We have developed a cancer vaccine candidate (hereafter denominated CIGB-247), based on recombina... more We have developed a cancer vaccine candidate (hereafter denominated CIGB-247), based on recombinant modified human vascular endothelial growth factor (VEGF) as antigen, and the adjuvant VSSP (very small sized proteoliposomes of Neisseria meningitidis outer membrane). In mice, previous work of our group had shown that vaccination with CIGB-247 extended tumor-take time, slowed tumor growth, and increased animal survival. Immunization elicited anti-human and murine VEGF-neutralizing antibodies, and spleen cells of vaccinated mice are cytotoxic in vitro to tumor cells that produce VEGF.
The neoliberal experiment in Latin America has consumed more than a generation of enormous resour... more The neoliberal experiment in Latin America has consumed more than a generation of enormous resources with very little economic results, disastrous social and environmental effects, and a deterioration in democratic legitimacy that will have to be recovered. A necessary, although insufficient, condition to recover a hopeful horizon on these fronts is the qualitative advancement toward a continental integration process that includes monetary and financial dimensions, even while the classic themes of trade and tariff integration are still far from being resolved. The Ecuadorian plan that was introduced at the multilateral negotiations in relation to Venezuelan president Hugo Chávez's initiative to create the Banco del Sur proposes the simultaneous and coherent promotion of a process to construct a New Regional Financial Architecture, in which the Banco del Sur would be the nucleus of one of the three fundamental pillars-that is, the transformation of the development bank. The other two pillars include the enrichment and coordination of the continental tasks of the central bank, connecting stabilization with development, and the convergence toward a common monetary scheme.
Use of a heterologous prime-boost strategy based on a combination of nonreplicative immunogens an... more Use of a heterologous prime-boost strategy based on a combination of nonreplicative immunogens and candidate attenuated virus vaccines against dengue virus in the same schedule is an attractive approach. These combinations may result in a condensed immunization regime for humans, thus reducing the number of doses with attenuated virus and the time spacing. The present work deals with the evaluation of the heterologous prime-boost strategy combining a novel chimeric protein (domain III-capsid) of dengue virus serotype 2 (DEN-2) and the infective homologous virus in the same immunization schedule in monkeys. Primed monkeys received one dose of infective DEN-2 and were then vaccinated with the recombinant protein. We found that animals developed a neutralizing antibody response after the infective dose and were notably boosted with a second dose of the chimeric protein 3 months later. The neutralizing antibodies induced were long lasting, and animals also showed the ability to induce a specific cellular response 6 months after the booster dose. As a conclusion, we can state that the domain III region, when it is properly presented as a fusion protein to the immune system, is able to recall the neutralizing antibody response elicited following homologous virus infection in monkeys. Further prime-boost approaches can be performed in a condensed regime combining the chimeric domain III-capsid protein and candidate live attenuated vaccines against DEN-2.
complexes as useful catalysts in the addition and/or insertion reaction of ethyl diazoacetate to ... more complexes as useful catalysts in the addition and/or insertion reaction of ethyl diazoacetate to saturated or unsaturated substrates; 31 refs.]. -(DIAZ-REQUEJO, M. M.; PEREZ, P. J.; J. Organomet. Chem. 690 (2005) 24-25, 5441-5450; Lab. Catal. Homogenea, Dep. Quim. Cienc. Mater., Univ. Huelva, E-21007 Huelva, Spain; Eng.) -Klein 25-233
Electron deficient azides are challenging substrates in CuAAC reactions. Particularly, when N-car... more Electron deficient azides are challenging substrates in CuAAC reactions. Particularly, when N-carbonyl azides are applied the formation of N-carbonyl triazoles has not yet been observed. We report herein the first example of this class of reaction, with a copper-based system that efficiently enables the synthesis of N-carbamoyl 1,2,3-triazoles by [3+2] cycloaddition of N-carbamoyl azides and alkynes.
ABSTRACT The complex [TpBr3Cu(NCMe)] (TpBr3=hydrotris(3,4,5-tribromo)pyrazolylborate) efficiently... more ABSTRACT The complex [TpBr3Cu(NCMe)] (TpBr3=hydrotris(3,4,5-tribromo)pyrazolylborate) efficiently catalyzes the CH functionalization of indole derivatives at C3 by carbene transfer from different diazoesters in a high-yield transformation involving low catalyst loadings and short reaction times. This system has shown that the previously proposed dichotomy of carbene addition (to the double bond) vs carbene insertion (to the CH bond) corresponds to two consecutive reaction steps: the cyclopropane intermediates, observed in the reaction mixtures, are the precursors of the final CH functionalization derivatives in a ring-opening process involving acid catalysis. Those in situ generated cyclopropanes undergo nucleophilic ring opening with Me2CuLi to afford both C2 and C3 functionalized indoles.
