Chemistry A European J - 2024 - Elterlein - Sniffing Out The Sustainable Future The Renewability Revolution in Fragrance

Review
Chemistry—A European Journal doi.org/10.1002/chem.202400006
www.chemeurj.org
Sniffing Out the Sustainable Future:

The Renewability Revolution in Fragrance Chemistry**
Franziska Elterlein,[a] Nikolas Bugdahn,[a] and Philip Kraft*[a]
Dedicated with all the best wishes to Heinz-Jürgen Bertram on the occasion of his 65th birthday and retirement
Chem. Eur. J. 2024, e202400006 (1 of 36) © 2024 Symrise AG. Chemistry - A European Journal published by Wiley-VCH GmbH
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Review
In this review, the impact of the transition from today’s sustainable manner. However, in the domain of green odorants,
resource-wasting petrochemical economy towards a 100/100 there is a lack of green chemistry for important key materials. In
renewable and biodegradable future is discussed with respect the floral family, renewability is more critical than biodegrad-
to the fragrance families: “citrus”, “green”, “fruity”, “floral”, ability, but cost is an issue. Thanks to Ambrox and maltol,
“floriental”, “oriental”, “woody”, “chypre” and “fougère”. After florientals and orientals will persist, while woody notes severely
benchmark data on ingredients usage, definitions on biodegra- lack an Iso E Super replacer. In the chypre genre, patchouli
dation and sustainability are given. Celebrating the 150th became the new moss, but more musks are increasingly in
anniversary of synthetic vanillin, its historic synthesis from demand. With their high percentage of linalool and dihydro-
renewable starting materials serves as introduction. In the myrcenol, the construction of fougères could well become a
grand scheme of things, citrus scents upcycled from the precedent for other families, despite challenges in vetiver and
beverages industry, are already an ideal case for 100/100 with salicylates. Still, the challenges exemplified here create im-
new opportunities for artificial essential oils. In the fruity mense opportunities for new perfumery materials.
domain, transparent and lactonic ingredients are available in a
‘I skate to where the puck is going to be, not where it has been.’ market, asking the question, ”Where are we skating to?“ :
Ice hockey legend Wayne Gretzky[1] Already being omnipresent on the shelves of perfumeries and
consumer markets, we can see an amalgam of claims such as,
‘A new bioeconomy is rising from the ashes of fossil fuels … “coming from natural sources,” “containing renewable ingre-
Our suppliers and innovation partners play a critical role dients,” “made with sustainably sourced materials,” “non-
through this transition: … we are calling on an economy-wide polluting” and “respecting biodiversity” (cf. Glossary), demon-
transformation in how we all use carbon.’ strating an increasingly dominant role in the industry. There-
Peter ter Kulve,[2] Unilever’s President of Home Care fore, it was hardly surprising, when Peter ter Kulve, President of
Home Care, Health and Wellbeing at Unilever, presented in April
2021 on YouTube[3] the 100/100 challenge “Cleaning has Mean-
ing”. The goal is to use only 100 % renewable and 100 %
1. Introduction: Challenges and Opportunities biodegradable materials by 2030, certainly the most stringent
in a 100/100 World approach in the consumer industry. In comparison, L’Oréal
projects to use > 50 % renewable perfume oils that must be
The writings on shampoo and shower-gel bottles, cosmetic > 85 % “readily biodegradable” by 2030. For Procter & Gamble
products, toiletries, or recently even on niche and prestige (P&G) the carbon footprint is their most important goal, with an
perfumes are like the proverbial writing on the wall. And if you objective by 2030 to reduce CO2 emissions across their own
read these, you know “where the puck is going to be” to refer operations by 50 %, and across their supply chain by 40 %.[4]
back to ice hockey legend Wayne Gretzky.[1] This popularized P&G is committed to net zero greenhouse-gas emissions (cf.
metaphor can find relevance in our observation of today’s Glossary) by 2040. Concerning perfumes, compaction with high-
impact ingredients is their most urgent task, while renewable
materials are key for the detergent chemicals which make up a
[a] Dr. F. Elterlein, Dr. N. Bugdahn, Dr. P. Kraft
Symrise AG, S&C Global Innovation Fragrances, Building D 209, much larger volume.
Mühlenfeldstraße 1, 37603 Holzminden, Germany In any case, by volume, the Flavor and Fragrance industry
E-mail: philip.kraft@symrise.com plays only a marginal role in the carbon economy. Without
Homepage: www.symrise.com
solvents, about 820’000 tons of aroma ingredients, that is flavor
[**] Note concerning trademarks: Trademarks are denoted from trivial and
and fragrance ingredients, are used in the F&F industry each
systematic compound names by capitalization and not by the trademark
® sign. This is done to increase legibility and should not be regarded as year, out of which 640’000 tons per annum account for
affecting the legal status of any trademark. Note regarding trade secrets: fragrances and 180’000 tons per annum for flavor
The assignment of the perfumers, the respective fragrance house as well compositions.[5] This pales in comparison to the overall global
as the year of launch was taken from either of the following public da-
industrial use of hydrocarbons which is estimated at
tabases www.fragrantica.com, www.parfumo.de, www.basenotes.com,
www.ourfragrances.com and www.wikiscents.com, and thus is based on 830’000’000 tons/year, making fragrance ingredients just
press releases. The authors checked for consensus, but do not assume 0.077 % of the share.[6] One can further compare to the volume
any liability for the correctness of the information provided. Note on of cosmetics (4’400’000 tons/year), and even more so to
perfume analysis: The quoted percentages of perfumery ingredients in
thermoplastics (440’000’000 tons/year) in general or the volume
market products are rounded figures mostly derived from GC (FID) area
percentages subject to analytical error and serve for illustration only. They of polyethylene terephthalate (PET, ca. 49’000’000 tons/year). It
are indicative only and purposely given with an accuracy that does not feels particularly small in comparison with the amount of palm
allow the copying of the respective perfume. oil used for consumer goods (81’400’000 tons/year in 2021/22),
© 2024 Symrise AG. Chemistry - A European Journal published by Wiley-VCH the volume of laundry detergents and softeners (33’000’000
GmbH. This is an open access article under the terms of the Creative
tons/year) or pesticides (55’000’000 tons/year) produced. Of all
Commons Attribution Non-Commercial NoDerivs License, which permits use
and distribution in any medium, provided the original work is properly cited, the aroma chemicals today, already 33 % stem from renewable
the use is non-commercial and no modifications or adaptations are made. resources, but as most of these are flavor ingredients, there
Review
remains 76 % of all perfumery ingredients or ca. 490’000 tons

which are of petrochemical origin. The other 24 % of the
perfumery materials are derived from renewable sources,
mainly pine turpentine, out of which 8 % are naturals, mainly
essential oils (Figure 1). The most important renewable feed-
stocks for perfumery ingredients are turpentine, tree-tapping
resins and waste products from the pulp industry. These
account for 96’000 tons of turpentine derivatives per annum in
perfumery or roughly 15 % of all fragrance materials. This is
followed by about 32’000 tons of essential oils for perfumery,
most of which are citrus oils as by-products from the food
industry. The amount of perfumery materials produced today
from renewable resources by biotechnological processes is
estimated at 1’650 tons annually, whereas solvents that are
mostly synthetic are estimated to account for 250’000 tons per
annum. Despite the big potential of biotechnology (cf. Glossary)
as documented in several recent review articles[7,8,9,10] the actual
impact of biotechnological processes in the production of
fragrance materials is limited, mainly due to oncosts (vide infra)
and therefore not focused in this review. Fragrances, cosmetics, Figure 1. The carbon economy of the fragrance industry with a total of
640’000 tons of perfume oils excluding solvents, which would add another
and toiletries are to a great extent luxury items that are
250’000 tons to the petrochemical segment. The data displayed was taken
expected to take a pioneering role in our inevitable transition from ref. [5,6] and also reflects that many low-cost high-volume ingredients
from today’s fossil-fuel based economy to a renewable and are of petrochemical origin. In terms of the perfumer’s ingredient palette,
approximately 45 % are already renewable with 2/3 being naturals and 1/3
sustainable future.
synthetics.
The current definition of what is a sustainable world goes
back to the so-called Brundtland Report[11] that came out of a
United Nations Commission on Environment and Development
Franziska Elterlein was born in Germany in Philip Kraft, born in Germany in 1969, studied
1993. After a French–German Bachelor pro- Chemistry at Kiel University and obtained his
gram in Chemistry named “Regio Chimica” in diploma and Ph.D. with Werner Tochtermann
Mulhouse (France) and Freiburg (Germany), on macrocyclic odorants in collaboration with
she studied Chemistry at the ETH Zürich, H&R. In 1996, he joined the fragrance research
performing the Master thesis in the group of of Givaudan, and was promoted to the ranks
Antonio Togni. She received her doctorate of chief chemist (2001), group leader (2008)
degree with Reinhard Brückner at the Univer- and research fellow (2015) with a special focus
sity of Freiburg (Germany), working on the on the rational design and synthesis of new
total synthesis of a C-glycosidic naphtho- odorants, molecular modeling, and structure–
quinonopyrano-γ-lactone. In 2022, she joined odor relationships. To keep Fragrance
Symrise AG as Lab Manager responsible for Chemistry visible to the scientific community,
the discovery and development of new fra- he co-organizes the ‘flavours & fragrances’
grance ingredients. conferences of GDCh since 2004, with the
next to take place in Göttingen in 2025. Since
Nikolas Bugdahn was born in Germany in
2008, he lectured on Fragrance Chemistry at
1979. Having studied Chemistry at the Phil-
the Universities of Bern and Zurich as well as
ipps University of Marburg he received his
at the ETH Zürich, and since 2021 at the
diploma and doctorate degree within the
University of Göttingen/Wöhler Research In-
group of Markus Oberthür and Mohamed A.
stitute for Sustainable Chemistry. Impressed
Marahiel in the field of Natural Product Syn-
by their leading role in sustainability, he
thesis. In 2012, he joined the bio-medicinal
joined Symrise, Holzminden, in 2021 as princi-
chemistry company ABX GmbH, Radeberg, in
pal chemist. He has authored 101 publica-
the field of cancer diagnostic and research as
tions, 43 patents, and invented 8 commercial
a research scientist and laboratory manager.
perfumery materials.
In 2016, he joined Symrise AG as Lab Manager
responsible for the development of new
cosmetic ingredients. Since 2021, he has been
working at Symrise AG as Director New
Molecules Synthesis, Global Innovation, Scent
& Care division. He authored > 20 patents,
publications and developed 3 commercial
cosmetic ingredients for the global market.
Review
(WCED). The report defined ’sustainable’ as “…meet[ing] the we thus want to discuss the impact of the 100/100 conundrum
needs of the present without compromising the ability of future with respect to the impact on the main perfume families
generations to meet their own needs”.[11] Sustainable ingre- (Figure 2), derived and inspired by the 2021 Symrise Fragrance
dients thus should be produced from renewable feedstocks and Genealogy.[22]
they should break down into innocuous degradation products,
in other words they should be biodegradable. To reduce the
carbon footprint by handling and transportation they should in
addition allow for compaction, and therefore should be of 2. Celebrating 150 Years of Sustainable
considerable sensory strength. High-impact ingredients may Vanillin: From Cambial Sap into Flacons
also reduce waste, but only if they are designed in an energy
efficient and atom economic way. Before diving into the fragrant ocean of the future, we can start
The generally accepted method to measure biodegradabil- by examining the renewable roots of the fragrance industry.
ity (cf. Glossary) is defined in the OECD guidelines 301 A F.[12] Since the latter emerged from the search for the odorous
For volatile compounds like odorants, the methods 301 C principle of nature, the starting materials were in fact very often
(Respirometry: oxygen consumption), 301D (Closed Bottle: natural products. One of the most precious odorous principles
dissolved oxygen) and 301F (Manometric Respirometry: oxygen was vanillin (3). Albeit sometimes crystallizing on the surface of
consumption) can be used. A material is considered ‘readily the pods themselves, the content of 3 is only around 1.69–
biodegradable’ if 60 % of the organic carbon in the material is 2.75 %.[23] This led to prices of > 10’000 rm/kg for natural
converted into carbon dioxide within 28 days with a 10-day vanillin in the 1870s, and made it an attractive synthetic
window that begins when the biodegradation has reached target.[24] While the vanilla scent of old books was common
10 %. When the biological oxygen demand (BOD) curve knowledge, it still took Wilhelm Kubel (1832–1903, later a
indicates that biodegradation did start and is > 20 % without a Holzminden pharmacist) by surprise when he observed a “most
plateau being reached by day 28, the test duration may be pleasant vanilla scent” upon heating coniferin (1) in diluted
prolonged to 60 days.[13] If the 60 % limit is then reached within hydrochloric or sulfuric acid.[25] Kubel worked on the cambial
the 60-day limit, the compound is likely to be ‘inherently
biodegradable’ (cf. Glossary), which is then established by a
Zahn–Wellens/EMPA test (OECD 302B and C).[14] To be consid-
ered ‘ultimately biodegradable’ the criteria is even more vague,
with some claiming the substance needs to break down by at
least 60 % within a 90-day period, but there is no official
classification as ‘ultimately biodegradable’. Despite many
attempts, notably the OASIS CATALOGIC simulation of abiotic
and microbial degradation of the Mekenyan laboratory,[15,16,17]
and recent advances and developments[18] up to now, the
biodegradability of a certain substance cannot be reliably
calculated by computer models or predicted with any accuracy
by other means. Today, around 54 % of the perfumer’s palette is
biodegradable, with 3/5 naturals and 2/5 synthetics.
In contrast, the renewability (cf. Glossary) of a substance can
be easily determined. Generally, substances are classified
‘renewable’ if > 50 % of its carbon atoms are obtained from
biomass. Around 45 % of the perfumer’s palette is already
renewable with 2/3 of it being naturals and 1/3 synthetics. Only
about 24 % is 100/100 renewable/biodegradable, with 3/4 of
these being naturals and 1=4 synthetics. Though it can be
planned intelligently, it remains a challenging task for the
synthetic chemist to wisely use the materials from nature or
upgrade materials from waste streams to design for 100/100.
Returning to the days of all-natural perfumery before the
synthetic access[19] to coumarin (1868) by William Henry Perkin
(1838–1907) or vanillin (1874) by Ferdinand Tiemann (1848–
1888) and Wilhelm Haarmann (1847–1931) is however no
option since essential oils and absolutes have the most
unfavorable carbon footprint of all perfumery ingredients due
to their low yields (generally 0.1–5 %) and the unsustainable use
Figure 2. Examples from the 2021 Fragrance Genealogy for the different
of land and water. Modern synthetic fragrance materials odor families that are discussed in this review with respect to the impact of
enabled the creative universe that perfumery is today,[20,21] and sustainability, renewability, and biodegradability.
Review
sap of larches, spruces and pines, from which he had isolated Tiemann approach was modified for an industrial synthesis of
the β-d-glucopyranoside coniferin (1, Scheme 1). In 1871, Kubel vanillin by a 1894 patent of M. C. Traub.[35] Despite being
gave 8 g of 1 to his student friend Wilhelm Haarmann[26] (1847– previously undesired, the formation of this by-product turned
1931) for his PhD thesis with Ferdinand Tiemann (1848–1899), out to be invaluable in the 1870s for the synthesis of
who led a subgroup in the laboratory of A. W. Hoffmann (1818– salicylaldehyde, and therefore the industrial production of
1892) in Berlin. By enzymatic hydrolysis of 1 with emulsin to coumarin by Perkin condensation.[19,36,37]
coniferyl alcohol (2) and subsequent oxidation with chromium Another process was in need, and that was again found by
trioxide, Haarmann was able to obtain vanillin (3),[27,28] for which Tiemann.[38,39] As depicted in Scheme 2, it uses another renew-
he was awarded his PhD. In 1874, Haarmann set up a factory in able but now more abundant starting material: eugenol (6),
his wooded hometown of Holzminden and was able to which occurs in 70–95 % in clove oil, could be easily isolated by
establish industrial production of vanillin (3, Scheme 1). The distillation. After protection of the free hydroxy function as
cambial sap of 5000 freshly felled spruce trees was collected by acetate by reaction with acetic anhydride eugenol acetate (7) is
25 women in Germsbach, which took about 12’000 h and obtained in near quantitative yield. Oxidative degradation of 7
yielded 20 kg of coniferin (1). This was then oxidatively cleaved with chromium trioxide, then furnished after deprotection with
to produce 7 kg of vanillin (3), the entire factory’s output in potassium hydroxide and acidic treatment with sulfuric acid,
1874.[29] At 9000 rm/kg, it was only slightly less expensive than would produce vanillin (3) on industrial scale. Of course, as
the natural vanillin (3) ex vanilla beans.[29] chromium(VI) is now known to be hemotoxic, genotoxic, and
Tiemann then involved another student, Karl Ludwig Reimer carcinogenic, this historic process is far from green; nevertheless
(1845–1883), who developed an alternative pathway to vanillin the concept of sustainability (cf. Glosssary) was already high on
(3) by formylation of guaiacol (4), by way of an “up-cycling” the agenda even in those days, even if only for cost
product from beechwood tar.[30] This Reimer–Tiemann considerations. Vanillin (3) is still a key ingredient and was
reaction[31,32] corresponds in a formal way to a formylation of famously overdosed by Annick Ménardo at 15 % in “Hypnotic
phenols with the non-existent formyl carbene using dichloro- Poison” (Dior, 1998) – more modern and green routes to vanillin
carbene as a synthon. It seemed much more attractive than the (3) are discussed in section 7.1 (vide supra).
laborious and costly isolation of coniferin (1) from spruces.
Reimer, therefore, joined the young vanillin factory in 1876 as a
companion, which thus became Haarmann & Reimer. However, 3. Citrus Notes
the high hopes in the Reimer–Tiemann synthesis of vanillin (3)
were shattered by the formation of 2-hydroxy-3-methoxybenz- 3.1. Fresh, Light, and Cold-Pressed
aldehyde (5) as by-product,[32,33] which had a strong salicylate
off-odor and turned out difficult to separate.[34] The Reimer– Going as far back as to the first conceptualized alcoholic
perfume, the “Aqua Admirabilis” that Giovanni Maria Farina
(1685–1766) launched in Cologne in 1709, the citrus family is
the oldest fragrances family. Its famous prototype, the “Kölnisch
Wasser” (“Eau de Cologne”) is based on a harmony of bergamot,
lemon, and orange in a musky-rosy context, contrasted by
neroli, petitgrain and rosemary. And just as this, citrus
fragrances in general feature a dominant note of citrus fruits
(Hesperidia). Most importantly, these comprise of bergamot,
orange, lemon, lime and grapefruit oils (Figure 3), while modern
Scheme 1. The first synthesis of vanillin (3) from coniferin (1) by Haarmann
and Tiemann[27,28] and the alternative Reimer–Tiemann reaction from Scheme 2. The economically viable synthesis of vanillin (3) from eugenol (6)
guaiacol (2.3) ex beechwood tar.[30] as carried out in the Haarmann & Reimer vanillin factory depicted.[38,39]
Review
Scheme 3. Synthesis of 2-decenal (20) in analogy to 2-hexenal using vinyl

