ORGANOCATALISIS AND PHOTO-REDOX CATALYSIS AS TOOLS OF SYNTHESIS OF NEW CHEMICAL ENTITIES (Q3139901)
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Project Q3139901 in Spain
| Language | Label | Description | Also known as |
|---|---|---|---|
| English | ORGANOCATALISIS AND PHOTO-REDOX CATALYSIS AS TOOLS OF SYNTHESIS OF NEW CHEMICAL ENTITIES |
Project Q3139901 in Spain |
Statements
47,190.0 Euro
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94,380.0 Euro
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50.0 percent
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1 January 2018
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31 December 2020
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UNIVERSIDAD DE VALENCIA
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39°30'32.62"N, 0°24'39.10"W
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46078
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EL PRESENTE PROYECTO ABORDA, DE MANERA GENERAL, LA SINTESIS DE NUEVAS ESTRUCTURAS QUIMICAS DE INTERES MEDIANTE LA UTILIZACION DE NUEVAS METODOLOGIAS RECIENTEMENTE INCORPORADAS AL ARSENAL DE HERRAMIENTAS DE LA QUIMICA ORGANICA. ES INDUDABLE EL GRAN AUGE QUE LA ORGANOCATALISIS ASIMETRICA Y LA CATALISIS FOTO-REDOX HAN ADQUIRIDO EN LA ULTIMA DECADA DEBIDO, ENTRE OTROS ASPECTOS, A LA SIMPLICIDAD OPERACIONAL DE AMBAS METODOLOGIAS Y A LA INCORPORACION DE NUEVOS MODOS DE ACTIVACION DE MOLECULAS ORGANICAS, A TRAVES DE MECANISMOS DISTINTOS A LOS TRADICIONALES, QUE PERMITEN LLEVAR A CABO NUEVAS TRANSFORMACIONES DE FORMA MUY EFICIENTE. _x000D_ EN ESTE CONTEXTO, NOS PROPONEMOS, EN PRIMER LUGAR, IMPLEMENTAR UN PROCESO DE DESIMETRIZACION ENANTIOSELECTIVA MEDIANTE EL USO DE LA REACCION AZA-MICHAEL INTRAMOLECULAR, LO QUE NOS PERMITIRA ACCEDER A NUEVAS FAMILIAS DE PIPERIDINAS Y PIRROLIDINAS DISUSTITUIDAS, QUE SON ESTRUCTURAS PRIVILEGIADAS DADA LA AMPLIA GAMA DE ACTIVIDADES BIOLOGICAS QUE INDUCEN. _x000D_ EN SEGUNDO LUGAR, PRETENDEMOS DISEÑAR NUEVOS PROCESOS TANDEM ORGANOCATALITICOS, COMBINANDO DOS ADICIONES CONJUGADAS INTRAMOLECULARES CONSECUTIVAS. DE ESTA FORMA, SE SINTETIZARAN HETEROCICLOS NITROGENADOS POLICICLICOS, CONCRETAMENTE SULTAMAS Y LACTAMAS, EN FORMA ENANTIOMERICAMENTE ENRIQUECIDA, CON GENERACION SIMULTANEA DE VARIOS ESTEREOCENTROS. _x000D_ EL TERCER OBJETIVO DE LA PRESENTE PROPUESTA ESTA RELACIONADO CON EL DESARROLLO DE UNA METODOLOGIA ADECUADA PARA LLEVAR A CABO UNA REACCION DE CICLOADICION 1,3-DIPOLAR INTRAMOLECULAR ENANTIOSELECTIVA DE NITRONAS CON TRIFLUOROMETIL ESTIRENOS COMO DIPOLAROFILOS. EN ESTE PROCESO SE OBTENDRAN DERIVADOS DE