Olfactory Chemistry: Stemone- Find Your Fig Leaf

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When I began really expanding my perfumed horizons one of my earliest discoveries were the fig-based fragrances done by perfumer Olivia Giacobetti.  Over the course of three fragrances: L’Artisan Premier Figuier, Diptyque Philosykos, and L’Artisan Premier Figuier Extreme. Though all three of these fragrances there was one aromachemical at the center of Mme Giacobetti’s compositions, Stemone.

stemone

Stemone is an interesting class of chemical called an oxime. Oximes are defined by a double bonded nitrogen(N) which is also bonded to an alcohol(OH), highlighted in red. It is a derivative of the more common fragrance ingredients known as ketones. In the figure above you see Stemone next to the ketone from which it is synthesized, 5-methyl-3-heptanone. As I like to demonstrate in this series even a simple change like you see above has a dramatic effect on the scent profile. 5-methyl-3-heptanone has a sweet herbal scent at a concentration of 10%; at 100% it becomes citrusier. It is not a common fragrance ingredient and it found its uses more as a flavoring to bring that citrus aspect to food products.

When it is converted to Stemone it stops being herbal and goes very green. It is a lighter stand-in for galbanum. It can also be used at higher concentrations to form a fresh-cut grass presence. Its most common usage is as a leafy component so much so that it is called “leafy oxime” by many perfumers.

When it comes to making a fig accord Stemone stands front and center usually representing the fig leaves. It is then left to the perfumer to form the fruit part of the accord from a selection of different lactones depending on the ripeness level of the fig the perfumer is attempting to achieve.

olivia-giacobetti

Olivia Giacobetti

The three perfumes by Mme Giacobetti are fabulous examples of how to tune this accord in different ways. In Premier Figuier the Stemone level is much higher and the lactone Mme Giacobetti employs is also creamier representing a ripe fig still on the tree. When she would move forward to Premier Figuier Extreme she adds to the lactones while pulling back on the Stemone; ripening her fig. For Philosykos she takes the Stemone down to a much more transparent level. This is the beginning of what will become Mme Giacobetti’s evolution to her signature style. It still smells like the fig leaf but an abstracted version. She again changes the lactones to less creamy versions elucidating a greener fig accord while keeping the volume at the same level as the Stemone.

Stemone has continued to be a key building block when a perfumer wants a green effect especially when looking for alternatives to the stronger green ingredients like galbanum. Fig leaves might have been the first clothing for Adam and Eve but in perfumery Stemone makes sure fig leaves have much more of a presence.

–Mark Behnke

Olfactive Chemistry: Geosmin- After the Storm

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As we come to the end of the first half of 2016 there has been an interesting trend from some of my favorite indie perfumers. There has been more usage of the aromachemical geosmin to different effect. Geosmin is one of the more interesting ingredients on the perfumer’s palette.

Everybody is familiar with the smell of geosmin in Nature. It is that smell in the air which hangs after a heavy rain. It comes about because there is a natural bacteria, Streptomyces, which leaves geosmin behind when it dies. The longer the dry spell the more the chemical is on the surfaces. If a thunderstorm comes along it releases the geosmin into the air. This is that smell also called petrichor. It is earthy and mineralic in turns. The actual chemical structure is below.

decalin geosmin

Geosmin is two six membered carbon rings fused together into a structure called a decalin. Then two methyl (CH3) groups and one alcohol (OH) are what it takes to transform the slightly mentholated odor of decalin into the after the rain smell of geosmin.

The isolation of geosmin is a fascinating study of the ancient and the modern. The ancient way comes from India. Dried out disks of earth which the monsoons have covered and now evaporated are produced. These disks are them placed in primitive distillation apparatus to form what is called mitti attar. This is the earliest isolation of geosmin. There is a great story in The Atlantic from April of 2015 which describes the entire process in detail.

