Gonzalo de Gonzalo - Academia.edu (original) (raw)

Papers by Gonzalo de Gonzalo

Catalysts, 2021

Baeyer–Villiger monooxygenases (BVMOs) are flavin-dependent oxidative enzymes capable of catalyzi... more Baeyer–Villiger monooxygenases (BVMOs) are flavin-dependent oxidative enzymes capable of catalyzing the insertion of an oxygen atom between a carbonylic Csp2 and the Csp3 at the alpha position, therefore transforming linear and cyclic ketones into esters and lactones. These enzymes are dependent on nicotinamides (NAD(P)H) for the flavin reduction and subsequent reaction with molecular oxygen. BVMOs can be included in cascade reactions, coupled to other redox enzymes, such as alcohol dehydrogenases (ADHs) or ene-reductases (EREDs), so that the direct conversion of alcohols or α,β-unsaturated carbonylic compounds to the corresponding esters can be achieved. In the present review, the different synthetic methodologies that have been performed by employing multienzymatic strategies with BVMOs combining whole cells or isolated enzymes, through sequential or parallel methods, are described, with the aim of highlighting the advantages of performing multienzymatic systems, and show the rece...

Molecules, 2020

The application of biocatalysts to perform reductive/oxidative chemical processes has attracted g... more The application of biocatalysts to perform reductive/oxidative chemical processes has attracted great interest in recent years, due to their environmentally friendly conditions combined with high selectivities. In some circumstances, the aqueous buffer medium normally employed in biocatalytic procedures is not the best option to develop these processes, due to solubility and/or inhibition issues, requiring biocatalyzed redox procedures to circumvent these drawbacks, by developing novel green non-conventional media, including the use of biobased solvents, reactions conducted in neat conditions and the application of neoteric solvents such as deep eutectic solvents.

Catalysts, 2019

The broad interdisciplinary nature of biocatalysis fosters innovation, as different technical fie... more The broad interdisciplinary nature of biocatalysis fosters innovation, as different technical fields are interconnected and synergized. A way to depict that innovation is by conducting a survey on patent activities. This paper analyses the intellectual property activities of the last five years (2014–2019) with a specific focus on biocatalysis applied to asymmetric synthesis. Furthermore, to reflect the inventive and innovative steps, only patents that were granted during that period are considered. Patent searches using several keywords (e.g., enzyme names) have been conducted by using several patent engine servers (e.g., Espacenet, SciFinder, Google Patents), with focus on granted patents during the period 2014–2019. Around 200 granted patents have been identified, covering all enzyme types. The inventive pattern focuses on the protection of novel protein sequences, as well as on new substrates. In some other cases, combined processes, multi-step enzymatic reactions, as well as pr...

Catalysts, 2017

A recently discovered, moderately thermostable Baeyer-Villiger monooxygenase, polycyclic ketone m... more A recently discovered, moderately thermostable Baeyer-Villiger monooxygenase, polycyclic ketone monooxygenase (PockeMO), from Thermothelomyces thermophila has been employed as a biocatalyst in a set of asymmetric sulfoxidations. The enzyme was able to catalyze the oxidation of various alkyl aryl sulfides with good selectivities and moderate to high activities. The biocatalytic performance was able to be further increased by optimizing some reaction parameters, such as the addition of 10% v v −1 of water miscible solvents or toluene, or by performing the conversion at a relatively high temperature (45 • C). PockeMO was found to display an optimum activity at sulfide concentrations of 50 mM, while it can also function at 200 mM. Taken together, the data show that PockeMO can be used as robust biocatalyst for the synthesis of optically active sulfoxides.

