Heck Macrocyclization in Forging Non-Natural Large Rings including Macrocyclic Drugs

The intramolecular Heck reaction is a well-established strategy for natural product total synthesis. When constructing large rings, this reaction is also referred to as Heck macrocyclization, which has proved a viable avenue to access diverse naturally occurring macrocycles. Less noticed but likewise valuable, it has created novel macrocycles of non-natural origin that neither serve as nor derive from natural products. This review presents a systematic account of the title reaction in forging this non-natural subset of large rings, thereby addressing a topic rarely covered in the literature. Walking through two complementary sections, namely (1) drug discovery research and (2) synthetic methodology development, it demonstrates that beyond the well-known domain of natural product synthesis, Heck macrocyclization also plays a remarkable role in forming synthetic macrocycles, in particular macrocyclic drugs.

Automated summary

The review provides a systematic account of the intramolecular Heck reaction in synthesizing non-natural macrocycles. It highlights the importance of this reaction in forming synthetic macrocycles, particularly macrocyclic drugs, beyond the realm of natural product synthesis. The review covers two sections, drug discovery research and synthetic methodology development, to demonstrate the versatile role of Heck macrocyclization.