The other way is by mimicking the natural bacteria to make it via biosynthesis. Professor David Cane and his group at Brown University discovered an enzyme from the natural bacteria Streptomyces coelicor. (Journal of the American Chemical Society, vol. 28, pg 8128-8129, 2006) This is the enzyme which transforms the non-cyclic farnesyl diphosphate into geosmin. The study of the transformation of farnesyl diphosphate into natural chemicals has led to the ability to imitate these processes to produce natural products for medicinal as well as olfactory purposes. In the scheme below you can see the process that the enzyme geosmin synthase uses to convert the acyclic to the cyclic. Now geosmin is readily available as a perfume ingredient.

farnesyl to geosmin

The odor profile of geosmin allows it to be used in marine styles of fragrance as perfumer Christi Meshell does in her House of Matriarch Albatross. In that perfume she uses it as the smell of the rocky coast of the Pacific Northwest. Shelley Waddington also is inspired by the same locale and her use of geosmin carries the damp forest milieu in En Voyage Rainmaker. Perhaps my favorite use so far this year comes from Zoologist Bat where perfumer Ellen Covey working under Victor Wong’s creative direction uses geosmin as a key component of the wet cave accord which grounds that fragrance.

If your fragrance carries the smell of after the storm geosmin is probably the reason.

–Mark Behnke

Olfactory Chemistry: beta-Santolol Derivatives- Figuring Out Sandalwood

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In my job as a medicinal chemist one of the ways I analyze data is through a process called Structure-Activity Relationship (SAR). What that means is I make a change to a molecule and see whether that gives me better binding (activity) or less. Through putting that data set together I come to understand the biological interaction I am working on. The same holds true for the chemists working on aromachemicals. They call their version Structure-Odor Replationship (SOR).

The gathering of SOR data is two-fold. The primary reason is to create a new raw material to be used as a fragrance. The secondary reason is to continue to add to the data set of molecules and how we perceive them. The hypothesis is the broader the amount of data points the more insight we will gain into the biological process which governs our sense of smell. A recent 2014 publication (Delasalle et. al.; Chemistry & Biodiversity, vol. 11, pg. 1843-1860, 2014) from the chemistry department at the University of Nice. In this study they were focused on the molecule which makes up most of sandalwood essential oil, beta-santolol.

The reason for looking for alternatives to sandalwood essential oil is the overharvesting which nearly drove the Mysore version to extinction. Now that particular version is tightly controlled by the Indian government. There have been more sustainable version cultivated in New Caledonia and Australia which have taken their place in newer perfume constructions. If an easily synthesizable beta-santolol could be discovered or alternatively a deeper understanding on how beta-santolol binds to allow for a more intelligent design then this would be another step to easing the stress on the natural sources.

betasantol

The research team  took beta-santolol and did a number of chemical transformations on the long sidechain indicated above. Also the OH group was hypothesized to be an important part of the molecule in creating the sandalwood odor profile. The results showed if that OH group was oxidized to an aldehyde in that specific configuration seen above it resulted in a much fainter sandalwood odor. If you changed the geography around the double bond at the end of the side chain it retained the same odor profile as beta-santolol. All of the remaining changes to the side chain or the OH group resulted in molecules describes as “sweaty” or odorless.

They would go on to analyze a set of 21 variations. This provided a further confirmation of the necessity of the OH group in that particular position for the molecule to have a strong sandalwood scent profile similar to beta-santalol.

This research team would purchase a number of other beta-santolol variations focused on the ring instead of the side-chain also looking for further insight into the SOR.

This research has added a new data set which allows for a further refinement on the biological reaction behind our sense of smell of sandalwood.

–Mark Behnke

Olfactory Chemistry: Low Atranol Oakmoss- Keeping the Bite

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In the ongoing saga of restricted materials the one which has elicited the most concern has been oakmoss. The reason for this concern is it is one of the key components of a chypre accord. When the restrictions were first being considered there was a lot of consternation over the effect it would have on the classic chypres like Guerlain Mitsouko. One solution was to bring chemistry to the rescue to see if the oakmoss absolute could be treated to remove the chemicals which were the suspected skin sensitizers.