Advanced Synthesis & Catalysis, 2017

Multi‐step processes catalysed by several catalysts working concurrently have been developed in n... more Multi‐step processes catalysed by several catalysts working concurrently have been developed in nature, thus improving reaction efficiency. The quest for novel and improved catalytic systems has led to the development of biocatalytic and later to organocatalytic procedures as very valuable tools in asymmetric synthesis while using mild reaction conditions in the absence of metal catalysts. As a timeless challenge, chemists are facing the need for process designs in which different sorts of catalysts can operate successfully in a one‐pot concurrent fashion. Likewise, such designs bring about the best of each catalyst and, in certain cases, enable us to improve problematic issues, such as reactivity, selectivity, solubility, inhibition, etc. Specifically, to combine these two types of catalysts in one‐pot, achieving high yields and selectivity, is a fascinating aspect of catalysis. This review covers representative advances in this field, in particular those in which biocatalysts and ...

Proceedings of The 20th International Electronic Conference on Synthetic Organic Chemistry, 2016

Ionic liquids (ILs) are largely used in biocatalysis, mainly as cosolvents of the biocatalyzed re... more Ionic liquids (ILs) are largely used in biocatalysis, mainly as cosolvents of the biocatalyzed reactions, but in the last few years ILs have been used as coating reagents in the immobilization of enzymes. In the present communication, we have developed a set of immobilized Baeyer-Villiger monooxygenases preparations in presence of different ILs. These immobilized biocatalysts have been tested in selective sulfoxidations with the aim of analyzing the activity and selectivity of the novel enzymatic preparations as well as their performance during different reaction cycles.

Chembiochem : a European journal of chemical biology, Jul 28, 2016

Eugenol oxidase (EUGO) from Rhodococcus jostii RHA1 was previously shown to convert only a limite... more Eugenol oxidase (EUGO) from Rhodococcus jostii RHA1 was previously shown to convert only a limited set of phenolic compounds. In this study, we have explored the biocatalytic potential of this flavoprotein oxidase resulting in a broadened substrate scope and a deeper insight into its structural properties. In addition to the oxidation of vanillyl alcohol and hydroxylation of eugenol, EUGO can efficiently perform the dehydrogenation of various phenolic ketones and the selective oxidation of a racemic secondary alcohol, 4-(hydroxy-1-ethyl)-2-methoxyphenol. EUGO was also found to perform the kinetic resolution of a racemic secondary alcohol. Crystal structures of the enzyme in complex with isoeugenol, coniferyl alcohol, vanillin, and benzoate have been determined. The catalytic center is a remarkable solvent-inaccessible cavity on the si side of the flavin cofactor. Structural comparison with vanillyl-alcohol oxidase from Penicillium simplicissimum highlights a few localized changes th...

Catalytic Methods in Asymmetric Synthesis, 2011

Tetrahedron: Asymmetry, 2009

Growing cells of the basiodiomycete Lentinus strigellus in potato-dextrose broth have been used f... more Growing cells of the basiodiomycete Lentinus strigellus in potato-dextrose broth have been used for the first time as a biocatalyst in the stereoselective reduction of aromatic and aliphatic ketones. Most of the aromatic ketones were converted into the corresponding optically active alcohols in up to >99% enantiomeric excess under very mild reaction conditions. Among the aliphatic ketones tested, 2-octanone was enzymatically reduced by this microorganism to enantiopure (S)-2-octanol with almost complete conversion.

Tetrahedron: Asymmetry, 2008

The enzymatic preparation obtained from a discard of Manihot esculenta roots has been successfull... more The enzymatic preparation obtained from a discard of Manihot esculenta roots has been successfully immobilized on calcium alginate hydrogels. This preparation has been tested as a chiral biocatalyst in the enzymatic acylation of a set of racemic aromatic alcohols. Depending on the reaction conditions, excellent enantioselectivities can be achieved. Some parameters that can alter the biocatalytic properties of the enzyme, such as solvent, temperature, acyl donor and substrate structure have been studied exhaustively in order to establish a deeper knowledge of this novel biocatalyst.