ethyl ether (18).
able 2-dodecenal (20) could be synthesized in analogy to 2-

hexenal by reacting natural decanal with vinyl ethyl ether (18)
in presence of a Lewis acid e. g. BF3 and subsequent hydrolysis
with diluted sulfuric acid.[56] Compound 20 is sold under the
trademark ‘Mandarin Aldehyde’ by Symrise[57] and ‘Aldehyde
Mandarin’ by Firmenich[58] both > 50 % renewable. The enal 20
occurs in nature in trace amounts in citrus fruits and is used to
create an aldehydic, mandarin-orange note in fragrances and
flavors alike (Scheme 3).[59]
Figure 3. The five essential oils mainly used in perfumery and their constitution
of main ingredients and the essential trace compounds (+)-valencene (14) and
(+)-nootkatone (15). * High content in bitter orange oil.
3.2. Artificial Essential Oils
Since citrus oils are produced by expression of the citrus peels

which have higher content in essential oils than flowers (0.5 %
variations, such as pomelo, yuzu and hassaku, are mostly vs. < 0.05 % yield for rose oil), they are generally far less
fantasy accords that with rare exceptions do not contain the expensive than the other essential oils, but still remain a
respective essential oils. Citrus oils provide refreshing and specialty offer with globally limited quantities. However, the big
effervescent top notes to all fragrance families and convey exception is the sweet orange oil from the peel of Citrus ×
cleanness and freshness as well as a sunny and optimistic sinensis (L.) Osbeck, a by-product from the orange juice
feeling – and they are all biodegradable. Looking closer into the industry, and limonene (8) thereof (vide infra). As it is difficult to
aforementioned five most used essential citrus oils, it becomes assess real production figures from the Brazilian orange market,
clear that their distinctive odor profiles result from shared as the largest producer globally, having a closer look at the
fingerprints of multiple components, varying in proportion. In annual volumes of oranges produced provides a sound
general, a clustering can be done into orange and lemon type estimate of the quantities produced. With 309’34 million boxes
oils, differing in their content of β-pinene (10), γ–terpinene of oranges of 40.8 kg each in the prime area in Brazil in 2023[60]
(11)[40] and citral (13). Lemon and lime oils show with up to and assumed 83 million tons of globally produced oranges[61]
14 % of β-pinene (10),[41] up to 22 % of terpinolene (26) and > 100’000 tons of orange oil and limonene (8) would be
3–13 % of citral (13)[42,43] a significantly higher content compared available. Decreasing crop yield due to weather and citrus
to sweet orange oil and grapefruit oil, where (R)-limonene (8)[44] greening disease (Huanglongbing HLB)[62] led to fluctuation in
remains the main constituent (Figure 3).[45] volumes and prices alike. Several attempts were undertaken to
Interestingly, a citrus oil’s character and value to perfumery transform α- or β-pinene from crude sulfate turpentine (CST)
is decided by the quality of the essential oil, represented by its into limonene (8/24) or mixtures comparable to citrus oils in an
profile of trace component. In detail this does not necessarily effort to cover the demand for sustainable solvents, biopolymer
mean trace impurities but odor relevant minor compounds like building blocks and starting materials for fine, flavor and
camphene (16)[46] α/β-sinensal (46 and 34), (+)-valencene (14)[47] fragrance chemistry. In addition, several attempts were under-
and (+)-nootkatone (15).[48,49] The latter can e derived by taken to produce limonene via biotechnological processes.[63]
oxidation or biotransformation[50] from natural (+)-valencene This closes the loop to valorize CST not only for terpenes and
(14) and represents with up to 1.8 % one key component in derivatives such as myrcene (23)[64] but also for limonene-based
grapefruit oil with use in perfumery and food and beverages chemicals (vide infra, section 5.2).
alike.[51] “Neroli Portofino” (Tom Ford, 2007) by Rodrigo Flores- Starting before 1942, Kirkpatrick[65] elaborated the isomer-
Roux uses > 10 % of lemon oil to create a reminiscence of a ization of α-pinene (9) using alkaline catalysts yielding up to
modern type cologne. Secondary quality attributes of citric 40 % of dipentene [mixture of (R)- (8) and (S)-limonene (24)]
essential oils are the content of fatty alcohols like octanal (12), with camphene (16) and ocimene as main side products
nonanal, decanal (17) and dodecanal, representing a pungent (Scheme 4). Aromatization of the terpinene fraction leads to p-
to fatty odor when used in high concentration which changes cymene (29) which is also utilized in perfumery for its citrusy
into a more citric[52] to orange peel odor when used in and piney odor. Derived from CST, cymene (29) is one of the
dilution.[53,54,55] Taking these aldehydes as inspiration, biodegrad- few aromatics which are renewable and readily
Review
Scheme 5. Synthetic approaches to β-sinensal (34) from myrcene (23)

responsible for the characteristic odor of freshly peeled oranges.
Scheme 4. Synthetic approaches to myrcene (23) from crude sulfate
turpentine (CST), and CST valorization towards artificial essential oil with
limonene (8) as focus.
condensation with the Schiff base 31, and subsequent treat-
ment with oxalic acid resulted in the key intermediate 32. This
biodegradable.[66] Recent improvements utilizing zeolites or aldehyde 32 can be transformed into β-sinensal (34) using an
immobilized acids increased yields and selectivity mainly LDA-mediated condensation with the Schiff base 33. A stereo-
towards limonene.[67] A review of the recent works was selective approach via the π-allyl nickel(II) complex 41 was
compiled by Golets et al.[68] A more sustainable approach was developed by Sato et al.[72] The nickel complex 41 was derived
undertaken by Kawahara et al.[69] and Anikeev[70] using a from the renewable bromide 30 and then reacted with acetal
catalyst-free isomerization of α- (9) and β-pinene (10) to 42 in DMF, resulting in the all-trans-configured β-sinensal (34)
limonene (8/24) in high yields and selectivity using supercritical with high selectivity after acidic deprotection of the acetal
solvents like water and ethanol beneficiating from the group. Bertele et al.[73] uses also myrcene (23) as starting
enhanced acidity under these conditions. This provides an material but subjects it to an ozonolysis with reductive workup
alternative for the use of limonene (8/24) in polymer and with dimethyl sulfate to provide aldehyde 35. Then, two
solvent applications, while the use in fragrances is limited due subsequent Wittig reactions with phosphonium salt 36 and
to the lack of valuable trace components in essential oils such triphenyl phosphorous ylide 37 follow to furnish β-sinensal (34).
as β-sinensal (34, vide infra). However, this time β-sinensal (34) is obtained with < 50 %
renewable carbon content due to cleavage of three renewable
carbon atoms during ozonolysis. Wada et al.[74] describes in their
3.3. Sinensal – the Orange Principle of Citrus×Sinensis publication an industrial approach towards β-sinensal (34)
starting from the epoxidation of myrcene to oxirane 38,
One of most characteristic sesquiterpenes from Citrus × sinensis followed by LDA-mediated ring opening and treatment with
(L.) Osbeck and other citrus oils like mandarin oil from Citrus triethyl ortho acetate affording the ester 40. Reduction with
reticulata are the two isomers of sinensal. Essential for the DIBAH provided aldehyde 32, the key intermediate towards β-
typical juicy smell of sweet oranges when freshly peeled is α- sinensal (34).
sinensal (46), with its pure sweet orange scent, and β-sinensal The synthesis of α-sinensal (46) could also commence from
(34), with its fresher orange to metallic character. The latter can the renewable aldehyde 32 derived from myrcene (23,
even develop an unpleasant fishy side note when used in high Scheme 6). Wittig reaction with phosphorane 43 resulted in the
concentrations. The sesquiterpene aldehyde 34 is often simply ester 44 which undergoes isomerization if treated with RhCl3
isolated from orange oil but can also be synthesized from forming a Δ9-cis-trans tetraene ester. Subsequent reaction with
renewable myrcene (23) as a starting material (Scheme 5). Büchi iron pentacarbonyl leads to the Δ9-trans tetraene ester 45 that
et al.[71] describes a selective oxygenation of the isopropylidene can be converted to all-trans α-sinensal (46) in good yields.
moiety followed by oxygen–bromide exchange towards the
allyl bromide 30. Lithium diisopropyl amide (LDA) mediated
Review
Scheme 6. Synthetic approach to renewable α-sinensal (46) from myrcene

(23) via RhCl3-mediated isomerization of aldehyde 32.
4. Green Notes
Scheme 8. Synthesis of methyl octyne carbonate (58), responsible for the
characteristic top note of “Fahrenheit” (Dior, 1988), and the synthetic road to
4.1. Green Floral and Galbanum
the structurally related NeoFolione (55).
Green perfumes portray the scent of dewy leaves and fresh cut
grass. These green impressions rank from warm vegetal to fresh
herbal notes, and from galbanum to green-apple notes. Green that the designation ‘renewable’ is likely due to the respective
aspects appear in many other olfactory families, but the solvent.
archetypical “Vent Vert” (Balmain, 1947) composed around The green, violet-leave note overdosed in the top note of
galbanum oil (ca. 0.7 %) by Germaine Cellier, reinterpreted in a the legendary “Fahrenheit” (Dior, 1988) by Jean-Louis Sieuzac,
more floral muguet way by Calice Becker (Balmain, 1990), Maurice Roger and Michel Almairac, is brought about by a
established a discrete family. The odorous principle of galba- heavy dose of methyl octyne carbonate (58). Chemically not a
num is the inherently biodegradable 1,3,5-undecatriene (50, carbonate but an alkynylated ester, methyl 2-nonynoate (58) is
Scheme 7).[75] One sustainable access to 50 starts with the accessible from heptanal (53) starting with an alkynylation as
oxidative cleavage of linoleic acid (47) and Wittig reaction of by Corey–Fuchs reaction as delineated in Scheme 8.[83] Oct-1-
the resulting hexanal (48)[76] with the phosphorus ylide 51, yne (56) can be treated with methyl chloroformate 57 or else
available from divinyl carbinol.[77] This leads to a 50 quality with with CO2 and methanol to introduce the conjugated ester
54 % carbon atoms from a renewable source. But there is one moiety. As a good Michael acceptor, methyl octyne carbonate
approach providing 1,3,5-undecatriene (50) from 100 % renew- (58) is also a strong sensitizer, and thus restricted in use by IFRA
able sources, which is the triene synthesis from sorbic acid (52) guidelines.[84] The structurally related NeoFolione (55) has a
and hexanal (48) reported by Fehr,[78] and delineated as well in similar green, fresh scent, and is less sensitizing. An industrially
Scheme 7. viable pathway is the condensation of heptanal (53) with
Interestingly, compound 50 sold under the name malonic acid and subsequent decarboxylation followed by
Galbanolene[79] by Firmenich is declared as > 50 % renewable, methylation. A more academic approach is the Horner–Wads-
whereas the Undecatriene of Givaudan[80] is declared as < 50 % worth–Emmons reaction of heptanal (53) with the
renewable. Undecatriene 10 %/TEC[81] is > 50 % renewable and phosphonium ylide of methyl ethanoate (54). So, this typical
Undecatriene Super[82] is again < 50 % renewable, indicating green violet-leaf note is in principle sustainably accessible from
castor oil,[85,86] though this has not yet been implemented
technically.
4.2. Lack of Green Chemistry for Green Leafy Odorants
In the domain of leaf alcohols there is, paradoxically, a serious

deficit in green chemistry (cf. Glossary). Many important green-
leafy odorants are not renewable, and some of them are not
even biodegradable. Most prominent example is α-Dynascone
(59), a key green, galbanum-smelling compound with a distinct
pineapple accent which is used in some deodorant applications
at levels > 5 %. Its industrial synthesis starts from dimedone
(60), itself prepared from petrochemical mesityl oxide (61) and
Scheme 7. Two different sustainable synthetic approaches to 1,3,5-undeca- diethyl malonate, which makes Dynascone (59) non-
triene (50), the smelling principle of galbanum gum resin. renewable.[87]
Review
Another important grassy-green, herbal odorant is Vertoci-

tral (62, Scheme 9),[88,89,90] which is synthesized by Diels–Alder
reaction of 2-methyl-1,3-pentadiene with acrolein (67), thus of
purely petrochemical origin. The similarly smelling Vernal-
dehyde (65)[91] is generally considered non-renewable, but if it is
synthesized by Diels–Alder reaction of methacrolein (63) and
myrcene (23), a renewable quality could be implemented in
short term.
Undecavertol (69) is a synthetic green-floral odorant, the
synthesis of which commenced from the propanal dimer 71.
Academic approaches for the dehydration of glycerol (66) to
acrolein (67) have been reported.[92,93,94] The corresponding
hydrogenation product propanal (68) is therefore in principle
accessible, but prohibitively expensive. Reaction of the propanal
dimer 71 with the pentyl Grignard reagent 70 provides
Undecavertol (69).[95] As this was tailored for industrial applic-
ability, it is a difficult target for substitution, making new
Undecavertol-type odorants from renewable building blocks
imperative.
cis-3-Hexenol (81), the so-called “leaf alcohol” is respon-
sible for the typical green odor of fresh-cut grass. It can be
isolated by extraction from plants using biotechnological
processes. Alternatively, Scheme 10 summarizes a variety of
approaches to its chemical synthesis, both academical and
Scheme 10. Synthetic pathways to cis-3-hexenol (leaf alcohol, 81), from
industrial. Butadiene (72) is usually isolated from naphtha, petrochemical and renewable sources, including biotechnological ap-
and its mono-reduction provides but-1-ene (75) as a key proaches.
building block.[96] It can also be synthesized from γ-valerolac-
tone (73),[97,98,99,100,101,102] available from levulinic acid. An
addition–elimination sequence on butene 75 affords but-1- pletes an applicable albeit lengthy synthesis of leaf alcohol
yne (78).[103] Reaction of the alkyne 78 with oxirane, followed (81). A shorter, and potentially renewable approach is the
by (Z)-selective Lindlar reduction of the triple bond com- Prins reaction of pent-1-ene (76) with formaldehyde (119) in
the presence of a Lewis acid.[104,105] The hetero-Diels–Alder
reaction of 1,3-pentadiene (74) and formaldehyde (119) leads
to dihydropyrane 77, which can be reduced to cis-3-hexenol
(81).[106] Sorbic acid (52) can also be reduced to “leaf alcohol”
(81) via the corresponding alcohol 82,[107,108] as well as hex-3-
enal (84), which is available by enzymatic degradation of
linolenic acid (83, Scheme 10).
Nonadienol (85, Scheme 10) is the character impact
component of cucumbers (Cucumis sativus L.) and melons
(Cucumis melo L.), and is accessible from cis-3-hexenol (81)
via its halide and the corresponding Grignard reagent.
Addition to acrolein (67) followed by allylic rearrangement
furnishes the green-watery, aromatic odorant 85. Despite
these potentially renewable roads to green odorants partic-
ularly in this fragrance family, there is much need for new
renewable alternatives to the already established petrochem-
ical perfumery materials.
5. Fruity Notes
5.1. Pears for Paradise
Contrary to flavors, where we find the whole spectrum of fruits,