atranol chloroatranol

In 1992 a team at Givaudan (International Journal of Cosmetic Science, vol. 14, pg. 121-130, 1992) used the nature of these molecules and their reactivity to remove them from oakmoss absolute. Atranol and Chloroatranol (shown above) were the suspected bad actors in oakmoss absolute. What you see highlighted in red is the aldehyde function. These are not the typical aldehydes associated with perfume. Those are at the end of long carbon chains. The ones depicted in Atranol and Chloroatranol are what are called aromatic aldehydes and they are much more likely to react. The team at Givaudan took advantage of that and used that reactivity. These aromatic aldehydes in the presence of an amino acid like Leucine will form a molecule called a Schiff Base. Under the right conditions this will form a solid which will fall out of solution. Then if you filter that solid off what remains is a version of oakmoss absolute with those molecules “washed” out. After some early success with a few amino acids by themselves they found a mixture of Leucine (the one pictured) and Lysine removed the Atranol and Chloroatranol down to barely detectable amounts.

atranol schiff base

The big question left to answer was would this treated oakmoss absolute still be able to be used in perfumery. If you’ve smelled oakmoss in a perfume in the last ten years it is likely this Low Atranol Oakmoss is what you smell. It retained enough of the nature of the oakmoss that the perfumers could add in other materials to replace whatever the Atranol and Chloroatranol would have otherwise brought to the scent profile. One of the more common materials used for this purpose is one of the synthetic oakmoss replacements Evernyl which by itself was not seen as a good alternative. When combined with the Low Atranol Oakmoss it helps fill in for the missing Atranol.

The further question about whether the removal of the Atranol now made these compounds less allergenic is not as clear cut. The most recent paper on the subject published in 2014 by a group from Odense University in Denmark (Contact Dermatitis, vol. 72, pg. 75-83, 2014) showed it was much less allergenic but not completely free of causing a reaction. What this means as far as potentially further restrictions will be determined by the regulatory agencies.

When preparing this article I asked a number of perfumers if they thought oakmoss was necessary to create a chypre. All of them replied there are enough synthetic and natural materials to create any chypre effect they desire. I hope the Low Atranol Oakmoss is still allowed to be used because there is something pleasing about the bite of a good chypre and I think oakmoss is part of that.

–Mark Behnke

Olfactory Chemistry: Calone Part 2- The Search for a Better Mousetrap

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Last month I introduced you to Calone the molecule which launched thousands of marine fragrances. It should come as no surprise that a molecule as important as Calone has attracted much interest for the chemists at the big perfume houses. As I showed in the article on Hedione there is always a better mousetrap to be discovered. In the case of Hedione it was through purifying a mixture down to one specific molecule to find Paradisone. The method used for Calone improvements is more similar to my “day job” in pharmaceutical research.

When I have a new molecule I methodically make changes around the molecule looking for an increase in activity against a particular target. Over time I learn the key pieces of the parent molecule which are necessary for that activity. We call that the pharmacophore. A researcher at Firmenich Jean-Marc Gaudin believes there is an aromachemical equivalent called an olfactophore; that there are essential pieces of a molecule to produce a desired odor profile. He presented this hypothesis in a paper published in January of this year (European Journal of Organic Chemistry, p. 1437-1447, 2015). Following up on a previous 2007 paper ( Helvetica Chimica Acta, vol. 90, p. 1245-1265, 2007) he has used Calone as his basis to explore this. In the figure below I show what was known about Calone.

Calone SAR

The Firmenich group had shown in the 2007 paper that increasing the size of the CH3 group made a “better” Calone. By lengthening it by two carbons they could reduce the “low tide” aspect in Aldolone. By branching it they both attenuated the “low tide” smell and enhanced the floral quality in Lilial.

Aldolone Lilial

Now it was time to work on the spacing and the double bonded carbon on the other side of the molecule. They quickly discovered if they reduced that oxygen to an alcohol they made it much weaker. The Lilial alcohol shown below is described as “fruity, without character, very weak”

Lilial Alcohol

The next idea was to open the ring up allowing for the double-bonded oxygen some flexibility to find the key interaction. The closest they would come is the Aldolone analog shown on the left below which carried a description of “perspiration, aldehydic, slightly aldehyde muguet, vanillic, slightly metallic, nice, too weak”

open and five membered calone analogs

The final idea was to decrease the size of the ring from seven atoms to five. This would keep the sheer flexibility of the molecule in check a bit. They also wanted to give the double-bonded oxygen a little flexibility by attaching it to the five membered ring instead of making it part of it. Here is where they found some success as the molecule on the right above was described as “watermelon, aldehydic, Aldolone, Cyclosal, green, oyster, ozone, watery” This sounds like a different level Calone as now the watermelon is made more prominent plus the idea of a greener Calone sounds really interesting to me.

