AROMA CHEMICALS : - IFEAT

Six-membered ring compounds are called delta-lactones.
O
O
δ-Decalactone
O
O
Jasmolactone
O
O
δ-2-Decenolactone
(2-Decen-5-olide)
Seven-membered ring types are called epsilon-lactones. Examples of macro-cyclic lactones
include cyclopentadecanolide (pentalide), cyclohexadecanolide and ambrettolide.
O
O
ε-Decalactone
O
O
15-Cyclopentadecanolide
Gamma-lactones, especially gamma-alkyl-gamma-lactones and delta-lactones, especially deltaalkyl-delta-lactones
are the focus here. They are also called gamma- or delta-C number lactone.
The number refers to the number of carbon atoms that constitute the lactone. For example,
gamma-decalactone is constituted from ten carbons, so it is called gamma-C10 lactone.
Lactones in nature
Gamma-alkyl-gamma-lactones and delta-alkyl-delta-lactones are found in various plants, animals
and insects. Table 1 shows the occurrence of 15 lactones, including 9 gamma-lactones and 6 deltalactones,
in peaches 1 .
A map of lactones in nature is shown in Table 2. This is compiled from examination of the BACIS
Computer Database 2 . It reveals that lactones are found in a wide variety of natural foods. This
information is often the starting point when we construct flavors and fragrances.
Odour characteristics of lactones
The odour characteristics of gamma-lactones and delta-lactones are shown in Table 3. The size of
the dots indicates to the comparative strength of an odour note. For example, gamma-C9 lactone
displays four notes : tonka-coumarin, coconut, peach, and floral and the coconut note is dominant.
The sugar-tobacco note exists in gamma-C5, 6, and delta-C8, 9 lactones, and especially in gamma-
C5 lactones.
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Lactones as aroma chemicals
Table 1. Volatile compounds in peaches (Ref. 1)
GC cont. (%)
Compound Hakuhou Hakutou Nishiki Kantou 5-gou Nectarine
Hydrocarbons (0.46) (0.43) (0.46) (0.00) (0.25)
Alcohols (49.83) (23.10) (16.40) (41.03) (50.81)
Carbonyls, aldehydes (2.23) (1.25) (6.07) (2.78) (4.36)
Carbonyls, ketones (0.00) (0.07) (0.00) (0.06) (0.09)
Acids (4.45) (1.87) (6.44) (2.87) (5.69)
Esters (5.01) (1.92) (10.15) (8.28) (5.78)
Lactones (28.93) (58.05) (43.80) (38.20) (24.89)
gamma-hexalactone 7.00 9.05 10.97 7.62 5.53
gamma-heptalactone 0.24 0.32 0.58 0.36 0.19
gamma-octalactone 0.92 1.79 1.51 1.56 0.63
delta-octalactone 0.39 0.38 0.68 0.29 0.15
gamma-nonalactone 0.09 0.14 0.24 0.27 0.10
gamma-decalactone 11.22 27.72 15.94 17.88 11.92
delta-decalactone 3.75 7.38 6.35 3.70 3.21
gamma-dodecalactone 0.35 4.60 1.88 1.24 0.11
gamma-tridecalactone - 0.10 0.09 0.05 -
delta-tetradecalactone - t - t -
trans-marmelolactone t 0.34 0.05 t t
cis-marmelolactone t 0.40 0.05 t t
trans-7-decen-5-olide - 0.32 0.14 0.43 -
cis-7-decen-5-olide 0.78 1.79 2.10 1.05 0.51
6-0entyl-alpha-pyrone 4.19 3.72 3.22 3.75 2.54
t:trace
Table 2. Map of lactones in nature (Ref. 2)
γ-lactones
δ-lactones
C5 C6 C7 C8 C9 C10 C11 C12 C6 C8 C9 C10 C11 C12 C13 C14
apricot ● ● ● ● ● ● ● ● ●
blackberry ● ● ● ● ● ● ● ● ● ●
melon ● ● ● ● ●
papaya ● ● ● ● ● ● ● ● ●
peach ● ● ● ● ● ● ● ● ● ● ●
pineapple ● ● ● ● ● ● ● ● ●
raspberry ● ● ● ● ● ●
strawberry fruit ● ● ● ● ● ● ● ● ●
butter ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●
