6611-97-8Relevant academic research and scientific papers
Bridged bicyclic 2,3-dioxabicyclo[3.3.1]nonanes as antiplasmodial agents: Synthesis, structure-activity relationships and studies on their biomimetic reaction with Fe(II)
D'Alessandro, Sarah,Alfano, Gloria,Di Cerbo, Luisa,Brogi, Simone,Chemi, Giulia,Relitti, Nicola,Brindisi, Margherita,Lamponi, Stefania,Novellino, Ettore,Campiani, Giuseppe,Gemma, Sandra,Basilico, Nicoletta,Taramelli, Donatella,Baratto, Maria Camilla,Pogni, Rebecca,Butini, Stefania
, (2019/06/13)
Despite recent advancements in its control, malaria is still a deadly parasitic disease killing millions of people each year. Progresses in combating the infection have been made by using the so-called artemisinin combination therapies (ACTs). Natural and synthetic peroxides are an important class of antimalarials. Here we describe a new series of peroxides synthesized through a new elaboration of the scaffold of bicyclic-fused/bridged synthetic endoperoxides previously developed by us. These peroxides are produced by a straightforward synthetic protocol and are characterized by submicromolar potency when tested against both chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum strains. To investigate their mode of action, the biomimetic reaction of the representative compound 6w with Fe(II) was studied by EPR and the reaction products were characterized by NMR. Rationalization of the observed structure-activity relationship studies was performed by molecular docking. Taken together, our data robustly support the hypothesized mode of activation of peroxides 6a-cc and led to the definition of the key structural requirements responsible for the antiplasmodial potency. These data will pave the way in future to the rational design of novel optimized antimalarials suitable for in vivo investigation.
A Failed Late-Stage Epimerization Thwarts an Approach to Ineleganolide
Horn, Evan J.,Silverston, Joel S.,Vanderwal, Christopher D.
supporting information, p. 1819 - 1838 (2016/03/15)
Significant efforts were made to complete a synthesis of the complex norcembranoid ineleganolide via a seemingly attractive strategy involving late-stage creation of the central seven-membered ring. While the two key enantioenriched building blocks were made via high-yielding sequences and their convergent union was efficient, the critical C4-C5 bond of this sterically congested natural product could never be forged. Several interesting examples of unexpected acid-base behavior and unanticipated proximity-induced reactivity accounted for most of the problems in the execution of the synthesis plan.
Organo[2-(hydroxymethyl)phenyl]dimethylsilanes as mild and reproducible agents for rhodium-catalyzed 1,4-addition reactions
Nakao, Yoshiaki,Chen, Jinshui,Imanaka, Hidekazu,Hiyama, Tamejiro,Ichikawa, Yoshitaka,Duan, Wei-Liang,Shintani, Ryo,Hayashi, Tamio
, p. 9137 - 9143 (2008/02/09)
Stable and reusable tetraorganosilicon reagents, alkenyl-, aryl-, and silyl[2-(hydroxymethyl)phenyl]-dimethylsilanes, undergo 1,4-addition reactions to α,β-unsaturated carbonyl acceptors under mild rhodium-catalysis. The reaction tolerates a diverse range of functional groups and is applicable to gram-scale synthesis. Use of a chiral diene ligand allows the achievement of the corresponding enantioselective transformations using the tetraorganosilicon reagents, providing the silicon-based approach to optically active ketones and substituted piperidones that serve as synthetic intermediates of pharmaceuticals. A rhodium alkoxide species is suggested to be responsible for a transmetalation step on the basis of the observed kinetic resolution of a racemic chiral phenylsilane in the enantioselective 1,4-addition reaction under the rhodium-chiral diene catalysis.
1,4-Addition of Triorganozincates and Silyldiorganozincates to α,β-Unsaturated Ketones
Tueckmantel, Werner,Oshima, Koichiro,Nozaki, Hitosi
, p. 1581 - 1593 (2007/10/02)
Lithium and magnesium triorganozincates, prepared by combination of ZnCl2(TMEDA) with 3 molar equivalents of RLi or RMgX, or from dialkylzinc and 1 molar equivalent of RLi or RMgX, react with 2-cyclohexen-1-one (1) under mild conditions to produce moderate to good yields of the 1,4-addition products 2.The approximate reactivity order obtained from the product distribution using unsymmetrical zincates is tBuCH2 tBu, Me Me2PhSi.The latter groups are transferred with good selectivity from mixed reagents derived from Me2Zn.This sequence differs strikingly from that exhibited by unsymmetrical cuprates which transfer neopentyl very easily, and also tert-butyl more easily than the corresponding zincates.The methylation with Me3ZnLi is catalyzed by cobalt complexes.Other enones (7-13) generally give poor yields, and the cobalt-catalyzed methylation of isophorone (3) is complicated by a Kharasch-type deconjugation.Mixed silyldialkylzincates, Me2PhSiZnR2Li, produce the β-silyl ketones from a variety of unhindered or moderately hindered enones in practically useful yields; one example of an α,β-unsaturated ester (12) is also included.
Alkenylcuprate reagents from arenesulfonylhydrazones
Kende, Andrew S.,Jungheim, Louis N.
, p. 3849 - 3852 (2007/10/02)
The use of ketone 2,4,6-triisopropylbenzenesulfonylhydrazones to generate alkenylcuprate reagents that add in 1,4-fashion to enones is described.