Tetrahedron: Asymmetry, 2010

Whole cells from the Brazilian beans feijão da corda (Vigna unguiculata) have been employed as bi... more Whole cells from the Brazilian beans feijão da corda (Vigna unguiculata) have been employed as biocatalyst in different bioreduction processes. Good to excellent selectivities can be obtained in the reduction of aromatic and aliphatic ketones, as well as βketoesters, depending the conversions and the chemoselectivity on the substrate structure. This biocatalyst was also able to reduce the nitro moiety of different aromatic nitro compounds, presenting also enoate reductase activity, chemoselectively catalyzing the double bond reduction of 4-phenyl-3-buten-2-one with moderate conversion.

Tetrahedron: Asymmetry, 2006

Recombinant 4-hydroxyacetophenone monooxygenase (HAPMO) from Pseudomonas fluorescens ACB has been... more Recombinant 4-hydroxyacetophenone monooxygenase (HAPMO) from Pseudomonas fluorescens ACB has been tested as a catalyst in sulfoxidation reactions on a set of aromatic sulfides. With a few exceptions, excellent enantioselectivities in the synthesis of chiral phenyl and benzyl sulfoxides were achieved. The bacterial Baeyer-Villiger monooxygenase was also shown to accept racemic sulfoxides, a prochiral diketone and an organoboron compound as substrates. This study demonstrates the great biocatalytic potential of this novel oxidative enzyme.

Organic & Biomolecular Chemistry, 2010

Parallel interconnected kinetic asymmetric transformations were performed in order to obtain enan... more Parallel interconnected kinetic asymmetric transformations were performed in order to obtain enantioenriched derivatives starting from a set of racemic or prochiral compounds. Thus, in a onepot reaction using two redox biocatalysts (a BVMO and an ADH) and a catalytic amount of cofactor that acts as a mediator, enantioenriched ketones, sulfoxides, and sec-alcohols were concurrently obtained in a strict parallel way minimising the quantity of reagents employed. By selecting the appropriate biocatalysts, this methodology is a potential tool for performing stereodivergent transformations. 65 65 this type of processes could be described as parallel interconnected kinetic asymmetric transformations. <Scheme 2 here> Scheme 2. Concurrent kinetic resolutions of (±)-1 and (±)-3 employing BVMOs and ADHs. Esters 5 are obtained as by-products through a cascade process.

Organic & Biomolecular Chemistry, 2010

Organic & Biomolecular Chemistry, 2011

Journal of Molecular Catalysis B: Enzymatic, 2010

Growing cells of the phytopathogen fungus Lasiodiplodia theobromae in potato dextrose broth have ... more Growing cells of the phytopathogen fungus Lasiodiplodia theobromae in potato dextrose broth have shown their potential for the stereoselective bioreduction of different prochiral aromatic and aliphatic ketones. Optically active alcohols were obtained under mild reaction conditions in high conversions (up to 90%) and moderate to excellent enantioselectivity (35–≥99% ee) depending on the ketone structure. Prelog alcohols were isolated, except in

Journal of Molecular Catalysis B: Enzymatic, 2012

Fil: Mascotti, Maria Laura. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Ci... more Fil: Mascotti, Maria Laura. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - San Luis. Instituto de Investigaciones en Tecnologia Quimica. Universidad Nacional de San Luis. Facultad de Quimica, Bioquimica y Farmacia. Instituto de Investigaciones en Tecnologia Quimica; Argentina

European Journal of Organic Chemistry, 2010

ABSTRACT Optically active sulfoxides are compounds of high interest in organic chemistry. Herein,... more ABSTRACT Optically active sulfoxides are compounds of high interest in organic chemistry. Herein, we report the preparation of a set of chiral heteroaryl alkyl, cyclohexyl alkyl, and alkyl alkyl sulfoxides by using enantioselective sulfoxidation reactions employing three Baeyer–Villiger monooxygenases (BVMOs). Careful selection of the reaction conditions, starting sulfide, and biocatalyst can be used to achieve good to excellent enantiomeric excess values. Thus, valuable chiral synthons can be obtained by performing the reactions under mild and environmentally friendly conditions. The most promising biotransformations that employ a BVMO cell-free extract preparation have been developed on a 250-mg scale to give the chiral sulfoxides in high yields in most of the reactions.

