Síntesis y estudio de las propiedades de sistemas poliheterocíclicos conjugados y BODIPYs α-sustituidos

Abstract

La relevancia de los compuestos heterocíclicos en áreas como la química orgánica o biológica hace que su estudio constituya un campo muy activo dentro de la química actual. En este contexto, el eje central de la presente Tesis Doctoral ha sido el estudio de derivados poliheterocíclicos conjugados, desde su síntesis al estudio de sus propiedades y su aplicación en distintas áreas. La tesis se ha estructurado en tres capítulos: En el primero, “Roseophilin derivatives”, se detalla la síntesis de nuevos compuestos, de tipo tambjamina y prodigiosina, basados en el núcleo del producto natural roseofilina. Estudio que ha permitido estudiar por primera vez la actividad anionofórica de sistemas con núcleo pirrolilfurano. En el segundo capítulo, denominado “Compuestos tetra(hetero)arílicos”, se han puesto a punto nuevas rutas sintéticas, basadas en la autocondensación de aldehídos pirrólicos, para la obtención de dipirrometenos simétricos α-sustituidos. Este capítulo se completa con el estudio de las propiedades fotofísicas y anionofóricas de estos sistemas, lo que ha permitido determinar la influencia de la sustitución en dichas propiedades. El tercer capítulo, “Derivados BODIPY”, se centra en el desarrollo de nuevas metodologías sintéticas para la obtención de meso-H BODIPYs 3,5-sustituidos. Además, para los BODIPYs sintetizados se han estudiado sus propiedades fotofísicas y espectroelectroquímicas, determinando especialmente cómo influyen los efectos electrónicos en ellas. Finalmente, se ha llevado a cabo el estudio de autoensamblaje supramolecular de BODIPYs con geometría angular, tratando de elucidar el mecanismo de agregación de estos sistemas y sus propiedades.

Heterocyclic compounds represent key players in modern chemistry because of their relevance in many areas of organic and biological chemistry. This PhD dissertation is focused on the development of different synthetic methodologies to obtain conjugated polyheterocyclic derivatives, which contain pyrrole and furan units in their structures, as well as studying their properties and applications in different areas, such as the anions transport across lipid membranes or the preparation of fluorophores. Taking the natural product rosephilin as an inspiration, the first chapter of the dissertation details the results in the synthesis of compounds by mimicking this type of structure, with the final aim of evaluating the anionophore activity of these products in lipid vesicle models. Thus, it was determined the influence of the introduction of several heterocyclic rings at different molecular positions on their anionophoric activity. Additionally, these studies were extended to other compounds inspired by the structure of other alkaloids such as the tambjamines. Chapters two and three of this dissertation have been focused on the synthesis and study of different -functionalized dipyrromethenic compounds. Dipyrromethenes are complex chromophoric systems with interesting properties and precursors of BODIPY-type fluorophores (4,4-difluoro-4-bora-3a, 4a-diaza-s-indacenes). Thereby, in the second chapter, two synthetic routes were designed, based on the selfcondensation of pyrrolic aldehydes, to obtain -substituted symmetric dipyrromethenes. The products obtained proved to have good photophysical properties, tunable through structural variations of the compounds, modifying their protonation state and by the effect of the concentration or the solvent. In addition, the anionophore activity of some of them was also demonstrated. On the other hand, the third chapter of the report has been oriented to the development of new methodologies for obtaining 3,5-substituted meso-H BODIPYs. First, the complexation reaction of -prefunctionalized dipyrromethenes was studied to obtain BODIPYs with groups of different nature in the C3/C5 positions. In addition, the scope of cross-coupling and nucleophilic aromatic substitution (SNAr) reactions was explored as strategies for the post-functionalization of BODIPYs through the derivatization of a 3,5-dibromo BODIPY. Thus, the use of cross-coupling reactions allowed to maximize the overall yield of the corresponding BODIPYs with respect to the prefunctionalization methodologies. On the other hand, the combination of SNAr with copper(I)-catalyzed azide alkyne cycloaddition (CuAAC) reactions facilitated the access to different regioisomers of symmetric click-BODIPYs. Likewise, by using amines as nucleophiles, asymmetric amino-BODIPYs, precursors of more complex products such as tambjamineBODIPYs, were isolated too. Some of the most important properties of synthesized BODIPYs were also explored in this chapter. In addition to the photophysical properties, similar to those that characterizing this type of fluorophores; the spectroelectrochemical properties of two -aryl BODIPYs were also studied, study that revealed their redox activity and the differences due to the different electronic nature of the substituents on the fluorophores. Finally, the application of some of the BODIPY derivatives as anion transporters was explored and, besides, derivatives of this type were prepared and studied considering a special design focused on the construction of supramolecular polymers through supramolecular self-assembly processes.