fragrance_the smell of success

8/6/2019 Fragrance_the Smell of Success

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40 |Chemistry World |February 2009 www.chemistryworld.org

The sweet scentof successA lot of work goes into discovering and developing the odour molecules that ensureevery Valentines bottle of perfume has the right chemistry. Emma Davies pokesher nose into some of the worlds most celebrated perfume molecules

Fragrance chemistry

JUPITERIMAGES


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Philip Kraft designs moleculeswhich elicit strong and immediateemotions in people. He creates newfragrances for Givaudan, a Swissflavour and fragrance company, and

some of his molecules play star rolesin best-selling perfumes. He has theunusual skill that when he smells acompound, he can almost visualiseits chemical structure. His work isdriven by an obsession to create newmolecules that will move people.

Kraft was drawn to fragrances andscience at a very young age. As a 12-year-old with a desire to understandthe science of teenage hormones,he bought a biochemistry textbookfrom his local university bookshopin Hamburg, Germany. A year later,his questions still unanswered,

Kraft returned to buy a chemistrytextbook. The shop assistant wasmost amused and gave him a testsubscription to a chemistry journalLiebigs Annalen der Chemie.

Kraft was captivated by an articleby Peter Weyerstahl, a fragrancechemist who had modified theodour of rose oxide. He had sentfragrance compounds to a companyfor evaluation so I wrote to thatcompany and they sent me somematerials, which I even used to givecourses at school.

Almost three decades on, Kraftis still entranced by fragrancemolecules. He creates patent-protected captive ingredientsfor Givaudan to hold in itsfragrance arsenal. The chemistry

is challenging: Its tough work anddespite all the molecular designtools, you still have to be lucky, hesays.

Scent searchFragrance researchers search highand low for chemical inspiration.Givaudan, for example, runsits much-publicised ScentTrekmissions to remote parts of theworld to capture new smells.

The easily accessible fragranceingredients were identified along time ago, explains KoenraadVanhessche, director of productand process research at Firmenich,another Swiss flavour and fragrancecompany. What is now happeningis that we are looking at tracecompounds a lot of these have lowthresholds or are relatively unstable.

But much of the work is doneby altering existing molecules,

or by searching for commerciallyviable synthetic routes for knowncompounds. Kraft likes to followa hardcore design approach,twisting, tweaking, and trimmingexisting molecules to modify odourand its intensity. When I smell anodour I can almost see the shapeof the molecule. You look at themolecule, make a hypothesis as towhy it smells like it does, and thentest this hypothesis by modifying themolecule and seeing if you get theodour you desire, he explains. OftenI make a molecule just to see how it

smells.Kraft and his team frequentlywork on paper, sketching outmolecular variations using balland stick models. They also useolfactophore models, whichshow the molecular features thatare key to a given odour, such ashydrophobic groups, and H-bonddonors and acceptors. You can playwith conformational elements thatdrive a certain molecular shape for example you can introducestructural elements that causea molecule to fold itself into a

horseshoe shape and thus smellmusky, explains Kraft. Addingrigidity to molecules often givesmore defined odour notes, he adds.Or you can make the molecule moreflexible to add new by-notes youcan cut some parts to make it lighterand more diffusive while conservingits overall shape.

But his team sometimes takesthe more traditional approach tocreating captive ingredients. Youcan have chemical inspiration youtake known odour compounds andsubmit them to a specific series of

In short

Nature provides awide variety of fragrantmolecules, from fruityfloral notes to deermusksFragrance chemistshave created an array ofnew aromas by modifyingthe structure of naturalscentsDeveloping a costeffective syntheticroute is a key hurdlebefore an aroma canbe incorporated into aperfumeDemand for newfragrances fromtodays consumers isunprecedented, fuellingthe search for newaromas

Despite allthe moleculardesign tools,you still have tobe lucky


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reactions to see how the odour ismodified. If you like something thenyou can follow up a certain aspect,says Kraft. Fragments of knownfragrance molecules can also beincorporated.