Scheme 9. Synthesis of Vernaldehyde (65) from renewable myrcene (23), perfumery is dominated by two main fruity notes, especially
and a potentially renewable access to Undecavertol (69). when they determine the overall character of a scent. On one
Review
hand, opaque lactonic notes in between peach and dried fruits to provide “pear ester” (93) albeit with a lot of phosphine oxide
that gained prominence with “Mitsouko” (Guerlain, 1919), waste.[119] The aldol condensation of hexanal (48) with malonic
“Femme” (Rochas, 1944) and “Poison” (Dior, 1985), on the other acid followed by decarboxylation leads to the unsaturated
hand fresh and juicy, non-sticky and transparent fruity notes carboxylic acid 100, that can be treated with bromine to furnish
that enhance the beauty and naturalness of floral hearts. The vinyl bromide 101 (X = Br) by an addition/elimination
latter comprise of melon, apple and most prominently pear. sequence.[120] The latter affords “pear ester” (93) either by
The archetypical pear odorant is (2E,4Z)-ethyl deca-2,4-dienoate addition of its Gilman cuprate to alkyne 97,[121,122] or by Heck
(93) that naturally occurs in apples, Bartlett pears and quince. coupling with ethyl acrylate (99).[120] Alternatively, vinyl iodide
Biochemically it is linked to linoleic acid and it's oxidative 101 (X = I!Li) can be used in a Bénary rearrangement with the
degradation product hexanal (48) with its typical green smell of amine 98 to access ethyl decadienoate (93).[123] As summarized
fresh-cut grass. in Scheme 11, there are several synthetic routes from sustain-
The most important synthetic routes to the smelling able starting materials to the pear odorant 93, although neither
principle of pear, the so-called “pear ester” (93), are delineated is environmentally friendly, nor industrially or economically
in Scheme 11: n-Pentyl bromide (86), renewably available from attractive.
pentanol biofuel in academic scale[109] can be alkynylated with Renewable pear odorants that are obtained within short
87 to provide the unsaturated aldehyde 88 after reaction sequences in an environmentally friendly fashion are
deprotection.[110] The “pear ester” (93) is then obtained by compiled in Scheme 12. Neryl acetate (102) is a fruity pear
Horner–Wadsworth–Emmons reaction with the phosphonate 89 odorant with rosy facets from the terpene family. The floral
and (Z)-selective Lindlar reduction of the resulting product odorant citronellol (103) can easily be converted into its
90.[110] Hexanal (48), available sustainably from linoleic formate 105, which evokes the scent of pears, rose and
acid[111,112,113] (cf. Scheme 7) is the starting material for several geranium. While these are common odorants, there is also one
alternative routes to 93. Addition of lithium acetylide to hexanal new captive pear odorant: Pearadise (108), which is derived
(48) affords alkynol 91.[114,115] Reaction with triethyl orthoacetate from itaconic acid (106), one of the oldest industrial fermenta-
provides allene 92 via Claisen rearrangement.[115,116] The allene tion products.[124] Itaconic acid (106) has been produced since
92 can also be obtained employing the copper enolate of ethyl the 1960s by fermentation of carbohydrates such as glucose or
acetate[117] and further rearrangement upon treatment with molasses with the fungi Aspergillus itaconicus Kinoshita or
Al2O3 providing ethyl decadienoate (93) in an industrial Aspergillus terreus Thom. Esterification of 106 with bioethanol to
applicable process.[118] By reduction and nucleophilic substitu- 107, followed by isomerization of the conjugated double bond
tion with hydrogen bromide, hexanal (48) can be transformed completes the industrial synthesis to the sustainable odorant
into hexyl bromide (94). Its corresponding phosphonium ylide Pearadise (108) that seduces with a lovely pear impression, but
95 serves as substrate for the Wittig reaction with aldehyde 96 works as well in other fruity accords.[124] It was for instance used
at 1.05 % by Alexandra Carlin in the juicy and natural blue-
berry–macarons central accord of the fruity-floral “Show Me
Love” (Escada, 2022).
Scheme 12. The renewable pear odorants neryl acetate (102), citronellyl
Scheme 11. Synthetic routes to ethyl (2E,4Z)-deca-2,4-dienoate (“pear ester”, formate (105) and Pearadise (108), the latter featured in ‘Show Me Love’
93), the principal odorant of pears. (Escada, 2022) by Alexandra Carlin.
Review
5.2. A Milky Way of Peach, Berries, and Dried Fruits sweaty facets. On the contrary, since the CST process leads to
sulfur-containing contaminations, the critical issue is to elimi-
Dark fruity perfumes feature notes of peach, plum, apricot, nate such trace impurities from the stream prior to utilization
raspberry, and strawberry. The peach–apricot note is well and further derivatization of this renewable feedstock.
represented by the sustainable odorants Aprifloren[125] (111, cf. While pear and peach odorants are already accessible from
Scheme 27) and Nectaryl (110, Scheme 13). The latter is a 67 % renewable starting materials, there is a lack of sustainable
renewable, readily biodegradable synthetic odorant recalling materials in the family of dried fruits, plums, and raisins, notes
the smell of nectarines and results from the radical addition of that are conveyed by damascones (Scheme 14, “rose ketones”).
cyclopentanone to (+)-limonene (8).[126] Nectaryl (110) is widely As structural isomers to ionones, they are accessible from these
used in all different kinds of applications including fabric care by carbonyl transposition. General access to both families
and household products.[127,128,129,130] Esterly (112) is a cyclohexyl commences with the cyclization of citral (13)[133] which can be
ethyl carboxylate, that combines the scent of ripe fruits with
connotations of apple and strawberry. Given that it is synthe-
sized by reduction from ethyl benzoate, it would be 100 %
renewable provided that a natural quality of benzoic acid is
used as a substrate. This is possible in principle since benzoic
acid can be obtained by degradation of lignin (193). An already
sustainable fruity-waxy odorant with a red-berry aspect is
provided by ethyl laureate (113), combining the berry with a
strong pineapple note. Ethyl laureate (113) is available by
esterification of lauric acid, isolated from coconut oil, with
bioethanol. Regarding examples of grapefruit odorants, Tropicol
(114) is a 100 % renewable β-mercapto alcohol.[131] It is available
from 2-methylpent-2-enol (115), the alcohol of the propanal
dimer 71 (cf. Scheme 9). Although sulfur-containing odorants
are used in tiny amounts only due to their extreme strength,
and since therefore they play a marginal role for the
sustainability score, their Green Chemistry has recently been
reviewed in detail.[132] Tropicol (114), for instance, is sold as a
0.1 % solution only. Other renewable terpene derivatives such
as thiogeraniol (116) and thiocineole (117) are also difficult to
dose and balance as they possess unpleasant onion-type and
Scheme 14. Dried fruit-like smelling rose ketones 126, 128, 129 and 132 as
important, albeit non-sustainable odorants. Their Michael-acceptor structural
motif (marked in yellow) makes rose ketones prone to react with skin
proteins causing dermal sensitization, therefore, they are use restricted by
Scheme 13. Sustainable peach and ripe fruit odorants. IFRA regulations.
Review
isolated from lemongrass oil (ca. 85 % of 13) or the essential oil allyl magnesium bromide (125) and subsequent oxidation
of litsea cubeba (Lour.) Pers. (ca. 75 % of 13). It is also accessible provides α-damascone (126), γ-damascone (136) and β-dam-
renewably by vapor-phase dehydrogenation of geraniol (140) ascone (128). The latter can alternatively be attained in a 3-step
that is available from myrcene (23), which in turn is produced transformation via its cyclocitral (127), that is accessible
from β-pinene (10, vide supra). However, these processes selectively by acid-catalyzed epoxide opening of 137.[138]
cannot compete with the petrochemical citral (13) processes, Although already performed on a 2000 kg scale, the pyronene
optimized for the synthesis of vitamin A. The BASF citral process (134 / 135) synthesis by treatment of myrcene hydrochloride
starts from the Prins reaction of isobutene (118) and with Me3N gas is not competitive with the route from natural
formaldehyde (119). The central isoprenol (120) intermediate is citral (13).[136] All commercial rose ketones feature enone
split up and one part is oxidized to isoprenal (121), the other moieties prone to Michael additions. Due to their dermal
isomerized to prenol (122). Claisen and Cope rearrangement sensitization potential, they are restricted in use by IFRA
then furnish citral (13)[134] which can be cyclized to the regulations. These properties with their non-renewability out-
respective α- (124) or β-cyclocitral (127) as detailed in line a challenging task for the fragrance chemist to keep the
Scheme 14. Finally, Grignard reaction with allyl magnesium future smelling rosy damascone.
bromide (125) and subsequent oxidation with isomerization of
the double bond into conjugation leads to the rose ketones
126 and 128. The synthetic efficiency of the petrochemical citral 6. Floral Notes
(13) processes is the reason why α-damascone (126) and
β-damascone (128) are usually non-renewable. The biodegrad- 6.1. Gunning for Roses
ability is influenced by the position of the double bond
(Scheme 14 marked in green). Only δ-damascone (132) is not Floral notes form the largest creative pool in perfumery, and
degradable at all, whereas the other rose ketones show accordingly the largest family in feminine fragrances, since
inherent biodegradability. β-Damascone (128) can be converted flowers conjure up femineity in the European, American and
upon allylic bromination and elimination to β-damascenone most non-Arabic cultures. Referring to a perfume as ‘floral’ does
(129), featured in “Black Opium” (Yves Saint Laurent, 2014) by not call to the scent of a specific flower, but the prevalence of
Nathalie Lorson, Marie Salamagne, Olivier Cresp and Honorine floral notes in general. Some flowers are, however, more
Blanc, as well as in “Olympéa” (Paco Rabanne, 2015) by Loc dominant than others, namely roses, lily of the valley and white
Dong, Anne Flipo and Dominique Ropion. δ-Damascone (132) is flowers (jasmine, gardenia, tuberose, and ylang-ylang). Floral
the cheapest of the damascones, being synthesized via Diels– notes are ubiquitous, as they contribute to the heart of almost
Alder reaction of piperylene (130) and mesityl oxide (61), every perfume. Even so, rose is the most prominent one and is
followed by isomerization to the cis-isomer and aldol condensa- used in high volumes in perfumes marketed as feminine.
tion with acetaldehyde, thus being non-renewable. Only the The CST process converts waste from the paper industry
(1’S,2’S)-diastereomer of 132 is responsible for the characteristic amongst other to pinene, which can be converted by pyrolysis
smell. into a variety of sesquiterpenes, amongst these some rose
An academic approach to sustainable damascones is the odorants (Scheme 16). Linalool (139) is transformed by allylic
conversion of myrcene (23, ex CST) to δ-pyronene (134) and rearrangement to geraniol (140) with pronounced green facets
γ-pyronene (135) as starting materials (Scheme 15).[135,136,137] of a rose, and to its (Z)-isomer nerol (141), smelling rosy with a
Treatment of the respective mono-epoxides 137 and 138 with sweet-citrusy connotation.[139,140,141,142] The 1 : 1 isomeric mixture
of 140 and 141 is reduced to citronellol (103) by allylic
hydrogenation. Citronellol (103) is characterized by a petally
rose scent, that can be described as the smell of the stems and
leaves of a rose. By a photooxygenation, known as Schenk–
Klein–Ohloff reaction, citronellol (103) is converted to l-rose
oxide (143) via its hydroperoxide 142, that cyclizes under
reductive conditions.[143] The rosy-metallic scent of 143 is
featured in “Zero” (Comme des Garçons, 2023) by Fanny Bal.
Geranodyle (145) is synthesized from citronellal (144) by acid
catalyzed cyclization.[144] It bears a second hydroxy group in
surprisingly close proximity and, as the name indicates, smells
like geranium flowers with a rosy undercurrent.
2-Phenylethyl alcohol (151), which is readily biodegradable,
possesses the most classical rosy scent with honey nuances
(Scheme 17). It can be purchased in a natural quality for about
14 times the price of the petrochemical quality. It can be
synthesized either by starting from petrochemical styrene (147),
Scheme 15. Academic approach to renewable α-, β- and γ-damascones (126, or from natural styrene (147), and is accessible by decarbon-
128 and 136) starting from myrcene (23) via pyronenes 134 and 135. ylation of cinnamaldehyde (146).[145] Styrene (147) is epoxidized
Review
6.2. Matching Muguet in a Natural Way
The 100/100 sustainable and biodegradable lily-of-the-valley (fr.

’muguet’) note of dihydrofarnesal (154), was marketed as
’Biomuguet’ and can be detected in the headspace of lily-of-
the-valley flowers (Convallaria majalis L.). It is produced by
Takasago by rhodium-catalyzed isomerization and oxidation of
β-farnesene (152, Scheme 18).[149] Myrcene (23) can be used,
according to the Takasago menthol process, in analogy to the
dihydrofarnesal (154) synthesis to give access to hydroxycitro-
nellal (156), which is a muguet odorant with a fresh green-
aldehydic vibe. The aldehyde 156, that is not occurring in
nature, is also accessible from citronellal (144), e. g. by zeolite-
supported dehydrogenation using metal oxide catalysts.[150]
Another means to use sustainable myrcene (23) is in the Diels–
Alder reaction with acrolein (67) to obtain the muguet odorant
Melafleur (155, isomeric mixture), in comparison to the syn-
thesis of Iso E Super (264/5) in Scheme 34.[151]
Besides myrcene (23) ex pinene (c.f. Scheme 4), (+)-limo-
nene (8) is a renewable building block that stems from the
waste of orange zests. For the synthesis of muguet odorants, 8
is hydroformylated at its exoskeletal double bond and the
aldehyde obtained is then reduced to cyclomethylene citronel-
lol (157), incorporating a petal rose connotation beside its
muguet note.[152]
Lyral (159), one of the most prominent muguet aldehydes
used in a plethora of perfumes, soaps, and cosmetics for its
Scheme 16. Rosy notes obtained from renewable sources. Terpenes from the
CST process (140, 141 and 145) including follow-up photooxygenation long-lasting creamy character, can also be produced from
chemistry to rose oxide (143). renewable myrcene (23) via Diels–Alder reaction with acrolein
(67, Scheme 19).[153,154] But since it was tested to be a strong
skin sensitizer, it was banned from the European market in
2019.[155] Thus, a replacer for this universal muguet odorant was
Scheme 17. Synthetic routes towards the classic rosy-honey odorant, phenyl-
ethylalcohol (151).
to styrene oxide, (148) affording 2-phenylethyl alcohol (151)

when hydrogenated.[146,147] Another renewable route is by
reduction of methyl phenylacetate (150), from esterification of
phenylacetic acid (149).[148]
Scheme 18. The sustainable muguet notes of dihydrofarnesal (154), Mela-

fleur (155), hydroxycitronellal (156) and cyclomethylene citronellol (157).
Review
Scheme 19. Synthetic pathways to Lyral (159), a sustainable but highly skin
sensitizing material that was banned by IFRA, as well as synthetic route to
Mahonial (163), a petrochemical Lyral replacer with similar structural
features.
in high demand. Mahonial (163) meets all olfactory needs, as

