Metal- and enzyme-based processes for the selective preparation of carbohydrate and flavonoid derivatives

Resumo

This Doctoral Thesis describes new synthetic procedures based on the use of metals and enzymes for the selective preparation of products derived from carbohydrates and flavonoids. This work is divided into three main parts: the first section, that includes the first and the second chapter, is based on the use of samarium diiodide; the second part, that includes the third chapter, combines traditional synthetic methods with enzymatic catalysts; while the last part of this Doctoral Thesis is constituted by the last two chapters, describing the use of ruthenium- and palladium-based catalysts, respectively, to perform selective hydrogenation reactions. The first chapter includes the optimization and generalization of a selective β-elimination reaction promoted by samarium diiodide, transforming α-halocarbinol acetates into (Z)-vinyl halides derived from carbohydrates. Finally, with the aim to demonstrate the synthetic usefulness of this methodology and the one of the synthesised products, the synthesis of an enyne is described through a cross-coupling reaction. In the second chapter, a detailed optimization study of a stereodivergent radical-coupling reaction between flavones or chalcones is presented using samarium diiodide. Therefore, this process allows the production of both stereoisomers for the corresponding 2,2’-biflavanones or 2,2’-bichromanones, this process being highly dependent on the reaction temperature. The third chapter describes the synthesis of racemic cis- and trans-flavan-4-ols from the corresponding flavanones through a sequential strategy consisting in a selective reduction, alcohol configuration inversion via Mitsunobu reaction and final deprotection reaction. Finally, the classical kinetic resolution of racemic trans-flavan-4-ol has been developed through an acetylation biocatalytic process using different lipases under mild conditions. The fourth chapter includes the design and optimization of a methodology for the reduction of flavanones based on the use of ruthenium catalysts under transfer hydrogenation conditions, allowing the selective synthesis of 2-(3-aryl-1-hydroxypropyl)phenols. Besides, the development of an asymmetric version of the same reaction is addressed trying to produce representative examples of this family of compounds in optically-active form. Last but not least, the fifth chapter describes the chemoeselective palladium-catalysed hydrogenation of 2’-hidroxychalcones, paying special attention to the solvent influence giving access to a series of reduced products such as dihydrochalcones, 2-(3-aryl-1-hydroxypropyl)phenols or 1,3-diarylpropanes. The synthetic utility of this methodology is evaluated by the synthesis of Bussealins, family of natural products with remarkable biological properties.