Rodolfo Lavilla - Academia.edu (original) (raw)
Papers by Rodolfo Lavilla
Chemical Communications, 1997
ABSTRACT
Angewandte Chemie-international Edition, 2007
European Journal of Organic Chemistry, 1999
European Journal of Organic Chemistry, 2001
ABSTRACT
Organic Letters, 2003
The three-component reaction of dihydropyridines, aldehydes, and p-methylaniline efficiently form... more The three-component reaction of dihydropyridines, aldehydes, and p-methylaniline efficiently forms highly substituted tetrahydroquinolines in a stereoselective manner through a Lewis acid-catalyzed formal [4 + 2] cycloaddition. InCl(3) and Sc(OTf)(3) are the catalysts of choice for this process. The in situ generation of a reactive 1,4-dihydropyridine through the regioselective nucleophilic addition of cyanide to pyridinium salts allows a one-pot four-component transformation.
Tetrahedron Letters, 1998
Iodine (or related species) addition to 1,4-dihydropyridines, with properly attached substituents... more Iodine (or related species) addition to 1,4-dihydropyridines, with properly attached substituents at the nitrogen atom, leads to the corresponding 3-iodotetrahydropyridinium ions, which undergo an internal nucleophilic attack to furnish regio- and stereoselectively iodobi(poly)lteterocyclic ring systems in good yields.
Journal of Organic Chemistry, 1990
... M.-Lluisa Bennasar, Mercedes Alvarez, Rodolfo Lavilla, Ester Zulaica, and Joan Bosch* Laborat... more ... M.-Lluisa Bennasar, Mercedes Alvarez, Rodolfo Lavilla, Ester Zulaica, and Joan Bosch* Laboratory of Organic Chemistry, Faculty of Pharmacy, University of Barcelona, Barcelona-08028, Spain Received July 6, 1989 ... 1970, 480. (b) Ziegler, 2. E.; Spitzner, EB J. Am. Chem. Soc. ...
ChemInform
Electrophilic Oxidative Additions upon 1,4-Dihydropyridines.
The Journal of Organic Chemistry
... Rodolfo Lavilla,* Oscar Coll, Rakesh Kumar, and Joan Bosch*. Laboratory of Organic Chemistry,... more ... Rodolfo Lavilla,* Oscar Coll, Rakesh Kumar, and Joan Bosch*. Laboratory of Organic Chemistry, Faculty of Pharmacy, University of Barcelona, 08028 Barcelona, Spain. J. Org. Chem. ... a review, see: Bennasar, M.-L.; Lavilla, R.; Alvarez, M.; Bosch, J. Heterocycles1988, 27, 789. ...
Chemistry - A European Journal
Nature Communications, 2015
Natural peptides show high degrees of specificity in their biological action. However, their ther... more Natural peptides show high degrees of specificity in their biological action. However, their therapeutical profile is severely limited by their conformational freedom and metabolic instability. Stapled peptides constitute a solution to these problems and access to these structures lies on a limited number of reactions involving the use of non-natural amino acids. Here, we describe a synthetic strategy for the preparation of unique constrained peptides featuring a covalent bond between tryptophan and phenylalanine or tyrosine residues. The preparation of such peptides is achieved in solution and on solid phase directly from the corresponding sequences having an iodo-aryl amino acid through an intramolecular palladium-catalysed C-H activation process. Moreover, complex topologies arise from the internal stapling of cyclopeptides and double intramolecular arylations within a linear peptide. Finally, as a proof of principle, we report the application to this new stapling method to relevant biologically active compounds.
An efficient, modular method for the synthesis of highly substituted tetrahydroquinoline systems ... more An efficient, modular method for the synthesis of highly substituted tetrahydroquinoline systems is described. The Lewis acid catalyzed interaction of dihydropyridines with glyoxalate and anilines affords the heterocyclic parent systems in good yields. Tandem one-pot processes allow the incorporation of additional components: a preliminary nucleophilic attack on pyridinium salts generates the reactive dihydropyridine in situ, and subsequent electrophilic reactions on the secondary amine complete the assembly of the final targets, which have up to 6 diversity points.
Chemical Communications, 1998
Electrophilic interaction of iodine with N-alkyl-1,4-dihydropyridines 1 in the presence of second... more Electrophilic interaction of iodine with N-alkyl-1,4-dihydropyridines 1 in the presence of secondary amines stereoselectively leads to the corresponding trans-2,3-diamino-1,2,3,4-tetrahydropyridines 2 in satisfactory yields (79-94%); the method allows the synthesis of piperidine, pyrrolidine, morpholine and piperazine derivatives.