demonstrated in “Missoni” (Missoni, 2015) by Quentin Bisch,
Scheme 20. Banned muguet block buster Lilial (165) as well as three other
which in addition has a low threshold of 0.025 ng/L air. Though members of the family: Bourgeonal (166), Silvial (167) and Cyclamenalde-
being readily biodegradable, Mahonial (163) is however hyde (168). For Nympheal (170) the retrosynthesis from petrochemical
obtained from petrochemically sourced 6-methylheptan-2-one methoxy toluene (172) is shown in comparison to a potentially renewable
access via Hagemann ester 169. On the bottom, the renewable and
(160) with a Claisen rearrangement from the vinyl ether of 164 biodegradable muguet odorant Lilybelle (177) is shown as featured in
as key step.[156] As delineated in Scheme 19, Mahonial (163) is a “Bloomastral” (J. U. S. Parfums, 2021).
seco-structure of Lyral (159) and as such, it remains an open
question if it might be as sensitizing as Lyral (159).
Lilial (165) can be synthesized either by starting from 4-tert-
butylbenzaldehyde via aldol condensation with propional[157] or two 100/100 sustainable and biodegradable muguet odorants
via electrochemical oxidation through the BASF[158] route from remain Biomuguet (154) and Lilybelle (177). The latter was
4-tert-butyl toluene, no matter how making 165 non-renewable, featured in the white-floral jasmine-osmanthus perfume
the same holds true for Bourgeonal (166, Scheme 20). Although “Bloomastral” (J. U. S. Parfums, 2021) by Alexandra Carlin. The
they do biodegrade, what might be an advantage in nature synthesis of Lilybelle (177) starts from renewable (+)-limonene
leads to a toxification in the liver with 4-tert-butylcarboxylic (8) that is upcycled from the waste of orange zests.[166] The side
acid as sperm toxic metabolite. Accordingly, these muguet chain is reduced and the endocyclic double bond is epoxidized
aromatic aldehydes were classified CMR substances, with Lilial to 173. Upon alkaline treatment, menthenol (174) is formed,
(165) in addition being suspected as an endocrine disruptor, which then reacts with butyl vinyl ether to the mixed acetal
and therefore banned from the EU market in March 2022.[159] To 175. Heating under acidic conditions initiates the elimination to
make matters worse, Lilial (165), Bourgeonal (166), their vinyl ether 176, that smoothly undergoes a Claisen rearrange-
p-isobutyl constitutional isomer Silvial (167) and their p- ment to Lilybelle (177).[166]
isopropyl isomer Cyclamenaldehyde (168) are skin sensitizers. Apart from the beforementioned aldehydic muguet odor-
However, the spermotoxicity of these muguet aldehydes could ants, there is the class of muguet alcohols, to which Mayol (180)
be blocked by the additional “magic methyl” group in is a freshly smelling, soft muguet example (Scheme 21).[167,168] It
Nympheal (170, marked in green, Scheme 20).[160] This methyl can be obtained sustainably from β-pinene (10) starting with an
group prevents the degradation to its carboxylic acid derivative, epoxidation to pinene epoxide (178). Upon acid treatment the
and thus the toxification. The retrosynthetic route leads back to four-membered ring is cleaved to give the isopropenyl group of
the acylated phenol 171, which is accessible from petrochem- perillyl acetate (179).[169] Its alcohol can be reduced cis-
ical 2-methoxy toluene (172).[161,162,163,164] A potentially renewable selectively or to the diastereomeric mixture depending on
synthesis route could be from the Hagemann's ester 169 by catalyst system for hydrogenation.
decarboxylation, α-alkylation and aromatization.[165] The only
Review
dosage. Looking at the side chain, Projasmon P (185) is

accessible from hexanal (48) available renewably from linoleic
acid (47, cf. Scheme 7). With 54 % of carbon atoms renewable, it
fulfills the criteria for a sustainable jasmine odorant, but is not
very performing. Myraldyl acetate (186), synthesized by Diels–
Alder reaction of myrcene (23) with acrolein (67), and
subsequent reduction and acetylation, is 66 % renewable and
possesses a jasmine, green, fruity smell. In summary, for the
Scheme 21. Synthesis of the muguet alcohol Mayol (180) starting from β- floral perfumes, besides Biomuguet (154) and Lilybelle (177)
pinene (10).
there is without doubt a big need for more non-toxic muguet
odorants and, most importantly, for a renewable version of
Hedione (184).
6.3. Booster and White Florals
Renewable (+)-limonene (8), an upcycled waste product from 7. Floriental Perfumes

orange peels, does not only serve as starting material for the
muguet Lilybelle (177), but also for the floral booster 7.1. Modern Vanillin from Waste Wood
Spicatanate (183, Scheme 22).[170] Limonene monoepoxide 181
is reduced to ( )-carvone (182). Partial reduction and acetyla- Florientals, now also referred to as florambers (cf. 8.1, vide
tion give access to a mixture of dihydrocarvyl acetate and carvyl supra), emerged from the floral family by overemphasis of
acetate, named Spicatanate (183) which has a floral odor but is the creamy-sweet vanilla foundation, which explains why,
also reminiscent of spearmint (Mentha spicata L.). It was when no separate gourmand family is specified, gourmand
featured in “Crazy Me” (Paco Rabanne, 2019) by Aliénore fragrances such as “Angel” (Thierry Mugler, 1992) and “Black
Massenet in a wasabi–mimosa creation. Opium” (Yves Saint Laurent, 2014) are also classified as
The most prominent material for white florals and booster (fl)orientals. In addition to an opulent floralcy, the character-
materials is the ubiquitous Hedione (184, Scheme 22). No istic vanillic sweetness of florientals is contrasted by spicy
matter if racemic or in HC (’high cis’) quality, the C5-side chain is accents such as carnation in “L’Origan” (Coty, 1905) with
obtained from pentanal, for which there is no renewable source isoeugenol (187), itself an oxidative precursor of vanillin (3,
so far. As cyclopentenone is not available renewably either, one vide infra), or hawthorn with p-anisaldehyde (188) as
major task in this olfactory family is to find the renewable epitomized in “Après L’Ondée” (Guerlain, 1906). Together
“Hedione of tomorrow” that can replace this much needed with François Coty’s masterpiece “L’Origan”, the latter
odorant, present in almost every application in up to 60 % heralded a floriental era that recently culminated in “La Vie
Est Belle” (Lancôme, 2012), “Joy” (Dior, 2018), and the salted
vanilla–hazelnut accord in “Olympéa” (Paco Rabanne, 2015),
with its overdose of 0.01 % of the high-impact Filbertone
(189), 1 % of Sandranol (200) and 1 % of natural vanilla bean
extract.
With a worldwide annual consumption of over 12’000
tons[171] it is completely impossible to satisfy the demand of
vanillin (3) for the perfumery industry from natural vanilla
beans – despite a Sustainable Vanilla Initiative (SVI) in place
for the flavor industry. In fact, only 0.2 % of the production
volume of 3 is extracted from vanilla beans.[171] Several
biotechnological production processes have been patented
and are employed, the most important being the Rhodia
process from ferulic acid (190),[172,173] but even these could
never satisfy the demand of vanillin (3) for the perfumery
industry. It was recently found that the spontaneous
oxidative cleave of isoeugenol (187) to vanillin (3), which is
the reason for the vanillic odor profile of the latter, can be
catalyzed by enzymes.[174] Guo et al.[175] recently summarized.
However, most of the vanillin (3) today is already produced in
an economically and ecologically sustainable way. As de-
picted in Scheme 23, the starting material is lignin (191), an
Scheme 22. Spicatanate (183) in “Crazy Me” (Paco Rabanne, 2019) by undesired waste material of the paper and pulp industry that
Aliénore Massenet, and a comparison in sustainability of white floral accounts for up to 35 % mass of lignocellulose and is
odorants Hedione (184), Projasmon P (185) and Myraldyl acetate (186). removed as it yellows and stiffens the paper. Thus, in the
Review
lactonic elements are essential, and sandalwood odorants are

the key component. The smelling principle of sandalwood
( )-(Z)-β-santalol (194) mimics 5α-androst-16-en-3α-ol which is
responsible, to a great extent, for the smell of milk.[177] Co-
expressing the genes for a farnesyl pyrophosphate synthase, a
santalene synthase, and a cytochrome P450 oxidase as well as
reductase in baker‘s yeast (Saccharomyces cerevisiae)[178] and
Escherichia coli cells[179] made 194 biotechnologically accessible
in the captive Dreamwood[180] together with other santalols as
well as bergamotols. Dreamwood is thus 100 % renewable, but
it is not readily biodegradable, and with an odor threshold of
0.5 ng/L air, it is not that powerful compared to the synthetic
santal odorants 198 and 201 (Scheme 24), especially in relation
to its cost. Dreamwood has recently been featured in the
floriental fragrances ”Fame” (Paco Rabanne, 2022) by Dora
Baghriche, Marie Salamagne, Alberto Morillas and Fabrice
Pellegrin, similarly in “Soleil Vibrant” (Lalique, 2022) by Nathalie
Lorson and Alexandra Monet, in which both are paired with
jasmine and a heavy dose of vanillin (3).
However, there is a whole family of readily biodegradable,
sustainable and cost efficient sandalwood odorants which
derived from campholenic aldehyde (196) as discovered in
1968 by Manfred Mühlstedt and co-workers at the VEB
Miltitz[181] formerly known as the renowned fragrance com-
pany Schimmel & Co.[182] Campholenic aldehyde (196) is easily
accessible from ( )-(1S,5S)-α-pinene [(1S,5S)-9] by Prilezhaev
epoxidation with peracids and acid-catalyzed isomerization
Scheme 23. Sustainable and renewable production of vanillin (3) from lignin of the resulting epoxide 195 employing Lewis acids such as
(191), the world’s largest resource of renewable aromatics. Vanillin (3) is
formed by letting isoeugenol (187) stand in air, and together with p-anisic zinc bromide (Scheme 24). Aldol condensation of campho-
aldehyde (188) it is used to contrast the vanillic body of florientals. lenic aldehyde (196) with propanal, followed by hydride
reduction with sodium borohydride or catalytic hydrogena-
tion provides the core structure of the series compound 198
known as Sandal Mysore Core, Sandelice or Santalinol which
production of about 220’000’000 tons of paper, roughly has a threshold of 0.1 ng/L air, 76.9 % renewable carbon
50’000’000–60’000’000 tons of accruing technical lignin (191)
are produced per annum, the vast majority of which is still
burnt as fuel.
In the production process of vanillin (3), the lignin waste
material 191 is first depolymerized by treatment with sodium
sulfite to afford sodium lignosulfonate (192). A saponification
with caustic soda then follows to furnish vicinal diol units 193
in the biopolymer that undergoes glycol cleavage on oxidative
treatment. The cleavage is carried out classically using nitro-
benzene or, in a recently reported green modification, with
sodium peroxodicarbonate as an oxidant which can be
produced by electrolysis of aqueous soda.[176] Thus, vanillin (3) is
a model compound for the production of other aromatic
products from lignin (191), and furthermore a sustainable
building block for new perfumery materials in its own right.
Surely, the sustainable future will smell as sweet vanillic as the
historic beginnings (cf. section 2).
7.2. Milky-Creamy Intimacy of Santal Odorants

Scheme 24. Renewable and biodegradable synthetic sandalwood odorants
When it comes to conjuring the creamy intimacy of florientals, from (1S,5S)-α-pinene [(1S,5S)-9] as well as the natural odor vector ( )-(Z)-β-
vanillin (3) is however not enough. Additional milky and santalol (194), which is accessible by a biotechnological process.[180]
Review
atoms and is readily biodegradable. Use of butan-2-one in (202), which is 83 % of pennyroyal oil (Mentha pulegium L.).
the aldol condensation leads to Sandalore (199), utilization of Treatment of 202 with substoichiometric amounts of iodine in
butanal to Sandranol (200) and alkaline deconjugation of the dimethyl sulfoxide (DMSO) provides the iodonium species 203
butan-2-one with strong bases prior to hydride reduction to that immediately collapses to the 2,3-annulated 2-iodo-2,5-
Ebanol (201). For illustration, we find 2.7 % of Ebanol (201) dihydrofuran 204, still violating the Erlenmeyer rule. This is
and 12 % of Sandranol (200) in the archetypal floriental resolved by elimination of hydrogen iodide affording a diene
perfume “Floriental” (Comme des Garçons, 2015) by Emilie system prone to Kornblum oxidation under the respective
Coppermann, whereas in “This Is Love! For Her“ (Zadig & reaction conditions to provide the double unsaturated lactone
Voltaire, 2020) by Sidonie Lancesseur there is 10 % of 205. Dehydration using dibutyl maleinate then affords the high-
Sandranol (200) and 2.6 % of Ebanol (201). In “Black Opium” impact material Tonkalactone (206), which proves its efficiency
(Yves Saint Laurent, 2014) by Nathalie Lorson, Marie Sala- at 0.07 % in “Tonka Blanc” (L’Artisan Parfumeur, 2022) by
magne, Olivier Cresp and Honorine Blanc there are however Alexandra Carlin, contrasted by a natural cauliflower extract and
only 0.7 % of Sandalore (199) and 0.4 % of Sandranol (200). In freshened up with bergamot and tangerine oil. In “Fabulous
any case, Sandal Mysore Core (198), Sandalore (199), Me” (Paco Rabanne, 2019) by Alienor Massenet, 0.08 %
Sandranol (200) and Ebanol (201) are the renewable and Tonkalactone (206) is used au contraire to prevent the sweet,
readily biodegradable mainstays of modern and certainly also thick pumpkin–rhubarb pie accord on sandalwood from falling
future perfumery. over on the sweet side.
There are also materials made directly out of sugars or
sugar waste such as pentosans. Mucilage is made up of
7.3. Tipsy and Sweet: Like Tonka on Tiramisu pentose sugar polymers, which is usually rich in arabinose or
xylose. Acidic hydrolysis of the pentosan xylan (210,
To combine the floralcy in the heart of florientals with the Scheme 26) is one of the oldest processes for the production
creamy-santal base notes, a little mediatory help by lactonic of renewable biomass.[191,192] It has been carried out for over
and balsamic notes is usually welcome. This can for instance be 100 years, since November 1921 to be exact.[193] Today, its
done with Tonkalactone (206)[183,184] or its hydrogenated primary product furfural (215) reaches production volumes of
analogue Koumalactone (207)[185] two high-impact materials 650’000 tons per year,[192,194] which should make 215 the ideal
both related to wine lactone (208),[186,187] and dill ether platform chemical. Due to its low overall yields of around
(209).[188,189] Wine lactone (208) confers to white and red wines a 50 %, furfural (215) is however still rather expensive. The
sweet coconut bouquet with woody facets and supposedly is reason for the inefficiency of the process is that after the fast
the compound that holds the record for the lowest odor hydrolysis of the pentosan 210 to its monomeric pentose
threshold.[190] Tonkalactone (206) and Koumalactone (207) are sugars 211, the dehydration to the pent-2-enal 212 and the
of similar intensity but more lactonic and balsamic in direction further steps to 214 happens slowly. The necessary keto-enol
of tonka beans and coumarin. As delineated in Scheme 25, tautomerization with rotation of 213 into the cyclization
Tonkalactone (206) is sustainably accessible from (+)-pulegone conformation leaves much time for the reactive intermedi-
Scheme 25. Synthesis of Tonkalactone (206) from renewable (+)-pulegone Scheme 26. Synthesis of Tiramisone (217) from furfural (215), a renewable
(202) via iodonium-mediated cyclization and Kornblum oxidation. platform chemical from pentosans like xylan (210).
Review
ates 212–214 to undergo side reactions and decomposition. 8. Oriental Perfumes

Much research is ongoing to improve the efficacy of the
process, but as pentosans are basically waste materials of 8.1. Ambrox: Nature vs. Biotech
only fuel value, furfural (215) remains an attractive building
block. The oxidation of furfural (215) to the respective The oriental fragrance concept typifies the legendary associa-
carboxylic acid 216, followed by reductive esterification tion to the sweet balms and resins of Arabia. Thus, the
under hydrogen atmosphere at 80–150 °C, provides the respective perfumes are based on a balsamic-culinary amber-
captive Tiramisone (217).[195] It has a typical Tiramisu odor gris–vanilla foundation. They feature principal ingredients of
with pronounced fruity, apple and gourmand-like aspects. the East such as clove, cassia and cinnamon, or pepper and
Tiramisone (217) was recently featured at 0.1 % in the milky pimento but also exotic spices like bay leaf, cardamom, and
floriental “212 VIP Rosé I ♥ NY” (Carolina Herrera, 2023) by mace. Incense (olibanum), styrax, benzoin and tolu balm, or
Emilie Coppermann where it frames the coffee accord and even civet and castoreum can provide additional sweetness; yet
bridges over to the jasmine–freesia heart. In the apricot top a key ingredient is ambergris. Ambergris is a pathological waxy
note of this 100 % vegan scent, we also find 0.2 % of metabolite of the sperm whale (Physeter macrocephalus L.),
Pearadise (108). formed after mechanical injuries of the digestive system, for
This brings us to the fragrant impression of apricot, which instance by squid beaks. These injuries are sealed by ambreine
together with peach is a prime lactonic theme. These lactones (222), and once excreted the resulting scab matures on the
occur not only in fruity but also the floral scents of nature, and surface of the ocean. By the action of air and sunlight, the color
thus perfectly integrate into the floriental theme. In April 1991, of the scab lumps turns from blood-red, brown to light grey or
Roman Kaiser[196] found cis-3-methyl-4-decanolide (111), previ- even greyish white, hence the term “ambre gris” (“gray amber”).
ously unknown in nature, in the warm sensual white-floral scent Since the descriptor ‘ambery’ is quasi synonymous with oriental,
of Aerangis kirkii (Rolfe) Schltr. that recalls tuberose and some replaced the term ‘oriental’ by ‘ambery’, when there was
gardenia. It is now known by its commercial name Aprifloren a growing concern that the former would be derogatory,
(111)[125] and sustainably produced by radical cyclization of discriminative and eurocentric. In the realm of scents, however,
methyl crotonate (221) and heptanol (220) as delineated in the term was never used that way, and therefore we continue
Scheme 27. It has been used at 0.2 % in “212 VIP Men” (Carolina to use it for historic consistency. In addition, the oriental
Herrera, 2011) by Emilie Coppermann with Dave Apel, Lucas sensuality evoked by such perfumes as “Shalimar” (Guerlain,
Sieuzac, and Carlos Vinals, together with 0.4 % of Ambrocenide 1925) by Jacques Guerlain and “Samsara” (Guerlain, 1989) by
(236 vide supra). Jacques Chabert and Jean-Paul Guerlain directly comes to mind.
As depicted in Scheme 27, the renewable heptanol (220) The smelling principle of ambergris is ( )-Ambrox (229),
stems from methyl ricinolate (218), which is available ex castor also known as Ambroxide, Ambrofix or Ambroxan. It is formed
oil produced by cold expression of castor beans (Ricinus in trace amounts by oxidative degradation of ambreine (222,
communis L.). Pyrolysis at 550 °C in the Oleris process provides Scheme 28). In 1934, Max Stoll (1899–1969), at the time head of
methyl undecylenate (UAME, 219) and heptanal (53), the latter research at Firmenich, supplied 10 kg of the best ambergris
which is reduced to heptanol (220). Reaction of this renewable worth 100’000,– CHF to his academic teacher Leopold Ružička
heptanol (220) with methyl crotonate provides in comparison (1887–1976)[197] who then started the structure elucidation.
to Aprifloren (111) the unsubstituted γ-decalactone known for Ružička[198] initially believed the 3,4-dihydro-2H-pyranolid sys-
its intense creamy-fruity peach odor also as ‘Pêche Pure’. Thus, tem 223 and its fully saturated analogue 224 to be responsible
the important fragrant mainstays of the florientals are available for the typical ambergris odor, combining marine elements
sustainably already. with earthy-mossy, balsamic, tobacco, warm musky, and
animalic fecal tonalities. Led by the faint ambery smell of
sclareol (225), the smelling principle ( )-Ambrox (229) and
lower homologue of 224 was discovered by Stoll[199] upon
oxidative degradation studies[200] before it was even found in
ambergris tincture. Its perfumistic value was however immedi-
ately recognized, as was a potential synthetic route via
sclareolide (227)[201] which is available from ( )-sclareol (225), a
minor component (2–3 %) of clary sage oil (Salvia sclarea L).
As delineated in Scheme 28, oxidation of the allylic alcohol
225 with chromium(VI) in the past, and nowadays
permanganate or most recently ozone[202] provides the hydroxy
acid 226, prone to spontaneous lactonization to (+)-sclareolide
(227). Hitherto completely renewable, the problem concerning
the sustainability of the process was the reductive removal of
the carbonyl group of 227 to the tetrahydrofuranoid ether 229.
Scheme 27. Synthesis of Aprifloren (111) from heptanal (53, Oleris) ex This classically required an expensive and wasteful alanate
methyl ricinoleate (218). reduction of 227 to 228, which then is cyclized by elimination
Review
Even lower production costs for ( )-Ambrox (229) were

