Dynamic systemic resolution.

Dynamic Systemic Resolution is a powerful technique for selecting optimal constituents from dynamic systems by applying selection pressures, either externally by addition of target entities, or internally within the system constraints. This concept is a subset of Constitutional Dynamic Chemistry, and the dynamic systems are generally based on reversible covalent interactions between a range of components where the systems are maintained under thermodynamic control. In the present chapter, the concept will be described in detail, and a range of examples will be given for both selection classes. For external pressure generation, target enzymes, in aqueous and/or organic solution, have been used to demonstrate the resolution processes. In a first example, a dynamic transthiolesterification system was generated in aqueous solution at neutral pH, and resolved by hydrolysis using serine hydrolases (cholinesterases). In organic solution, lipase-catalyzed acylation was chosen to demonstrate asymmetric resolution in different dynamic systems, generating chiral ester and amide structures. By use of such biocatalysts, the optimal constituents were selectively chosen and amplified from the dynamic systems in one-pot processes. In internal selection pressure resolution, self-transformation and crystallization-induced diastereomeric resolution have been successfully used to challenge dynamic systems. The technique was, for example, used to identify the best diastereomeric substrate from a large and varied dynamic system in a single resolution reaction.