This paper makes a small incursion into the hypothesis that an olfactophore exists but it is but one part of the biochemical enigma that our sense of smell presents to scientists.

–Mark Behnke

Header: Picture of the Board Game "Mouse Trap"

Olfactory Chemistry: Calone- The Smell of the Sea (and Watermelon)

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When you look back over the history of perfume making there are only a few ingredients which can be said to be that which launched an entire genre. When it comes to the aquatic class of fragrance there is one chemical which is responsible for this, Calone.

calone

Calone has the trivial name of Watermelon Ketone and for once the name is actually chemically correct as Calone (see above) is a cyclic ketone. It was discovered in 1951 by chemists working at Pfizer. It was being designed as a food flavoring agent to “give a watermelon taste and odor to foods.” according to the 1970 US Patent.

Calone by itself does not have any of the pleasant smell you associate with it in fragrance. At full concentration, in its white crystalline form, it has a nose–searing acrid smell. It takes significant dilution before the more palatable aspects become apparent. Because of the kind of molecule Calone is it also has a ferocious tenacity to it. Another reason there was so much interest in using it; especially for the crowd which equates longevity with quality. Mix Calone and one of the synthetic musks and you have a perfume which will literally last for days.

NewWest by Aramis

It would make its perfume debut in 1988 when perfumer Yves Tanguy would use it in Aramis New West. In that perfume you got the hint of what it would become known for as it provided this fresh sea-breeze quality. It also adds in the watermelon part too. For all that the Pfizer chemists wanted to use it as a flavor and the trivial name makes it seem like this should be a fruity note; it really isn’t. The watermelon part is not the rich pulp of the fruit but more the watery rind with subtle fruity facets. In New West that watery fruity quality is very much on display especially in the heart when the marine breeze has died down a bit.

It would take two more years before it was the centerpiece of the aquatic perfume which launched a genre, Davidoff Cool Water. Perfumer Pierre Bourdon would take Calone out and let it become the crashing surf as wave after wave of aquatic sea breeze washes over you. In Cool Water the melon quality is really overwhelmed by the marine character.

Calone has become one of the most common ingredients in fragrance. If it says “sea breeze” on it; it is very likely there is Calone in it. That kind of ubiquitous presence has taken Calone from groundbreaking to cliché over the last twenty-five years. The overwhelming tidal wave of aquatics featuring it continues to this day. It has become almost a note which perfumers shy away from because it has become so overused.

Chemists at Firmenich have been working on making a better version of Calone and just at the beginning of this year published a paper on that work. Next month’s Olfactory Chemistry will take you into how changing the structure of Calone leads to some interesting new smells.

–Mark Behnke

Olfactive Chemistry: Indole- The Sour Inside

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In the middle of the movie America Hustle one of the characters has this quote, “It’s like that perfume you love, that you can’t stop smelling even when there’s something sour in it.” Of course I have no idea exactly what she is referring to but in my mind while watching there was only one perfume ingredient which fit this description, indole.

Indole is the “bad girl” of perfumery. Cue Donna Summer. They are found naturally in the group of floral notes dubbed “white flowers”. Jasmine is the leader of that family and in the specific species of jasmine called jasminum sambac you will find the highest amount of natural indole. It is why the synthetic jasmines exist, to remove the indole, to get a brighter fresher version of jasmine. I very often make the distinction in reviews with the essential oil being a little more experienced and the synthetic being a scrubbed-fresh debutante. Both have their place on the perfumer’s palette.

indole skatle

Indole gets a bad rep because of the methyl-substituted version of indole known as Skatole. As you can see above there is only the addition of one methyl group different between Indole and Skatole. Skatole is the smell of feces and it is what many associate with the word indole. Indole by itself in high concentration smells more like mothballs. What is particularly magical is what happens as you dilute indole down in alcohol solutions. When you have a 10% solution of indole in alcohol it smells like an old closet. Dilute it in half to 5% and you get that dirty skin smell. Dilute it again in half to 2.5% and now a subtle kind of decaying sweetness becomes evident. Take it to 1.25% and an almost floral-like quality comes out. Reduce it finally to 0.5% and you have a building block to work with.