achieved on a route commencing from biobased (cf. Glossary)
β-farnesene (230), which was produced by Amyris, now part of
dsm-firmenich. The (E)-configured β-farnesene (230) is pro-
duced from sugar cane by yeast fermentation with Saccharo-
myces cerevisiae Meyen ex E.C. Hansen via a heterologous
expressed farnesyl synthase from sweet wormwood, Artemisia
annua L. Since S. cerevisiae tolerates high concentrations of up
to 23.8 g of β-farnesene (230) per 100 g of glucose, the process
is highly productive as the β-farnesene (230) easily separates
from the culture broth. It is sold as sustainable and inexpensive
biofuel under the name “Biofene”.[209,210] As delineated in
Scheme 29, Biofene (230) is however more than a biofuel as it is
also the starting material for a 3-step biotechnological process
to ( )-Ambrox (229) or Ambrofix (229) as it is called in
Givaudan.[211] In the first step, the (E)-configured β-farnesene
(230) is selectively cyclopropanated in a flow process at the
monosubstituted terminal double bond employing diazome-
thane, generated in situ from N-nitroso-N-methylurea (NMU)
and potassium hydroxide in the presence of a palladium(II)
catalyst.[212] Though the process is carried out in a flow system,
NMU is still a potent carcinogen, mutagen, and teratogen as is
Scheme 28. Classical 100 % sustainable and renewable synthesis of Ambrox diazomethane; so despite being elegant, efficient and atom-
(229) from ( )-sclareol (225) ex clary sage oil (Salvia sclarea L.) involving an
expensive hydride reduction step from (+)-sclareolide (227) to diol 228. economic, the process can hardly be considered green accord-
ing to the 12 Principles of Green Chemistry.[213] After complete
cyclopropanation, the resulting product 231 is subjected to
cyclopropyl–carbinyl rearrangement by phase-transfer medi-
of water leading to ( )-Ambrox (229) with the desired natural ated bromination and transformation into the corresponding
stereochemistry (Scheme 28).[203] This reduction step is reflected acetate, after which saponification affords the (E,E)-configured
in the price which in the past was around US$1000 per kg with homoallyl alcohol 232 (Scheme 29), the substrate for the
a world consumption growing from 15–25 t/a in the 1990s to squalene–hopene cyclase (SHC) mediated cyclization.[214,215]
> 100 t/a in 2020 with the diterpene starting material 225 at US Unlike other terpene cyclases, SHC does not require a
$150-200 per kg.[204] So, process cost is both an indicator and phosphorylated precursor, but progresses on a simple proto-
driver for sustainability, especially if waste disposal and energy nation pathway, which makes it an ideal enzyme for high
consumption are accounted for in an accurate and realistic way. substrate conversion, product titer, and biocatalyst load. By
Recent improvement of the process in Scheme 28 consequently means of directed evolution, the space–time yield was further
involved the catalytic hydrogenation of (+)-sclareolide (227) improved to achieve full conversion of 125 g L 1 (E,E)-
with ruthenium(II) catalysts in the presence of a base such as homofarnesol (232) to ( )-Ambrox (229) within 72 h, and
KOMe.[205] But of course, the direct biocatalytic conversion of recently the volumetric productivity was increased further to
( )-sclareol (225) to ( )-sclareodiol (228) constitutes an
attractive alternative as well, which finally was realized with
Hyphozyma roseoniger.[206] However, ( )-sclareol (225) is cyto-
toxic to many cells, and therefore economically viable concen-
trations seem difficult to reach. Group VIII metal catalysts on the
other hand are expensive, so very high turnover numbers are a
prerequisite. Researchers of Firmenich bioengineered an indus-
trial fermentation pathway to produce ( )-sclareol (225) by
expressing the labdadienyl diphosphate and the sclareol
synthase of Salvia sclarea in Escherichia coli strains genetically
modified to co-express the geranylgeranyl diphosphate syn-
thase from Pantoea agglomerans Gavini et al.[207] That way titers
of up to 1.5 g L 1 of ( )-sclareol (225) were reached, and the
resulting quality of 229 was introduced in 2016 as “Ambrox
Super”, anyhow employing a chemical oxidation and reduction
Scheme 29. Biotechnological synthesis of Ambrofix (229) from β-farnesene
step of ( )-sclareol (225) to the final product 229.[208] The result (230) by selective cyclopropanation of β-farnesene (Biofene, 230), subse-
of this new pathway managed to bring down the production quent cyclopropyl–carbinyl rearrangement and concluding cyclization medi-
cost of Ambrox (Super, 229) to about US$ 150 per kg. ated squalene–hopene cyclase (SHC).[216]
Review
300 g L 1 substrate[216] which we would estimate to translate to

production costs of around US$ 100 per kg. This Ambrofix (229)
process thus establishes new standards for biocatalytic proc-
esses in industry, but due to the NMU cyclopropanation it is
only 94 % renewable in comparison to the 100 % of the classical
or the ‘Ambrox Super’ route of dsm-firmenich. Furthermore,
due to hazardous reagents and the unsafe cyclopropanation
chemistry, it cannot be considered as ‘green’. Since the classical
route from ( )-sclareol (225) already uses renewable starting
materials, we see that in practice costs outweigh the other
green principles.
In any case, whether on the ‘Ambrox Super’ or the
‘Ambrofix’ route, ( )-Ambrox (229) ascended from its throne
and will be a commodity in the sustainable future. Conse-
quently, we will smell previously unimaginable levels of 229 in
future creations, a trend that started already 20 years ago with
13.6 % of 229 in “Bois d’Argent” (Dior, 2004) by Annick
Menardo, 5.3 % of 229 in “Versace pour Homme” (Versace,
2008) by Alberto Morillas, and 5.1 % of 229 in “Alien” (Thierry
Mugler, 2005) by Laurent Bruyere and Dominique Ropion. The
future will therefore smell of more ( )-Ambrox (229) than ever
before, not only for its biodegradability, but also for its pleasant
Scheme 30. Renewable synthesis of Ambrocenide (236) from α-cedrene
hedonics in all concentrations. (233) as well as some novel derivatives 237–239, aiming at improving both
the odor intensity and the biodegradation.
8.2. Dry Ambers from Cedarwood
Independent of ( )-Ambrox (229), there has been a trend for of 0.02 ng/L air (Scheme 30). Although being efficient in use as
extreme amber notes in masculine perfumery already for at well as renewable and sustainable, it is not biodegradable.
least the past decade, as documented in the success of “1 To further improve on the efficiency in use, the side chain
Million” (Paco Rabanne, 2008) by Christophe Raynaud, Olivier on the acetal moiety was extended by acetalization of 235 with
Pescheux and Michel Girard and its quasi-successor “Invictus” 2-pentanone.[218] This improved substantivity and boosted dry,
(Paco Rabanne, 2013) by Anne Flipo, Dominique Ropion, Olivier salty elements. The respective material 237 was introduced to
Polge and Véronique Nyberg. This trend does not revolve perfumery as ‘Ambrostar’ (237) and has been used at 0.3 % in
around the tobacco-type marine-balsamic amber tonality of “Rosenrot” (Rammstein, 2020) by Alexandre Illan to boost the
( )-Ambrox (229) but around an extremely intense dry-woody, dry facets of the metallic blood accord of the rose thorns. One
mineral-metallic amber note. The latter is characterized by a also finds 0.038 % of Ambrostar (237) in “C” (Courrege, 2021) by
sharp animalic intensity as is present in oud, highly prized in Suzy Le Helley and Annick Menardo, and 0.067 % of 237 in
the Middle East and as one of the most precious perfumery “Major Me” (Paco Rabanne, 2021) by Emilie Bevierre-Copper-
materials. mann in a cherry–oud–incense accord on a rose–patchouli
Whether or not this trend resulted from the adoption of foundation. Introducing an oxygen in the side chain at the
oud notes to western perfumery, it is today almost impossible acetal moiety intensifies the ambergris, woody odor in the
not to catch a dry woody-ambery whiff on a night out or in a methoxy compound 238, which is accessible from α-cedrene-
men’s locker room, and the archetypical odorant from which it diol (235) and methoxy acetone.[219] While the ether oxygen
originated was Ambrocenide (236). Alessandro Gualtieri used lowers the threshold, it also makes the compound 235 more
the extreme overdose of 3.4 % of Ambrocenide (236) in polar and thus more bioavailable; however, this methoxy-
“Blamage” (Nasomatto, 2014); yet, already at 1.5 % Ambrocenide substituted Ambrocenide (238) is also not biodegradable. The
(236) crystals are most prominent in “Uncut Gem” (Frédéric nor-analogue 239, a cyclic ortho ester, patented in 2020 by
Malle, 2022) by Maurice Roucel. Discovered as a trace constitu- researchers of Firmenich[220] is however readily biodegradable
ent during electrochemical epoxidation experiments on cedar- (82 %, 28 d) and 83 % renewable, smelling dry woody with
wood fractions in acetone, Ambrocenide (236) is synthesized ambery tonality; yet, it is too instable to be of any use in
from α-cedrene (233).[217] As delineated in Scheme 30, Prilezhaev perfumery, as the ortho ester moiety decomposes already in
epoxidation of α-cedrene (233) provides Andrane (234) that fine fragrance applications, even without the action of bacteria
already possesses a woody-ambery scent with tobacco and or enzymes.
santal accents. Alkaline hydrolysis of 234 and ketalization of the Thus, the challenge to find biodegradable alternatives to
resulting α-cedrenediol (235) then furnishes Ambrocenide (236) these modern ambers that lend signature, projection, and long-
with an exceptionally intense ambergris note and low threshold lastingness to perfume composition has not yet been met.
Review
Scheme 31 details further non-biodegradable examples of on the example of Ysamber K (271), which is the only derivative
related dry-woody, ambery odorants from renewable sources to that is both renewable and biodegradable.
illustrate the difficulty. These ketals were inspired by a ketal
that Oskar Jeger discovered upon degradation studies of
(+)-manool in 1954 (Jeger’s ketal, Amberketal, Z11).[221] Spiram- 8.3. It’s a Gourmandy Girl’s World
brene (240)[222] as used in “Kenzo pour Homme” (Kenzo, 1991)
by Christian Mathieu is produced from 3-carene (241) ex Indian What modern ambers are to masculine scents, so are maltol
turpentine oil after isomerization to the 2-carene, hydroformyla- (251) and ethyl maltol (259) to women’s perfumes. And what
tion and reaction with two equivalents of formaldehyde (119) started out in “Angel” (Thierry Mugler, 1992) with the subtle
by which aldol reaction and Cannizzaro disproportionation lead dose of 0.5 % of ethyl maltol (259), juxtaposed against patchouli
to a diol that is reacted with acetone to furnish the to counterbalance its sweetness, is today used untamed in up
corresponding ketal 240. Belambre (242)[223] uses (+)-camphor to six times that amount. To some these crème caramel scents
(243) as feedstock, which is subjected to a vinyl magnesium even coined an own gourmand family, but in any case, these
Grignard reaction, hydroboration/oxidation, and concluding fragrances relate back to the vanillic sweetness of the orientals.
ketalization with isobutyric aldehyde. It was featured in “Metal- Maltol (251) had been first isolated in 1862 from the bark of
done” (Aether, 2017) by Rodrigo Flores-Roux and the unusual the larch tree Pinus Larix L. by Scottish chemist John Stenhouse,
“Sonar” (27 87 perfumes, 2019) by Jacques Huclier. Symroxane who already commented on its pleasant odor.[226] Still, before
(244)[224] and Ambermax (246)[225] finally both derive from ( )- the 1990s 251 was almost exclusively used in flavors. The name
isolongifolene (245), itself a rearrangement product of ‘maltol’ was given only some 30 years later by J. Brand, who
(+)-longifolene (266, vide supra Scheme 35), which occurs in up found it to be the main smelling principle produced in the
to 30 % in the resin of the chir pine, Pinus roxburghii Sarg., an roasting process of malt production.[227] Yet, maltol (251) occurs
Indian pine tree native to the Himalayas. Allylic oxidation of widely in nature, such as coffee, cocoa, chicory and many other
( )-isolongifolene (245) with Na2Cr2O7 in glacial acetic acid or roasted foodstuffs. It can also be found in wood tars and oils, in
by air affords the corresponding enone that is reduced to the strawberries and raspberries, and in a variety of other plants
alcohol and then methylated to Symroxane (244), prominently including licorice, clover, ginseng, paprika and pepper. Maltol
featured in “Givenchy Play for Her” (Givenchy, 2010) and “212 (251) was traditionally made by extraction of the dry distillation
VIP Men” (Carolina Herrera, 2011) both by Lucas Sieuzac and products of cellulose materials, but is today already sustainably
Emilie Coppermann. produced from kojic acid (247).[228,229] The pyrone 247 is a by-
Ambermax (246) is synthesized by epoxidation of ( )- product in the fermentation process of malting rice, as used in
isolongifolene (245) with peracids, Lewis acid-catalyzed rear- the production of sake. Thus, kojic acid (247) is oxidized to
rangement to the corresponding ketone (“Piconia”, 270, comenic acid (248) by means of oxygen in the presence of
Scheme 35) and subsequent Wittig–Horner reaction with noble metal catalysts such as palladium or platinum. Thermic
EtPPh3Br, followed by Prins reaction with formaldehyde (119). decarboxylation of 248 at 220–250 °C, followed by reaction of
Ambermax (246) was utilized in the sensual fond of “Toy Boy” the resulting pyromeconic acid (249) with formaldehyde (119)
(Moschino, 2019) by Yann Vasnier, and is also prominent in the at around pH 8 then affords hydroxy maltol (250) as delineated
mineral, powdery “Peau” (Arquiste, 2021) by Rodrigo Flores- in Scheme 32. Its reduction with zinc in acidic medium furnishes
Roux. Ambermax (246) is however also only renewable but not maltol (251).
biodegradable. The longifolene rearrangement will be detailed As illustrated in Scheme 33, an alternative renewable
process for both “methyl maltol” (251) and ethyl maltol (259)
commences from the corresponding alkylfurfuryl alcohols
Scheme 32. Sustainable maltol (251) synthesis from kojic acid (247) by a
Scheme 31. Related dry-woody, ambery odorants 240, 242, 244 and 246 sequence of oxidation, decarboxylation, formylation, and
from renewable sources, none of which however found biodegradable. hydrogenolysis.[228,229]
Review
9. Woody Notes
9.1. I am Trash: Iso E Super
The name is a concept in this fragrance family characterized by

