Scent Scholarship (June): Hedione, β‑Ionone, (–)‑Ambrox, Calone

Michelle Burk
Jun 17
2 min read

June 2025

Image (generated with AI): Hedione, Ionene, Ambrox, Calone

Hedione (methyl dihydrojasmonate) can amplify cortisol release and cardiovascular stress responses in women, even though they don’t feel more stressed subjectively 

Exposure to Hedione at subliminal levels (undetectable consciously) enhanced physiological stress markers—including blood pressure and cortisol levels—in women subjected to social stress, even though they didn’t report feeling more stressed 56 women in their follicular phase underwent a Trier Social Stress Test in a room scented (unbeknownst to them) with Hedione. Results: measurable cortisol rise and cardiovascular activation; no change in subjective stress perception.

It’s among the first human studies showing a fragrance molecule act like a covert biochemical modulator of stress, uncoupling subjective feelings from bodily responses. ➡️ Source: Pützer A, Wolf OT, et al. Effects of the odorant Hedione on the human stress response. Psychoneuroendocrinology, 2021.

β‑Ionone has been shown to activate the OR51E2 olfactory receptor in human prostate cells, triggering signals that inhibit cancer cell proliferation and reduce inflammation .

β‑Ionone activates the olfactory receptor OR51E2 (aka PSGR) in human prostate cancer, melanoma, and retinal cells—triggering intracellular calcium flux, ERK1/2 pathway activation, reduced proliferation, and differentiation .

Key Findings:
- Induces Ca²⁺ spikes in various cells 
- Triggers ERK MAP kinase activation with an EC₅₀ ≈ 20 µM
- Reduces cancer cell migration/invasiveness in vitro

➡️ Source: Neuhaus EM, et al. Odorant receptor OR51E2 agonist β‑ionone regulates Ca²⁺ signaling and proliferation in prostate, melanoma, RPE cells. JBC & Front Pharmacol, 2022 – 2025.

(–)‑Ambrox (Ambroxan) is the precise chiral molecule responsible for ambergris’s scent. Of 16 possible stereoisomers, only one hits the signature “amber” sweet-woody note.

While (–)-Ambrox was historically derived from sperm whale ambergris, today it is made sustainably via yeast fermentation and enzyme catalysis, involving (E)-β-farnesene converted to homofarnesol, enzymatically cyclized using engineered squalene-hopene cyclases, resulting in Ambrofix™—a biodegradable fragrance ingredient used in ~30% of perfumes worldwide .

A molecule once sourced from whales is now produced by tailored microbes and enzymes, eliminating need for animal products and enabling ethical, scalable green chemistry. ➡️ Source: Maurer A, Eichhorn E. Sustainable (–)-Ambrox Production: Chemistry Meets Biocatalysis. Chimia, 2024; and associated Nat Biotech patents and reviews.

Calone was discovered by Pfizer in 1966. The “watermelon‑ketone” was a side-product from tranquilizer-related chemistry, yet it went on to define the entire “aquatic” fragrance genre .

Calone (aka 7-methyl-1,5-benzodioxepin-3-one) was first synthesized in 1966 during Pfizer’s benzodiazepine tranquilizer research. A serendipitous byproduct bore a striking “watermelon with ocean breeze” aroma, launching the aquatic fragrance genre . ➡️ Source: Pfizer chemists (Beereboom, Cameron, Stephens), 1966; Ullmann’s Encyclopedia of Industrial Chemistry; Calone profiles & patents; MDPI Scent Occurrence reviews.

Scent Scholarship (June): Hedione, β‑Ionone, (–)‑Ambrox, Calone

Hedione (methyl dihydrojasmonate) can amplify cortisol release and cardiovascular stress responses in women, even though they don’t feel more stressed subjectively

β‑Ionone has been shown to activate the OR51E2 olfactory receptor in human prostate cells, triggering signals that inhibit cancer cell proliferation and reduce inflammation .

(–)‑Ambrox (Ambroxan) is the precise chiral molecule responsible for ambergris’s scent. Of 16 possible stereoisomers, only one hits the signature “amber” sweet-woody note.

Calone was discovered by Pfizer in 1966. The “watermelon‑ketone” was a side-product from tranquilizer-related chemistry, yet it went on to define the entire “aquatic” fragrance genre .

Recent Posts

Comments

Hedione (methyl dihydrojasmonate) can amplify cortisol release and cardiovascular stress responses in women, even though they don’t feel more stressed subjectively

β‑Ionone has been shown to activate the OR51E2 olfactory receptor in human prostate cells, triggering signals that inhibit cancer cell proliferation and reduce inflammation .

(–)‑Ambrox (Ambroxan) is the precise chiral molecule responsible for ambergris’s scent. Of 16 possible stereoisomers, only one hits the signature “amber” sweet-woody note.

Calone was discovered by Pfizer in 1966. The “watermelon‑ketone” was a side-product from tranquilizer-related chemistry, yet it went on to define the entire “aquatic” fragrance genre .

Comments

Hedione (methyl dihydrojasmonate) can amplify cortisol release and cardiovascular stress responses in women, even though they don’t feel more stressed subjectively 

β‑Ionone has been shown to activate the OR51E2 olfactory receptor in human prostate cells, triggering signals that inhibit cancer cell proliferation and reduce inflammation .

Calone was discovered by Pfizer in 1966. The “watermelon‑ketone” was a side-product from tranquilizer-related chemistry, yet it went on to define the entire “aquatic” fragrance genre .