Muscone is a

macrocyclic Macrocycles are often described as molecules and ions containing a ring of twelve or more atoms. Classical examples include the crown ethers, calixarenes, porphyrins, and cyclodextrins. Macrocycles describe a large, mature area of chemistry. ...

ketone In organic chemistry, a ketone is an organic compound with the structure , where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group (a carbon-oxygen double bond C=O). The simplest ketone is acetone ( ...

, an

organic compound Some chemical authorities define an organic compound as a chemical compound that contains a carbon–hydrogen or carbon–carbon bond; others consider an organic compound to be any chemical compound that contains carbon. For example, carbon-co ...

that is the primary contributor to the odor of

deer musk Deer musk is a substance with a persistent odor, obtained from the caudal glands of the male musk deer. Although more commonly referred to as " musk", the term itself is often used to describe a wide variety of "musky" substances from other anim ...

. Natural muscone is obtained from musk, a glandular secretion of the

musk deer Musk deer can refer to any one, or all eight, of the species that make up ''Moschus'', the only extant genus of the family (biology), family Moschidae. Despite being commonly called deer, they are not true deer belonging to the family Cervidae, b ...

, which has been used in perfumery and medicine for thousands of years. Since obtaining natural musk requires killing the endangered animal, nearly all muscone used in perfumery and for scenting consumer products today is synthetic. It has the characteristic smell of being "

musk Musk is a class of aromatic substances commonly used as base notes in perfumery. They include glandular secretions from animals such as the musk deer, numerous plants emitting similar fragrances, and artificial substances with similar odors. ' ...

y".

Chemical structure and synthesis

The chemical structure of muscone was first elucidated by

Leopold Ružička Leopold Ružička (; born Lavoslav Stjepan Ružička; 13 September 1887 – 26 September 1976) was a Croatian-Swiss scientist and joint winner of the 1939 Nobel Prize in Chemistry "for his work on polymethylenes and higher terpenes" "including ...

. It is a 15-membered ring ketone with one

methyl In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula (whereas normal methane has the formula ). In formulas, the group is often abbreviated as ...

substituent in the 3-position. It is an oily liquid that is found naturally as the (−)-

enantiomer In chemistry, an enantiomer (Help:IPA/English, /ɪˈnænti.əmər, ɛ-, -oʊ-/ Help:Pronunciation respelling key, ''ih-NAN-tee-ə-mər''), also known as an optical isomer, antipode, or optical antipode, is one of a pair of molecular entities whi ...

, (''R'')-3-methylcyclopentadecanone. Muscone has been synthesized as the pure (−)-enantiomer as well as the

racemate In chemistry, a racemic mixture or racemate () is a mixture that has equal amounts (50:50) of left- and right-handed enantiomers of a chiral molecule or salt. Racemic mixtures are rare in nature, but many compounds are produced industrially as r ...

. It is very slightly soluble in water and miscible with alcohol. One

asymmetric synthesis Enantioselective synthesis, also called asymmetric synthesis, is a form of chemical synthesis. It is defined by IUPAC as "a chemical reaction (or reaction sequence) in which one or more new elements of chirality are formed in a substrate molecul ...

of (−)-muscone begins with commercially available (+)-

citronellal Citronellal or rhodinal ( C10 H18 O) is a monoterpenoid aldehyde, the main component in the mixture of terpenoid chemical compounds that give citronella oil its distinctive lemon scent. Citronellal is a main isolate in distilled oils from the ...

, and forms the 15-membered ring via

ring-closing metathesis Ring-closing metathesis (RCM) is a widely used variation of olefin metathesis in organic chemistry for the synthesis of various Saturated and unsaturated compounds, unsaturated rings via the intramolecular olefin metathesis, metathesis of two term ...

A more recent enantioselective synthesis involves an intramolecular aldol addition/

dehydration reaction In chemistry, a dehydration reaction is a chemical reaction that involves the loss of an H2O from the reacting molecule(s) or ion(s). This reaction results in the release of the H2O as water. When the reaction involves the coupling of two molecu ...

of a

diketone In organic chemistry, a dicarbonyl is a molecule containing two carbonyl () groups. Although this term could refer to any organic compound containing two carbonyl groups, it is used more specifically to describe molecules in which both carbonyls ...

Isotopologs

Isotopologs of muscone have been used in a study of the mechanism of

olfaction The sense of smell, or olfaction, is the special sense through which smells (or odors) are perceived. The sense of smell has many functions, including detecting desirable foods, hazards, and pheromones, and plays a role in taste. In humans, ...

. Global replacement of all hydrogen atoms in muscone was achieved by heating muscone in

heavy water Heavy water (deuterium oxide, , ) is a form of water (molecule), water in which hydrogen atoms are all deuterium ( or D, also known as ''heavy hydrogen'') rather than the common hydrogen-1 isotope (, also called ''protium'') that makes up most o ...

(D₂O) at 150 °C in the presence of a

rhodium Rhodium is a chemical element; it has symbol Rh and atomic number 45. It is a very rare, silvery-white, hard, corrosion-resistant transition metal. It is a noble metal and a member of the platinum group. It has only one naturally occurring isot ...

on carbon catalyst. It was found that the human

-recognizing receptor,

OR5AN1 Olfactory receptor 5AN1 is a protein that in humans is encoded by the ''OR5AN1'' gene. Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory recept ...

, identified using a heterologous

olfactory receptor Olfactory receptors (ORs), also known as odorant receptors, are chemoreceptors expressed in the cell membranes of olfactory receptor neurons and are responsible for the detection of odorants (for example, compounds that have an odor) which give ...

expression system and robustly responding to muscone, fails to distinguish between muscone and the so-prepared isotopolog ''

in vitro ''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...

''. OR5AN1 is reported to bind to muscone and related musks such as

civetone Civetone is a macrocyclic ketone and the main odorous constituent of civet oil. It is a pheromone sourced from the African civet. It has a strong musky odor that becomes pleasant at extreme dilutions. Civetone is closely related to muscone, the ...

through hydrogen-bond formation from tyrosine-260 along with hydrophobic interactions with surrounding aromatic residues in the receptor.

References

{{reflist Flavors Perfume ingredients Macrocycles Ketones