Deconstructive Amide Functionalisations

The development of new synthetic methodologies is a fundamental aspect of chemical research. New reactions and methods enable access to novel drug scaffoldsor more economical access to existing scaffoldsand thus broaden the compound space available in the chemical industry. In this project, we will explore the use of a widely available class of molecules, known as amides, in the development of new transformations. Based on the previous work from the Maulide group, we aim to discover new reactivity profiles of this type of molecules which could be used in both academia and industry. Amides are essential and widespread in nature, with the amide bond constituting a key element in proteins and enzymes. Furthermore, amides often participate in the key interactions of drug molecules with their target. Because of their high demand, there is a plethora of synthetic methods available for chemists to synthesize this type of molecules. Given the availability of amides, it is not a surprise that they have found widespread application. However, the vast majority of chemical transformations of amides revolve around well-established reactivity patterns, typically leaving the connectivity of an amide bond intact. In contrast to standard amide chemistry, we propose to utilize various chemical activation protocols to generate highly reactive species and engage these in subsequent chemical transformations. In this way. We aim to alter the original amide bond connectivity, allowing rapid access to new types of compounds possessing versatile chemical functionalities. To engage otherwise much less reactive amide groups in new types of transformations, we will apply existing amide activation protocols and simultaneously develop new activation methods. The choice of reactant to intercept the reactive species generated upon amide activation to form new chemical bonds is a further crucial parameter to investigate. By carefully optimizing the system, we hope to access novel chemical spacesomething that would be difficult using established synthetic strategies. Finally, we aim to develop skeleton-editing methodologies based on amide activation, which could enable efficient and rapid modification of molecular scaffolds at a late stage, with potential applications in medicinal chemistry.