Browsing by Author "Gorobets, Evgueni"
Now showing 1 - 6 of 6
Results Per Page
Sort Options
- ItemOpen AccessAvoiding the classical resolution during the synthesis of MeO-BIPHEP and 3,3-disubstituted derivatives(Elsevier, 2005) Keay, Brian A.; Gorobets, Evgueni; Wheatley, Bronwen M. M.; Hopkins, J. Matthew; McDonald, Robert
- ItemOpen AccessBeyond geminal diesters: increasing the scope of metal-mediated vinylcyclopropane annulations while decreasing pre-activation(2018-01) Brownsey, Duncan K.; Gorobets, Evgueni; Derksen, Darren J.The utilization of unactivated substrates in annulation reactions provides access to complex products without the need for subsequent removal of the activating group. Vinylcyclopropanes (VCPs), occurring naturally in several monoterpene natural products, are an important building block for organic chemistry, and can be activated by electron withdrawing substituents directly on the cyclopropane to facilitate ring opening reactions. However, many VCPs that lack these activated groups remain reactive with several group 8, 9 and 10 transition metals, by alternative modes of activation, forming metallacycles. These useful intermediates produce annulation products in reactions with unsaturated π-units, providing rapid access to new carbocycles. Several formal cycloadditions that incorporate unactivated VCPs as substrates have been developed, including [5 + 2], [5 + 2 + 1], [5 + 1 + 2 + 1], [3 + 2], [3 + 2 + 1], [5 + 1], and others, using Rh, Ni, Ru, Ir, Fe and Co based catalysts. Mono- and polycyclic ring systems have been made using these methods with their utility demonstrated through the synthesis of complex natural products. This review will summarize the annulations of VCPs that lack geminal diesters, but retain reactivity via transition metal catalysts.
- ItemOpen AccessA General Strategy for the Preparation of Thalidomide-Conjugate Linkers(2017-01) Papatzimas, James; Gorobets, Evgueni; Brownsey, Duncan; Maity, Ranjan; Bahlis, Nizar; Derksen, DarrenThe synthesis of small-molecule linkers for installation of thalidomide-based conjugates is described. Linker properties have been recognized as vital to conjugate success in drug discovery and delivery systems. These small-molecule tethers act as linkages between molecules, can also aid in cell permeability, and act as solubilizing agents. This work shows our progress in synthesizing conjugates with a variety of linker characteristics. The adaptability and manipulation of these and other linkers holds potential in improving synthetic control of chemical connectivities toward therapeutic development.
- ItemOpen AccessNatural-Product-Derived Transient Receptor Potential Melastatin 8 (TRPM8) Channel Modulators(2016-01) LeGay, Christina M; Gorobets, Evgueni; Iftinca, Mircea; Ramachandran, Rithwik; Altier, Christophe; Derksen, Darren JA library of novel structural hybrids of menthol and cubebol was tested for each derivative's ability to interact with the transient receptor potential subfamily melastatin member 8 (TRPM8) channel. This structure-activity relationship study revealed three potent modulators of the TRPM8 ion channel: a novel agonist (4) with an EC50 value of 11 ± 1 μM, an antagonist (15) with an IC50 value of 2 ± 1 μM, and an allosteric modulator (21) that minimized channel desensitization toward menthol. Each of these novel exocyclic olefin analogues of menthol is readily accessible by synthesis and was tested using Ca(2+) assays and electrophysiology.
- ItemOpen AccessSynthesis, resolution and applications of 3,3'-bis(RO)-MeO-BIPHEP derivatives(Elsevier, 2004) Keay, Brian A.; Gorobets, Evgueni; Sun, Guang-Ri; Wheatley, Bronwen M. M.; Parvez, Masood
- ItemOpen AccessUse of 1H NMR chemical shifts to determine the absolute configuration and enantiomeric purity for enantiomers of 3,3' -disubstituted-MeO-BIPHEP derivatives1(National Research Council Canada, 2006) Gorobets, Evgueni; Parvez, Masood; Wheatley, Bronwen M.M.; Keay, Brian A.