Fluorinated Musk Fragrances: The CF₂ Group as a Conformational Bias Influencing the Odour of Civetone and (R)‐Muscone

Abstract

Abstract:The difluoromethylene (CF2) group has a strong tendency to adopt corner over edge locations in aliphatic macrocycles. In this study, the CF2 group has been introduced into musk relevant macrocyclic ketones. Nine civetone and five muscone analogues have been prepared by synthesis for structural and odour comparison. X-Ray studies indeed show that the CF2 groups influence ring structure and they give some insight into the preferred ring conformations, triggering a musk odour as determined in a professional perfumery environment. The historical conformational model of Bersuker et al. for musk fragrance generally holds, and structures that become distorted from this consensus, by the particular placement of the CF2 groups, lose their musk fragrance and become less pleasant.

Molecular mechanism of activation of human musk receptors OR5AN1 and OR1A1 by ( R )-muscone and diverse other musk-smelling compounds

“…This approach has recently been explored by replacing a ring CH 2 by a CF 2 group to influence the odors of macrocyclic musk compounds, including cyclopentadecanone (60), musk lactones (61), civetone, and (R)-1 (62). In particular, when the CF 2 group was inserted in different ring positions the odor intensity of (R)-muscone varied by human smell analysis (perfumery "nose" panel) (62). Here, we extend this analysis to investigate the response of the muscone receptor OR5AN1 to various CF 2 -containing macrocyclic (R)-muscone analogs (compounds 28-37, Fig.…”

Muscone Ameliorates Ovariectomy-Induced Bone Loss and Receptor Activator of Nuclear Factor-κb Ligand-Induced Osteoclastogenesis by Suppressing TNF Receptor–Associated Factor 6-Mediated Signaling Pathways

“…Muscone was identified in the natural extract of deer musk as early as 1906. It is used in a large number of fine perfumes (Callejo et al, 2016). And it is also known as an effective drug with anti-inflammatory effects for multiple systems (Wang et al, 2014;Liu et al, 2014;Du et al, 2018).…”

Effect of Fluorination on Skin Sensitization Potential and Fragrant Properties of Cinnamyl Compounds

“…One such approach is to subtly alter the electronic properties of typical olfactive compounds without heavily influencing their overall shapethus seeking to maintain their olfactive properties. [9] [10] It is interesting to note that the electronic influence of the fluorine atom has never been used in fragrance ingredients in order to alter their toxicological footprint. Surprisingly few fragrance ingredients bearing one or more fluorine atoms have been disclosed, especially when comparing with the large body of fluorinated pharmaceutical and agrochemical products which are introduced each year.…”