- Synthesis and characterization of novel polystyrene-supported TBD catalysts and their use in the Michael addition for the synthesis of Warfarin and its analogues
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In the search for efficient and polymeric supports for organic bases to be used in environmentally friendly media and conditions, novel polystyrene-bound 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) has been prepared and characterized. Their catalytic properties have been tested in the Michael additions of 4-hydroxycoumarin to α,β-unsaturated ketones as a representative useful process for the syntheses of 4-hydroxy-3-(3-oxo-1-phenylbutyl)-2H- chromen-2-one (Warfarin), 4-hydroxy-3-(1-(4-nitrophenyl)-3-oxobutyl)-2H- chromen-2-one (Acenocumarol), 4-hydroxy-3-(1-(4-chlorophenyl)-3-oxobutyl) -2H-chromen-2-one (Coumachlor), and 4-hydroxy-3-(1-(4-methoxyphenyl)-3- oxobutyl)-2H-chromen-2-one. Products were obtained in high to quantitative conversion yields. The novel catalytic systems showed promising catalytic properties, and they could be all easily recovered by filtration and have been reused for three representative consecutive runs without any significant lowering of their activity.
- Alonzi, Matteo,Bracciale, Maria Paola,Broggi, Alessandra,Lanari, Daniela,Marrocchi, Assunta,Santarelli, Maria Laura,Vaccaro, Luigi
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- New selective cyclooxygenase-2 inhibitors from cyclocoumarol: Synthesis, characterization, biological evaluation and molecular modeling
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In this work, a serie of cyclocoumarol derivatives was designed, synthesized, characterized and studied for their potentialities as selective inhibitors of COX-2. All target compounds have been screened for their anti-inflammatory activity by the assay of PGE2 production. Among them, compound 5d exhibited the most potent inhibitory activity with a PGE2 inhibition compared to NS-398 (79% and 88% respectively) and showed non-inhibitory activity towards the COX-1 enzyme. Docking studies revealed the capacity of this compound to occupy the selective COX-2 cavity establishing additional hydrogen bonds between the oxygen of the methoxy group and the His90 and Arg513 of the binding site of the enzyme.
- Rayar, Anita Marie,Lagarde, Nathalie,Martin, Frederique,Blanchard, Florent,Liagre, Bertrand,Ferroud, Clotilde,Zagury, Jean-Fran?ois,Montes, Matthieu,Sylla-Iyarreta Veitía, Maité
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p. 577 - 587
(2018/02/10)
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- NMR and DFT Insight into the Synergistic Role of Bovine Serum Albumin–Ionic Liquid for Multicomponent Cascade Aldol/Knoevenagel–thia-Michael/Michael Reactions in One Pot
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The synergistic combination of two catalysts is an emerging strategy towards the formation of unprecedented complex molecules, and herein bovine serum albumin (BSA) and the neutral ionic liquid 1-butyl-3-methylimidazolium bromide ([bmim]Br) are used together for the first time towards multiple C?C and C?S bond-formation reactions in one pot under metal-free, acid-free, and base-free conditions by merging two classical named reactions, that is, aldol condensation (AC) and thia-Michael addition (TMA) for the cascade chemoselective generation of β-aryl-β-sulfido carbonyl compounds from aliphatic ketones, aromatic aldehydes, and thiols. NMR spectroscopy and DFT calculations studies provided insight into the synergism, progress, and mechanism of the reaction, and control experiments highlighted that the single catalysts (BSA or IL) alone did not allow even the first AC step to proceed. Moreover this synergistic BSA–[bmim]Br catalytic system offers the step-economical synthesis of the anticoagulant warfarin through sequential aldol–Michael addition reactions and potent pyridine analogues through a Knoevenagel–Michael route. Besides, the recyclability of the catalytic system (up to 5 times) with the generation of water as a byproduct makes our one-pot protocol more economically efficient and synthetically attractive than traditional methods.
- Thopate, Yogesh,Singh, Richa,Sinha, Arun K.,Kumar, Vikash,Siddiqi, Mohammad Imran
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p. 3050 - 3056
(2016/10/11)
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- Gas phase retro-Michael reaction resulting from dissociative protonation: Fragmentation of protonated warfarin in mass spectrometry
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A mass spectrometric study of protonated warfarin and its derivatives (compounds 1 to 5) has been performed. Losses of a substituted benzylideneacetone and a 4-hydroxycoumarin have been observed as a result of retro-Michael reaction. The added proton is initially localized between the two carbonyl oxygens through hydrogen bonding in the most thermodynamically favorable tautomer. Upon collisional activation, the added proton migrates to the C-3 of 4-hydroxycoumarin, which is called the dissociative protonation site, leading to the formation of the intermediate ion-neutral complex (INC). Within the INC, further proton transfer gives rise to a proton-bound complex. The cleavage of one hydrogen bond of the proton-bound complex produces the protonated 4-hydroxycoumarin, while the separation of the other hydrogen bond gives rise to the protonated benzylideneacetone. Theoretical calculations indicate that the 1, 5-proton transfer pathway is most thermodynamically favorable and support the existence of the INC. Both substituent effect and the kinetic method were utilized for explaining the relative abundances of protonated 4-hydroxycoumarin and protonated benzylideneacetone derivative. For monosubstituted warfarins, the electron-donating substituents favor the generation of protonated substituted benzylideneacetone, whereas the electron-withdrawing groups favor the formation of protonated 4-hydroxycoumarin. Copyright
- Zhang, Jia,Chai, Yunfeng,Jiang, Kezhi,Yang, Huameng,Pan, Yuanjiang,Sun, Cuirong
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p. 1059 - 1064
(2012/11/07)
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