Catalysts, 2021

Baeyer–Villiger monooxygenases (BVMOs) are flavin-dependent oxidative enzymes capable of catalyzi... more Baeyer–Villiger monooxygenases (BVMOs) are flavin-dependent oxidative enzymes capable of catalyzing the insertion of an oxygen atom between a carbonylic Csp2 and the Csp3 at the alpha position, therefore transforming linear and cyclic ketones into esters and lactones. These enzymes are dependent on nicotinamides (NAD(P)H) for the flavin reduction and subsequent reaction with molecular oxygen. BVMOs can be included in cascade reactions, coupled to other redox enzymes, such as alcohol dehydrogenases (ADHs) or ene-reductases (EREDs), so that the direct conversion of alcohols or α,β-unsaturated carbonylic compounds to the corresponding esters can be achieved. In the present review, the different synthetic methodologies that have been performed by employing multienzymatic strategies with BVMOs combining whole cells or isolated enzymes, through sequential or parallel methods, are described, with the aim of highlighting the advantages of performing multienzymatic systems, and show the rece...

Molecules, 2020

The application of biocatalysts to perform reductive/oxidative chemical processes has attracted g... more The application of biocatalysts to perform reductive/oxidative chemical processes has attracted great interest in recent years, due to their environmentally friendly conditions combined with high selectivities. In some circumstances, the aqueous buffer medium normally employed in biocatalytic procedures is not the best option to develop these processes, due to solubility and/or inhibition issues, requiring biocatalyzed redox procedures to circumvent these drawbacks, by developing novel green non-conventional media, including the use of biobased solvents, reactions conducted in neat conditions and the application of neoteric solvents such as deep eutectic solvents.

Catalysts, 2019

The broad interdisciplinary nature of biocatalysis fosters innovation, as different technical fie... more The broad interdisciplinary nature of biocatalysis fosters innovation, as different technical fields are interconnected and synergized. A way to depict that innovation is by conducting a survey on patent activities. This paper analyses the intellectual property activities of the last five years (2014–2019) with a specific focus on biocatalysis applied to asymmetric synthesis. Furthermore, to reflect the inventive and innovative steps, only patents that were granted during that period are considered. Patent searches using several keywords (e.g., enzyme names) have been conducted by using several patent engine servers (e.g., Espacenet, SciFinder, Google Patents), with focus on granted patents during the period 2014–2019. Around 200 granted patents have been identified, covering all enzyme types. The inventive pattern focuses on the protection of novel protein sequences, as well as on new substrates. In some other cases, combined processes, multi-step enzymatic reactions, as well as pr...

Catalysts, 2017

A recently discovered, moderately thermostable Baeyer-Villiger monooxygenase, polycyclic ketone m... more A recently discovered, moderately thermostable Baeyer-Villiger monooxygenase, polycyclic ketone monooxygenase (PockeMO), from Thermothelomyces thermophila has been employed as a biocatalyst in a set of asymmetric sulfoxidations. The enzyme was able to catalyze the oxidation of various alkyl aryl sulfides with good selectivities and moderate to high activities. The biocatalytic performance was able to be further increased by optimizing some reaction parameters, such as the addition of 10% v v −1 of water miscible solvents or toluene, or by performing the conversion at a relatively high temperature (45 • C). PockeMO was found to display an optimum activity at sulfide concentrations of 50 mM, while it can also function at 200 mM. Taken together, the data show that PockeMO can be used as robust biocatalyst for the synthesis of optically active sulfoxides.