opulent compositions of woods such as cedar, sandalwood,
patchouli, guaiac wood, and vetiver. The prominent perfume
family thus spans from dry, sharp cedar and vetiver themes via
resinous and balmy compositions, to honeyed animalic fragran-
ces. But it is safe to say that one fragrance material is almost
omnipresent in woody scents: Iso E Super (264/5), the woody-
ambery filler par excellence, easily accessible from renewable
myrcene (23). The chemistry behind it is detailed in Scheme 34,
and was first patented by Günther Ohloff for Dragoco (now
Symrise) in 1956.[231]
Myrcene (23) is reacted with a dienophile such as mesityl
Scheme 33. Renewable synthesis of maltol (251) and ethyl maltol (259) by oxide (61) in a Diels–Alder reaction under high pressure and
Achmatowicz rearrangement.[230] temperature to afford the corresponding adduct 260, the so-
called “Precyclemones”. These are then cyclized to the corre-
sponding 1,1-dimethyloctahydro naphthalenes such as 261,
which possesses a woody-ambery, velvety, soft, and creamy
(252).[230] 2,5-Addition of chlorine in methanol across the odor (Scheme 34). However, the yield of the Diels–Alder
furanoid “enol ether”-type ring system leads to intermediate reaction with mesityl oxide (61) was 10 % only, and Ohloff did
253. Its methanolysis then affords the 1,1-chlorohydrine 254, not exemplify too many dienophiles; thus, Hall and Sanders[232]
although violating the Erlenmeyer rule of two functional groups of IFF applied the process on methyl sec-butenyl ketone (262)
at the same carbon atom. Spontaneous elimination of HCl from which then furnished via 263 Iso E Super (264). The claimed
254 provides the 1,5-chlorohydrine 255 which by elimination of structure 264 is, however, close to odorless (th 500 ng/L air)
another equivalent of HCl with cyclization concludes the and the odor of the commercial material is due to the minor
Achmatowicz rearrangement of 252 to 256. The enone double impurity 265 (Iso E Super Plus, Arborone, th 0.005 ng/L air,
bond of the 2H-pyran-3(6H)-one 256 is then epoxidized to 257 100’000×), formed in the cyclization by isomerization of the
under Prilezhaev conditions using a peracid, which by treat- endocyclic double bond and rotation of the side chain of
ment with an acid under elimination of methanol furnishes the intermediate 263.[233]
enol form 258 that is of course keto–enol tautomeric to methyl Jean Claude Ellena used some 55 % Iso E Super (264/5) in
(251) and ethyl maltol (259), respectively. “Terre d’Hermès” (Hermès, 2006), while Geza Schön utilizes 65 %
These renewable syntheses demonstrate that we will not in “escentrıc01” and even more so 100 % usage in “molecule01”
have to live without methyl (251) or ethyl maltol (259) in the (both escentrıc molecules, 2005). As myrcene (23) is produced
sustainable future; the trend to further increase their dosage in renewably from the waste material CST (crude sulfate terpen-
feminine fragrances will instead be amplified rather than tine), Iso E Super (264/5) is an upcycled material and as such
diminished. When no one expected maltol levels to rise was featured as a main ingredient in 36 % in “I Am Trash – Les
anymore, Francis Kurkdjian launched his outstanding creation Fleurs du Déchet” (Etat Libre d’Orange, 2018) by Daniela
“Baccarat Rouge 540” (Maison Francis Kurkdjian, 2015) that
although initially intended as a niche perfume found tremen-
dous appeal with the general public. “Baccarat Rouge 540”
features an outrageous amount of ca. 3 % of ethyl maltol (259)
tamed by a no-less monstrous combo of ca. 12 % Evernyl
(Veramoss, 316, vide supra) and ca. 15 % Ambrox(an) (229),
thanks to which it is even listed in the woody family. But there
is no indication that the sustainable future will smell less
caramelized than today, and presumably this trend will expand
into masculine creations as we already saw with “Bad Boy
Extreme” (Carolina Herrera, 2022) by Louise Turner, Quentin
Bisch and Yann Vasnier, and its functional perfumery inspiration
“Dark Temptation” (Axe, 2013), which fuses dry modern ambers
and maltol sweetness with 0.7 % of ethyl maltol (259) and
woody notes.
Scheme 34. Synthesis of Iso E Super (264) as well as of an earlier mesityl
oxide analogue 261 and the structure 265 of its smelling principle.[233]
Review
Andrier. “Iso E” (= OTNE, 264/5) is, however, not a substance

without concern. Though it lacks structural alerts, it was found
to be a skin irritant (R38, H315) and sensitizer (R43, H317). Most
critical is the biodegradability for this ubiquitous material. Even
after 42 days Iso E (264/5) did not show any biodegradation in
a manometric respiratory test (OECD 301 C and 302 C, test
reports 95-E03 and 95-E28) as performed by Givaudan-Roure in
1995.[234] However, in 2021 IFF commissioned another study
(OECD 301 F) with activated sludge from the Nanjing Tiebei
Sewage Treatment Plant and the amazing outcome was 96.3 %
biodegradation at the end of the 28 d window, and > 60 %
within 10 d window. As Iso E bears two quaternary carbon
atoms in a 9,10-octalin skeleton, this study was challenged by
authorities and competitors alike, and we may well be curious
about the result. Scheme 35. Synthesis of Ysamber K (271) from (+)-longifolene (266)
involving a skeletal longifolene–isolongfolene rearrangement to 266 by a
Amongst some perfumers there is the belief that Iso E Super series of Wagner–Meerwein rearrangements.[236]
is such an eminent cultural asset, that people should not mind
whether it is biodegradable or not.[235] To us, however, even
innocuous persistent perfumery materials do not belong into
the trash as bioaccumulation may lead not only to sensitization (Tom Ford, 2019) and “Sexy Blossom” (Michael Kors, 2016) both
but also endocrine disruptive properties depending on the at 1.3 % is in principle also available from renewable starting
concentration. If the biodegradability of Iso E Super (264/5) materials: Its synthesis starts from geranyl chloride (272), which
cannot be verified, it has no place in the future of perfumers, is accessible from the CST (crude sulfate terpentine) feedstock.
no matter how renewable it is. This would lead to a renewability factor of 67 %, which even
increases to 88 % in case natural acetic acid is used. As
delineated in Scheme 36, geranyl chloride (272) is coupled with
9.2. Biodegradable Alternatives: Ysamber K and Polywood allyl magnesium chloride in a Wurtz reaction. The resulting
triene 273 is then cyclized by treatment with a mixture of
That does, however, not imply that Iso E Super (264/5) is by any formic and sulfuric acid, which leads to a diastereomeric
means easy to replace; this is anything but true. Until now, mixture of trans-decalinols 274. Acetylation with acetic anhy-
there are only two perfumery materials that convey a similar dride under Einhorn conditions in the last step then furnishes
olfactory effect as “Iso E” (264/5): Ysamber K (271) and Polywood as a mixture of α- (275) and β-isomers (276), the
Polywood (275/6), both of which are more tilted towards the latter of which however is very weak to odorless, smelling only
ambery side than Iso E Super (264/5). fatty-floral and slightly rosy. The overall woody-ambery Iso-E-
Ysamber K (271)[236] is the notable exception that proves the Super type odor of the readily biodegradable mixture therefore
rule that acetals generally do not biodegrade. It has shown a is due almost exclusively to the α-isomer (275). Polywood (275/
biodegradability of 59.1 % in 28 d, and as it is synthesized from 6) is comparable to Iso E Super (264/5) not only in character
( )-isolongifolene (245), just like Symroxane (244) and Amber- but also in terms of olfactory performance and overall strength;
max (246) in Scheme 31, its renewability factor is 88 %. ( )- yet, as is apparent from the synthesis outlined in Scheme 36,
isolongifolene (245) in turn is the rearrangement product of the manufacturing cost of Polywood (275/6) is significantly
(+)-longifolene (266), a sesquiterpene that occurs up to 30 % in
the resin of Pinus roxburghii Sarg., the Indian longleaf pine or
chir pine. Via a series of Wagner–Meerwein rearrangements
initiated by protonation of the methylene double bond, the 8-
methylene tricyclo[5.4.0.02,9]undecane system of 266 releases
ring strain to the tricyclo[6.2.1.01,6]undec-5-ene skeleton of ( )-
isolongifolene (245), an interesting building block for fragrance
materials (Scheme 35). The double bond of the sesquiterpene
245 is then epoxidized by means of Prilezhaev conditions
employing a peracid. The resulting isolongifolene epoxide (269)
is isomerized to the corresponding ketone Piconia (270), which
is then ketalized with ethylene glycol to the commercial
odorant 271, with a refined woody-amber odor profile that, by
its clean, smooth, and luminous character can convey an Iso-E
type effect to perfumery compositions. Scheme 36. Synthesis of Polywood (275/6) via elongation of geranyl chloride
Polywood (275/6)[237] which was used for instance in “Boss (272) by Wurtz coupling with allyl magnesium chloride, acid-catalyzed
Bottled Marine” (Hugo Boss, 2022) at 48 % and in “Métallique” cyclization to the decalinol 274 and concluding Einhorn acetylation.
Review
higher than that of Iso E Super (264/5), especially if renewable

geranyl chloride is employed.
Though in the context of unrelated new terpene skeletons,
Mori and coworkers[238] presented an alternative route to
2-decalones from dihydro ionones after carbomethoxylation
with dimethyl carbonate and olefinic cyclization of the resulting
product in the presence of tin(IV) chloride in wet
dichloromethane.[238] Decarboxylative saponification, reduction
of the keto group and acetylation would open up an alternative
access to Polywood (275/6) from renewable dihydro ionones.
As these are also not accessible at attractive cost, the task to
find a biodegradable replacer of Iso E Super (264/5) at
affordable cost is still not solved and constitutes one of the
biggest challenges for a 100/100 perfumery world.
Scheme 37. The allergens atranol (277) and chloroatranol (278) formed by
decomposition of depsides such as chloro atranorin (279) and the industrial
process towards Clearwood by yeast fermentation of sucrose from sugar
cane with the main constituent ( )-patchoulol (282).
10. The Chypre Genre
10.1. Patchouli Taking Over

sucrose (280) is directly transformed via (2Z,6E)-farnesyl
The creation of chypre family can be attributed to the many pyrophosphate (281) to an essential oil-like terpene mixture
compositions inspired by the legendary perfume “Chypre” rich in ( )-patchoulol (282).[240] The resulting product known as
(Coty, 1917) created by François Coty (1874–1934). “Chypre” Clearwood is “a soft and clean version of patchouli,” that can
means Cyprus in French and is the olfactory incarnation of the however easily be distinguished from the natural oil by its less
rugged mountainous Mediterranean island with its typical pronounced camphoraceous, woody–earthy character. Another
vegetation of cypresses, oaks and stunted herbs, characterized example of biotechnological transformation of complex natural
by its warmth and dryness. Contrary to the overall sweetness in ingredients is Akigalawood, which is produced from patchouli
most perfumery families, there is a certain bitterness inherent waste fractions by laccase mediated oxidation.[241] Yet, the
to chypre perfumes which results from the interplay of chypre concept can be realized both by natural patchouli oil,
patchouli with oakmoss. Akigalawood and Clearwood alike, so it is already 100/100
The sharp aromatic structure was traditionally based on the future-proof.
contrast of a citrus top with this mossy-animalic fond made up
from oakmoss, patchouli and musks. The floralcy in the middle
note traditionally assigned the gender identity with rose– 10.2. Musks – That Certain Sexy Something
jasmine for feminine creations as “Mitsouko” (Guerlain, 1919)
and geranium–carnation for masculine creations as seen in Generally speaking, there is no perfume without musk, so musk
“Kouros” (Yves Saint Laurent, 1981). The oakmoss constituents belongs in every perfume family; in the chypre concept, they
atranol (277) and chloroatranol (278) are formed in the are however of utmost important to counterbalance the bitter-
decomposition process of depsides such as chloro atranorin ness of the fond. While there are even five families of musks,
(279, Scheme 37). Since they constitute two of the most potent i. e. macrocycles, nitroarens, polycycles, linear alicyclic, and
contact allergens, responsible for > 20 % of all fragrance dienones, only two musks are meeting the 100/100 criteria: the
allergies, they have been restricted to levels < 100 ppm in macrocyclic Ambrettolide (288) and the alicyclic Romandolide
oakmoss extracts. This led to a significant price increase and a (309). Most of the other macrocycles derive from petrochemical
de facto ban of oakmoss in perfumery. The pragmatic way cyclododecanone (‘CDon’) by ring-enlargement chemisty.[242] As
forward was to simply raise the patchouli levels to sustain the CDon is made by Wilke trimerization of 1,3-butadiene, this
subliminal bitterness, first successfully implemented by Jacques directly leads us to the steam cracker, naphtha and the mass-
Polge with “Coco Mademoiselle” (Chanel, 2001). What was balance approach (cf. Glossary). There is a biomass-based bio-
projected as a flanker testing the new concept, was met with naphtha and pyrolysis oil/syngas from plastic waste; yet, what
such overwhelming success that it redefined the genre. can be fed into today’s steam crackers is in the low-to-mid
Patchouli oil[239] is readily biodegradable, and it is renewably single digit percentages, so still far from the > 50 % boundary. A
available by steam distillation (1–3.5 % yield) of the dried and cost-competitive renewable 1,3-butadiene still is a formidable
fermented leaves of Pogostemon cablin (Blanco) Benth. with a challenge. Thus, for the moment, Ambrettolide (288) is the only
production volume of 1600–1800 tons/year. In addition, due to 100/100 macrocyclic musk.
the robustness of the patchoulol synthase, patchouli oil was the As is summarized in Scheme 38, it is synthesized from
first perfumery material to be produced biotechnologically by aleuritic acid (283) which is the reason it bears a (10E)-double
fermentation with Escherichia coli cells expressing patchoulol bond and should not be confused with the natural (8Z)-
synthase SEQ ID NO:10. Thereby, as sketched out in Scheme 37, configured product[243] that Max Kerschbaum[244] isolated from
Review
Scheme 38. Synthesis of renewable Ambrettollide (288) from aleuritic acid

(283), the main acidic constituent of shellac, a resin secreted by the female
lac bug used also as nail varnish.
Ambrette seed oil (Abelmoschus moschatus Medik. syn. Hibiscus

abelmoschus L.). This (10E)-quality is the industry standard, used
for instance at 8.5 % in the modern chypre “Rouge Velours”
(Yves Saint Laurent – Le Vestiaire, 2021), at 20 % in “Dans Paris”
(Celine, 2019), at 15 % in the black musk accord of “Falkar”
(Bvlgari, 2019) and at 10 % in both “Jahwara Oriental” (Armani
Scheme 39. Synthesis of vegan AmbreXolide (288, vegan) by cross-meta-
Privé, 2021) and “Miss Dior Rose N’Roses” (Dior, 2020). thesis, hence the ‘X’ in the name. As the alcohol component 294 for the
Aleuritic acid (283) is the main acidic constituent of shellac, metathesis substrate 295 is only available petrochemically, the overall
a resin secreted by the female lac bug Kerria lacca Kerr, living renewable carbon content is only 56 % though.
on palash [Butea monosperma (Lam.) Taub.], ber (Ziziphus
mauritiana Lam.) and kusum trees [Schleichera oleosa (Lour.)
Oken] in the Bihar region of India. Reaction of 283 with enal (293) which is then reduced to the corresponding alcohol
orthoformate provides the 2-methoxy-1,3-dioxolane derivative 294. The substrate 295 which results from the esterification of
284[245] that by reaction with acetic anhydride first eliminates 294 with 291 is then subjected to metathetic polymerization in
the methoxy group to then decompose by elimination of CO2 the presence of a suitable catalyst, for instance N-[4-bromo-
to bengalene acid (286). This is then subjected to the polymer- 2,3,5,6-tetraphenyl phenoxy(2,5-dimethyl-1H-pyrrol-1-yl)(2-
ization–depolymerization procedure developed by Charles methyl-2-phenylpropyli-dene)molybdenumylidene]-2,6-bis-
Collaud[246,247] to furnish the warm-powdery, seedy smelling (prop-2-yl)aniIine.[251] From the resulting polymer there are then
Ambrettolide (288) 100 % renewably, at prices of around 200 €/ three principle routes towards AmbreXolide (288, vegan):[252]
kg. The depolymerization according to the Collaud process em-
A pricewise more attractive and additionally vegan renew- ploys catalytic amounts of NaOMe and distills out the
able route to 288, which is then called AmbreXolide (288, AmbreXolide (288, vegan) accompanied by homo-dimers 297
vegan), makes use of olefin metathesis as is delineated in and 298. The transesterification with MeOH in the presence of
Scheme 39. Methyl oleate (289), a component of biodiesel and NaOMe with the isolation of the methyl bengalenate (299) is
produced from palm, candlenut, or sunflower seed oil is made then separately subjected to Collaud cyclization, and finally the
by transesterification with MeOH in the presence of zeolites. reactive distillative removal of the most volatile compound, i. e.
Ethenolysis of methyl oleate (289), for instance with a first- AmbreXolide (288, vegan), which should be the most attractive,
generation Grubbs catalyst[248] provides dec-1-ene (290) and potentially lowering the price by half.
methyl decenoate (291) as renewable feedstock. The latter is AmbreXolide (288, vegan) was featured by Quentin Bisch in
used as a substrate for cross-metathesis by esterification with “Ambre Chromatique” (Maison Crivelli, 2022) and by Yann
oct-7-en-1-ol (294), which however is only available petro- Vasnier in “Divine, l’été” (Divine, 2023). Besides the price
chemically by dimerization of butadiene (72) in the presence of advantage and the vegan designation, AmbreXolide (288,
water and a Pd catalyst.[249] Isomerization of the allylic double vegan) is only 56 % renewable and potentially boosts palm oil
bond of 292 employing a Cu/Cr oxide[250] catalyst affords oct-7- consumption as most inexpensive source of methyl oleate
Review
(289), leading to increased rainforest deforestation. Shellac