Indole is easily synthesized in metric ton quantities and is one of the more cost-effective perfume materials to use. Once you get used to handling it in its different iterations depending on the concentration. It allows a perfumer on a budget to take synthetic jasmine and a bit of indole to create a simulation of jasminum sambac.

Good examples of indolic perfumes are naturally the jasmine-focused ones. Serge Lutens A La Nuit and Diptyque Olene really wear their indole on their sleeve. One which is composed of indoles and synthetics is the original Calvin Klein Eternity which not only sports a high concentration of indole but also Iso E Super, and Galaxolide. Eternity is one of the best-selling perfumes of all time. While the time period is not right it is the perfume I think best represents the quote I began this with.  

–Mark Behnke

Olfactory Chemistry: Aldehyde C-16- The UN-Aldehyde

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One of the joys of living in farm country is waiting for late May and the start of strawberry picking. It is the beginning of what will be months of going and picking fresh fruit right off the tree or vine. Strawberry is also one of the most common fragrance components in all kind of products from perfumes to bath products. The great majority of the time when you smell strawberry in a product what you smell is the aromachemical called Aldehyde C-16.

aldehyde c-16

From a chemist’s perspective that name is very much a misnomer as Aldehyde C-16 is not an aldehyde. It does not contain 16 carbons as the C-16 might lead you to believe. As shown in the figure above the closest aromachemical relative to Aldehyde C-16 which is actually an aldehyde is Cinnamaldehyde. When I wrote about peach lactone in an earlier installment which is also not an aldehyde I had no clue where these names came from because they make zero sense to a chemist.

What I have been told by a couple of people from the industry is these groups of faux aldehydes were given the name of aldehyde to keep their structure hidden a little while longer. When a company develops a new aromachemical if they just gave it the correct chemical name another chemist could use it as a starting point to make a competing aromachemical. By calling these molecules things like Aldehyde C-16 if any other chemist thought it was an aldehyde they were starting off in the completely wrong direction. Which I have been told was the intent behind these names. I have found no corroboration of this in any reference book I can find so this remains conjecture.

Aldehyde C-16 is actually an epoxide ester. Esters are many of the most common molecules in perfumery. They also often have very strong fruity and sweet aroma profiles. Aldehyde C-16 is often described as smelling like “fantasy strawberry”. It means that a little goes a long way.

Besides adding in the strawberry to many perfumes Aldehyde C-16 also carries a sweet floral undertone. This characteristic makes it a perfect partner to the strong floral notes like rose, jasmine, or osmanthus. A perfumer can use it like a tuning fork dialing in a specific effect on a prominent floral note or accord. It is one of the more versatile ingredients on the perfumer’s palette.

While I confine my strawberry picking to the farm fields many perfumers pick Aldehyde C-16 when they want to add strawberry to a fragrance.

–Mark Behnke

Olfactory Chemistry: Hedione- My Fair Jasmine

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When you look back at perfumery there are some specific moments where the use of a new aroma chemical sparks a flurry of creativity. In 1966 perfumer Edmond Roudnitska introduced the world to Hedione in the classic men’s perfume Christian Dior Eau Sauvage.

Hedione was a synthetic jasmine discovered by chemist Edouard Demole. Dr. Demole was part of the team at Firmenich who discovered that the component in natural jasmine essential oil was a molecule called Methyl Jasmonate. From a synthetic perspective the double bond was problematic as far as synthesizing and making large quantities of this molecule. Dr. Demole discovered if he removed the double bond he formed a transparent version of jasmine chemically called Methyl Dihydrojasmonate and trademarked as Hedione.

hedione1

For many jasmine essential oil was a very difficult ingredient to use in moderation. Not only for the strong floral character but also for the presence of strong-smelling indoles in high percentage it made jasmine something which was strong. Maybe too strong. Hedione was a version of jasmine in which Dr. Demole played Henry Higgins and cleaned up jasmine removing the filthy skanky indoles. He also made it much less overwhelming. Hedione provides a unique middle ground between volatile top note and heavier base note. It is probably overstating things a bit to call Hedione the missing link for many perfumers looking for a diffusive floral transparency but it has been a part of thousands of perfumes over the last fifty years.

