29.01.2021

Biopolymer synthesis and derivatization with on-resin multicomponent reactions.

Solid-phase synthesis and multicomponent reactions have traditionally represented two distinct approaches in synthetic chemistry. The former consists of repeated coupling reactions on a reactant immobilized on a column material. Solid-phase synthesis offers enormous advantages in handling and automation, especially in the construction of biopolymers, because intermediates do not have to be laboriously isolated after each coupling but can be purified directly on the matrix by washing steps. However, apart from the building blocks introduced with each coupling cycle, no functional diversity is generated in the reaction products. With multicomponent reactions, on the other hand, chemists can synthesize a pool of product variants by combining specific reactants in short, batchwise procedures. With that approach, one can introduce both skeletal and appendage diversity in reaction products. The benefits of combining the strengths of both synthesis methods are obvious. Researchers from IPB Halle, Cuba and Belgium have now published a review focusing on the recent developments in combining the two methodological approaches.

Their review presents relevant experimental details and addresses the synthetic scope of such on-resin multicomponent procedures employed to accomplish specific biopolymer covalent modifications that are practically inviable by traditional solution-phase methodologies. The chemists provide recommendations for solid phase-supported protocols and advise on selecting resin, solvent and reagents.

Furthermore, they describe multicomponent lipidation, biotinylation and labeling of both termini and side chains, as well as traceless on-resin multicomponent synthesis of ligated and cyclic peptides and derivatization of DNA oligonucleotides. The authors herewith provide a comprehensive review on methods that will benefit biologists and medicinal chemists to construct tailormade functionalized biopolymers for a variety of applications including library generation and screening.

Original publication:
Rivera, D.G., Ricardo, M.G., Vasco, A.V., Wessjohann, L.A. & Van der Eycken, E.V. On-resin multicomponent protocols for biopolymer assembly and derivatization. Nat Protoc (2021). https://doi.org/10.1038/s41596-020-00445-6