Мускон

What muscone is

Muscone is a 15-membered ring ketone with one methyl substituent in the 3-position. It is an oily liquid that is found naturally as the (−)-enantiomer, (R)-3-methylcyclopentadecanone. Muscone has been synthesized as the pure (−)-enantiomer as well as the racemate. It is very slightly soluble in water and miscible with alcohol.

Musk and the musk deer

The musk secretion of the male deer comprises various compounds, including steroids, but muscone is the most important molecule. Musk has been used in perfumery and medicine for thousands of years. Killing one deer yields only about 25 grams of dried musk pods. CITES made musk deer a protected species. The Siberian musk deer is classified as Vulnerable by the IUCN. The muskrat produces a musky secretion too, but it has not been commercialised.

How the structure was found

The chemical structure of muscone was first elucidated by Leopold Ružička. Muscone had been isolated in 1904, but it was not identified as 3-methylcyclopentadecanone until Ružička suspected a macrocycle. Up to the mid-1920s, chemists believed that rings with more than eight atoms were unstable and could not exist. Muscone and civetone were the first natural products shown to have rings with more than six atoms. Ružička also developed a method for synthesising macrocycles, now known as the Ružička large ring synthesis, which he demonstrated by preparing civetone in 1927. Ružička shared the 1939 Nobel Prize in Chemistry. Natural musk was used extensively in perfumery until the late 19th century, when economic and ethical motives led to the adoption of synthetic musk.

Macrocyclic musks and the musk receptor

Synthetic musks can be divided into three major classes: aromatic nitro musks, polycyclic musk compounds, and macrocyclic musk compounds. Civetone, with the formula C₁₇H₃₀O, is a very similar musky molecule that is obtained from the anal glands of the African civet cat without killing the animal. Civetone is closely related to muscone, and the structure of both compounds was elucidated by Leopold Ružička. In general, musks from animals are ketones, and plant musks are lactones (cyclic esters). Ring size matters for the smell of these ring compounds, whether ketones or lactones; molecules with about 14 to 19 atoms in the ring tend to have a musky smell.

OR5AN1 responds to macrocyclic and nitromusk compounds, two groups of synthetic musks, while OR1A1 responds prominently only to nitromusks. OR5AN1 shows chiral selectivity for (R)-muscone over (S)-muscone, found experimentally and confirmed computationally. OR5AN1 is reported to bind to muscone and related musks such as civetone through hydrogen-bond formation from tyrosine-260, along with hydrophobic interactions with surrounding aromatic residues in the receptor.