Boron-Mediated Lignocellulose Degradation. Design, Synthesis, Properties, and Applications of Boron-Containing Naphthoids

Abstract

Lewis acidity is a molecule’s tendency to accept a pair of electrons. Trivalent boron compounds are archetypical Lewis acids due to the presence of a vacant p orbital, leading to many uses in organic synthesis. For example, boron trihalides use their intrinsic Lewis acidity to accept ether oxygen electrons, facilitating ether cleavage reactions. On the other hand, organoboron compounds are commonly used in catalysis, such as in the Corey-Bakshi-Shibata reduction method. An interesting class of organoboron compounds that have recently gained prominence in the field of medicinal chemistry is boron-containing heterocycles. They are used in a number of fascinating applications and, in particular, have appeared in several FDA approved drugs. Despite the significance of boron-containing compounds, many aspects of their physicochemical properties, reactivity, and potential applications remain underexplored. Lignocellulose is a plant biomass formed by ether and acetal linkages of phenolic and sugar monomers. Chapter 2 of this thesis describes the use of a mild method that utilizes mixed boron trihalides for processing lignocellulose into cellulose and lignin components. Such materials may offer a route to sustainable chemical production, alleviating the need for non-renewable petroleum-based feedstocks. The applicability of this method was demonstrated with a sample of white pine sawdust, followed by spectroscopic analyses and dye-staining methods. Boron-containing heterocycles are an important motif in material science and drug discovery. As such, a comprehensive understanding of their properties is needed to enable new applications. The acidic nature of certain hemiboronic acids, such as boron-containing naphthoids, has been a point of argument for a long time, and there has been no definite evidence regarding their aromatic character. Chapter 3 addresses these questions, along with other characteristics of boron-containing naphthoids, such as their stability and their boranol (B—OH) exchange with alcohols. Overall, this study clarifies a large body of conflicting results reported in the literature over several decades and provides important conclusions for the systematic applications of boron-containing naphthoids in the areas of catalysis and medicinal chemistry. Chapter 4 further examines the physical properties of boron-containing naphthoids and their suitability as drug scaffolds. Moreover, new and chemoselective synthetic strategies and purification procedures are described. Small prototypical compound libraries for different boron-containing naphthoid scaffolds were produced. Many such compounds are drug bioisosteres and were subsequently evaluated in biological activity assays.