The selectivity of the cyclopropanation of olefins with ethyl phenyldiazoacetate has been tested ... more The selectivity of the cyclopropanation of olefins with ethyl phenyldiazoacetate has been tested using different gold complexes bearing phosphine, phosphite or N-heterocyclic as ligands. A comparative study with related copper and silver complexes as catalysts is also presented.
Even in the context of hydrocarbons&a... more Even in the context of hydrocarbons' general resistance to selective functionalization, methane's volatility and strong bonds pose a particular challenge. We report here that silver complexes bearing perfluorinated indazolylborate ligands catalyze the reaction of methane (CH(4)) with ethyl diazoacetate (N(2)CHCO(2)Et) to yield ethyl propionate (CH(3)CH(2)CO(2)Et). The use of supercritical carbon dioxide (scCO(2)) as the solvent is key to the reaction's success. Although the catalyst is only sparingly soluble in CH(4)/CO(2) mixtures, optimized conditions presently result in a 19% yield of ethyl propionate (based on starting quantity of the diazoester) at 40°C over 14 hours.
ABSTRACT A series of complexes Tp(x)Cu (Tp(x) = homoscorpionate ligand) have been tested as the c... more ABSTRACT A series of complexes Tp(x)Cu (Tp(x) = homoscorpionate ligand) have been tested as the catalysts for the olefin aziridination reaction using PhINTs as the nitrene source. Very high yields of aziridines have been obtained with a group of representative substrates, including nonactivated terminal olefins. The high activity of these catalysts has allowed the use of equimolar amounts of PhINTs and olefins, avoiding the requirement of excess olefin. In an effort to eliminate nondesired byproducts, chloramine-T has been employed as the nitrene source, in a reaction that produces sodium chloride as the sole residue, with high degrees of conversions also being obtained.
Kinetic studies of the ethyl diazoacetate (EDA) decomposition reaction in the presence of BpCu (1... more Kinetic studies of the ethyl diazoacetate (EDA) decomposition reaction in the presence of BpCu (1) and in the presence or absence of olefin have led to the determination of several kinetic and thermodynamic parameters, and a consistent mechanism has been proposed for the olefin cyclopropanation reaction. Related studies with the complexes [Cu(bipy) 2 ]I (bipy ) bipyridine) and [Cu(bis(oxazoline)) 2 ]OTf have shown strong similarities with the results obtained with 1. A general mechanism covering the copper-based systems reported in the literature has been proposed, the real catalyst (i.e., the species to be reacted with EDA) in all cases being a neutral, 14-electron fragment of composition (L-L)Cu (L-L ) Bp-and Tp-like ligands, semicorrins, salicylaldehyde derivatives) or, alternatively, the isoelectronic, cationic [(L-L)Cu] + (for L-L ) bis(oxazoline), bipyridine). (22) kobsd values were calculated by means of kobsd ) (1/t) ln([EDA]0/ [EDA]). 17
Carbon-halogen (C-X) bonds (X=Cl, Br) can be easily functionalized with ethyl diazoacetate (N 2 C... more Carbon-halogen (C-X) bonds (X=Cl, Br) can be easily functionalized with ethyl diazoacetate (N 2 CHCO 2 Et) in the presence of silver-based catalysts containing the Tp x Ag core (Tp x = hydrotrispyrazolylborate ligand). Polyhalomethanes are converted into products derived from the formal insertion of the carbene CHCO 2 Et units into the C-X bond. In the case of monohaloalkanes (C 4 -C 6 ), cleavage of the C-X bond is observed, with formation of XCH 2 CO 2 Et and the corresponding olefin. Experimental evidence and theoretical calculations have led to the proposal of a novel mechanism to account for these transformations, in which the metal participates along the pathway in all the reaction steps. Among the experimental data, the first example of a metal-induced, asymmetric functionalization of a C-Cl bond by carbene insertion is included (ee=14 ( 2%). (36) Drudis-Sole, G.; Maseras, F.; Lledos, A.; Vallribera, A.; Moreno-Manas, M. Eur. J. Org. Chem. 2008, 5614.
