHOR]

The synthesis and characterization of four new tetracyanobutadiene (TCBD) derivatives (1-3 and 2') incorporating 2- or 2,7-fluorenyl and diphenylamino moieties are reported. The electroactivity of 1-3 and 2' was studied by cyclic voltammetry (CV), while the linear optical and (thirdorder) nonlinear optical (NLO) properties were investigated by electronic spectroscopy and Z-scan studies, respectively. All experimental investigations were rationalized by DFT computations, providing an insight into the electronic structure of these derivatives and on their application potential. We show that these derivatives are nonluminescent in solution at ambient temperatures, but become fluorescent in solvent glasses. This finding constitutes an unprecedented observation for TCBD derivatives. Also, we show by Z-scan studies that these derivatives behave as two-photon absorbers in the near-IR range (800-1050 nm). These third-order NLO properties are discussed and compared with those of their alkynyl precursors (4-6), which have been investigated by two-photon excited fluorescence (TPEF). [ABSTRACT FROM AUTHOR]

The chitinase-like proteins YKL-39 (chitinase 3-like-2) and YKL- 40 (chitinase 3-like-1) are highly expressed in a number of human cells independent of their origin (mesenchymal, epithelial or haemapoietic). Elevated serum levels of YKL-40 have been associated with a negative outcome in a number of diseases ranging from cancer to inflammation and asthma. YKL-39 expression has been associated with osteoarthritis. However, despite the reported association with disease, the physiological or pathological role of these proteins is still very poorly understood. Although YKL-39 is homologous to the two family 18 chitinases in the human genome, it has been reported to lack any chitinase activity. In the present study, we show that human YKL-39 possesses a chitinase-like fold, but lacks key active-site residues required for catalysis. A glycan screen identified oligomers of N-acetylglucosamine as preferred binding partners. YKL-39 binds chitooligosaccharides and a newly synthesized derivative of the bisdionin chitinase-inhibitor class with micromolar affinity, through a number of conserved tryptophan residues. Strikingly, the chitinase activity of YKL-39 was recovered by reverting two non-conservative substitutions in the active site to those found in the active enzymes, suggesting that YKL-39 is a pseudo-chitinase with retention of chitinase-like ligand-binding properties. [ABSTRACT FROM AUTHOR]

Summary: Acidic mammalian chitinase (AMCase) is produced in the lung during allergic inflammation and asthma, and inhibition of enzymatic activity has been considered as a therapeutic strategy. However, most chitinase inhibitors are nonselective, additionally inhibiting chitotriosidase activity. Here, we describe bisdionin F, a competitive AMCase inhibitor with 20-fold selectivity for AMCase over chitotriosidase, designed by utilizing the AMCase crystal structure and dicaffeine scaffold. In a murine model of allergic inflammation, bisdionin F-treatment attenuated chitinase activity and alleviated the primary features of allergic inflammation including eosinophilia. However, selective AMCase inhibition by bisdionin F also caused dramatic and unexpected neutrophilia in the lungs. This class of inhibitor will be a powerful tool to dissect the functions of mammalian chitinases in disease and represents a synthetically accessible scaffold to optimize inhibitory properties in terms of airway inflammation. [ABSTRACT FROM AUTHOR]