European Journal of Medicinal Chemistry, 2014
Optimization of an essentially inactive 3,4-dihydro-2H-pyrano[3,2-c]quinoline carboxylic ester de... more Optimization of an essentially inactive 3,4-dihydro-2H-pyrano[3,2-c]quinoline carboxylic ester derivative as acetylcholinesterase (AChE) peripheral anionic site (PAS)-binding motif by double O → NH bioisosteric replacement, combined with molecular hybridization with the AChE catalytic anionic site (CAS) inhibitor 6-chlorotacrine and molecular dynamics-driven optimization of the length of the linker has resulted in the development of the trimethylene-linked 1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridine-6-chlorotacrine hybrid 5a as a picomolar inhibitor of human AChE (hAChE). The tetra-, penta-, and octamethylene-linked homologues 5b-d have been also synthesized for comparison purposes, and found to retain the nanomolar hAChE inhibitory potency of the parent 6-chlorotacrine. Further biological profiling of hybrids 5a-d has shown that they are also potent inhibitors of human butyrylcholinesterase and moderately potent Aβ42 and tau anti-aggregating agents, with IC50 values in the submicromolar and low micromolar range, respectively. Also, in vitro studies using an artificial membrane model have predicted a good brain permeability for hybrids 5a-d, and hence, their ability to reach their targets in the central nervous system. The multitarget profile of the novel hybrids makes them promising leads for developing anti-Alzheimer drug candidates with more balanced biological activities.
Advances in Experimental Medicine and Biology, 2010
Convenient synthetic procedures for 1,2,3,6,7, 11b-hexahydro-4H-pyrimido[6, 1 -a] isoquinolin-4-t... more Convenient synthetic procedures for 1,2,3,6,7, 11b-hexahydro-4H-pyrimido[6, 1 -a] isoquinolin-4-thiones and 2,3,6,7,12,12b-hexahydro-1H-pyrimido[1 ,6 :1,2]pyrido [3,4-b]indole-4-thiones have been developed. Structural factors which influence on a cascade cyclization process have been elucidated.
ChemInform, 2008
ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance t... more ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform, 2009
Fused pyridine derivatives R 0450 Multicomponent Access to Functionalized Mesoionic Structures Ba... more Fused pyridine derivatives R 0450 Multicomponent Access to Functionalized Mesoionic Structures Based on TFAA Activation of Isocyanides: Novel Domino Reactions. -Mesoionic imidazo[1,2-a]azines are formed by reaction of azines with doubly α-fluorinated anhydrides and isocyanides. The method tolerates a wide range of substitution patterns on each component. In some cases, competitive reaction pathways lead to dipoles of type (X). The acid fluoride moiety of mesoionic products (IV) can be readily functionalized with nucleophiles. -(AREVALO, M. J.; KIELLAND, N.; MASDEU, C.; MIGUEL, M.; ISAMBERT, N.; LAVILLA*, R.; Eur.
ChemInform, 2008
ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance t... more ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Chemical Communications, 1997
ABSTRACT
Angewandte Chemie-international Edition, 2007
European Journal of Organic Chemistry, 1999
European Journal of Organic Chemistry, 2001
ABSTRACT
Organic Letters, 2003
The three-component reaction of dihydropyridines, aldehydes, and p-methylaniline efficiently form... more The three-component reaction of dihydropyridines, aldehydes, and p-methylaniline efficiently forms highly substituted tetrahydroquinolines in a stereoselective manner through a Lewis acid-catalyzed formal [4 + 2] cycloaddition. InCl(3) and Sc(OTf)(3) are the catalysts of choice for this process. The in situ generation of a reactive 1,4-dihydropyridine through the regioselective nucleophilic addition of cyanide to pyridinium salts allows a one-pot four-component transformation.
Tetrahedron Letters, 1998
Iodine (or related species) addition to 1,4-dihydropyridines, with properly attached substituents... more Iodine (or related species) addition to 1,4-dihydropyridines, with properly attached substituents at the nitrogen atom, leads to the corresponding 3-iodotetrahydropyridinium ions, which undergo an internal nucleophilic attack to furnish regio- and stereoselectively iodobi(poly)lteterocyclic ring systems in good yields.
Journal of Organic Chemistry, 1990
... M.-Lluisa Bennasar, Mercedes Alvarez, Rodolfo Lavilla, Ester Zulaica, and Joan Bosch* Laborat... more ... M.-Lluisa Bennasar, Mercedes Alvarez, Rodolfo Lavilla, Ester Zulaica, and Joan Bosch* Laboratory of Organic Chemistry, Faculty of Pharmacy, University of Barcelona, Barcelona-08028, Spain Received July 6, 1989 ... 1970, 480. (b) Ziegler, 2. E.; Spitzner, EB J. Am. Chem. Soc. ...
ChemInform
Electrophilic Oxidative Additions upon 1,4-Dihydropyridines.
The Journal of Organic Chemistry
... Rodolfo Lavilla,* Oscar Coll, Rakesh Kumar, and Joan Bosch*. Laboratory of Organic Chemistry,... more ... Rodolfo Lavilla,* Oscar Coll, Rakesh Kumar, and Joan Bosch*. Laboratory of Organic Chemistry, Faculty of Pharmacy, University of Barcelona, 08028 Barcelona, Spain. J. Org. Chem. ... a review, see: Bennasar, M.-L.; Lavilla, R.; Alvarez, M.; Bosch, J. Heterocycles1988, 27, 789. ...
