Material guide: ambrein — the main constituent of ambergris, two suppliers, and a notes field that gets the whale wrong

About 5 minutes.

Short version

• Name: ambrein, CAS 473-03-0, EINECS 207-460-3
• Formula C30H52O, MW 428.74 — a triterpene alcohol
• Odour type: amber; odour: ambergris, labdanum, amber, woody
• Strength: medium, rank 2; substantivity 400 hours at 100%
• Extreme physical properties: logP 9.60, boiling point 495–496 °C, water solubility 6.9×10⁻⁷ mg/L
• Suppliers: 2
• Intraperitoneal mouse LD50 7500 mg/kg (Japanese Journal of Pharmacology, 1992)
• occurrence: ambergris

This is upstream of ambroxan

Moser and colleagues state the relationship in their opening lines in Yeast in 2020:

The triterpenoid (+)-ambrein is the major component of ambergris, a coprolite of the sperm whale that can only be rarely found on shores. Upon oxidative degradation of (+)-ambrein, several fragrance molecules are formed, amongst them (−)-ambrox, one of the highest valued compounds in the perfume industry.

So "the smell of ambergris" is not the smell of ambrein. It is the smell of what ambrein becomes when it oxidises.

Their paper moves that route into yeast. They boosted intracellular squalene supply in Saccharomyces cerevisiae by overexpressing an N-terminally truncated HMG-CoA reductase (tHMG) and squalene synthase (ERG9), while inhibiting squalene epoxidase (ERG1) with an experimentally defined amount of terbinafine to reduce flux towards ergosterol while retaining enough activity to keep cells alive and growing. They then heterologously expressed a promiscuous variant of Bacillus megaterium tetraprenyl-β-curcumene cyclase (BmeTC-D373C).

Note how the terbinafine is used. They did not knock ERG1 out; they partially inhibited it, because switching it off entirely kills the cell. That is a common trade-off in metabolic engineering, and it is stated openly in the abstract.

(Making fragrance materials by fermentation is collected in Biomanufactured fragrance materials, and ambroxan itself is Material guide: ambroxan. This article is about that route's starting point.)

The database says it has an odour; the literature frames it differently

This was the part I had to handle most carefully.

The database gives it a full set of odour fields: odour type amber, odour "ambergris, labdanum, amber, woody", strength medium, substantivity 400 hours, and an odour description reading "at 100.00%: amber ambergris labdanum woody".

The literature's framing is that fragrance molecules form on oxidative degradation of ambrein — which implies ambrein itself is not the source of that smell.

The two need not contradict each other. A triterpene alcohol of MW 428 with logP 9.6 and a boiling point of 495 °C has a vanishingly low vapour pressure and is unlikely to smell strongly in the first place; and left in air it oxidises slowly, so part of what anyone smells when they smell ambrein may be its degradation products.

But I cannot separate those two from the fields. So I am putting both here rather than picking one.

(A material's odour description actually describing "it plus its degradation products" also came up with linalool, where oxidation raises sensitisation.)

That 2007 paper made ten derivatives

Shen and colleagues isolated ambrein from ambergris and prepared ten new derivatives by chemical transformation in the Journal of Natural Products in 2007.

The method is the interesting part: oxidation and/or cyclisation was effected with selenium oxide, p-toluenesulfonyl chloride, or shortwave UV light. Structures were established spectroscopically, with one compound's structure and relative configuration confirmed by single-crystal X-ray crystallography.

The shortwave UV is the striking item — that is exactly what ambergris meets while drifting at sea. The oxidative cyclisation they ran in a flask is the same class of reaction that years of sunlight and air perform on a floating lump.

They went on to test these compounds for cytotoxicity against four human carcinoma cell lines and for anti-inflammatory activity on human neutrophil function. That is outside perfumery and I am not summarising those results.

Ten records, two real CAS numbers

The database holds ten records with ambergris or ambrein in the name:

Record	CAS	Suppliers	Odour type
Ambergris specialty	none	26	amber
Ambergris naphthol	41199-19-3	10	amber
Ambergris tincture (FEMA 2049)	8038-65-1	8	amber
Ambergris tincture replacer	none	3	animal
Ambreine specialty	none	2	amber
Ambreine fragrance	none	2	amber
Ambrein (this article)	473-03-0	2	amber
Ambergris fragrance	none	2	amber
Ambergris natural	8038-65-1	1	marine
Ambergris extract	84836-94-2	0	—

Only two carry a CAS pointing at a defined molecule: ambrein (473-03-0) and ambergris naphthol (41199-19-3, a synthetic). 8038-65-1 is a natural-product number, and five records have no CAS at all.

And the two records under 8038-65-1 have different odour types. The tincture is amber (ambergris, sweet, dry, amber, woody, mossy), while "ambergris natural" is marine (ambergris, animal, marine, seashore). One CAS, two odour types — 35.6% of shared-CAS groups in this database are like that.

Incidentally, the tincture's assay field reads "20.00 to 100.00" — an eighty-point range, because a tincture's strength is whatever the seller made it. Its strength field reading "low" at rank 1 is consistent with that.

The notes field gets the whale wrong

Ambrein's notes field:

"a degraded triterpene; ambrein, cholesterol and benzoic acid are major components of ambergris; from intestinal secretion of sperm blue whale (pyseter carodon)."

Two problems:

1. There is no such animal as a "sperm blue whale". The sperm whale (Physeter macrocephalus) and the blue whale (Balaenoptera musculus) are different species. Ambergris comes from the sperm whale.
2. "pyseter carodon" is a misspelling of Physeter catodon, an older synonym for the sperm whale.

The ambergris tincture record in the same database gets it right, via the TSCA definition: "irregularly shaped gray, waxy opaque masses from the intestines of the sperm whale. it consists primarily of cholesterol, ambrein, and benzoic acid."

The point is not to score a hit. It is that the notes field is free text and its quality is uneven. Whenever this series quotes a notes field, it is a lead rather than a fact — Veramoss is the other case, where the database says the molecule is not found in nature and that is wrong.

How to use it (if you can even get it)

• Two suppliers is research-grade availability, not a formulation material.
• For the ambergris effect, use ambroxan. That is the molecule actually in use, with 61 suppliers.
• logP 9.60 means it is essentially water-insoluble and will not be happy in ethanol either. The solubility field lists only alcohol and water, the latter at 6.9×10⁻⁷ mg/L — which is insoluble.
• Boiling point 495 °C and substantivity 400 hours: it will not go anywhere, but it does not evaporate either, so "smellable" and "stays put" are separate questions.

What this doesn't establish

• I have not smelled it, or ambergris. The whole article is fields, database-wide counts and two papers.
• The database says it has an odour and the literature frames the odour as coming from its degradation products, and I cannot adjudicate. I have put both here, and that is the biggest uncertainty in this article.
• Moser's paper is about engineering yeast to make ambrein, not about odour. What I quote is its statement of the ambrein-to-ambrox relationship.
• I am not summarising Shen's cytotoxicity and anti-inflammatory results. That is pharmacology, unrelated to perfumery, and outside my competence to assess.
• "The notes field is wrong" is my own judgement from the binomials. I did not trace where that sentence came from.
• The ten-record table was pulled by name keyword (ambergris / ambrein); other naming may not have been caught.
• Obtaining ambergris involves conservation and local law — sperm whales are CITES-listed, and rules on beach-found material differ by country. This article does not address that layer at all. Check your own jurisdiction before buying.