Merging Metal Catalysis & DFT Studies toward the C-H Functionalization of a-Amino Carbonyl Compounds.

240 p.El principal objetivo de esta Tesis Doctoral consiste en el diseño de nuevos métodos catalíticos viafuncionalización de enlaces C¿H dirigidos a la modificación selectiva de aminoácidos y péptidos. Enparticular, se han desarrollado dos nuevas metodologías: una reacción de alcoxicarbonilación dederivados de Phe por activación de enlaces C(sp2)¿H catalizada por sales de Pd, y una reacción dehidroxilación de derivados de Tyr por funcionalización enlaces C(sp2)¿H catalizada por sales de Ru. Elmecanismo a través del cual ocurren dichos procesos se ha estudiado mediante cálculos computacionales.Así mismo, estudios de DFT han permitido elucidar el mecanismo a través del cual ocurren las reaccionesde CDC entre unidades de N-aril glicinas e indoles en presencia de sales de cobalto. En global, esta TesisDoctoral ha permitido avanzar en el desarrollo de nuevas estrategias sintéticas para modificarselectivamente biomoléculas de alto valor añadido

Late-Stage C-H Acylation of Tyrosine-Containing Oligopeptides with Alcohols

The selective tagging of amino acids within a peptide framework while using atom-economical C-H counterparts poses an unmet challenge within peptide chemistry. Herein, we report a novel Pd-catalyzed late-stage C-H acylation of a collection of Tyr-containing peptides with alcohols. This water-compatible labeling technique is distinguished by its reliable scalability and features the use of ethanol as a renewable feedstock for the assembly of a variety of peptidomimetics.The authors are grateful to the Ministerio de Ciencia e Innovacion (RTI2018-093721-B-I00, MCI/AEI/FEDER, UE) and the Basque Government (IT1033-16) for financial support. The authors thank the technical and human support provided by the Central Service of Analysis-SGIker of UPV/EHU and European funding (ERDF and ESF). In~aki Urruzuno thanks UPV/EHU for the postdoctoral research grant (EspDoc2020

Palladium-Catalyzed Site-Selective C(sp2)−H Acetoxylation of Tyrosine-Containing Peptides

A Pd-catalyzed C(sp2)−H acetoxylation of Tyr-containing peptides is described. The method relies on the use of a removable 2-pyridyloxy group as directing group and is distinguished by its reliable scalability and easily tuned regioselectivity to perform mono- and diacetoxylation reactions. Remarkably, the assembly of L–DOPA peptidomimetics is beyond reach upon cleavage of the directing group.We are grateful to Ministerio de Ciencia e Innovación (RTI2018-093721-B-I00, MCI/AEI/FEDER, UE) and Basque Government (IT-1741-22) for financial support. We thank for the technical and human support provided by Central Service of Analysis-SGIker of UPV/EHU and European funding (ERDF and ESF)

Ru-Catalyzed C-H Hydroxylation of Tyrosine-Containing Di- and Tripeptides toward the Assembly of L-DOPA Derivatives

[EN] The development of catalytic tools for the late-stage modification of amino acids within a peptide framework is a challenging task of capital importance. Herein, we report a Ru-catalyzed C(sp(2))-H hydroxylation of a collection of Tyr-containing di- and tripeptides featuring the use of a carbamate as a removable directing group and PhI(OCOCF3)(2) (PIFA) as oxidant. This air-compatible tagging technique is reliable, scalable and provides access to L-DOPA (L-3,4-dihydroxyphenylalanine) peptidomimetics in a racemization-free fashion. Density Functional Theory calculations support a Ru(II)/Ru(IV) catalytic cycle.We are grateful to Ministerio de Ciencia e Innovacion (RTI2018-093721-B-I00, MCI/AEI/FEDER, UE) and Basque Government (IT1033-16 and IT1254-19) for financial support. We thank for technical and human support provided by SGIker of UPV/EHU and European funding (ERDF and ESF). P. A.-S. thanks DIPC for the research contract

On the Mechanism of Cross-Dehydrogenative Couplings between N-Aryl Glycinates and Indoles: A Computational Study