production, however, preserves nature since the lac cultivators
are the local forest keepers. As long as the lac is in demand,
there is an incentive for them to protect the host trees. It is
anything but apparent which product is more sustainable.
However, there is a fully renewable alternative that does not
depend on inexpensive palm oil, and is as well vegan:
Ambrettolide HC (’high cis’).[253] It was for instance used in the
already mentioned “new chypre” prototype “Coco Mademoi-
selle” at 0.6 %, at 7.5 % in the floral chypre “Nomade Naturelle”
(Chloé, 2022) by Caroline Dumur, and even in 20 % in the fruity
chypre “Cosmic Cloud” (Louis Vuitton, 2021) by Jacques
Cavallier. As presented in Scheme 40, genetically engineered
Escherichia coli produce the fatty acid ω-hydroxy-cis-Δ7-hexade-
canoic acid (302) from sugars such as sucrose (280). This is then
Scheme 41. Sustainable synthesis of the alicyclic musk odorant Romandolide
cyclized in classical Collaud fashion by initial polymerization in (309) from pinane (21) via citronellene (305) and Cyclodumol (307).
the presence of for instance titanium(IV) butoxide and ethylene
glycol at 30 mbar.[253] Subsequent depolymerization of the
resulting polyester 303 at 2 mbar and elevated temperatures
then furnishes the monomeric Ambrettolide HC (304) possess- This instability in applications is however more than
ing a floral, ambrette-seeds like musk odor. This biotechnolog- compensated for by its cost-efficient, simple and sustainable
ical route comes with an on-cost of 50 % to the one from synthesis outlined in Scheme 41. Pinane (21), abundantly
aleuritic acid (283) but appears to be the most sustainable one. available by catalytic hydrogenation of α-pinene (9), is thermally
The other sustainable and biodegradable musk besides the opened to citronellene (305), which in the presence of acids
different isomeric ambrettolides is Romandolide/Ecomusk R typically used for hydroxylation, in this case sulfuric acid,
(309), which was discovered by Alvin S. Williams of dsm- cyclizes under ring contraction via 306 to Cyclodumol (307).[256]
firmenich in 2000.[254] It is a linear alicyclic musk that imitates This is then either directly esterified with 2-chloro-2-oxoethyl
the perimeter of macrocylic musks with its horseshoe-type propanoate[254] or stepwise with 2-chloroacetic acid, followed by
shape. Its unusual diester structure was devised to avoid the esterification with propionic acid. The resulting Romandolide
polyether formation in the etherification of Cyclodumol (307) (309) has a musky, fruity, herbal odor with the fruity aspects
with isobutylene oxide in the Helvetolide synthesis.[255] It acts as between red fruits and pear. Together with metallic hot-iron
a biodegradation handle, albeit it also increases the water musks, 309 coined white musk accords that recall clean
solubility thereby lowering deposition on fabric in the deter- (“white”) ironed linen, as opposed to the dirty-animalic black
gent suds. Since the diester motive also cleaves readily by musk we met previously in “Falkar” (vide infra Section 10.2).
action of lipases and bases, Romandolide/Ecomusk R (309) Romandolide (309) was used in 47 % in “Valentina Pink”
proves less efficient for fragrance in laundry-care products. (Valentino, 2015), in 35 % in “Sun Fruit” (Ellis Brooklyn, 2022),
and 21 % in “L'eau Kenzo florale” (Kenzo, 2022). More common
are doses of around 10 % as in “A Kiss from a Rose” (by Kilian,
2021), “Replica Coffee Break” (Maison Martin Margiela, 2019)
and the typical chypre “Mon Paris Intensement” (Yves Saint
Laurent, 2020). But two 100/100 musks are not enough for
chypre perfumes, and certainly much less sufficient for the
entire universe of perfumes.
10.3. The Oaky Timbre of Evernyl
While the constituents atranol (277) and chloroatranol (278, cf.

Scheme 37) cause the sensitization issues of the natural
extracts, the odorous principle of oakmoss is Evernyl (Veramoss,
315), together with related orcin derivatives. Evernyl (315)
possesses a powdery woody oakmoss odor with slight phenolic
Scheme 40. Synthesis of Ambrettolide HC (304) from sucrose (280) with the and earthy facets, and is safe to use in perfumery, even
aid of E. coli, genetically engineered to produce the fatty acid 302 by undergoing 63 % biodegradation within 28 days (61 % within 10
expression of key enzymes such as thioesterases (TesA) and ester synthases
(ES9). The macrocyclization is then carried out by a classical polymerization– d), making it readily biodegradable.
depolymerization process. The established industrial synthesis is based on a route
elaborated in 1929 by Adolf Sonn[257] commencing with the
Review
11. Fougère Perfumes
11.1. Strong and Masculine?
Despite many attempted coups to feminize this first family of

modern perfumery, fougères remain reserved for the masculine
domain. Lavender, oakmoss and coumarin form the basic
accord of the fougère concept. In the top, hesperidic and
Provençal elements may join, and in the heart, we classically
find geranium and linalool. Vetiver often accompanies in the
Scheme 42. Improved green and potentially renewable synthesis of the dry down; yet, just as the image of masculinity has much
readily biodegradable Evernyl (Veramoss, 315).[258] changed over the past year, so has the fougère concept, which
itself has become an increasingly unisex ‘Cool Water’.
Pinane (21) is transformed into the respective diastereo-
meric hydroperoxides (316) upon treatment with molecular
Michael addition of methyl acetoacetate to methyl crotonate oxygen or for instance tBuOOH (Scheme 43).[260] Subsequent
(221) and subsequent intramolecular acetoacetic ester conden- hydrogenation leads to cis- and trans-pinanol (cis-/trans-317).
sation. The resulting methyl dihydroresorcinyl ester is alkylated Thermolysis of 317 then provides linalool (139),[261,262,263] a
with methyl iodide, brominated, and then dehydrohalogenated sweet-floral, fresh-citrusy lavender odorant with slightly spicy
with Pd/CaCO3 to the aromatic system. An improved green- rosy accents that occurs also naturally in many plants like shui
chemistry one-pot synthetic route that is potentially renewable oil (80–85 %) or coriander oil (60–70 %). Even though perfectly
is presented in Scheme 42 starting with the Michael addition of sustainable, linalool suffers from the disadvantage of being a
hex-4-en-3-one (310) to dimethyl malonate (311) using 0.4 eq. sensitizer, therefore, risks to be further limited in the future. For
of NaOMe in AcOMe.[258] Intramolecular Claisen condensation fougère notes, even more important is linalyl acetate (318),
initiated by addition of further 0.6 eq. of NaOMe followed by providing like 139 fresh citric impressions on lavender, thus
acidic work-up provides intermediate 313 which is chlorinated being the benchmark bergamot odorant. It can be extracted
in the next step by action of trichloroisocyanuric acid (TCCA)[259] from bergamot oil (30–45 %), from lavender oil (30–60 %), and is
to afford 314. Spontaneous dehydrochlorination of 314 under also the major component of clary sage oil (Salvia sclarea; up to
aromatization concludes the synthesis without using any 75 %).[264] Of course, as shown in Scheme 43, it can also be
elemental bromine or chlorine. Hex-4-en-3-one (310) is avail- sustainably prepared by acetylation of linalool (139).
able by aldol condensation of acetaldehyde with butan-2-one. First introduced in “Azzaro pour homme” (Azzaro, 1978) by
While patchouli already took the role of oakmoss in chypres Gerard Anthony and Richard Wirtz, dihydromyrcenol (320)
to some certain extent, at least potentially, one oakmoss quickly became famous for its fresh, citric-bergamot smell
perfumery ingredient is future-proof in being biodegradable underlining the masculine character of fougère perfumes. Its
and potentially renewable. Besides, Evernyl (315) has become
fairly popular lately with the already mentioned 12 % in
“Baccarat Rouge 540” (Maison Francis Kurkdjian, 2015), 11 % in
the related “Instant Crush” (Mancera, 2019), 7.5 % in “Explorer
Platinum” (Montblanc, 2023) by Bruno Jovanovic, Nathalie
Lorson and Fabrice Pellegrin, 7.1 % in the mineral “Ganymede”
(Marc-Antoine Barrois, 2019) by Quentin Bisch, and 4.9 % in the
marine “Megamare” (Orto Parisi, 2020) by Alessandro Gualtieri.
The marine fragrances that appeared in the 1990s around
“Kenzo pour Homme” (Kenzo, 1991) by Christian Mathieu are a
subfamily of the chypre genre, and since substituted 2,4-
dihydro-3H-1,5-benzodioxepin-3-ones are neither biodegrad-
able nor renewable, these notes are under severe threat in a
100/100 world. Unless new 100/100 marine odorants are
discovered, mossy and algae notes might seize the marine
family, just as patchouli did with the chypres.
Scheme 43. Synthesis of sustainable linalool (139) from pinane, obtained via
the CST process out of paper waste.
Review
synthesis commences from citronellene (305, also known as

dihydromyrcene) using an acid like sulfuric acid, formic acid or
an Amberlyst in an aqueous media at elevated temperatures
(Scheme 44).[265,266,267] Dihydromyrcenol (320) is now used in
large amounts as in “Cool Water” (Davidoff, 1988) by Pierre
Bourdon with 24 % of dihydromyrcenol (320), 12 % linalyl
acetate (318) and 5 % of linalool (139), evoking the scent of a
man fresh out of the shower. This iconic perfume modernized
the fougère family, brought lavender freshness back on the
scene, and demonstrates how the perfumes of the future can
be built with a considerable proportion of a 100/100 biodegrad-
able and renewable fillers. Following in the footsteps of “Cool
Water” were “Fierce” (Abercrombie & Fitch, 2003) by Christophe
Laudamiel and Bruno Jovanovic in an aromatic-rosemary Figure 4. Salicin (321), the natural salicylate precursor, important salicylates
direction with 10 % of dihydromyrcenol (320), 1 % linalyl acetate 322, 323, 325–327 and the safe salicylate replacers 324 and 328.
(318) and 0.4 % of linalool (139), “Bleu” (Chanel, 2010) by
Jacques Polge with a fresh grapefruit–citrus vibe and with 7 %
of dihydromyrcenol (320), 5.5 % linalyl acetate (318) and 2.5 % 321 is cleaved by glycosidases upon ingestion, and then
of linalool (139), and “Legend” (Montblanc, 2011) by Celine oxidized to salicylic acid in the liver. Salicylic acid inhibits a
Perdriel and Olivier Pescheux in a mossy–dried fruity way with cyclooxygenase in the biosynthesis of prostaglandin that causes
3.4 % of dihydromyrcenol (320), 0.7 % linalyl acetate (318) and fever, pain, and inflammations. In this way, salicylic acid acts as
0.3 % of linalool (139). The recent success of “Sauvage” (Dior, a non-steroid anti-inflammatory drug, but with negative side
2015) by François Demachy with its spicy–citrusy woody effects such as stomach irritation and bleeding. To improve
orientation proves that the trend is far from over, but rather solubility, pharmacokinetics and tolerability, Felix Hoffmann on
seen in modern feminine chypres such as “Chance” (Chanel, a suggestion of Arthur Eichengrün prepared in 1897 the acetyl
2005), with some fresh masculine fougère citations of 2.5 % of derivative that was marketed by Bayer in 1899 as “Aspirin“.[269]
dihydromyrcenol (320), 5 % linalyl acetate (318) and 6 % of Today, Aspirin is the most successful and most widely used
linalool (139). drug, and thanks to Hermann Kolbe’s synthesis from carbon
dioxide and sodium phenoxide, salicylic acid was already
adequately available since 1856. Thus, at about the same time
11.2. Endangered Medicine: Salicylates as Hoffmann and Eichengrün, there was also Georges Darzens
(1867–1954). Then a chemist at L. T. Piver, the oldest perfumery
Since the coumarin replacement by Tonkalactone (206) and of Paris (estd. 1774), he derivatized salicylic acid and discovered
Koumalactone (207) was discussed in Section 7.3 and oakmoss in isoamyl salicylate (322) a new odorant recalling “a blossom-
treated in Section 10.3, the basic fougère accord is already ing clover field in the warmth of August”.[270] Darzens with his
covered. Yet, there’s more to fougère; a mild floralcy beyond perfumer colleague Jacques Rouché added 322 to a fougère
geranium recalling azaleas and the invigorating wintergreen skeleton, and the resulting “Trèfle Incarnat” (Piver, 1898)
freshness of a mouthwash: the effect of salicylates is an became an immediate success, revolutionizing the fougère
essential element of most fougère fragrances. family.
The Greek physician Hippocrates of Kos (460 BC – 377 BC), Today, however, methyl salicylate (323) is far more
father of modern medicine, advised extracts of willow bark and important in perfumery than 322, and it is sustainably available
leaves against pain and to reduce fever.[268] The active by isolation from wintergreen oil. Besides, it is characteristic for
ingredient of the willow tree is salicin (321, Figure 4), first mango, birch tree, meadowsweet and guelder rose. It is also a
isolated in 1828 by Johann Andreas Buchner. The β-glucoside mild antiseptic for oral care, but in 2022 was classified CMR 2
due to its reprotoxicity. The EU Scientific Committee on
Consumer Safety (SCCS) considered it safe, but severely
restricted its use levels. Since this reprotoxicity is due to the
release of salicylic acid by saponification, one way out is carba
derivatives such as 324 as a “methyl carba salicylate” which
Jean-Marc Gaudin reported to have olfactory properties
between methyl and ethyl salicylate with somewhat pro-
nounced camphoraceous aspects.[271]
This “carba trick” works also with isoamyl salicylate (322)
and benzyl salicylate (325), the latter being the salicylate with
the highest volume, estimated around 8500 tons per annum.[271]
Scheme 44. Exemplary conversion of citronellene (305) to dihydromyrcenol While faint, it smells balsamic, sweet, floral, and recalls ylang
(320). ylang. Its carba analogue is more in magnolia–hyacinth
Review
direction, and this white floralcy is accompanied by animalic smelling principle norziza-2a-yl acetate (330)[280] is not looking
facets in the direction of labdanum–castoreum. While only at any better. Neither is the odorous principle 330 biodegradable,
around 600 tons per annum, (3Z)-hexenyl salicylate (326) often nor is there any prospect for a sustainable synthetic or
accompanies benzyl salicylate (325) in a ratio of around 1 : 10 to biotechnological route. Therefore, hopes are pinned on a
introduce an aromatic green naturality. An example is “CK be” renewable Vertenex (Oryclon, 331), the workhorse vetiver in
(Calvin Klein, 1996) by René Morgenthaler, who incorporated functional perfumery.
the extreme amounts of 22 % benzyl salicylate (325) and about While a tert-butyl substituent is in general a most critical
2 % (3Z)-hexenyl salicylate (326). structural feature impeding biodegradation, Vertenex (Oryclon,
Since carba salicylates are easily available by Fries rear- 331) is readily biodegradable with even 88 % degradation in
rangement from the corresponding phenyl esters, they are in 29 days. Its creamy woody vetiver odor is mainly due to the cis-
principle accessible sustainably from renewable phenol (340) as isomer, which is well in agreement with an empirical rule that
will be discussed in the next section. However, only esters with states that a vetiver odorant should bear a quaternary carbon
acyl components stable enough to withstand the harsh atom 5.0 � 0.5 Å away from a carbonyl functionality.[281] This is
conditions of the Fries reaction are accessible. Therefore, (3Z)- not the case in the conformations around the global energy
hexenyl salicylate (326) and Karmaflor (327), a captive Roman minimum, but within a window of 10 kcal/mol a number of cis-
Kaiser first discovered in the scent of the Ashoka tree[272] are not configured conformers meet this criterion as delineated in
easy to mimic with a “carba trick”. Jordi Fernández nicely Figure 5. While the cost–performance ratio and biodegradability
demonstrated the mango–passion fruit side of salicylates in of Vertenex (Oryclon, 331) seems ideal, it is for the moment not
“Oud Maracujá” (Maison Crivelli, 2023), where he highlighted available from renewable starting materials. A potentially
this fruity side of salicylates with ca. 4 % Karmaflor (327), ca. 9 % sustainable process is outlined in Scheme 45.
of benzyl salicylate (325) and ca. 5.6 % of (3Z)-hexenyl salicylate Besides the transformation of polysaccharides into highly
(326). In addition to the replacement of the ester oxygen by a oxidized platform chemicals such as 5-hydroxymethyl furfural
carbon atom, it seems in certain cases possible to replace the or furfural (215, Scheme 26) by hydrolysis–dehydration proc-
hydroxy function of salicylates by a methyl group and retain esses, there is also a pathway to aromatic compounds as
some of the olfactory properties as for instance seen in the outlined in Scheme 45. On this route, Borealis produces renew-
olfactory similarity of ethyl 2-methylbenzoate (328) and methyl able phenol (340) via cumene (336) from benzene (335) that
salicylate (323);[273] yet, here it is the ethyl ester 328 that is Neste generates from “bio naphtha” (334). In the Liquid-Phase
closest to the methyl ester 323. The methyl ester analogue of Cellulose to Naptha (LPCtoN) process[282] cellulose (333) is first
328 is known as Ylanganate.[274] A renewable natural quality of hydrolyzed in a biphasic solvent system in the presence of acid
benzoic acid is for instance available from cassia oil. catalysts such as zeolites. The resulting glucose units in the
11.3. Relaxing Vibes: Vertenex and Vetiver
Finally, the warm, sweet-mossy coumarin–oakmoss dry-down of

