A new strategy for direct access to fully substituted polycyclic imidazolium ionic liquids, based on the interaction of α-enaminones with proline in the presence of a variety of counter-ions, is reported. The developed open-fl ask operation is catalyst-, metal-, and Lewis acid-free green process, which requires no ion-exchange step, is not limited to aryl substituents, and generally results in good yields and minimal formation of side products.
Neurotropic activity and safety of methylene-cycloalkylacetate (MCA) derivative 3-(3-allyl-2-methylenecyclohexyl) propanoic acid. Lahiani, A., Hacham-Geula, D., Lankri, D., Cornell-Kennon, S., Schaefer, E. M., Tsvelikhovsky, D., Lazarovici, P.
The Institute for Drug Research, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel.
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Polyneuropathy is a disease involving multiple peripheral nerves injuries. Axon regrowth remains the major prerequisite for plasticity, regeneration, circuit formation, and eventually functional recovery and therefore, regulation of neurite outgrowth might be a candidate for treating polyneuropathies. In a recent study, we synthesized and established the methylene-cycloalkylacetate (MCAs) pharmacophore as a lead for the development of a neurotropic drug (inducing neurite/axonal outgrowth) using the PC12 neuronal model. In the present study we extended the characterizations of the in vitro neurotropic effect of the derivative allylmethylene-cyclohexyl-propanoic acid (MCA-13) on dorsal root ganglia and spinal cord neuronal cultures and analyzed its safety properties using blood biochemistry and cell counting, acute toxicity evaluation in mice and different in vitro “off-target” pharmacological evaluations. This MCA derivative deserves further preclinical mechanistic pharmacological characterizations including therapeutic efficacy in in vivo animal models of polyneuropathies, toward development of a clinically relevant neurotropic drug.
Yelena Mostinski (left) graduated in 2018 from the Institute for Drug Research, School of Pharmacy at the Hebrew University of Jerusalem. In 2013, she started her M.Sc. in Medicinal Chemistry under the supervision of Dr. Tsvelikhovsky and continued towards her Ph.D. via a direct track. The object of her research was the regio- and stereoselective access to natural and natural-like tricyclic spiranoid lactones.
David Lankri (right) received his B.Pharm. and M.Sc. degree in Medicinal Chemistry from the Hebrew University of Jerusalem in 2014 and 2016, respectively. Since 2016, he has been a Ph.D. student at the Institute for Drug Research, School of Pharmacy at the Hebrew University. His research interests focus on the development of methods for the synthesis of tricyclic angularly fused lactones.
An unprecedented Palladium-catalyzed cascade Wacker–Heck lactonization- cyclization sequence is reported. The process provides a facile approach to bi- and tricyclic spiranoid lactones in good yields. The reaction shows general substrate scope and a broad functional group tolerability. In addition, a rare 4-exo trig Heck-type cyclization is demonstrated.
HOT PAPER - FRONTISPIECE
A general, parallel, and collective synthesis of 5/5/5- and 5/5/6-ring fusion topologies of tricyclic spiranoid lactones through the controlled cyclizations of easily accessible, common key precursors is described. The rapid composition of key cycloalkyl methylene precursors yielded an assembly of bicyclic diastereoisomeric iodolactones, which were individually converted into a wide range of tricyclic, angularly fused spiranoid lactones in a regioselective and stereodirected fashion through the diastereoisomeric differentiation of a collective key precursor.
Tsvelikhovsky‚ D. ; Buchwald‚ S. L. (2011)
Concise Palladium-Catalyzed Synthesis of Dibenzazepins and Structural Analogues, J. Am. Chem. Soc. 133‚ 14228
Tsvelikhovsky‚ D. ; Buchwald‚ S. L. (2010)
Synthesis of Heterocycles via Pd-Ligand Controlled Cyclization of 2-Chloro-N-(2-vinyl)aniline: Preparation of Carbazoles‚ Indoles‚ Dibenzazepins and Acridines, J. Am. Chem. Soc. 132‚ 14048
Highlighted in [Science & Tech] Chemical & Engineering News, 88(44), 2010
Rozin, L. ; Tsvelikhovsky‚ D.; Schwarzeb, M.; Schomackerb, R.; Fanun, M.; Blum, J. (2010)
Dependence of the Heck coupling in aqueous microemulsion by supported palladium acetate on the surfactant and on the hydrophobicity of the support, J. Mol. Catal. A-Chem. 323‚ 65.
Tsvelikhovsky, D.; Popov, I.; Gutkin, V.; Rozin, A.; Shvartsman, A.; Blum, J. (2009)
On the Involvement of Palladium Nanoparticles in the Heck and Suzuki Reactions, Eur. J. Org. Chem. 98
Tsvelikhovsky, D.; Pessing, D.; Avnir, D.; Blum, J. (2008)
Forcing a cis-Product by Matrix Imprinting: Heck Reaction Catalyzed by Palladium Acetate Entrapped within cis-Imprinted Sol-Gel Derived Silicates, Adv. Syn. Catal. 350, 2856
Highlighted in Synfacts, 2009, 4, 462.
Tsvelikhovsky, D.; Blum, J. (2008)
Three Phase Microemulsion/Sol-Gel System for Aqueous C-C Coupling of Hydrophobic Substrates, Eur. J. Org. Chem. 201
Tsvelikhovsky, D.; Schumann, H.; Blum, J. (2006)
Cerium(IV)-Promoted Ethylation of Schiff Bases by Triethylaluminum, SYNTHESIS, 11, 1819
Tsvelikhovsky, D.; Gelman, D.; Molander, G. A.; Blum, J. (2004)
Lanthanide-Promoted Ethylation of Schiff Bases by Triethylaluminum, Org. Lett. 6, 1995
Gelman, D.; Tsvelikhovsky, D.; Molander, G. A.; Blum, J. (2002)
Palladium-Catalyzed Cross-Alkynylation of Aryl Bromides by Sodium Tetraalkynylaluminates, J. Org. Chem. 67, 6287