0000000000006431
AUTHOR
Jose Luis Acena
showing 21 related works from this author
First Fluorous Synthesis of Fluorinated Uracils
2006
This paper describes a novel fluorous synthesis of fluorinated uracils 4. In this new protocol, fluorous alcohols 1, which are used as fluorous tags, are acetylated to yield acetates 2, which in turn are treated with a base to form their enolates. These are then reacted with fluorinated nitriles to furnish tagged β-enamino esters 3. Although this condensation step had been performed easily in previous solution and solid-phase syntheses, it proved to be very elusive in the fluorous version. Meticulous control of the reaction conditions was thus essential in order to achieve satisfactory yields of β-enamino esters 3. The final treatment of compounds 3 with isocyanates or isothiocyanates effic…
Synthetic and Biological Applications of Fluorous Reagents as Phase Tags
2011
The search for new and better techniques for the purification of organic compounds has made the recent emergence of fluorous chemistry in the field of organic synthesis possible. Using fluorous reagents as phase tags allows for the access of different synthetic routes, and this has been translated into a time reduction and higher simplicity compared to standard, nonfluorous procedures. The synthesis in fluorous phase of target molecules can be pursued in a parallel or combinatorial manner in order to access chemical libraries with structural and/or stereochemical diversity. The preparation of radiolabeled molecules also benefits from the advantages of fluorous synthesis. Finally, biochemica…
A new strategy for the synthesis of fluorinated 3,4-dihydropyrimidinones
2009
A new family of 3,4-dihydropyrimidinones (DHPMs) bearing fluorinated substituents at C6 have been prepared from gem-difluorinated nitriles, alkyl 3-butenoates and iso(thio)cyanates. This novel Biginelli-type process relies on the gamma-addition of the ester-derived enolate to fluorinated nitriles. A tandem nucleophilic addition aza-Michael reaction sequence completes the synthetic process. (C) 2009 Elsevier B.V. All rights reserved.
ChemInform Abstract: Cross-Metathesis Reactions as an Efficient Tool in the Synthesis of Fluorinated Cyclic β-Amino Acids.
2009
The synthesis of enantiomerically pure, cyclic, gamma,gamma-difluorinated beta-amino acids with various ring sizes has been carried out with a cross-metathesis (CM) reaction being one of the key steps, followed by a Dieckmann-type condensation to bring about the cyclization. Subsequent catalytic hydrogenation under microwave irradiation with (-)-8-phenylmenthol as a chiral auxiliary led to the successful chemo- and diastereoselective chemical reduction of the resulting cyclic beta-enamino esters. The efficiency and scope of the CM reaction with different types of fluorinated imidoyl chlorides and unsaturated esters has also been studied in order to determine the optimal reaction conditions …
ChemInform Abstract: An Approach to 2,4-Substituted Pyrazolo[1,5-a]pyridines and Pyrazolo[1,5-a]azepines by Ring-Closing Metathesis.
2014
Based on the title approach, the diastereoselective synthesis of potential peptidomimetics [(XI) and (XIV)] is described.
Cross-Metathesis Reactions as an Efficient Tool in the Synthesis of Fluorinated Cyclic β-Amino Acids
2009
The synthesis of enantiomerically pure, cyclic, gamma,gamma-difluorinated beta-amino acids with various ring sizes has been carried out with a cross-metathesis (CM) reaction being one of the key steps, followed by a Dieckmann-type condensation to bring about the cyclization. Subsequent catalytic hydrogenation under microwave irradiation with (-)-8-phenylmenthol as a chiral auxiliary led to the successful chemo- and diastereoselective chemical reduction of the resulting cyclic beta-enamino esters. The efficiency and scope of the CM reaction with different types of fluorinated imidoyl chlorides and unsaturated esters has also been studied in order to determine the optimal reaction conditions …
Tiratricol neutralizes bacterial endotoxins and reduces lipopolysaccharide-induced TNF-alpha production in the cell.