Any new fragrance moleculescreated in the lab are assessed byperfumers. Sometimes it can bethat a few love your molecule, whilesome hate it. If you love a certainmolecule it can be frustrating if yousee that other people dont like it,

says Kraft. Firmenich employs 67perfumers. We have one very specialperson who is a chemist and alsoan excellent perfumer. He gets thefeedback from his colleagues onwhat consumers want and interpretsthe information in olfactorytonalities, explains Toni Gautier,corporate vice-president of R&D atFirmenich.

When the perfumers take a likingto a new molecule, its often not longbefore new fragrances bearing thesignature compound hit the highstreet. Looking back at perfume

trends, it is clear when chemicalbreakthroughs have taken place inthe industry, says Gautier.

Chart toppersTo make a fine fragrance, newmolecules are mixed with oldfavourites. But which fragrancecompounds are most valued byindustry a kind of fragrancetop 10? Its a difficult questionto answer. Gautier has no doubtabout the value of Hedione (methyldihydrojasmonate), used in almostall fine fragrances and Firmenichs

top seller in terms of volume. Thecompound was discovered atFirmenich in the early 1960s as ananalogue of methyl jasmonate, akey component of jasmine oil. Saidto give a warm floraljasmine note,Hedione has been used in perfumesfor over 40 years, first starring inDiorsEau Sauvage in 1966.

The synthesis of Hedione givesfour stereoisomers, explainsGautier. Only one of them trulycontributes to the odour (+)-cis-

methyl dihydrojasmonate whilethe others are thought to modulateother fragrances. Over the yearsweve been able to synthesise newversions of Hedione which have amuch higher quantity of the rightisomer.

Gautier also has a soft spot forthe rose ketones: damascenone,and alpha and beta damascone.Firmenich is famed for theirdiscovery and synthesis in the1960s during a quest to identify thecharacteristic smell of Bulgarianrose oil. But batch purity problems

meant that damascenone was notreleased commercially until 1982.Then came alpha-damascone (roseapple note) and beta-damascone(blackcurrantplum note). The roseketones broke new groundin the 1980s, giving femaleperfumes such as DiorsPoison their unusual anddistinctive fragrance.Today, beta-damascenoneand beta-damasconeremain two of the mostimportant fragranceingredients.

Chemists are forever improvingon the rose ketones, which are stilltrendsetters. One of Krafts recentand very successful captivesis Pomarose, a cut-open seco-damascone. Pomarose introducedthe dried-fruit character ofPoisonto the male market and had itsdebut in DKNYs male fragranceBedelicious Men. It has a very specificnote of cooked apple, rose, anddried plums. Its very diffusive so itgives a lot of bloom to a fragrance,enthuses Kraft. Givaudans processdevelopment team had to try 19different synthesis routes beforeit managed to produce Pomarose.Initially we thought we couldntproduce it. It was a crazy idea thatoriginated from a 1 per cent impurityfor which different structureswere proposed based on the NMRspectrum. After we had discoveredthe correct structure we synthesised

the wrong proposal for fun butit turned out to be so powerful,recalls Kraft. Interestingly, it wasntthe impurity itself that becamePomarose, but one of the alternativestructures.

Pomarose was recently used inhigh concentrations in Unforgivableman by Sean Jean also knownas US rapper P Diddy who issaid to have been quite taken withthe compounds champagne-likequalities.

