From Ambergris to (−)-Ambrox: Chemistry Meets Biocatalysis for Sustainable (−)-Ambrox Production

(−)-Ambrox, the most prominent olfactive component of ambergris is one of the most widely used biodegradable fragrance ingredients. Traditionally it is produced from the diterpene sclareol, modified and cyclized into (−)-ambrox by classical chemistry steps. The availability of the new feedstock (E)-β-farnesene produced by fermentation opened new pathways to (E,E)-homofarnesol as a precursor to (−)-ambrox. Combining chemical transformation of (E)-β-farnesene to (E,E)-homofarnesol and its enzymatic cyclization at the industrial scale to (−)-ambrox with an engineered squalene hopene cyclase illustrates the potential of biotechnology for a more sustainable process, thus meeting the increasing consumers' demand for sustainably produced high quality perfumery and consumer goods. This review traces back to the origin of ambergris and the search for the source of its mysterious odor, leading to the discovery of (−)-ambrox as its main olfactive principle. It discusses the plethora of ways explored for its synthesis from diverse starting materials and presents the development of a process with significantly improved carbon efficiency for the industrial production of (−)-ambrox as 100% renewable Ambrofix.