2008
Contains fulltext : 70610.pdf (Publisher’s version ) (Closed access) The screening of a commercially available library of compounds has proved a successful strategy for the identification of a lead compound in a drug discovery programme. Here, we analysed 880 off-patent drugs, which initially comprised the Prestwick Chemical library, as sources of bacterial endotoxin neutralizers. We identified 3,3',5-triiodo-thyroacetic acid (tiratricol) as a non-antibacterial compound that neutralizes the toxic lipopolysaccharide.
ChemInform Abstract: A General Overview of the Organocatalytic Intramolecular Aza-Michael Reaction
2015
The organocatalytic intramolecular aza-Michael reaction gives access to enantiomerically enriched nitrogen-containing heterocycles in a very simple manner. Enals, enones, conjugated esters and nitro olefins have been employed as Michael acceptors, while moderate nitrogen nucleophiles such as sulphonamides, carbamates and amides have been shown to be appropriate Michael donors in this type of reaction. Additionally, the process has been performed under both covalent and non-covalent catalysis, with diaryl prolinols, imidazolidinones, thioureas and chiral binol phosphoric acids being the most frequently used catalysts. The level of efficiency reached with this protocol is demonstrated by the …
ChemInform Abstract: Organocatalytic anti-Selective Mannich Reactions with Fluorinated Aldimines: Synthesis of anti-γ-Fluoroalkyl-γ-amino Alcohols.
2010
The asymmetric Mannich reaction between fluoroalkyl aldimines and aldehydes catalyzed by α,α-diphenylprolinol trimethylsilyl ether is reported. The corresponding Mannich adducts were reduced in situ to afford anti-β-alkyl-γ-fluoroalkyl-γ-amino alcohols in moderate yields and with very high diastereo- and enantioselectivities. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Role of the gem-Difluoro Moiety in the Tandem Ring-Closing Metathesis−Olefin Isomerization: Regioselective Preparation of Unsaturated Lactams
2006
Careful selection of the metathesis catalyst, solvent, and reaction conditions allows for the efficient and regioselective synthesis of isomeric fluorinated and nonfluorinated lactam derivatives II and III from precursor amides I through a ring-closing metathesis (RCM) reaction or a tandem RCM-isomerization protocol, respectively. The presence of the gem-difluoro moiety in the starting materials exerts a pivotal effect by directing the isomerization step, making the overall tandem transformation a regioselective process. The scope, limitations, and synthetic usefulness of this protocol are also discussed.
ChemInform Abstract: Fluorous TBAF: A Convenient and Selective Reagent for Fluoride-Mediated Deprotections.
2010
A fluorous analogue of TBAF has been developed for its use in the clean removal of silicon-derived protecting groups. Purification of the crude mixtures by fluorous solid-phase extractions allowed alcohols, amines, and carboxylic acids to be obtained in high purity, with no need of chromatographic separations. The moderate reactivity of fluorous TBAF was exploited in selective deprotections of several bifunctional molecules.
Biochemical quantitation of the eIF5A hypusination in Arabidopsis thaliana uncovers ABA-dependent regulation.
2014
The eukaryotic translation elongation factor eIF5A is the only protein known to contain the unusual amino acid hypusine which is essential for its biological activity. This post-translational modification is achieved by the sequential action of the enzymes deoxyhypusine synthase (DHS) and deoxyhypusine hydroxylase (DOHH). The crucial molecular function of eIF5A during translation has been recently elucidated in yeast and it is expected to be fully conserved in every eukaryotic cell, however the functional description of this pathway in plants is still sparse. The genetic approaches with transgenic plants for either eIF5A overexpression or antisense have revealed some activities related to t…
Synthesis and biological evaluation of new bicyclic fluorinated uracils through ring-closing metathesis.
2006
Two families of bicyclic fluorinated uracils have been prepared starting from a gem-difluorinated unsaturated nitrile, by means of a ring-closing metathesis reaction to form the new ring, which is fused at the C-5/C-6 or N-1/C-6 positions of the uracil moiety. The selective formation of olefin regioisomers in the metathesis process can be controlled according to the reaction conditions (catalyst, solvent, and temperature). The acaricidal activities of the resulting compounds have also been investigated.
