Biomimetic asymmetric catalysis with bioinspired helical foldamers.

Abstract

Organocatalysis is a rapidly expanding methodology enabling challenging chemical transformations to be performed in the broad context of sustainable chemistry (metal-free procedures, catalyst recycling). Potential applications include the rapid elaboration of advanced and useful building blocks for pharmaceutical development. Despite major achievements, organocatalysts generally suffer from low rate acceleration and turnover and the need for relatively high amounts to achieve good conversion and selectivity. Enzymes are generally regarded as very efficient catalysts at low loading levels and commonly act through a dual activation mechanism involving multiple cooperative interactions. A fundamental paradigm in nature is the connection between biopolymer function (transport, sensing, signaling, catalysis) primary sequence and folding (e.g. protein tertiary structure). In enzymes, precise organization of active-site side chains in the 3D space, participation of cofactors, electrostatic interactions through folding of the backbone are inherent elements which contribute to enhance the interaction with the substrate ultimately leading to the catalytic activity. The ability to synthesize artificial sequence-based oligomers that fold with high fidelity (i.e. foldamers) raises new prospects for mimicking biopolymers and for creating molecules with emergent functions tailored to various applications including catalysis. The presented works build upon previously published data by the team in an effort to explore new reactions that can be catalysed by oligourea foldamers.