Another essential and oncecontroversial group of flavour

compounds is the macrocyclicmusks, which are extremelyimportant to the industry, saysGautier. Musks once had a badname, in the days when they werederived from the musk pods ofthe Asian musk deer. These days,musk odourants are all synthetic.Replacing the musk ingredientscaused something of a stir but theindustry is probably better offnow because it has biodegradableingredients with no environmentaleffects, says John Leffingwell offlavour and fragrance consultants

Leffingwell and associates.Musks belong to several

classes that are structurally verydifferent. Those synthesised bythe industry are generally nitromusks, polycyclic musks andmacrocyclic musks. Gautier wouldlike to add Helvetolide, a linear muskdiscovered by Firmenich in 1990, tothe most-valued list. Helvetolidehad a totally different structure toexisting musk compounds and itsdiscovery opened up a whole newdomain of musk chemistry, saysGautier. Together with macrocyclic

Theres something inthe air

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Alpha (top) and betadamascone are fruitycomponents of rose oil

Fragrance chemistry

JUPITERIMAGES

GIVAUDAN


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Chemistry World |February 2009 |43www.chemistryworld.org

musks, Helvetolide is key towhite musk compounds, said tobe reminiscent of freshly ironedlinen. These are currently very

fashionable, says Kraft.

Out of the woodsWoody fragrances such as Iso ESuper, a compound known as afloraliser and used in most newfine fragrances, also rate highly,says Gautier. Some people smella cedarwood note in Iso E Super,while others perceive it to be musky.The male fragranceFahrenheit (Dior,1988) is 25 per cent Iso E SuperwhilePerles de lalique (Lalique,2007) is 80 per cent Iso E Super. Thecommercial Iso E Super owes its

woody smell to a 5 per cent impuritywhich has an odour threshold about100 000 times lower than that of themain product.

In 1999, Krafts team at Givaudanisolated this impurity by epoxidationof a commercial Iso E Super andproposed a structure based on NMRspectra. The team came up with away to synthesise the compoundbut it was not commercially viableand the structure turned out tobe too complex for an alternativesynthetic procedure. But out ofseveral synthesised analogues, one

had an almost equal odour thresholdand smelled even better. What ismore, its industrial synthesis isstraightforward and it has become

a big hit used by Givaudan as thecaptive material Georgywood.However, on strictly cash terms,

the most valuable fragrances arethe natural products. For example,East Indian sandalwood oil is oneof the most precious and expensiveperfumery raw materials.

Beta-santalol is the main olfactoryconstituent of sandalwood oil.It wasnt until 1990 that beta-santalol could be prepared in thelab this took an 11-step reactionthat was unsuitable for industrialscale-up. The best sandalwood oil

substitutes are derivatives of alpha-campholenic aldehyde, preparedfrom inexpensive alpha-pinene,most of which is a byproduct of thepaper industry.

The components in sandalwoodoil are not easy to make,acknowledges Gautier. But whatFirmenich has done is screenedall around that kind of structureto try to find woody notes. Wehave a lot of substitutes so thatperfumers can create somethingclose to sandalwood withoutneeding sandalwood oil. Kraft

agrees that there are excellentsynthetic substitutes out there.For example, the campholenicaldehyde derivatives typically have

a good sandalwood smell. Theother olfactory parts of naturalsandalwood oil such as thesmokey, cedar-like aspects caneasily be added using, for example,cedarwood oil, says Kraft.

Sandalwood was initiallyquite cheap (Guerlains Samsaracontained 25 per cent sandalwood)but overharvesting has led to Indiansandalwood trees being listed onthe World Conservation Unionsthreatened species red list.

Theres still a good market forsandalwood oil and the price has

gone, in the past six or seven years,from $1000 [680] per kg to over$2000, says Leffingwell. OneAustralian firm, TFS Corporation,has taken the initiative andplanted over 1700 hectares of theendangered Indian sandalwood(Santalum album) in plantations inWestern Australia.

After sandalwood comes thehippy favourite patchouli oil.Its fragrance comes largely frompatchoulol. Its a truly uniqueingredient that is ideal for perfumes.But it is a molecule that we have not

Alpha- (top) and beta-santalol are constituentsof the prized East Indiansandalwood oil

Perfumerscan createsomethingclose tosandalwood

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been able to make cost-effectively bysynthesis. So this is one of the holygrails of organic synthesis to finda route to make patchoulol, saysGautier.