A general overview of the organocatalytic intramolecular aza-Michael reaction
2014
The organocatalytic intramolecular aza-Michael reaction gives access to enantiomerically enriched nitrogen-containing heterocycles in a very simple manner. Enals, enones, conjugated esters and nitro olefins have been employed as Michael acceptors, while moderate nitrogen nucleophiles such as sulphonamides, carbamates and amides have been shown to be appropriate Michael donors in this type of reaction. Additionally, the process has been performed under both covalent and non-covalent catalysis, with diaryl prolinols, imidazolidinones, thioureas and chiral binol phosphoric acids being the most frequently used catalysts. The level of efficiency reached with this protocol is demonstrated by the …
Organocatalyticanti-Selective Mannich Reactions with Fluorinated Aldimines: Synthesis ofanti-γ-Fluoroalkyl-γ-amino Alcohols
2009
The asymmetric Mannich reaction between fluoroalkyl aldimines and aldehydes catalyzed by α,α-diphenylprolinol trimethylsilyl ether is reported. The corresponding Mannich adducts were reduced in situ to afford anti-β-alkyl-γ-fluoroalkyl-γ-amino alcohols in moderate yields and with very high diastereo- and enantioselectivities. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
New Fluorinated 1,3-Vinylogous Amidines as Versatile Intermediates: Synthesis of Fluorinated Pyrimidin-2(1H)-ones.
2006
The condensation of the azaenolates derived from readily available ketimines with fluorinated nitriles offers an efficient and straightforward entry to new fluorinated 1,3-vinylogous amidines. These versatile compounds, in turn, react with triphosgene to yield new fluorinated pyrimidin-2(1H)-ones in high yields.
ChemInform Abstract: A New Strategy for the Synthesis of Fluorinated 3,4-Dihydropyrimidinones.
2010
A new family of 3,4-dihydropyrimidinones (DHPMs) bearing fluorinated substituents at C6 have been prepared from gem-difluorinated nitriles, alkyl 3-butenoates and iso(thio)cyanates. This novel Biginelli-type process relies on the γ-addition of the ester-derived enolate to fluorinated nitriles. A tandem nucleophilic addition aza-Michael reaction sequence completes the synthetic process.
ChemInform Abstract: Diastereoselective Intramolecular Additions of Allyl- and Propargylsilanes to Iminium Ions: Synthesis of Cyclic and Bicyclic Qua…
2010
Cyclization of the chiral imino lactones with allylic or propargylic groups required acidic conditions to afford spirocyclic (II) or (XII).
Fluorous TBAF: A Convenient and Selective Reagent for Fluoride-Mediated Deprotections
2009
A fluorous analogue of TBAF has been developed for its use in the clean removal of silicon-derived protecting groups. Purification of the crude mixtures by fluorous solid-phase extractions allowed alcohols, amines, and carboxylic acids to be obtained in high purity, with no need of chromatographic separations. The moderate reactivity of fluorous TBAF was exploited in selective deprotections of several bifunctional molecules.
Diastereoselective Intramolecular Additions of Allyl- and Propargylsilanes to Iminium Ions: Synthesis of Cyclic and Bicyclic Quaternary Amino Acids
2010
Chiral imino lactones derived from (R)-phenylglycinol containing an allyl- or propargyltrimethylsilyl group in the side chain readily cyclized in the presence of acidic reagents to afford spirocyclic compounds with high diastereoselectivity. Removal of the chiral auxiliary produced 2-substituted 1-aminocycloalkanecarboxylic acids, whereas further cyclizations by means of metathesis or hydroamination reactions led to bicyclic derivatives of pipecolic acid and proline.
An Approach to 2,4-Substituted Pyrazolo[1,5-a]pyridines and Pyrazolo[1,5-a]azepines by Ring-Closing Metathesis
2013
The ring-closing metathesis (RCM) reactions of dienylpyrazoles have been employed in the synthesis of pyrazolo[1,5-a]pyridine and pyrazolo[1,5-a]azepine derivatives. Based on this approach, the diastereoselective synthesis of potential peptidomimetics containing four amino acid residues with the second (i+1) and third (i+2) fragments having been substituted by bicyclic frameworks is described.