Copper complexes containing chiral N-heterocyclic carbene ligands catalyze the regioselectiVe nuc... more Copper complexes containing chiral N-heterocyclic carbene ligands catalyze the regioselectiVe nucleophilic boryl attack at the -carbon of R, -unsaturated esters with enantioselectiVities up to 74% ee, depending on the nature of the ester group.
The complexes [Tp Br3 Ag] 2 ‚CH 3 COCH 3 (1) and Tp Br3 Ag(thf) (2) catalyze the insertion of the... more The complexes [Tp Br3 Ag] 2 ‚CH 3 COCH 3 (1) and Tp Br3 Ag(thf) (2) catalyze the insertion of the :CHCO 2 Et group from ethyl diazoacetate (EDA) into the saturated C-H bonds of several C5, C6, and C8 linear and branched alkanes. In addition to secondary and/or tertiary sites, the unprecedented insertion into the primary C-H bonds of the substrates studied has been observed with variable regioselectivity, toward the methyl groups, within the range of 40-60% for branched and nearly 25% for linear alkanes.
Facile alkane functionalization by means of the insertion of :CHCO 2 Et, from ethyl diazoacetate,... more Facile alkane functionalization by means of the insertion of :CHCO 2 Et, from ethyl diazoacetate, into carbon-hydrogen bonds mediated by catalytic amounts of (NHC)MCl (NHC ) N-heterocyclic ligand; M ) Cu, Au) and a halide scavenger MX has been achieved. This chemistry includes the insertion of the carbene fragment into alkane primary positions with Cu-and Au-based catalysts. The nature of the counterion X and of the NHC ligand have a significant effect on the overall yields and regioselectivity of the reaction.
Since its discovery in the late 1970s, Rh 2 (OAc) 4 has been the catalyst of choice for the above... more Since its discovery in the late 1970s, Rh 2 (OAc) 4 has been the catalyst of choice for the above transformations. 5 This complex catalyzes the insertion of several diazo compounds 6,7 into the O−H bond of saturated alcohols at room temperature and in high yield. Other metals ...
We have developed a cancer vaccine candidate (hereafter denominated CIGB-247), based on recombina... more We have developed a cancer vaccine candidate (hereafter denominated CIGB-247), based on recombinant modified human vascular endothelial growth factor (VEGF) as antigen, and the adjuvant VSSP (very small sized proteoliposomes of Neisseria meningitidis outer membrane). In mice, previous work of our group had shown that vaccination with CIGB-247 extended tumor-take time, slowed tumor growth, and increased animal survival. Immunization elicited anti-human and murine VEGF-neutralizing antibodies, and spleen cells of vaccinated mice are cytotoxic in vitro to tumor cells that produce VEGF.
The neoliberal experiment in Latin America has consumed more than a generation of enormous resour... more The neoliberal experiment in Latin America has consumed more than a generation of enormous resources with very little economic results, disastrous social and environmental effects, and a deterioration in democratic legitimacy that will have to be recovered. A necessary, although insufficient, condition to recover a hopeful horizon on these fronts is the qualitative advancement toward a continental integration process that includes monetary and financial dimensions, even while the classic themes of trade and tariff integration are still far from being resolved. The Ecuadorian plan that was introduced at the multilateral negotiations in relation to Venezuelan president Hugo Chávez's initiative to create the Banco del Sur proposes the simultaneous and coherent promotion of a process to construct a New Regional Financial Architecture, in which the Banco del Sur would be the nucleus of one of the three fundamental pillars-that is, the transformation of the development bank. The other two pillars include the enrichment and coordination of the continental tasks of the central bank, connecting stabilization with development, and the convergence toward a common monetary scheme.
