82201-80-7Relevant academic research and scientific papers
Conformation-based restrictions and scaffold replacements in the design of hepatitis C virus polymerase inhibitors: Discovery of deleobuvir (BI 207127)
LaPlante, Steven R.,B?s, Michael,Brochu, Christian,Chabot, Catherine,Coulombe, René,Gillard, James R.,Jakalian, Araz,Poirier, Martin,Rancourt, Jean,Stammers, Timothy,Thavonekham, Bounkham,Beaulieu, Pierre L.,Kukolj, George,Tsantrizos, Youla S.
supporting information, p. 1845 - 1854 (2014/04/03)
Conformational restrictions of flexible torsion angles were used to guide the identification of new chemotypes of HCV NS5B inhibitors. Sites for rigidification were based on an acquired conformational understanding of compound binding requirements and the roles of substituents in the free and bound states. Chemical bioisosteres of amide bonds were explored to improve cell-based potency. Examples are shown, including the design concept that led to the discovery of the phase III clinical candidate deleobuvir (BI 207127). The structure-based strategies employed have general utility in drug design.
Synthesis of spiro-bisperoxyketals
Ghorai, Prasanta,Dussault, Patrick H.,Hu, Chunhua
supporting information; experimental part, p. 2401 - 2404 (2009/05/11)
(Chemical Equation Presented) Syntheses of spirocyclic bis-1,2-dioxolanes, bis-1,2-dioxanes, and bis-1,2-dioxepanes are achieved through intramolecular ketalizations of hydroperoxy ketones or intramolecular alkylations of gem-dihydroperoxides. The spirope
Stereo- and regioselectivity of cyclization reactions in conformationally restricted epoxy ketones: Evaluation of C- versus O-alkylation process
Crotti, Paolo,Badalassi, Fabrizio,Di Bussolo, Valeria,Favero, Lucilla,Pineschi, Mauro
, p. 8559 - 8572 (2007/10/03)
The intramolecular addition reaction of metal enolates of ketones to oxiranes has been applied to a series of epoxy ketones derived from cyclohexene oxide. γ-Hydroxy ketones (γ-HKs, C-alkylation products) or hydroxy enol ethers (HEEs, O-alkylation products) are obtained, depending on the nature of the cyclic transition state in each case involved and the application of the Fu?rst-Plattner rule. The formation of HEEs by reaction of the same epoxy ketones under acid conditions is also described. In some cases, regioconvergent or chemoselective processes are conveniently obtained.
Lewis Acis Induced Ene Cyclization of ω-Olefinic Trifluoromethyl Ketones: Access to BIcyclic Compounds Bearing a CF3 Group
Abouabdellah, Ahmed,Begue, Jean-Pierre,Bonnet-Delpon, Daniele,Lequeux, Thierry
, p. 5800 - 5808 (2007/10/02)
Lewis acid induced ene cyclization of ω-olefinic trifluoromethyl ketones provides (trifluoromethyl)decalins and (trifluoromethyl)hydrindans in high yield. δ-(1-Cyclohexenyl) trifluoromethyl ketone 1a leads stereoselectively to 1-(trifluoromethyl)-1-hydroxy-Δ5,10-octalin 3a or 10-chloro-1-(trifluoromethyl)-1-hydroxydecalin 6a, depending on the choice of Lewis acid. γ-(1-Cyclohexenyl) trifluoromethyl ketone 2a leads to a mixture of 9-chloro-1-(trifluoromethyl)-1-hydroxyhydrindans 10a and 11a.Similar reactions were performed successfully with the corresponding β-keto esters 1b and 2b.
Intramolecular and Intermolecular Lewis Acid Catalyzed Ene Reactions Using Ketones as Enophiles
Jackson, Andrew C.,Goldman, Boris E.,Snider, Barry B.
, p. 3988 - 3994 (2007/10/02)
Alkylaluminium halide catalyzed intramolecular ene reactions of β-keto esters proceed in high yield to give cyclohexanols, via either a type I or type II process.Treatment of β-keto ester 3 with Me2AlCl gives cis-fused ene adduct 5 in 67percent yield.Simi
A Novel Synthesis of (+/-)-Perhydrohistrionicotoxin
Keck, Gary E.,Yates, John B.
, p. 3590 - 3591 (2007/10/02)
A formal total synthesis of (+/-)-perhydrohistrionicotoxin is reported, which utilizes an intramolecular ene reaction for construction of the spirocyclic skeleton.