cheddar cheese ● ● ● ● ● ● ●
milk ● ● ● ● ● ● ● ● ● ●
yogurt ● ● ● ●
beef ● ● ● ● ● ● ● ● ● ● ● ● ●
chicken ● ● ● ● ● ● ● ● ● ● ● ● ● ●
pork ● ● ● ● ● ● ● ● ● ● ● ● ● ●
coconut oil ● ● ● ● ● ● ●
shiitake mushroom ● ● ● ●
tomato ● ● ● ● ●
black tea ● ● ● ● ● ● ● ● ●
green tea ● ● ● ●
rum ● ● ● ● ● ●
bourbon whisky ● ●
red wine ● ● ● ● ●
white wine ● ● ● ● ● ● ● ● ● ●
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Gamma-C9 lactone appears in four notes, tonka-coumarin/coconut/peach/floral, but with the
coconut note dominating. A sugar-tobacco note exists in gamma-C5 and -C6, in delta-C8 and -C9
lactones, and it is particularly strong in gamma-C5 lactones.
The bottom row of Table 3 provides our proposal on the odour character contributed by individual
lactones.
NOTES
Table 3. Odour characteristics of lactones
γ-lactones
δ-lactones
C5 C6 C7 C8 C9 C10 C11 C12 C8 C9 C10 C11 C12
Sugar-Tobacco ● ● ● ●
Tonka-Coumarin ● ● ● ● ● ● ●
Coconut ● ● ● ● ● ●
Peach ● ● ● ● ● ● ●
Floral ● ● ● ● ● ●
Milk-Butter ● ● ● ●
proposal
Jasmin Hay Hay Tuberose Jasmin Milk Rum Osmanthus Plum
Musk Nut Tuberose Cream Whisky Nectarine
Hay Osmanthus Tropical Fruits
Chiral lactones
A single peak is observed when lactones are analyzed by normal gas chromatography,. However,
this peak can represent a 50:50 racemic mixture of two ‘chiral’ enantiomers (spatial mirror
images). Separation of enantiomers is difficult since almost all their physical properties are the
same. It has taken approximately ten years to develop a new technology of chiral gas
chromatography for separating racemates into two peaks by as shown in Figure 1.
Enantiomers are distinguished, according to their spatial structure as an (R)-isomer or an (S)-
isomer. The identity as an (R) or (S)-isomer is determined as shown in Figure 2 by the following
steps :
• First of all, the four groups attached to the stereogenic carbon are identified and given
priorities according to the Cahn-Ingold-Prelog sequence rule (1 = high, 4 = low).
• Once priority numbers have been established, we imagine looking-down the bond from the
stereogenic atom (usually carbon) toward the atom of lowest priority (4, often H). The
other three substituents (1, 2, 3) will be facing you.
• Next connect these three atoms with an arrow running from highest to lowest priority
number (1->2->3).
• If this arrow runs clockwise, the enantiomer is called (R) (Latin: rectus, ‘right’) but if it
runs counterclockwise, it is called (S) (Latin: sinister, ‘left’)
It should be noted that not all lactones in nature are racemic, chiral, optically active or optically
enriched, and this means that they are not racemates.
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Lactones as aroma chemicals
Figure 1. Gas chromatography of gamma-lactones by chiraldex G-TA column
Figure 2 : Designation of chiral identity
O
2
4 ≡
O H
1 C6 H
3 13
O
O
H
(R) Enantiomer;
the arrow 1→2→3
runs clockwise
(R)-gamma-decalactone
O
2
1
O
4
H
C 6 H
3 13
≡
O
O
H
(S) Enantiomer;
the arrow 1→2→3
runs couterclockwise
(S)-gamma-decalactone
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Table 4. Odour characteristics of gamma-lactones 4
(Key : A = 1ppm ; B = 10ppm ; C = 20ppm.)