Use of a heterologous prime-boost strategy based on a combination of nonreplicative immunogens an... more Use of a heterologous prime-boost strategy based on a combination of nonreplicative immunogens and candidate attenuated virus vaccines against dengue virus in the same schedule is an attractive approach. These combinations may result in a condensed immunization regime for humans, thus reducing the number of doses with attenuated virus and the time spacing. The present work deals with the evaluation of the heterologous prime-boost strategy combining a novel chimeric protein (domain III-capsid) of dengue virus serotype 2 (DEN-2) and the infective homologous virus in the same immunization schedule in monkeys. Primed monkeys received one dose of infective DEN-2 and were then vaccinated with the recombinant protein. We found that animals developed a neutralizing antibody response after the infective dose and were notably boosted with a second dose of the chimeric protein 3 months later. The neutralizing antibodies induced were long lasting, and animals also showed the ability to induce a specific cellular response 6 months after the booster dose. As a conclusion, we can state that the domain III region, when it is properly presented as a fusion protein to the immune system, is able to recall the neutralizing antibody response elicited following homologous virus infection in monkeys. Further prime-boost approaches can be performed in a condensed regime combining the chimeric domain III-capsid protein and candidate live attenuated vaccines against DEN-2.
complexes as useful catalysts in the addition and/or insertion reaction of ethyl diazoacetate to ... more complexes as useful catalysts in the addition and/or insertion reaction of ethyl diazoacetate to saturated or unsaturated substrates; 31 refs.]. -(DIAZ-REQUEJO, M. M.; PEREZ, P. J.; J. Organomet. Chem. 690 (2005) 24-25, 5441-5450; Lab. Catal. Homogenea, Dep. Quim. Cienc. Mater., Univ. Huelva, E-21007 Huelva, Spain; Eng.) -Klein 25-233
Electron deficient azides are challenging substrates in CuAAC reactions. Particularly, when N-car... more Electron deficient azides are challenging substrates in CuAAC reactions. Particularly, when N-carbonyl azides are applied the formation of N-carbonyl triazoles has not yet been observed. We report herein the first example of this class of reaction, with a copper-based system that efficiently enables the synthesis of N-carbamoyl 1,2,3-triazoles by [3+2] cycloaddition of N-carbamoyl azides and alkynes.
ABSTRACT The complex [TpBr3Cu(NCMe)] (TpBr3=hydrotris(3,4,5-tribromo)pyrazolylborate) efficiently... more ABSTRACT The complex [TpBr3Cu(NCMe)] (TpBr3=hydrotris(3,4,5-tribromo)pyrazolylborate) efficiently catalyzes the CH functionalization of indole derivatives at C3 by carbene transfer from different diazoesters in a high-yield transformation involving low catalyst loadings and short reaction times. This system has shown that the previously proposed dichotomy of carbene addition (to the double bond) vs carbene insertion (to the CH bond) corresponds to two consecutive reaction steps: the cyclopropane intermediates, observed in the reaction mixtures, are the precursors of the final CH functionalization derivatives in a ring-opening process involving acid catalysis. Those in situ generated cyclopropanes undergo nucleophilic ring opening with Me2CuLi to afford both C2 and C3 functionalized indoles.
The selectivity of the cyclopropanation of olefins with ethyl phenyldiazoacetate has been tested ... more The selectivity of the cyclopropanation of olefins with ethyl phenyldiazoacetate has been tested using different gold complexes bearing phosphine, phosphite or N-heterocyclic as ligands. A comparative study with related copper and silver complexes as catalysts is also presented.
Even in the context of hydrocarbons&a... more Even in the context of hydrocarbons' general resistance to selective functionalization, methane's volatility and strong bonds pose a particular challenge. We report here that silver complexes bearing perfluorinated indazolylborate ligands catalyze the reaction of methane (CH(4)) with ethyl diazoacetate (N(2)CHCO(2)Et) to yield ethyl propionate (CH(3)CH(2)CO(2)Et). The use of supercritical carbon dioxide (scCO(2)) as the solvent is key to the reaction's success. Although the catalyst is only sparingly soluble in CH(4)/CO(2) mixtures, optimized conditions presently result in a 19% yield of ethyl propionate (based on starting quantity of the diazoester) at 40°C over 14 hours.
ABSTRACT A series of complexes Tp(x)Cu (Tp(x) = homoscorpionate ligand) have been tested as the c... more ABSTRACT A series of complexes Tp(x)Cu (Tp(x) = homoscorpionate ligand) have been tested as the catalysts for the olefin aziridination reaction using PhINTs as the nitrene source. Very high yields of aziridines have been obtained with a group of representative substrates, including nonactivated terminal olefins. The high activity of these catalysts has allowed the use of equimolar amounts of PhINTs and olefins, avoiding the requirement of excess olefin. In an effort to eliminate nondesired byproducts, chloramine-T has been employed as the nitrene source, in a reaction that produces sodium chloride as the sole residue, with high degrees of conversions also being obtained.
