Macrocycles: lessons from the distant past, recent developments, and future directions

• DOI: 10.1039/c4sc03089c
• Publication Date: 2014-11-03T13:30:28Z
• Authors: Andrei K. Yudin
• Keywords: Chemistry; 01 natural sciences; 0104 chemical sciences

A noticeable increase in molecular complexity of drug targets has created an unmet need the therapeutic agents that are larger than traditional small molecules. Macrocycles, which cyclic compounds comprising 12 atoms or more, now recognized as molecules "are up to task" interrogate extended protein interfaces. However, because macrocycles (particularly ones based on peptides) equipped with large polar surface areas, achieving cellular permeability and bioavailability is anything but straightforward. While one might consider this be Achilles' heel class compounds, synthetic community continues develop creative approaches toward synthesis their site-selective modification. This perspective provides overview both mechanistic structural issues bear a unique The reader offered historical foray into some classic studies have resulted current renaissance macrocycles. In addition, attempt made more recent developments give hope indeed turn useful modality.