Fabricio R. Bisogno
University of Oviedo
Network
Latest external collaboration on country level. Dive into details by clicking on the dots.
Publication
Featured researches published by Fabricio R. Bisogno.
Chemistry: A European Journal | 2010
Fabricio R. Bisogno; Eduardo García‐Urdiales; Haydee Valdes; Iván Lavandera; Wolfgang Kroutil; Dimas Suárez; Vicente Gotor
To ensure the quasi-irreversibility of the oxidation of alcohols coupled with the reduction of ketones in a hydrogen-transfer (HT) fashion, stoichiometric amounts of α-halo carbonyl compounds have been employed as hydrogen acceptors. The reason that these substrates lead to quasi-quantitative conversions has been tacitly attributed to both thermodynamic and kinetic effects. To provide a clear rationale for this behavior, we investigate herein the redox equilibrium of a selected series of ketones and 2-propanol by undertaking a study that combines experimental and theoretical approaches. First, the activity of the (R)-specific alcohol dehydrogenase from Lactobacillus brevis (LBADH) with these substrates was studied. The docking of acetophenone/(R)-1-phenyethanol and α-chloroacetophenone/(S)-2-chloro-1-phenylethanol in the active site of the enzyme confirms that there seems to be no structural reason for the lack of reactivity of halohydrins. This assumption is confirmed by the fact that the corresponding aluminum-catalyzed Meerwein-Ponndorf-Verley-Oppenauer (MPVO) reactions afford similar conversions to those obtained with LBADH, showing that the observed reactivity is independent of the catalyst employed. While the initial rates of the enzymatic reductions and the IR ν(C=O) values contradict the general belief that electron-withdrawing groups increase the electrophilicity of the carbonyl group, the calculated ΔG values of the isodesmic redox transformations of these series of ketones/alcohols with 2-propanol/acetone support the thermodynamic control of the reaction. As a result, a general method to predict the degree of conversion obtained in the HT-reduction process of a given ketone based on the IR absorption band of the carbonyl group is proposed, and a strategy to achieve the HT oxidation of halohydrins is also shown.
Green Chemistry | 2009
Fabricio R. Bisogno; Aníbal Cuetos; Iván Lavandera; Vicente Gotor
A simple preparation on gram-scale of thiocyanate derivatives via nucleophilic substitution of halogenated compounds with SCN salts at high substrate concentrations in a few minutes and excellent yields was successfully accomplished in hydroalcoholic media. The obtained compounds were employed for the efficient synthesis of valuable 5-aryl-2-imino-1,3-oxathiolane derivatives (a one-pot approach is also presented).
Chemcatchem | 2010
Fabricio R. Bisogno; Ana Rioz-Martínez; C. Rodríguez; Iván Lavandera; Gonzalo de Gonzalo; Daniel E. Torres Pazmiño; Marco W. Fraaije; Vicente Gotor
Oxidoreductases are an important class of enzymes that catalyze redox processes, transferring electrons from a reductant to an oxidant. These biocatalysts are widely applied due to their usually exquisite chemo-, regio-, and stereoselectivities through mild and environmentally friendly procedures. Probably the oxidoreductases most often employed are the alcohol dehydrogenases (ADHs, EC 1.1.1.x.), which are able to perform stereoselective carbonyl reductions or enantioselective alcohol oxidations. Another type of redox biocatalysts are Baeyer–Villiger monooxygenases (BVMOs; EC 1.14.13.x.) that catalyze the oxidation of ketones, sulfides, and other heteroatoms by atmospheric oxygen. Besides all the advantages that biocatalyzed oxidations present over chemical methods, the requirement of the expensive nicotinamide NADPH cofactor necessitates effective cofactor regeneration by, for example, chemical, electrochemical, photochemical, or enzymatic methods. The methodology most often exploited is the ‘enzyme-coupled’ approach, in which a second, preferably irreversible, enzymatic reaction is used to shift the equilibrium towards the desired product. Recently, “designer bugs,” whole cells containing the overexpressed genes of the desired enzymes (ADH/BVMO plus enzyme for the recycling system), or “self-sufficient” BVMOs, in which the recycling enzyme has been covalently linked to the monooxygenase, have been developed with very promising results. Nevertheless, such enzyme-coupled transformations depend on a sacrificial coupled reaction which lowers the atom-efficiency environmental factor, E, of the overall process. We have recently developed a system in which two productive redox reactions are connected through internal cofactor recycling. In this manner , it was possible to obtain simultaneously up to three enantioenriched derivatives starting either from two racemic mixtures or a racemate plus a prochiral compound, maximizing the redox efficiency of the whole process and allowing parallel interconnected kinetic asymmetric transformations (PIKAT; Scheme 1). Herein we have broadened the scope of the system combining the stereoselective oxidation of several sulfides with the enantioselective oxidation of different sec-alcohols. The cofactor concentration employed in these processes was optimized, which resulted in good performance, even when using micromolar concentrations of the NADP connector. Firstly, the enzymatic resolution of ( )-2-octanol (1a, 2 equivalents) catalyzed by two commercially available ADHs (LBADH from Lactobacillus brevis and ADH-T from Thermoanaerobacter sp.) was coupled with the sulfoxidation of different sulfides (4a–e, 1 equivalent) in the presence of the Baeyer–Villiger monooxygenases PAMO from Thermobifida fusca, its M446G mutant or HAPMO from Pseudomonas fluorescens ACB (Scheme 2). The results are summarized in Table 1. For these reactions, PAMO and M446G were used at 30 8C and HAPMO at 20 8C. Scheme 1. Concurrent obtaining of enantioenriched derivatives through parallel interconnected kinetic asymmetric transformation (PIKAT) method.