Chemistry - A European Journal
Nature Communications, 2015
Natural peptides show high degrees of specificity in their biological action. However, their ther... more Natural peptides show high degrees of specificity in their biological action. However, their therapeutical profile is severely limited by their conformational freedom and metabolic instability. Stapled peptides constitute a solution to these problems and access to these structures lies on a limited number of reactions involving the use of non-natural amino acids. Here, we describe a synthetic strategy for the preparation of unique constrained peptides featuring a covalent bond between tryptophan and phenylalanine or tyrosine residues. The preparation of such peptides is achieved in solution and on solid phase directly from the corresponding sequences having an iodo-aryl amino acid through an intramolecular palladium-catalysed C-H activation process. Moreover, complex topologies arise from the internal stapling of cyclopeptides and double intramolecular arylations within a linear peptide. Finally, as a proof of principle, we report the application to this new stapling method to relevant biologically active compounds.
An efficient, modular method for the synthesis of highly substituted tetrahydroquinoline systems ... more An efficient, modular method for the synthesis of highly substituted tetrahydroquinoline systems is described. The Lewis acid catalyzed interaction of dihydropyridines with glyoxalate and anilines affords the heterocyclic parent systems in good yields. Tandem one-pot processes allow the incorporation of additional components: a preliminary nucleophilic attack on pyridinium salts generates the reactive dihydropyridine in situ, and subsequent electrophilic reactions on the secondary amine complete the assembly of the final targets, which have up to 6 diversity points.
Chemical Communications, 1998
Electrophilic interaction of iodine with N-alkyl-1,4-dihydropyridines 1 in the presence of second... more Electrophilic interaction of iodine with N-alkyl-1,4-dihydropyridines 1 in the presence of secondary amines stereoselectively leads to the corresponding trans-2,3-diamino-1,2,3,4-tetrahydropyridines 2 in satisfactory yields (79-94%); the method allows the synthesis of piperidine, pyrrolidine, morpholine and piperazine derivatives.
European Journal of Medicinal Chemistry, 2014
Optimization of an essentially inactive 3,4-dihydro-2H-pyrano[3,2-c]quinoline carboxylic ester de... more Optimization of an essentially inactive 3,4-dihydro-2H-pyrano[3,2-c]quinoline carboxylic ester derivative as acetylcholinesterase (AChE) peripheral anionic site (PAS)-binding motif by double O → NH bioisosteric replacement, combined with molecular hybridization with the AChE catalytic anionic site (CAS) inhibitor 6-chlorotacrine and molecular dynamics-driven optimization of the length of the linker has resulted in the development of the trimethylene-linked 1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridine-6-chlorotacrine hybrid 5a as a picomolar inhibitor of human AChE (hAChE). The tetra-, penta-, and octamethylene-linked homologues 5b-d have been also synthesized for comparison purposes, and found to retain the nanomolar hAChE inhibitory potency of the parent 6-chlorotacrine. Further biological profiling of hybrids 5a-d has shown that they are also potent inhibitors of human butyrylcholinesterase and moderately potent Aβ42 and tau anti-aggregating agents, with IC50 values in the submicromolar and low micromolar range, respectively. Also, in vitro studies using an artificial membrane model have predicted a good brain permeability for hybrids 5a-d, and hence, their ability to reach their targets in the central nervous system. The multitarget profile of the novel hybrids makes them promising leads for developing anti-Alzheimer drug candidates with more balanced biological activities.
Advances in Experimental Medicine and Biology, 2010
Convenient synthetic procedures for 1,2,3,6,7, 11b-hexahydro-4H-pyrimido[6, 1 -a] isoquinolin-4-t... more Convenient synthetic procedures for 1,2,3,6,7, 11b-hexahydro-4H-pyrimido[6, 1 -a] isoquinolin-4-thiones and 2,3,6,7,12,12b-hexahydro-1H-pyrimido[1 ,6 :1,2]pyrido [3,4-b]indole-4-thiones have been developed. Structural factors which influence on a cascade cyclization process have been elucidated.
ChemInform, 2008
ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance t... more ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform, 2009
Fused pyridine derivatives R 0450 Multicomponent Access to Functionalized Mesoionic Structures Ba... more Fused pyridine derivatives R 0450 Multicomponent Access to Functionalized Mesoionic Structures Based on TFAA Activation of Isocyanides: Novel Domino Reactions. -Mesoionic imidazo[1,2-a]azines are formed by reaction of azines with doubly α-fluorinated anhydrides and isocyanides. The method tolerates a wide range of substitution patterns on each component. In some cases, competitive reaction pathways lead to dipoles of type (X). The acid fluoride moiety of mesoionic products (IV) can be readily functionalized with nucleophiles. -(AREVALO, M. J.; KIELLAND, N.; MASDEU, C.; MIGUEL, M.; ISAMBERT, N.; LAVILLA*, R.; Eur.
ChemInform, 2008
ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance t... more ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.