Reversible covalent chemistries compatible with the principles of constitutional dynamic chemistry: New reactions to create more diversity

Abstract

An approach to make chemical diversity space more manageable is to search for smaller molecules, or fragments, and then combine or elaborate these fragments. Dynamic Combinatorial Chemistry (DCC) is a powerful approach whereby a number of molecular elements each with binding potential can be reversibly combined via covalent or noncovalent linkages to generate a dynamic library of products under thermodynamic equilibrium. Once a target molecule has been added, the distribution of products can be shifted to favor products that bind to the target. Thus the approach can be employed to identify products that selectively recognize the target. Although the size of the repertoire of reversible covalent reactions suitable for DCC has increased significantly over the past 5-10 years, the discovery of new reactions that satisfy all the criteria of reversibility and biocompatibility remains an exciting challenge for chemists. Increasing the number of chemical reactions will enable the engineering of larger and more diverse DCLs, which remains a key step toward a broader use of DCC. In this review, we aim to provide a nonexhaustive list of reversible covalent reactions that are compatible with the concept of DCC, focusing mainly on the most recent examples that were reported in the literature in the past 5 years. © 2011 Springer-Verlag Berlin Heidelberg.