Organic and Biomolecular Chemistry | 2010
Ana Rioz-Martínez; Fabricio R. Bisogno; C. Rodríguez; Gonzalo de Gonzalo; Iván Lavandera; Daniel E. Torres Pazmiño; Marco W. Fraaije; Vicente Gotor
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 one-pot 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 represents a potential tool for performing stereodivergent transformations.
Steroids | 2007
Fabricio R. Bisogno; Alejandro A. Orden; Celeste Aguirre Pranzoni; Diego A. Cifuente; Oscar S. Giordano; Marcela Kurina Sanz
5,6-Epoxycholestan-3beta-ol derivatives were hydrolyzed in a diastereoconvergent manner by growing and resting cells of several strains of Aspergillus niger, particularly A. niger ATCC 11394. These strains displayed opposite regioselectivity toward each isomer in an alpha and beta epoxide mixture, thus, the nucleophilic attack took place at the less substituted and the most substituted carbon atom on each diasteromer, respectively. These biocatalysts opened trisubstituted oxiranes but were unable to hydrolyze the disubstituted oxiranes in the tested sterol derivatives. These findings suggest that A. niger strains possess another hydrolytic ability different from the commercial A. niger epoxide hydrolase (EH) that did not accept this kind of steroidal oxiranes as substrates.
Steroids | 2016
M. Laura Mascotti; Martín A. Palazzolo; Fabricio R. Bisogno; Marcela Kurina-Sanz
The research on the synthesis of steroids and its derivatives is of high interest due to their clinical applications. A particular focus is given to molecules bearing a D-ring lactone like testolactone because of its bioactivity. The Aspergillus genus has been used to perform steroid biotransformations since it offers a toolbox of redox enzymes. In this work, the use of growing cells of Aspergillus parasiticus to study the bioconversion of dehydro-epi-androsterone (DHEA) is described, emphasizing the metabolic steps leading to D-ring lactonization products. It was observed that A. parasiticus is not only capable of transforming bicyclo[3.2.0]hept-2-en-6-one, the standard Baeyer-Villiger monooxygenase (BVMO) substrate, but also yielded testololactone and the homo-lactone 3β-hydroxy-17a-oxa-D-homoandrost-5-en-17-one from DHEA. Moreover, the biocatalyst degraded the lateral chain of cortisone by an oxidative route suggesting the action of a BVMO, thus providing enough metabolic evidences denoting the presence of BVMO activity in A. parasiticus. Furthermore, since excellent biotransformation rates were observed, A. parasiticus is a promising candidate for the production of bioactive lactone-based compounds of steroidal origin in larger scales.
Chemcatchem | 2014
Kinga Kędziora; Fabricio R. Bisogno; Iván Lavandera; Vicente Gotor-Fernández; Jose Montejo-Bernardo; Santiago García-Granda; Wolfgang Kroutil; Vicente Gotor
Alcohol dehydrogenases (ADHs) were identified as suitable enzymes for the reduction of the corresponding α,α‐dihalogenated ketones, obtaining optically pure β,β‐dichloro‐ or β,β‐dibromohydrins with excellent conversions and enantiomeric excess. Among the different biocatalysts tested, ADHs from Rhodococcus ruber (ADH‐A), Ralstonia sp. (RasADH), Lactobacillus brevis (LBADH), and PR2ADH proved to be the most efficient ones in terms of activity and stereoselectivity. In a further study, two racemic α‐substituted ketones, namely α‐bromo‐ α‐chloro‐ and α‐chloro‐α‐fluoroacetophenone were investigated to obtain one of the four possible diastereoisomers through a dynamic kinetic process. In the case of the brominated derivative, only the (1R)‐enantiomer was obtained by using ADH‐A, although with moderate diastereomeric excess (>99 % ee, 63 % de), whereas the fluorinated ketone exhibited a lower stereoselectivity (up to 45 % de).
Organic chemistry frontiers | 2017
Silvia M. Soria-Castro; Fabricio R. Bisogno; Alicia B. Peñéñory
A novel, one-pot synthesis of structurally diverse benzo-fused thiacycles via a Cu-catalysed intermolecular C–S coupling/cyclisation tandem process, employing the same catalytic system, has been developed. Thus, 3,4-dihydro-2H-benzo[e][1,3]thiazines and 4H-benzo[e][1,3]thiazines were selectively obtained by this one-pot tandem process from (2-iodophenyl)methanamine and aldehydes or 1-(azidomethyl)-2-iodobenzene, respectively. These reactions proceeded in toluene at 100 °C with potassium thioacetate, thiobenzoate or ethyl xanthogenate in moderate to good isolated yields. The first one avoids the imine isolation step. A similar approach to benzo[b]thiophene derivatives from 2-(2-iodophenyl)acetonitrile was also developed.
Journal of Organic Chemistry | 2009
Fabricio R. Bisogno; Iván Lavandera; Wolfgang Kroutil; Vicente Gotor
Journal of Agricultural and Food Chemistry | 2007
Fabricio R. Bisogno; Laura Mascoti; Cecilia Sanchez; Francisco M. Garibotto; Fernando Giannini; Marcela Kurina-Sanz; Ricardo D. Enriz