Despite the widespread use of cross-dehydrogenative couplings in modern organic synthesis, mechanistic studies are still rare in the literature and those applied to α-amino carbonyl compounds remain virtually unexplored. Herein, the mechanism of Co-catalyzed cross-dehydrogenative couplings of N-aryl glycinates with indoles is described. Density functional theory studies supported the formation of an imine-type intermediate as the more plausible transient electrophilic species. Likewise, key information regarding the role of the N-aryl group and free NH motif within the reaction outcome has been gained, which may set the stage for further developments in this field of expertise.Ministerio de Ciencia e Innovación (RTI2018-093721-B-I00) Eusko Jaurlaritza (IT1033-16; IT1254-19

DESENVOLVIMENTO DE APLICAÇÃO IMERSIVA EDUCACIONAL: O SISTEMA SOLAR EM REALIDADE VIRTUAL

Com o avanço e, consequentemente, a popularização de determinadas tecnologias, é comum o uso de sistemas computacionais nas mais diversas áreas, tais como: jogos digitais, educação, publicidade e propaganda, construção civil, arquitetura, entre outras. Ademais, o uso da tecnologia junto às metodologias ativas de ensino, possibilita que as atividades sejam mais dinâmicas e se tornem diferenciais no processo de ensino e aprendizagem. No entanto, cabe-se o questionamento de como tornar essa aplicação interessante aos olhos dos alunos, sem se apoiar apenas no chamariz da tecnologia. Esse problema direcionou a pesquisa ao objetivo de desenvolver uma aplicação imersiva, utilizando de Realidade Virtual (RV), para uso no ambiente educacional. A temática escolhida para a aplicação foi “O sistema solar”, e essa se desenvolveu sob duas frente, a primeira teórica, fundamenta os dados exibidos durante a interação, estuda sua viabilidade, as ferramentas computacionais utilizadas e a usabilidade dentro da Experiência do Usuário (UX); a segunda observa o desenvolvimento prático: proposta de modelos 3D e implementação do ambiente virtual. Essa pesquisa demonstra a criação de uma aplicação mobile em Realidade Virtual, discute sua viabilidade em ambientes de ensino formais e/ou não formais sob a luz da Experiência do Usuário. &nbsp

Iron-Catalyzed Late-Stage Radical C–H Alkylamination of Phenol-Containing Drugs and Biomolecules

A modular site-selective iron-catalyzed radical amination of a number of phenol-containing biomolecules such as tyrosine-containing peptides, estrogens and other phenol-based pharmaceuticals has been developed. The method features the use of the cost-efficient combination of FeBr3 as catalyst along with triflic acid as Brønsted acid, thereby enabling the predictable appendance of morpholine and related heterocycles at the ortho C–H bond of phenols in a late-stage fashion. This alkylamination technique leverages the electron-rich nature of phenols to undergo oxidation to the corresponding phenoxyl radicals and further coupling with in situ formed electrophilic aminium radical cation species

Pd-Catalyzed C–H Alkoxycarbonylation of Phenethyl- and Benzylamines with Chloroformates as CO Surrogates

The site‐selective functionalization of C−H bonds within a complex molecule remains a challenging task of capital synthetic importance. Herein, an unprecedented Pd‐catalyzed C(sp2)−H alkoxycarbonylation of phenylalanine derivatives and other amines featuring picolinamide as the directing group (DG) is reported. This oxidative coupling is distinguished by its scalability, operational simplicity, and avoids the use of toxic carbon monoxide as the C1 source. Remarkably, the easy cleavage of the DG enables the efficient assembly of isoindolinone compounds. Density Functional Theory calculations support a PdII/PdIV catalytic cycle.We are grateful to MINECO (RTI2018‐093721‐B‐I00) and the Basque Government (IT1033‐16 and IT1254‐19) for financial support. We thank the technical and human support provided by SGIker of UPV/EHU and European funding (ERDF and ESF). Dr. I. Rivilla is kindly acknowledged for his support with HPLC analysis

Assessing User Experience in Immersive Virtual Reality Environment: a review of interconnected terms and meanings

This article reports a research project aiming to identify aspects that influence User Experience (UX) in Immersive Virtual Reality (IVR) environments.</p