Advanced Synthesis & Catalysis, 2017

Multi‐step processes catalysed by several catalysts working concurrently have been developed in n... more Multi‐step processes catalysed by several catalysts working concurrently have been developed in nature, thus improving reaction efficiency. The quest for novel and improved catalytic systems has led to the development of biocatalytic and later to organocatalytic procedures as very valuable tools in asymmetric synthesis while using mild reaction conditions in the absence of metal catalysts. As a timeless challenge, chemists are facing the need for process designs in which different sorts of catalysts can operate successfully in a one‐pot concurrent fashion. Likewise, such designs bring about the best of each catalyst and, in certain cases, enable us to improve problematic issues, such as reactivity, selectivity, solubility, inhibition, etc. Specifically, to combine these two types of catalysts in one‐pot, achieving high yields and selectivity, is a fascinating aspect of catalysis. This review covers representative advances in this field, in particular those in which biocatalysts and ...

Proceedings of The 20th International Electronic Conference on Synthetic Organic Chemistry, 2016

Ionic liquids (ILs) are largely used in biocatalysis, mainly as cosolvents of the biocatalyzed re... more Ionic liquids (ILs) are largely used in biocatalysis, mainly as cosolvents of the biocatalyzed reactions, but in the last few years ILs have been used as coating reagents in the immobilization of enzymes. In the present communication, we have developed a set of immobilized Baeyer-Villiger monooxygenases preparations in presence of different ILs. These immobilized biocatalysts have been tested in selective sulfoxidations with the aim of analyzing the activity and selectivity of the novel enzymatic preparations as well as their performance during different reaction cycles.

Chembiochem : a European journal of chemical biology, Jul 28, 2016

Eugenol oxidase (EUGO) from Rhodococcus jostii RHA1 was previously shown to convert only a limite... more Eugenol oxidase (EUGO) from Rhodococcus jostii RHA1 was previously shown to convert only a limited set of phenolic compounds. In this study, we have explored the biocatalytic potential of this flavoprotein oxidase resulting in a broadened substrate scope and a deeper insight into its structural properties. In addition to the oxidation of vanillyl alcohol and hydroxylation of eugenol, EUGO can efficiently perform the dehydrogenation of various phenolic ketones and the selective oxidation of a racemic secondary alcohol, 4-(hydroxy-1-ethyl)-2-methoxyphenol. EUGO was also found to perform the kinetic resolution of a racemic secondary alcohol. Crystal structures of the enzyme in complex with isoeugenol, coniferyl alcohol, vanillin, and benzoate have been determined. The catalytic center is a remarkable solvent-inaccessible cavity on the si side of the flavin cofactor. Structural comparison with vanillyl-alcohol oxidase from Penicillium simplicissimum highlights a few localized changes th...

Catalytic Methods in Asymmetric Synthesis, 2011

Tetrahedron: Asymmetry, 2009

Growing cells of the basiodiomycete Lentinus strigellus in potato-dextrose broth have been used f... more Growing cells of the basiodiomycete Lentinus strigellus in potato-dextrose broth have been used for the first time as a biocatalyst in the stereoselective reduction of aromatic and aliphatic ketones. Most of the aromatic ketones were converted into the corresponding optically active alcohols in up to >99% enantiomeric excess under very mild reaction conditions. Among the aliphatic ketones tested, 2-octanone was enzymatically reduced by this microorganism to enantiopure (S)-2-octanol with almost complete conversion.

Tetrahedron: Asymmetry, 2008

The enzymatic preparation obtained from a discard of Manihot esculenta roots has been successfull... more The enzymatic preparation obtained from a discard of Manihot esculenta roots has been successfully immobilized on calcium alginate hydrogels. This preparation has been tested as a chiral biocatalyst in the enzymatic acylation of a set of racemic aromatic alcohols. Depending on the reaction conditions, excellent enantioselectivities can be achieved. Some parameters that can alter the biocatalytic properties of the enzyme, such as solvent, temperature, acyl donor and substrate structure have been studied exhaustively in order to establish a deeper knowledge of this novel biocatalyst.