TETRAHIDRONAFTALENO CON UN CENTRO ESTEREOGENICO CUATERNARIO PORTADOR DE UNA AGRUPACION TRIFLUOROMETILO. LA GENERACION DE ESTE TIPO DE ESTEREOCENTROS ES UN RETO SINTETICO MUY IMPORTANTE, RESUELTO SOLO PARCIALMENTE MEDIANTE ADICIONES CONJUGADAS. _x000D_ COMO CUARTO OBJETIVO, NOS PROPONEMOS ADENTRARNOS EN EL CAMPO DE LA CATALISIS FOTO-REDOX. DADA NUESTRA EXPERIENCIA PREVIA EN EL EMPLEO DE "BUILDING BLOCKS" FLUORADOS PARA LLEVAR A CABO DIFERENTES TRANSFORMACIONES QUIMICAS, Y LA GRAN VARIEDAD DE RADICALES FLUOROALQUILO QUE SE HAN DESCRITO UTILIZANDO PROCEDIMIENTOS FOTOCATALITICOS, PENSAMOS QUE UNA BUENA FORMA DE INTRODUCIRNOS EN ESTA INTERESANTE AREA ES EXTENDER LA GENERACION DE ESTE TIPO DE RADICALES A PRECURSORES QUE NUNCA SE HAN UTILIZADO CON ESTE FIN, COMO SON LOS SISTEMAS BROMODIFLUOROPROPARGILICOS Y LOS HALUROS DE IMIDOILO FLUORADOS. ASI PUES, SE ESTUDIARA LA VIABILIDAD DE ESTOS INTERMEDIOS RADICALARIOS Y SE EVALUARA DE FORMA PRELIMINAR SU REACTIVIDAD EN REACCIONES DE INSERCION SOBRE DIVERSOS SISTEMAS INSATURADOS. COMO UNA APLICACION DE ESTA METODOLOGIA, SE PROCEDERA A LA SINTESIS DE GAMMA-AMINOACIDOS FLUORADOS. _x000D_ FINALMENTE, NOS HEMOS PLANTEADO UTILIZAR ALGUNOS DE LOS COMPUESTOS NITROGENADOS ENANTIOMERICAMENTE ENRIQUECIDOS, PREVIAMENTE SINTETIZADOS, PARA LA FORMACION DE COMPLEJOS CON METALES DE TRANSICION, QUE SE EVALUARAN COMO AGENTES DE RECONOCIMIENTO DEL ADN Y QUE NOS PERMITIRAN POTENCIALMENTE OBTENER METALONUCLEASAS EFECTIVAS Y SELECTIVAS. DE ESTE MODO, PRETENDEMOS EXTRAER CONCLUSIONES DE CARACTER FUNDAMENTAL SOBRE LA INTERACCION DE DICHOS COMPLEJOS CON EL ADN EN LAS QUE SE PUEDA APOYAR UN DISEÑO RACIONAL DE NUEVOS COMPLEJOS CON ACTIVIDAD ANTITUMORAL. (Spanish)
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THE PRESENT PROJECT ADDRESSES, IN A BROAD SENSE, THE SYNTHESIS OF NEW CHEMICAL ENTITIES OF INTEREST MAKING USE OF NOVEL SYNTHETIC METHODOLOGIES RECENTLY INCORPORATED INTO THE TOOLBOX OF ORGANIC CHEMISTRY: ORGANOCATALYSIS AND PHOTOREDOX CATALYSIS. BOTH METHODOLOGIES HAVE WITNESSED AN IMPRESIVE DEVELOPMENT IN THE LAST DECADES. THIS SUCCESS IS MAINLY DUE TO TWO FACTORS, THE OPERATIONAL SIMPLICITY AND THE INCORPORATION OF NEW ACTIVATION MODES OF ORGANIC MOLECULES, BY MEANS OF NON-CONVENTIONAL MECHANISMS, THAT ALLOW TO CARRY OUT NEW TRANSFORMATIONS IN A VERY EFFICIENT MANNER._x000D_ IN THIS CONTEXT, THE FIRST GOAL OF THIS PROPOSAL IS THE IMPLEMENTATION OF AN ENANTIOSELECTIVE DESYMMETRIZATION PROCESS BASED ON THE USE OF THE INTRAMOLECULAR AZA-MICHAEL REACTION. THIS PROTOCOL WOULD GIVE ACCESS TO NEW FAMILIES OF DISUBSTITUTED PIPERIDINES AND