S -isomers
γ-lactones
R -isomers
nearly odorless
(B)sweet, caramel (C)sweet, spicy
sweet, creamy coconut, with some woody aspects
(B)herbaceous
fatty, coconut note, with fruity-sweet aspects, less intens than R -isomer
(B)coconut, faint sweet, nutty
fatty, coconut note less intens than R -isomer
(A)coconut (B)coconut, extremely sweet more intense than R -isomer
fatty, moldy, weak coconut note less intense than R -isomer
coconut, more intense than R -isomer (B)coconut, less intense than R -isomer
soft, sweet coconut note with fruity-fatty aspects
(B)creamy, peach note
fatty-sweet aldehyde note less intense than R -isomer]
(A)sweet, caramel (B)sweet, lactone character
fatty-fruity, milky note less intense than R -isomer
(A)fruity-sweet lactone (B)less intense than R -isomer
C5
C6
C7
C8
C9
C10
C11
C12
faint, sweet
(B)sweet, caramel (C)sweet, spicy
faint, sweet coconut with a fatty herbaceous hay note
(B)herbaceous
sweet, spicy, herbaceous hay note, reminiscent of coumarin
(B)coconut, faint sweet, nutty
spicy-green, coconut note, with almond notes
(A)coconut (B)coconut, extremely sweet
strong, sweet, soft coconut with fatty-milky aspects
(A)coconut (B)coconut
strong, fatty-sweet fruity note, some reminiscence to coconut, caramel
(B)creamy, peach note
strong, fatty-sweet, reminiscent of peach, with some bloomy aspects
(A)sweet, caramel (B)sweet, lactone character
strong, fruity-sweet, bloomy note with aldehyde and woody aspects
(A)fruity-sweet, peach, apricot, lactone character (B)sweet peach note
Note :
• The upper line is for odour appraisal using a solution (1 %, propylene glycol) tested on smelling strip.
• The lower line taste appraisal of a solution in invert sugar (10 %) + 0.015 % citric acid.
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Lactones as aroma chemicals
Odour characteristics of chiral lactones
Chiral lactones are considered interesting materials for flavors and fragrances, because (R ) and (S)
isomers have been shown 4,5 to exhibit different odour characteristics as listed in Tables 4 and 5.
Table 5. Odour characteristics of delta-lactones (Ref. 5)
S-isomer δ -
lactone
More fatty,but less intensive coco note
C8
Creamy,fruity, nutty, less intensive than (R)
antipode.
Fruit-sweet,creamy peach note with a fatty,
buttery tonality, more intensive than (R) antipode. C10
R-isomer
Soft, distinct coco note with spicy-sweet
aspects and a weak coumarin–note.
Creamy, fruity, nutty.
Fruity-sweet, milky note.
Similar to (R) antipode, but more intensive.
Similar to (R) antipode, but more intensive, with
distinct aldehyde and sweet note.
Fruity, creamy, more intensive than (R) antipode.
C12
Creamy, fruity peach, apricot note.
Fruity-sweet, apricot note with fatty-green
aspects.
Fruity-sweet apricot note.
Note :
• The upper line describes the odour in a solution (1%, propylene glycol) tested on a smelling strip.
• The lower line describes the taste of a 2ppm solution in 10% invert sugar.
Chiral lactones in nature
The development of chiral chromatography technology has resulted in the discovery of many
natural chiral lactones. For example, chiral gamma-lactones in the peach variety ‘hakuhou’ 1 are
shown in Table 6. All of the reported lactones, except for gamma-C7 lactone, are rich in the (R)-
isomer.
Table 6. Chiral lactones in peach “hakuhou” (Ref. 1)
lactone ee (%)
gamma- hexalactone 63.0(R)
gamma- hept alact one 9.2(S)
gamma- octalactone 70.2(R)
gamma- decalact one 79.8(R)
gamma- dodecalactone 89.8(R)
delt a- decalact one 96.8(R)
Figure 3 (overleaf) shows that in nature the (R)-isomer of chiral delta-decalactone is usually
dominant 8 .
