Molecular Evolution on chiro-Inositol Dibenzoate Using Intramolecular Acyl Migration and Selection by Phenyl Boronic Acid

摘要

Molecular evolution incorporating the dynamic combinatorial library (DCL) approach has identified new host-guest systems. Two key features of molecular evolution are the selection and amplification of a particular species in the DCL. A DCL allows for a reversible equilibrium of library members in which a concentration change in one library member results in a new equilibrium distribution following Le Chatelier's principle. The molecular recognition event in the DCL induces the stabilization of the fittest binder, resulting in the shift of the equilibrium, amplifying the fittest binder with a decrease of others. To date, a number of DCLs have been prepared using such diverse chemical reactions as intermolecular transesterification enzyme catalyzed peptide-bond exchange imine bond exchange of hydrazones or oximes olefin metathesis disulfide bond exchange photoisomerization hydrogen bond exchange and metal-ligand coordination Although some DCLs have successfully demonstrated molecular evolution's proof of concept, the development of a highly efficient, practical system remained challenging. An ideal molecular evolution system requires an even distribution of the DCL components, an efficient selection method, and a nondestructive/continuous equilibrium in order to generate a "winning" binder for amplification. Herein, we report a highly efficient molecular evolution system utilizing intramolecular acyl migration on a carbohydrate scaffold coupled with boronic acid as a selector.