A macrocyclization-induced phosphorescence enhancement (MIPE) strategy involving macrocyclization of phosphorescent pyridine/pyridinium units by methylene linkers is reported and proved to have good effectiveness universality.

Macrocycles play an increasing role in drug discovery, but their synthesis is often demanding. Computational tools that suggest macrocyclization based on a known binding mode and that estimate the binding affinity of these macrocycles could have a substantial impact on the medicinal chemistry design process. For both tasks, we established a workflow with high practical value. For five diverse p...

The macrocyclization of linear peptides is very often accompanied by significant improvements in their stability and biological activity. Many strategies are available for their chemical macrocyclization, however, enzyme-mediated methods remain of great interest in terms of synthetic utility. To date, known macrocyclization enzymes have been shown to be active on both peptide and protein substr...

Macrocyclization carried out by thioesterase domains of multimodular nonribosomal peptide synthetases (NRPSs) is a key step in the biosynthesis of many biologically active peptides. The thioesterase excised from tyrocidine synthetase is a versatile macrocyclization catalyst and a useful tool for chemoenzymatic synthesis of diverse cyclic peptides. However, its utility is limited by its short li...

Constrained, cyclic peptides encoded by plant genes represent a new generation of drug leads. Evolution has repeatedly recruited the Cys-protease asparaginyl endopeptidase (AEP) to perform their head-to-tail ligation. These macrocyclization reactions use the substrates amino terminus instead of water to deacylate, so a peptide bond is formed. How solvent-exposed plant AEPs macrocyclize is poorl...

Macrocyclization is typically the key step in syntheses of cyclophane-type natural products. Considering compounds with axially chiral biaryl moieties, control atroposelectivity essential for biological activity and synthetically challenging. Herein we report on atroposelective macrocyclization involving an oxidative Heck type process enabling first atropo-enantiopure synthesis isoriccardin C. ...

While the synthesis of linear polymers with both ends conserved is severely impeded due to inevitable macrocyclization in step-growth polymerization, this work provides a new idea mainly formation polymer chains.

Several kinetic models for the macrocyclization of a C₂ pseudopeptide with a dihalide through a S(N)2 reaction have been developed. These models not only focus on the kinetic analysis of the main macrocyclization reaction, but also consider the competitive oligomerization/polymerization processes yielding undesired oligomeric/polymeric byproducts. The effect of anions has also been included in ...

Macrocyclization between head, tail or sidechains is a frequently employed strategy to enhance peptide and peptidomimetic stability, selectivity affinity.

An intramolecular Prins macrocyclization reaction was successfully employed in the synthesis of polycavernoside A.