In cheddar cheese (Figure 4), all of the chiral delta-lactones have a great preponderance of the (R)-
isomer.
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Figure 3 : Chiral delta-decalactones in nature 8
osmanthus oil
cheddar cheese
peach
raspberry
100 80 60 40 20 0 20 40 60 80 100
S-isomer
R-isomer
Figure 4 : Chiral delta-lactones in cheddar cheese 3
C10
Figure 3. Chiral delta-lactones in cheddar cheese (Ref. 3)
C11
C12
C13
C14
100 80 60 40 20 0 20 40 60 80 100
S-isomer
R-isomer
Chiral lactones are found also in insects. It has been proposed 6 that the pheromone responsible for
some aspects of the social behavior of queens and workers of the Oriental hornet, Vespa orientalis,
is delta-hexadecalactone which should be a chiral lactone, but the absolute configuration has not
been defined as yet. Also, (S)-gamma-decalactone was found in the Japanese beetle, Osmoderma
opicum 7 .
Applications of chiral lactones
An isomer of a lactone from nature can be used to create flavours and fragrances with a more
‘natural’ note. Also, there is the possibility of using other isomers from nature to make innovative,
artificial flavours and fragrances.
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Lactones as aroma chemicals
Preparation of chiral lactones
There are two approaches to obtain a chiral lactones, stereoselective synthesis and optical
resolution of a racemic mixture obtained by asymmetric synthesis, as shown in Figure 5.
Optical resolution is achieved by chromatographic or chemical or enzymatic methods. It is
important to carefully consider the most appropriate method since each process has both good and
bad points.
Figure 5 : Preparation of chiral lactones
How to access chiral lactones
Chemical synthesis
to make one isomer
(1) stereoselective synthesis
(2) asymmetric synthesis
Chiral Lactones
Optical resolution
to separate one isomer
(1) chromatography
ex. LC with chiral stationary phase
(2) chemical methods
ex. diastereomer salt formation
(3) enzymatic methods
ex. using lipases
In the case of the Soda Aromatic Company, optically enriched gamma-decalactone, gammaundecalactone,
and gamma-dodecalactone are manufactured and have been launched on the
market.
Conclusions
The progressive growth in availability of the range of chiral lactones is expected to result in both
the reduced usage of racemic lactones, which have a less ‘natural’ organoleptic character, and to
the creation of new types of flavours and fragrances.
Sigeru Wada is a graduate of the Department of Applied Chemistry of Keio University in Tokyo
and has 15 years experience in the synthesis of aroma chemicals. He joined the Soda Aromatic
Company in 1985. During 1998-1999, he engaged in research on synthetic organic chemistry as
an associated researcher at University of Pittsburgh in U.S.A..
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References
1. Youichi Yamamoto and Nobutomo Ichimura (1992) Koryo, 173, 97
2. VCF 00 Database of Volatile Compounds in Food, Data by TNO Nutrition and Food
Research, Boelens Aroma Chemical Information Service (BACIS), The Netherlands.
3. P. Werkhoff, S. Brennecke and W. Bretschneider (1991) Chem. Mikrobiol. Technol.
Lebensm., 13, 129
4. Armin Mosandl and Claus Gunther (1989) J. Agric. Food Chem., 37, 413
5. Armin Mosandl and Martin Gessner (1988) Z Lebensm Unters Forsch, 187, 40
6. Stefano Servi (1983) Tetrahedron Lett., 24, 19, 2023
R. Ikan, R. Gottlieb, E. D. Bergman and J. Ishay (1969) J. Insect Physiol., 15, 1709
7. Tatsuya Kodama, Hideo Nakanishi in The 43 rd Symposium on the Chemistry of Terpenes,
Essential Oils, and Aromatics(TEAC43), Japan, 1III-05 (1999)
8. P. Werkhoff et al. (1993) Z Lebensm Unter Forsch, 196, 307
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