You will notice that unlike the drawing of Methyl Jasmonate which has the dashed and solid wedges to designate a specific geometry I didn’t draw Hedione that way because it is a mixture of all four possible variations. The chemists at Firmenich would go on to continue to synthesize ever more specific structures of that mixture. It would take thirty-seven years, in 1993, when it was discovered if you had a mixture of the two compounds shown below you got an enriched effect by having the two compounds where the side chains were on the same side of the molecule. This is called cis- in chemistry speak. In the structure of Methyl Jasmonate above that would be called trans- when the side chains are on different sides.

hedionehcparadisone

The mixture would be called Hedione HC which stood for “High Cis” meaning a high percentage of the cis-isomers. It would take three more years to develop a synthesis of the single isomer responsible for most of the effect in Hedione, and Hedione HC. That is the structure on the right and it is called Paradisone.  Paradisone is Hedione on steroids as now there is nothing to attenuate the power. The shy Eliza Doolittle of Hedione has become a stunning version which turns heads.

Perfumer Alberto Morillas has been one of the more contemporary perfumers who uses these molecules in interesting ways. One of the more recent uses of both Hedione and Paradisone was in 2013’s Penhaligon’s Iris Prima. Together they make the jasmine and iris heart feel like it has no horizon, almost infinitely expansive.

It may have taken forty years for the chemists at Firmenich to finally arrive at Paradisone but it all started with a simple reduction of a double bond on the natural molecule.

–Mark Behnke

Olfactory Chemistry: Iso E Super- Size Matters

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One of the most widely used aroma chemicals in perfumery is Iso E Super. Iso E Super was synthesized by International Flavor & Fragrances (IFF) chemists John B. Hall and James M. Sanders in 1973. In the book “Scent and Chemistry, The Molecular World of Odors” by Philip Kraft and Gunther Orloff they write that it had one of the most pronounced effect on fragrance development since Edmond Roudnitska introduced Hedione in Dior Eau Sauvage in 1966. What makes this such an influential molecule? One of the reasons that I will explore today is its size. If you look below at the structure of Iso E Super next to Limonene you can see they are closely structurally related but they have very different effects when used in perfume.

iso e super limonene

Limonene is one of the chemicals extracted from lemon rind. As is common citrus notes tend not to last very long on skin when used in a perfume and Limonene is no exception to that. Iso E Super has a very different effect. It is one of the great fixatives and base notes in all of perfumery. It is more well-known for its use in high percentages in some particularly seminal perfumes like Lancome Tresor, Hermes Terre D’Hermes, Perles de Lalique and of course Geza Schoen’s Molecule 01 which is 100% Iso E Super. In high percentages it does have a unique odor profile. Iso E Super has the influence cited my Kraft and Orloff for the effect it adds when used in small quantities.

Perfumer Andy Tauer has the best description of Iso E Super in small quantities in his blog entry of October 9, 2012. In that post he likens it to a layer in graphics program Photoshop. He says, “It adds lift, and it soften all notes, and it brings out contrasts and optimizes a fragrance in quite a spectacular way. In a sense it is present by its effect, and less by its scent. It is not by chance that you find Iso E Super in so many scents these days. Actually, the analogy to a photoshop layer is not so bad.” It is that lift and the ability to add to the longevity of the perfume which makes it so influential. That property is also related to its size.

One of the more unique features of Iso E Super is that some people can’t smell it easily, called anosmia. Just as people show anosmia for the large macrocyclic musks which are at similar molecular weight they do the same for Iso E Super.

When it comes to aromachemicals size does matter and Iso E Super is one of the larger molecules in regular use, and influence.

–Mark Behnke

Title Picture: Bloom County by Berkley Breathed– “Size Matters”