Tetrahedron: Asymmetry, 2010

Whole cells from the Brazilian beans feijão da corda (Vigna unguiculata) have been employed as bi... more Whole cells from the Brazilian beans feijão da corda (Vigna unguiculata) have been employed as biocatalyst in different bioreduction processes. Good to excellent selectivities can be obtained in the reduction of aromatic and aliphatic ketones, as well as βketoesters, depending the conversions and the chemoselectivity on the substrate structure. This biocatalyst was also able to reduce the nitro moiety of different aromatic nitro compounds, presenting also enoate reductase activity, chemoselectively catalyzing the double bond reduction of 4-phenyl-3-buten-2-one with moderate conversion.

Tetrahedron: Asymmetry, 2006

Recombinant 4-hydroxyacetophenone monooxygenase (HAPMO) from Pseudomonas fluorescens ACB has been... more Recombinant 4-hydroxyacetophenone monooxygenase (HAPMO) from Pseudomonas fluorescens ACB has been tested as a catalyst in sulfoxidation reactions on a set of aromatic sulfides. With a few exceptions, excellent enantioselectivities in the synthesis of chiral phenyl and benzyl sulfoxides were achieved. The bacterial Baeyer-Villiger monooxygenase was also shown to accept racemic sulfoxides, a prochiral diketone and an organoboron compound as substrates. This study demonstrates the great biocatalytic potential of this novel oxidative enzyme.

Organic & Biomolecular Chemistry, 2010

Parallel interconnected kinetic asymmetric transformations were performed in order to obtain enan... more Parallel interconnected kinetic asymmetric transformations were performed in order to obtain enantioenriched derivatives starting from a set of racemic or prochiral compounds. Thus, in a onepot reaction using two redox biocatalysts (a BVMO and an ADH) and a catalytic amount of cofactor that acts as a mediator, enantioenriched ketones, sulfoxides, and sec-alcohols were concurrently obtained in a strict parallel way minimising the quantity of reagents employed. By selecting the appropriate biocatalysts, this methodology is a potential tool for performing stereodivergent transformations. 65 65 this type of processes could be described as parallel interconnected kinetic asymmetric transformations. <Scheme 2 here> Scheme 2. Concurrent kinetic resolutions of (±)-1 and (±)-3 employing BVMOs and ADHs. Esters 5 are obtained as by-products through a cascade process.

Organic & Biomolecular Chemistry, 2010

Organic & Biomolecular Chemistry, 2011

Journal of Molecular Catalysis B: Enzymatic, 2010

Growing cells of the phytopathogen fungus Lasiodiplodia theobromae in potato dextrose broth have ... more Growing cells of the phytopathogen fungus Lasiodiplodia theobromae in potato dextrose broth have shown their potential for the stereoselective bioreduction of different prochiral aromatic and aliphatic ketones. Optically active alcohols were obtained under mild reaction conditions in high conversions (up to 90%) and moderate to excellent enantioselectivity (35–≥99% ee) depending on the ketone structure. Prelog alcohols were isolated, except in

Journal of Molecular Catalysis B: Enzymatic, 2012

Fil: Mascotti, Maria Laura. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Ci... more Fil: Mascotti, Maria Laura. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - San Luis. Instituto de Investigaciones en Tecnologia Quimica. Universidad Nacional de San Luis. Facultad de Quimica, Bioquimica y Farmacia. Instituto de Investigaciones en Tecnologia Quimica; Argentina

European Journal of Organic Chemistry, 2010

ABSTRACT Optically active sulfoxides are compounds of high interest in organic chemistry. Herein,... more ABSTRACT Optically active sulfoxides are compounds of high interest in organic chemistry. Herein, we report the preparation of a set of chiral heteroaryl alkyl, cyclohexyl alkyl, and alkyl alkyl sulfoxides by using enantioselective sulfoxidation reactions employing three Baeyer–Villiger monooxygenases (BVMOs). Careful selection of the reaction conditions, starting sulfide, and biocatalyst can be used to achieve good to excellent enantiomeric excess values. Thus, valuable chiral synthons can be obtained by performing the reactions under mild and environmentally friendly conditions. The most promising biotransformations that employ a BVMO cell-free extract preparation have been developed on a 250-mg scale to give the chiral sulfoxides in high yields in most of the reactions.