Callitropsis nootkatensis (primary natural source); also Citrus paradisi, Vetiveria zizanioides
Appearance
white crystalline solid with grapefruit odor
Producing Countries
Europe, United States
Pyramid
Top
The molecule that makes grapefruit smell like grapefruit. Sharp, bitter-zesty peel backed by a dry cedarwood floor — not the sweet citrus of orange or the sour bite of lemon, but that specific, slightly acrid, morning-juice bitterness.
Bitter grapefruit peel — sharper and more specifically citrus than limonene, less floral than bergamot, without the sweetness of orange oil. A dry cedarwood undertone provides unexpected depth for a citrus molecule. More acrid than lemon, less green than lime, with a zesty bite that sits on the palate as much as in the nose. Where bergamot has Earl Grey elegance, nootkatone has the blunt honesty of a grapefruit half eaten without sugar. On skin, the initial bitter-citrus burst gives way within an hour to a clean, woody-dry murmur that outlasts most monoterpene citrus materials by an order of magnitude.
Evolution over time
Immediately
Immediately
Sharp bitter-grapefruit burst. Zesty, acrid peel character with a green-herbaceous edge. Unmistakable — no other citrus molecule smells quite like this.
After a few hours
After a few hours
Woody-cedary heart emerges as the citrus brightness retreats. Clean, dry, with a faint vetiver-like earthiness. Still recognizably grapefruit but darker, more resinous.
After a few days
After a few days
Persistent woody-dry base. Remarkable tenacity for a citrus-classified molecule — the sesquiterpene backbone keeps it anchored long after monoterpene citruses have vanished.
The Full Story
CAS 4674-50-4. A bicyclic sesquiterpene ketone of the eremophilane class. Molecular formula C₁₅H₂₂O, molecular weight 218.34. First isolated in 1962 by Holger Erdtman and Yoshiteru Hirose from the heartwood of Alaska yellow cedar (Callitropsis nootkatensis), and named after that tree — which itself takes its epithet from Nootka Sound on Vancouver Island, traditional territory of the Nuu-chah-nulth people.
The scent is unmistakably grapefruit. Not the generic citrus of limonene, not the aromatic-floral citrus of bergamot — nootkatone delivers the specific bitter-zesty peel character that distinguishes Citrus paradisi from every other citrus fruit. A dry, cedary undertone connects it to its other natural source. On blotter, it opens sharp and bitter-fresh, then settles into a woody-clean drydown that can persist for days. TGSC records 236 hours substantivity at 20% in dipropylene glycol — extraordinary for a molecule classified as a top note.
Found naturally in three sources: grapefruit peel oil (0.1–1% concentration, yet the character-impact compound responsible for the fruit's identity), vetiver oil from Vetiveria zizanioides (~5%, explaining the grapefruit quality detectable in Haitian vetiver), and Alaska yellow cedar heartwood. Commercial production has shifted to biotechnology: engineered yeast (Saccharomyces cerevisiae) oxidizes valencene — a cheap, abundant sesquiterpene from orange peel — into nootkatone via the cytochrome P450 enzyme CYP706M1. This fermentation route, developed by Evolva and Isobionics (now BASF), reduced the price from roughly $4,000/kg to $2,000/kg.
The molecule exhibits a dramatic cases of chiral olfactory asymmetry in flavor chemistry. The natural (+)-enantiomer has an odor threshold of 30 ppm in saturated vapor; the (−)-enantiomer requires 66,000 ppm — a 2,200-fold difference. In August 2020, the EPA registered nootkatone as the first new active ingredient for insect repellents in over a decade, effective against ticks and mosquitoes — a rare molecule that repels insects while being a food-grade flavor compound.
The two mirror-image forms of nootkatone differ in odor potency by a factor of 2,200. (+)-Nootkatone — the natural enantiomer — has an odor threshold of 30 ppm in saturated vapor, while (−)-nootkatone requires 66,000 ppm to be detected. In taste, the gap is even wider: 0.8 ppm versus 600 ppm. This is a extreme cases of chiral olfactory discrimination known in flavor chemistry.
Extraction & Chemistry
Extraction method: Not obtained by simple distillation of a single botanical. Three historical routes: (1) Fractional distillation of grapefruit peel oil, where nootkatone represents only 0.1–1% of total oil — roughly 400,000 kg of grapefruit to yield 1 kg of isolated nootkatone, making direct extraction economically prohibitive. (2) Isolation from vetiver oil (Vetiveria zizanioides), where it occurs at ~5% concentration — more concentrated, but vetiver oil itself is expensive. (3) Biotechnological production, now the dominant commercial route: valencene (an abundant sesquiterpene from orange peel oil, ~$50/kg) is oxidized to nootkatone using engineered Saccharomyces cerevisiae yeast expressing valencene oxidase (CYP706M1). This biotech pathway, commercialized by Evolva (via its acquisition of Allylix) and by Isobionics (acquired by BASF), brought the price from ~$4,000/kg (grapefruit extraction) to ~$2,000/kg (fermentation). Melting point 32–37°C; the compound is a white crystalline solid at room temperature.
Molecular Formula
C15H22O
CAS Number
4674-50-4
Botanical Name
Callitropsis nootkatensis (primary natural source); also Citrus paradisi, Vetiveria zizanioides
IFRA Status
Restricted. Dermal sensitization limit of 40% in fragrance compound. Purity specification: minimum 98%, melting point minimum 32°C. Lower-purity grades not permitted as fragrance ingredients.
Synonyms
Nootka oil
Physical Properties
Appearance
white crystalline solid with grapefruit odor
Boiling Point
125.00 to 130.00 °C. @ 0.50 mm Hg
Flash Point
> 200.00 °F. TCC ( > 93.33 °C. )
Specific Gravity
1.00300 to 1.03200 @ 25.00 °C.
Refractive Index
1.51000 to 1.52300 @ 20.00 °C.
Melting Point
32.00 to 37.00 °C. @ 760.00 mm Hg
In Perfumery
Top-to-heart note with anomalous tenacity for a citrus material. Nootkatone is a sesquiterpene (C15), heavier than the monoterpenes (C10) that dominate most citrus oils — limonene, linalyl acetate, citral. This extra molecular weight translates directly into staying power: TGSC records 236 hours substantivity at 20% in DPG, unheard of for a citrus molecule. Where limonene vanishes in minutes, nootkatone persists for days. It functions as a signature note in grapefruit and pamplemousse accords, a naturalness modifier in synthetic citrus bases (adding the bitter-peel quality that limonene alone cannot deliver), and a bridge between citrus top notes and woody-vetiver hearts. The molecule appears in vetiver oil at roughly 5% concentration, which explains the grapefruit quality some noses detect in Haitian vetiver. Critical in citrus-woody, hespéridé, and neo-cologne compositions.