Kinetic studies of the ethyl diazoacetate (EDA) decomposition reaction in the presence of BpCu (1... more Kinetic studies of the ethyl diazoacetate (EDA) decomposition reaction in the presence of BpCu (1) and in the presence or absence of olefin have led to the determination of several kinetic and thermodynamic parameters, and a consistent mechanism has been proposed for the olefin cyclopropanation reaction. Related studies with the complexes [Cu(bipy) 2 ]I (bipy ) bipyridine) and [Cu(bis(oxazoline)) 2 ]OTf have shown strong similarities with the results obtained with 1. A general mechanism covering the copper-based systems reported in the literature has been proposed, the real catalyst (i.e., the species to be reacted with EDA) in all cases being a neutral, 14-electron fragment of composition (L-L)Cu (L-L ) Bp-and Tp-like ligands, semicorrins, salicylaldehyde derivatives) or, alternatively, the isoelectronic, cationic [(L-L)Cu] + (for L-L ) bis(oxazoline), bipyridine). (22) kobsd values were calculated by means of kobsd ) (1/t) ln([EDA]0/ [EDA]). 17
Carbon-halogen (C-X) bonds (X=Cl, Br) can be easily functionalized with ethyl diazoacetate (N 2 C... more Carbon-halogen (C-X) bonds (X=Cl, Br) can be easily functionalized with ethyl diazoacetate (N 2 CHCO 2 Et) in the presence of silver-based catalysts containing the Tp x Ag core (Tp x = hydrotrispyrazolylborate ligand). Polyhalomethanes are converted into products derived from the formal insertion of the carbene CHCO 2 Et units into the C-X bond. In the case of monohaloalkanes (C 4 -C 6 ), cleavage of the C-X bond is observed, with formation of XCH 2 CO 2 Et and the corresponding olefin. Experimental evidence and theoretical calculations have led to the proposal of a novel mechanism to account for these transformations, in which the metal participates along the pathway in all the reaction steps. Among the experimental data, the first example of a metal-induced, asymmetric functionalization of a C-Cl bond by carbene insertion is included (ee=14 ( 2%). (36) Drudis-Sole, G.; Maseras, F.; Lledos, A.; Vallribera, A.; Moreno-Manas, M. Eur. J. Org. Chem. 2008, 5614.
Copper complexes containing chiral N-heterocyclic carbene ligands catalyze the regioselectiVe nuc... more Copper complexes containing chiral N-heterocyclic carbene ligands catalyze the regioselectiVe nucleophilic boryl attack at the -carbon of R, -unsaturated esters with enantioselectiVities up to 74% ee, depending on the nature of the ester group.
The complexes [Tp Br3 Ag] 2 ‚CH 3 COCH 3 (1) and Tp Br3 Ag(thf) (2) catalyze the insertion of the... more The complexes [Tp Br3 Ag] 2 ‚CH 3 COCH 3 (1) and Tp Br3 Ag(thf) (2) catalyze the insertion of the :CHCO 2 Et group from ethyl diazoacetate (EDA) into the saturated C-H bonds of several C5, C6, and C8 linear and branched alkanes. In addition to secondary and/or tertiary sites, the unprecedented insertion into the primary C-H bonds of the substrates studied has been observed with variable regioselectivity, toward the methyl groups, within the range of 40-60% for branched and nearly 25% for linear alkanes.
Facile alkane functionalization by means of the insertion of :CHCO 2 Et, from ethyl diazoacetate,... more Facile alkane functionalization by means of the insertion of :CHCO 2 Et, from ethyl diazoacetate, into carbon-hydrogen bonds mediated by catalytic amounts of (NHC)MCl (NHC ) N-heterocyclic ligand; M ) Cu, Au) and a halide scavenger MX has been achieved. This chemistry includes the insertion of the carbene fragment into alkane primary positions with Cu-and Au-based catalysts. The nature of the counterion X and of the NHC ligand have a significant effect on the overall yields and regioselectivity of the reaction.
Since its discovery in the late 1970s, Rh 2 (OAc) 4 has been the catalyst of choice for the above... more Since its discovery in the late 1970s, Rh 2 (OAc) 4 has been the catalyst of choice for the above transformations. 5 This complex catalyzes the insertion of several diazo compounds 6,7 into the O−H bond of saturated alcohols at room temperature and in high yield. Other metals ...
Uploads
Papers by pedro perez