fougère perfumes is very often accompanied by vetiver notes,
which link with their grapefruit aspects the fresh-citrusy top-
note of linalyl acetate (318) to the woody-mossy fond that
harmonizes with the creamy woody-ambery dry-down of
vetiver oil. Thus, vetiver oil and vetiveryl acetate, the latter
produced by acetylation of the sesquiterpene alcohol fraction
of vetiver oil, are ideal links to soothe a composition and
introduce a relaxing ambience.
The smelling principle of vetiver oil, 2-epi-ziza-6(13)-en-3-
one (329), has only been established by total synthesis in
2021.[275] Together with an Aroma Extract Dilution Analysis
(AEDA) by Belhassen et al.,[276,277,278] this finally put an end to a
long debate about the compound mainly responsible for the
characteristic transparent suave and sweet woody-ambery,
earthy odor of vetiver oil. Yet, despite an extremely low
threshold of 29 pg/L air, 2-epi-ziza-6(13)-en-3-one (329) is
neither biodegradable nor synthetically accessible from renew-
able sources. A biosynthetic route could offer a solution; yet, Figure 5. The structures and biodegradation properties of 2-epi-ziza-6(13)-
while a method for producing (+)-zizaene had been en-3-one (329) and norziza-2a-yl acetate (330), the smelling principle of
patented[279] it is still quite a way for an industrial process of a vetiver and vetiveryl acetate, respectively, Vertenex (Oryclon, 331), depicted
as the stronger high-cis (HC) isomer with a conformer fulfilling the criteria of
synthetic vetiver oil or a biotechnological route to 2-epi-ziza- a vetiver odor rule[281] and Epivone (332), the biosynthetic 5-epimer of
6(13)-en-3-one (329). The situation for vetiveryl acetate and its β-vetivone, which finally was not launched by Evolva.
Review
biotechnology as such is neither always green nor the answer

to all sustainability issues. To justify the high costs required to
develop efficient biotech processes limits these to existing
high-price biodegradable materials, which consequently limits
their innovation potential to cost improvements. The same is
true for biotech copies of essential oils. These will not advance
creativity in perfumery; new sustainable and biodegradable
captives by green chemistry will.
12. Concluding Thoughts
In answer to the question, “Do fragrances harm the environ-

ment?”, Luca Turin provokingly stated, “nobody ever died from
wearing Mitsouko, but lots of babies were born as a result of
it.”[285] Though this holds probably true, these babies are also
entitled to have unobjectionable breast milk free from musks,
and an unspoiled environment free from Iso E Super (264/5).
The essence and purpose of perfumes is to enchant and
Scheme 45. The Liquid-Phase Cellulose to Naptha (LPCtoN) process from delight.[286] Having served this purpose, perfumes should
cellulose (333) to bio naphtha (334) that leads after dehydrogenation/
dehydrocyclization to renewable benzene (335) which is processed via Hock
discretely disappear, without posing any harm to people or the
phenol synthesis to a renewable quality of phenol (340). The latter can be environment, even if the impact of perfumes on the environ-
converted into Vertenex HC (331) by Friedel–Crafts alkylation, hydro- ment is admittedly close to neglectable in comparison with
genation, and acetylation.
other consumer chemicals. The responsibility for future gener-
ations becomes a moral imperative especially when it concerns
such luxury and lifestyle goods as (prestige) perfumes. In that
aqueous layer are then catalytically hydrogenated to sorbitol respect, fragrances serve as a role model for other consumer
which, in the organic layer, is reductively dehydrated to linear goods – including carbon footprint, climate neutrality and net
and cyclic C6 and C5 alkanes (334). Dehydration and dehydro- zero emissions (cf. Glossary).
cyclization of the resulting “bio naphtha” (334) leads to a We saw that many perfumery ingredients are already or
renewable quality of benzene (335). Following the classical potentially sustainably available, though most often at an
Hock phenol synthesis[283] Friedel–Crafts alkylation of 335 with inferior price-performance ratio due to certain on-costs. Since
propene at 30 bar/250 °C in the presence of a Lewis acid affords prices are a function of the economy of scale, established
cumene (336) that is transformed to the corresponding hydro- petrochemical processes are challenging to compete with
peroxide 337 by radical reaction with oxygen. Via anionotropic unless a renewable waste stream becomes available, or a low-
rearrangement to 338, the cumene hydroperoxide (337) then cost upcycling opportunity arises (cf. Glossary). Biotechnological
decomposes in the presence of aqueous acids. The resulting processes on the other hand generally require many evolu-
oxocarbenium ion 338 then reacts with water to the hemiacetal tionary runs for optimization, and then often still have
339 that hydrolyses to phenol (340) and acetone. unfavorable volume yields and an unsatisfactory productivity.
From renewable phenol (340), it is just three short steps The investment in a biotechnological process therefore only
away to Vertenex HC (331): Friedel–Crafts alkylation with pays off for existing high-margin products of substantial volume
isobutylene, cis-selective hydrogenation and acetylation such as Ambrox (229), not for new captive odorants that still
(Scheme 45); so, a 50 % renewable high-cis quality of Vertenex are to establish new trends in perfumery.[287] In addition, as well
(Oryclon, 331) is literally around the corner. illustrated by Pablo Domínguez de María, biotechnology as
At the end of the vetiver section, let us look at Epivone, the such is not the magic formula for sustainability.[288] Besides the
5-epi-β-vetivone (332, Figure 5) of Swiss SynBio firm Evolva. By cost, blooming and long lastingness are two performance
expressing the premnaspirodiene synthase gene of Hyoscyamus criteria particularly effected when it comes to materials being
muticus in yeast, ( )-premnaspirodiene was produced from both renewable and biodegradable. Consumers as well as
glucose. However, the required oxidation of its allylic carbon to consumer companies thus will have to balance and potentially
a carbonyl function either required chromium(VI) in halogen- compromise biodegradability and renewability with cost and
ated solvents or gave yields below 20 % employing t-butyl performance.
hydroperoxide.[284] That cannot be considered green, and in Of course, some perfumery materials will legally be banned
addition the Epivone is lacking the suave and sweet earthy and vanish due to their environmental considerations, their
woodiness of vetiver oil. It is essentially a grapefruit odorant carbon footprint (cf. Glossary) and their persistency (cf. Glos-
with woody accents and vetiver facets. Announced in 2012, it sary). Karanal (342, Figure 6) was the first substance to be
was never used to any meaningful extent, and the patent was prohibited due to its highly persistent and bioaccumulative
dropped in 2020. So, renewability is not enough, and nature. Other non-biodegradable materials are endangered too,
Review
ability by general consensus in the F&F industry refers to

inherent biodegradability.
Biodiversity: The biological diversity defined as variety and
interaction of living things on Earth, including terrestrial, marine
and other aquatic ecosystems.
Biotechnology: The use of enzymes, microorganisms and
living systems in general to develop or manufacture products
from all sorts of organic raw materials. An ingredient is biotech
if at least one transformation involves a biotechnological
Figure 6. Structure and odor description of Karanal (342) and today’s most
decisive evaluation criteria for future perfumery ingredients. process. A color code denotes the different areas of biotech
activities. White biotechnology uses enzymes and genetically
modified microorganisms to produce value-added compounds
from renewable resources. Green biotechnology also termed
which creates opportunities for new biodegradable and renew- agritech uses microbiological techniques to genetically modify
able odorants far beyond the ambra domain. plants and crops to improve their production quantity and/or
Perhaps the singular largest opportunity lies in the woody nutritional quality. Blue biotechnology is assigned to aqua-
family, although it impacts all other families as well: a culture and activities and applications involving coastal and
biodegradable and renewable replacer for Iso E Super (264/5). marine organisms and bioresources.
In the floral and musky domain, renewability is more critical Carbon Footprint: The amount of carbon-based greenhouse
than biodegradability. In any case, looking into the future is gases usual reported in tons per year for a given entity such as
key, and no doubt is the puck going at high-speed towards a products, populations, or industry sectors to allow comparison
climate-neutral, eco-friendly and sustainable economy. The for the environmental impact.
cost–performance ratio will no longer be the decisive, most Carbon Neutrality: Equivalent to net zero emissions (climate
crucial criterion; biodegradability and renewability are already neutrality, vide supra) except that only the contribution of CO2
today at least of equal importance in designing and developing is considered.
new perfumery ingredients (Figure 6). Green Chemistry: Design of energy and resource efficient
Perfumers as humans in general have the tendency to chemical processes from renewable feedstock and (ideally
follow a behavioral economy in constructing perfumes, but catalytic) syntheses of biodegradable and sustainable products
well-established accords and easy-to-use ingredients that once that minimize, prevent, or eliminate waste materials and
seemed ideal for creation now become a problem. The environmental pollution by solvents, auxiliaries and hazardous
perfumes of the future will be based on a cost-optimized main chemicals.
skeleton of renewable and biodegradable fillers accompanied Mass-Balance Approach: The amount of renewable feed-
by selected high-impact captives with unique signatures. These stock (e. g. bio naptha obtained from vegetable oils) that is
will have to be renewable and biodegradable as well but can intermixed with conventional petrochemical feedstock for
tolerate certain on-costs. Perfumery will have to reinvent itself instance in a steam cracker when accounted for in specific end
and Fragrance Chemistry once again will be its motor. products after the chemical transformations have taken place.
This chain-of-custody model is standardized by ISO
22095 : 2020.
13. Glossary Natural: Equivalent to biobased. A material from renewable
plant, marine, and forestry-based resources that is free from any
Biobased: Derived from biomass, which according to norm EN petroleum-derived products.
16575 : 2014 is a material from renewable plant, marine, and Net Zero Emissions (Climate Neutrality): The greenhouse
forestry-based resources free from any petroleum products. gases released when offset by removing an equivalent amount
Biodegradability: Biological processes that break down of gases from the atmosphere and storing it permanently in
organic compounds by action of microorganisms into natural soil, plants or other organic materials.
building blocks such as carbon dioxide, water and minerals. In Odor threshold: The smallest perceptible concentration of
the standard definition of the EU > 90 % of the organic material an odorant in a solvent by a statistically significant number of
must be converted to CO2, H2O and minerals within 6 months. panelists. It varies critically with the solvent and is generally
Furthermore, the degree of biodegradability is classified accord- determined in water or air. Threshold values are usually
ing to the OECD guideline 301[12] and 302 as readily (> 60 % for reported as geometrical means of the different individual values
OECD 301B/C/D/F and > 70 % for OECD 301 A/E converted into of the different panelists and are given in gram (or fractions of
CO2 within 28 d) or inherently (> 60 % for OECD 301B/C/D/F it) of the respective compound per liter of solvent (air).
and > 70 % for OECD 301 A/E converted into CO2 within 60 d). Perfumery ingredient: The fragrant materials in a composi-
Often ultimately biodegradable (> 60 % converted into CO2 tion that contribute to the olfactory impression of a perfume.
within 90 d) is used as well, but not mentioned by the IFRA Depending on their volatility, their amount and their odor
environmental Task Force.[289] If not further specified, biodegrad- threshold they are grouped into certain ingredient classes: Top
note materials that are perceived immediately after application,
Review
middle or heart note ingredients around which the main theme Data Availability Statement
is constructed, and fond or base note ingredients that relate to
the dry down and prolong the sensory impact. Within these Data sharing is not applicable to this article as no new data
classes there is a differentiation according to the function in the were created or analyzed in this study.
perfume formula: high-impact materials with extremely low
odor thresholds that are dosed in trace amounts only, Keywords: Crude sulfate terpentine · green chemistry ·
nuanceurs that modify certain odor aspects, fixateurs that fixate fragrances · odorants · olfactory properties · renewability ·
certain odor qualities, signature notes that provide character to sustainability · terpenoids
a fragrance, and filler materials that on the opposite possess
low intensity but high transparency and provide volume.
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Chem. Biodiversity 2014, 11, 1821–1842. Version of record online: ■■■, ■■■■
REVIEW
What will the Sustainable Future Dr. F. Elterlein, Dr. N. Bugdahn, Dr. P.
smell like? The way into a resource- Kraft*
friendly economy will have different
1 – 37
impact on the various perfumery
families, but it will not be an avenue Sniffing Out the Sustainable Future:
to all-natural fragrances as these have The Renewability Revolution in
the highest carbon footprint. In this Fragrance Chemistry
report, you can find out what a world
with 100 % renewable and biodegrad-
able fragrances smells like, and which
opportunities for new ingredients
arise.

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Chemistry—A European Journal doi.org/10.1002/chem.202400006

Sniffing Out the Sustainable Future:

remains 76 % of all perfumery ingredients or ca. 490’000 tons

Scheme 3. Synthesis of 2-decenal (20) in analogy to 2-hexenal using vinyl

able 2-dodecenal (20) could be synthesized in analogy to 2-

Since citrus oils are produced by expression of the citrus peels

Scheme 5. Synthetic approaches to β-sinensal (34) from myrcene (23)

Scheme 6. Synthetic approach to renewable α-sinensal (46) from myrcene

4.2. Lack of Green Chemistry for Green Leafy Odorants

In the domain of leaf alcohols there is, paradoxically, a serious

Another important grassy-green, herbal odorant is Vertoci-

5.1. Pears for Paradise

Contrary to flavors, where we find the whole spectrum of fruits,

6.2. Matching Muguet in a Natural Way

The 100/100 sustainable and biodegradable lily-of-the-valley (fr.

to styrene oxide, (148) affording 2-phenylethyl alcohol (151)

Scheme 18. The sustainable muguet notes of dihydrofarnesal (154), Mela-

in high demand. Mahonial (163) meets all olfactory needs, as

dosage. Looking at the side chain, Projasmon P (185) is

Renewable (+)-limonene (8), an upcycled waste product from 7. Floriental Perfumes

lactonic elements are essential, and sandalwood odorants are

7.2. Milky-Creamy Intimacy of Santal Odorants

ates 212–214 to undergo side reactions and decomposition. 8. Oriental Perfumes

Even lower production costs for ( )-Ambrox (229) were

300 g L 1 substrate[216] which we would estimate to translate to

8.2. Dry Ambers from Cedarwood

9.1. I am Trash: Iso E Super

The name is a concept in this fragrance family characterized by

Andrier. “Iso E” (= OTNE, 264/5) is, however, not a substance

higher than that of Iso E Super (264/5), especially if renewable

10.1. Patchouli Taking Over

Scheme 38. Synthesis of renewable Ambrettollide (288) from aleuritic acid

Ambrette seed oil (Abelmoschus moschatus Medik. syn. Hibiscus

(289), leading to increased rainforest deforestation. Shellac

10.3. The Oaky Timbre of Evernyl

While the constituents atranol (277) and chloroatranol (278, cf.

11. Fougère Perfumes

11.1. Strong and Masculine?

Despite many attempted coups to feminize this first family of

synthesis commences from citronellene (305, also known as

11.3. Relaxing Vibes: Vertenex and Vetiver

Finally, the warm, sweet-mossy coumarin–oakmoss dry-down of

biotechnology as such is neither always green nor the answer

12. Concluding Thoughts

In answer to the question, “Do fragrances harm the environ-

ability by general consensus in the F&F industry refers to

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