2016-01- Mycobacterial pathogen subverts immunity by selective blockade of the Sec61 translocon
Demangel, C. ; Baron, L. ; Paatero, A. ; Morel, J.-D. ; Impens, F. ; Guenin-Macé, L. ; Saint-Auret, S. ; Blanchard, N. ; Dillmann, R. ; Niang, F. ; Pellegrini, S. ; Taunton, J. ; Paavilainen, V. J. Exp. Med. 2016, 213, 2885-2896.
Mycolactone, an immunosuppressive macrolide released by the human pathogen Mycobacterium ulcerans, was previously shown to impair Sec61-dependent protein translocation, but the underlying molecular mechanism was not identified. Our data provide definitive genetic evidence that Sec61 is the host receptor mediating the diverse immunomodulatory effects of mycolactone and identify Sec61 as a novel regulator of immune cell functions.
Stereoselective hydrometalation reactions of aryl- and alkyl- substituted trifluoromethylated alkynes with triethylsilane, tributylstannane, and triphenylgermane have been investigated. Applications of the (Z)- and (E)-α-CF3-vinylgermanes in palladium-catalyzed cross-coupling reactions with aryl halides having diverse electronic requirements were also investigated. The corresponding (Z)- and (E)-α-CF3-styrenes were obtained as single isomers, thus demonstrating the utility of these versatile synthons for the synthesis of stereodefined trifluoromethylated alkenes.
γ-Trifluoromethylated allenamides were obtained in good to excellent yields through a base-induced isomerization from the corresponding protected trifluoromethylated propargylic amines. This method, which simply required the treatment of the starting propargylic amines with sodium hydroxide in THF, was found to be fairly general and tolerates various alkyl and aryl substituents and a range of protecting groups on the nitrogen atom.
Due to their stability and reactivity, ynamides have emerged as remarkably useful building blocks. The development of robust methods for their preparation resulted in the development of efficient processes starting from these building blocks which also recently found various applications in medicinal chemistry and natural product synthesis. Our contributions to the chemistry of ynamides are overviewed in this highlight review
2016-05- Inverse Electron-Demand [4 + 2]-Cycloadditions of Ynamides: Access to Novel Pyridine Scaffolds
Duret, G.; Quinlan, R.; Martin, R. E.; Bisseret, P.; Neuburger, M.; Gandon, V.; Blanchard, N. Org. Lett.2016, 18, 1610.
Functionalized polycyclic aminopyridines are central to the chemical sciences, but their syntheses are still hampered by a number of shortcomings. These nitrogenated heterocycles can be efficiently prepared by an intramolecular inverse electron demand hetero Diels−Alder (ihDA) cycloaddition of ynamides to pyrimidines. This ihDA/rDA sequence is general in scope and affords expedient access to novel types of aminopyridinyl scaffolds that hold great promise in terms of exit vector patterns.
The photochemical and electrochemical investigations of commercially available, safe, and cheap fluorescent brighteners as well as their original use as photoinitiators of polymerization upon light emitting diode (LED) irradiation are reported. The underlying photochemical mechanisms are investigated by electron-spin resonance-spin trapping, fluorescence, cyclic voltammetry, and steady-state photolysis techniques.
2016-07- Synthesis of cyclopropanated [2.2.1] heterobicycloalkenes: An improved procedure
Carlson, E.; Duret, G.; Blanchard, N.; Tam, W., Synth. Commun. 2016, 46, 55-62.
A safer and improved method to our previous report on palladium-catalyzed cyclopropanation of heterobicyclic alkenes has been developed. Using this methodology, yields to previously reported products were markedly increased, and 10 new cyclopropanated [2.2.1] heterobicyclic products were prepared. In addition, this work accounts for the first reported cyclopropanation of 2,3-diazabicyclic alkenes, which all gave excellent yields of >90%.
