Aromatic Oligoamide Foldamer as a modular scaffold for the control of the reactivity of a PLP-mimic

Details

Supervisors

Singleton, Michael L. ; Robiette, Raphaël

Faculty

Faculté des sciences

Degree label

Master [120] en sciences chimiques, à finalité approfondie

Abstract

Pyridoxal-5’-Phosphate, the main active form of the vitamin B6, has intrigued chemists and biochemists, since its discovery, by its ability to catalyze a dozen different reaction by binding to more than 140 enzymes. More than half a century of investigations have highlighted the importance of the direct environment around the cofactor in determining its reactivity. This environment is the direct consequence of the ability of enzymes to fold on themselves to adopt well-defined 3D structures based on their amino acid sequence. Inspired by the high efficiency and diversity of enzymes, chemists have investigated plenty of ways of building supramolecular architectures during the last decades. Among them, a class of oligomers, known as foldamers, have drawn attention because of their ability to fold on themselve to adopt well-defined 3D structures allowing application in enzyme mimicking, molecular recognition and catalysis. Inspired by this, this master’s thesis aims to gain in-depth understanding of the structurereactivity relationship in the PLP-cofactor catalytic system. To this end, we aim to include a PLP-mimic in a foldamer with a well-defined 3D structure in order to precisely control the environment around the reaction center. For this, we grafted a 4-carbaldehyde motif on a quinoline, commonly used as a monomer in Aromatic Oligoamide Foldamers, and demonstrated that the synthesized mimic is capable to behave as a catalyst toward a transamination reaction of primary amines in the presence of a sacrifical α-keto acid with a yield of 28 % in 10 mol% catalytic loading. The potential of the mimic toward decarboxylative transamination is also shown, further supporting its ability to behave similarly to the PLP-cofactor. In order to include the obtained mimic into an Aromatic Oligoamide Foldamer, we performed the synthesis of the other compounds relevant to obtaining the desired sequence in a rapid manner. Finally, in-depth understanding of non-covalent interactions or 3D structures can be achieved with the help of computational means, for this reason we describe here the first steps toward structural optimization and non-covalent interaction investigation by computational means.