Firmenich works with farmersto cultivate research crops, oneof which is patchouli, grownin Indonesia. It is of extremeimportance to the industrythat we are able to improve anyway of making this product be it by organic synthesis or plantcultivation, improvement of thestrains, and extraction from theplant, says Gautier.

Finally, theres nootkatone, a keyingredient in grapefruit, and muchvalued for todays light and fruityperfumes. This, says Leffingwell, isa very expensive chemical that cancurrently only be synthesised from abyproduct from the citrus industry,which is in short supply. Only one of

its isomers has the grapefruit odour((+)-(4R,4aS,6R)-nootkatone)). Theother, ()-(4S,4aR,6S)-nootkatone, isvery weak, with almost no grapefruitcharacter.

Perfume challengeThe perfume industry is also facingnew challenges from regulators,particularly from the EU, whichis limiting the use of possibleallergenic compounds in perfumes.Current legislation means thatfine fragrance producers have todeclare on packaging if a perfume

contains any of a list of 26 allergens.Leffingwell thinks that theresa risk that before long fragranceproducers wont even be able touse orange oil and lemon oil (thesecontain limonene, which at highconcentrations can cause a skinreaction). Its ridiculous. If youtook all these things away from theperfumer theyd have real difficultymaking nice fragrances, he says.

But the industry is reacting ina positive way. Our clients wouldprefer not to have allergens on thelabel so in a lot of cases we are now

generating fragrances that dont havethe compounds in them, says Gautier.

It is a bit more difficult whenclients want you to take thesemolecules out of existing perfumeswithout having any change. Wedo have replacers but they are notexactly equivalent. To have the sameorganoleptic, physical and economicproperties is a challenge.

There is also the issue of

biodegradability. Fragrancechemists have to be careful to keepthe molecular building blocks forfragrances relatively inert. We tryto avoid reactions in the perfume.Most of the compounds are carbonylcompounds. If the pH is neutral youdont get aldol reactions so we dontuse a lot of acids in fragrancesexcept a few for honey notes, saysKraft.

A few years ago, the perfumeindustry ran into problems becauseits molecules were too inert anddidnt biodegrade, recalls Kraft. Now

were going back to makethem biodegradable. Its a challenge

to make them stable enough thatthey dont decompose in the perfumeitself.

Fickle fragrance

The demand for new fragrancecompounds is driven by todaysconsumers, who are always on thelookout for something different.Unlike 30 years ago, the life of aperfume today is relatively short. Inmany cases now a fragrance will bevery popular for a year or two, thenthe consumers move on, explainsLefingwell.

Since 2000, over 5000 newperfumes have been introduced, saysMichael Edwards, who compilesthe bookFragrances of the world ,commonly described as the perfumebible. He thinks that customers areconfused. Why do all fragrancessmell alike? he asks. The problemis that product managers want as

broad an audience as possible. If yougo for broad appeal it s very hard tocome up with a fragrance that has gotguts and signature. He thinks thatthe industry doesnt need to searchperpetually for new compounds.Were not using the great materialsthat we already have imaginativelyenough. Look at Iso E Super, firstused in 1975 and now becoming a starin its own right. Its really a case ofimagination over raw materials.

From what Ive seen, itsimagination that leads to newmaterials. And theres no stopping

the fragrance chemist in the addictivesearch for the next hit and theensuing public reaction. Asking themto stop what theyre doing would belike asking the Rolling Stones to stopperforming. Perfumery can be verygratifying because, as with music,you create a real effect you cancreate sensuous moments for people,says Kraft. My mother doesntunderstand any chemistry but witha smelling strip containing one of mymolecules she can feel the chemistryof the molecule.

Emma Davies is a science writer basedin Bishops Stortford, UK

Fragrance chemistry

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Hedione, from jasmineoil, is used in almost allfine fragrances

If you go forbroad appealits very hard tocome up witha fragrance

with guts andsignature

fragrance_the smell of success

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