Macrocyclic musks: Trends in development and synthetic strategies

Abstract

Macrocyclic musks are popular amongst perfumers for their captivating, long-lasting, and mesmerizing aroma. Renowned for their ability to harmonize with almost every olfactory group, these compounds play a crucial role in enhancing fragrance compositions. Over the last 100 years, numerous approaches have been developed to synthesize these precious compounds. This review aims to consolidate these diverse approaches in a single comprehensive manner. It is structured into four parts for clarity and coherence. The first part is a compilation of structures of macrocyclic compounds that have a musk or musk-like odor and are classified according to the ascending ring size. In the second part, we have attempted to cover as many approaches as possible to synthesize macrocyclic musks. These are based on the key reaction used for constructing the macrocyclic ring and do not follow any specific order. However, we have maintained an ascending order for the ring size in each approach so readers can compare the strategies and starting materials used for different ring sizes. The third part is dedicated to other approaches that are difficult to classify and accommodate in any other previous approach. Finally, the fourth section highlights biocatalytic and enzymatic approaches, reflecting the growing interest in sustainable and biologically inspired synthesis.