PYRROLIDINES, WHICH ARE PRIVILEGED STRUCTURES GIVEN THE WIDE VARIETY OF BIOLOGICAL ACTIVITIES INDUCED BY THESE SCAFFOLDS. _x000D_ SECONDLY, WE INTEND TO DESIGN NEW ORGANOCATALYTIC TANDEM PROCESSES, COMBINING TWO CONSECUTIVE INTRAMOLECULAR CONJUGATE ADDITIONS. IN THIS MANNER, SEVERAL POLYCYCLIC NITROGEN-CONTAINING HETEROCYCLES, NAMELY SULTAMS AND LACTAMS, WILL BE SYNTHESIZED IN ENANTIOMERICALLY ENRICHED MANNER, WITH THE SIMULTANEOUS GENERATION OF SEVERAL STEREOCENTERS. _x000D_ THE THIRD OBJECTIVE OF THE PRESENT PROPOSAL RELIES ON THE DEVELOPMENT OF AN ADEQUATE METHODOLOGY TO PERFORM AN ENANTIOSELECTIVE INTRAMOLECULAR 1,3-DIPOLAR CYCLOADDITION REACTION OF NITRONES AND TRIFLUOROMETHYL STYRENES AS DIPOLAROPHILES. IN THIS PROCESS, NEW TETRAHYDRONAPHTHALENE DERIVATIVES BEARING A QUATERNARY STEREOGENIC CENTER WITH A TRIFLUOROMETHYL MOIETY WILL BE OBTAINED. THE GENERATION OF THIS TYPE OF STEREOCENTERS IS AN IMPORTANT SYNTHETIC CHALLENGE, SOLVED ONLY PARTIALLY BY MENAS OF CONJUGATE ADDITION REACTIONS. _x000D_ IN THE FOURTH SECTION OF THE PROPOSAL WE INTEND TO DELVE INTO THE FIELD OF PHOTOREDOX CATALYSIS. GIVEN OUR EXPERIENCE IN THE USE OF FLUORINATED BUILDING BLOCKS TO CARRY OUT DIFFERENT CHEMICAL TRANSFORMATIONS, AND THE GREAT VARIETY OF FLUOROALKYL RADICALS GENERATED BY MEANS OF PHOTOCATALYTIC PROCEDURES, WE THINK THAT A GOOD WAY TO INTRODUCE OURSELVES IN THIS INTERESTING AREA IS TO EXTEND THE GENERATION OF THESE RADICALS TO PRECURSORS THAT HAVE NEVER BEEN EMPLOYED FOR THIS PURPOSE, SUCH AS BROMODIFLUOROPROPARGYLIC SYSTEMS AND FLUORINATED IMIDOYL HALIDES. THUS, THE FEASIBILITY OF THESE RADICAL INTERMEDIATES WILL BE STUDIED AND THEIR REACTIVITY WILL BE PRELIMINARILY EVALUATED IN INSERTION REACTIONS OVER DIFFERENT UNSATURATED SYSTEMS. TO EXEMPLIFY THE UTILITY OF THIS METHODOLOGY, WE WILL ATTEMPT THE SYNTHESIS OF FLUORINATED GAMMA-AMINO ACIDS. _x000D_ FINALLY, WE ARE PLANNING TO UTILIZE SOME OF THE PREVIOUSLY SYNTHESIZED ENANTIOMERICALLY ENRICHED NITROGEN HETEROCYCLES FOR THE FORMATION OF TRANSITION METAL COMPLEXES WHICH WILL BE FURTHER EVALUATED AS DNA RECOGNITION AGENTS AND WHICH WILL ALLOW US TO POTENTIALLY OBTAIN EFFECTIVE AND SELECTIVE METALLONUCLEASES. THESE EXPERIMENTS WILL HELP US IN THE UNDERSTANDING OF THE FUNDAMENTAL MECHANISMS OF THE INTERACTION OF THESE COMPLEXES WITH DNA AND WILL LET US TO TACKLE A RATIONAL DESIGN OF NEW COMPLEXES WITH ANTITUMOR ACTIVITY. (English)
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Burjassot
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Identifiers
CTQ2017-85026-R
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