Structure-Odor Relationship Study on Geraniol, Nerol, and Their Synthesized Oxygenated Derivatives

Article abstract of DOI:10.1021/acs.jafc.6b04534

Despite being isomers having the same citrus-like, floral odor, geraniol, 1, and nerol, 3, show different odor thresholds. To date, no systematic studies are at hand elucidating the structural features required for their specific odor properties. Therefore, starting from these two basic structures and their corresponding esters, namely, geranyl acetate, 2, and neryl acetate, 4, a total of 12 oxygenated compounds were synthesized and characterized regarding retention indices (RI), mass spectrometric (MS), and nuclear magnetic resonance (NMR) data. All compounds were individually tested for their odor qualities and odor thresholds in air (OT). Geraniol, the Z-isomer, with an OT of 14 ng/L, was found to be more potent than its E-isomer, nerol, which has an OT of 60 ng/L. However, 8-oxoneryl acetate was the most potent derivative within this study, exhibiting an OT of 8.8 ng/L, whereas 8-oxonerol was the least potent with an OT of 493 ng/L. Interestingly, the 8-oxo derivatives smell musty and fatty, whereas the 8-hydroxy derivatives show odor impressions similar to those of 1 and 3. 8-Carboxygeraniol was found to be odorless, whereas its E-isomer, 8-carboxynerol, showed fatty, waxy, and greasy impressions. Overall, we observed that oxygenation on C-8 affects mainly the odor quality, whereas the E/Z position of the functional group on C-1 affects the odor potency.

Full text of DOI:10.1021/acs.jafc.6b04534

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Article
Structure-odor relationship study on geraniol,
nerol and their synthesized oxygenated derivatives
Shaimaa Elsharif, and Andrea Buettner
J. Agric. Food Chem., Just Accepted Manuscript • DOI: 10.1021/acs.jafc.6b04534 • Publication Date (Web): 29 Oct 2016
Downloaded from http://pubs.acs.org on October 30, 2016
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Page 1 of 46
Journal of Agricultural and Food Chemistry
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StructureꢀOdor Relationship Study on Geraniol, Nerol and Their
Synthesized Oxygenated Derivatives
†
, ,‡
3
Shaimaa Elsharif and Andrea Buettner* †
†
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Department of Chemistry and Pharmacy, Food Chemistry, Emil Fischer Center,
FriedrichꢀAlexanderꢀUniversität ErlangenꢀNürnberg, Henkestr. 9, 91054 Erlangen,
Germany.
‡
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Department of Sensory Analytics, Fraunhofer Institute for Process Engineering and
Packaging (IVV), Giggenhauser Str. 35, 85354 Freising, Germany,
andrea.buettner@ivv.fraunhofer.de
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* Correspondence:
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Corresponding Author
Phone: +49ꢀ9131ꢀ85 22739
Email: andrea.buettner@fau.de
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Abstract
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Despite being isomers having the same citrusꢀlike, floral odor, geraniol, 1, and nerol,
3, show different odor thresholds. To date, no systematic studies are at hand
elucidating the structural features required for their specific odor properties.
Therefore, starting from these two basic structures and their corresponding esters,
namely geranyl acetate, 2, and neryl acetate, 4, a total of 12 oxygenated compounds
was synthesized and characterized regarding retention indices (RI), mass
spectrometric (MS) and nuclear magnetic resonance (NMR) data. All compounds
were individually tested for their odor qualities and odor thresholds in air (OT).
Geraniol, the Zꢀisomer, with an OT of 14 ng/L, was found to be more potent than its
E-isomer, nerol, which has an OT of 60 ng/L. However, 8ꢀoxoneryl acetate was the
most potent derivative within this study exhibiting an OT of 8.8 ng/L, while 8ꢀoxonerol
was the least potent with an OT of 493 ng/L. Interestingly, the 8ꢀoxo derivatives
smell musty, fatty, while the 8ꢀhydroxyꢀderivatives show odor impressions similar to
those of 1 and 3. 8ꢀCarboxygeraniol was found to be odorless, while its Eꢀisomer, 8ꢀ
carboxynerol, showed fatty, waxy and greasy impressions. Overall, we observed that
oxygenation on Cꢀ8 affects mainly the odor quality, while the E/Z position of the
functional group on Cꢀ1 affects the odor potency.
Keywords
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8ꢀHydroxygeraniol; Odor threshold in air; Retention indices Gas Chromatographyꢀ
;
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Olfactometry; Mass Spectrometry.
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Introduction
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Geraniol, 1, or (2E)ꢀ3,7ꢀdimethyloctaꢀ2,6ꢀdienꢀ1ꢀol, and its Zꢀisomer nerol, are
1
fragrant substances of great value. The smell of geraniol has previously been
described as sweet, fruity and berryꢀlike, while nerol has been reported as having
2
floral, citrusꢀlike and sweet smell properties. Geraniol, 1, and geranyl acetate, 2, are
major components of the essential oil of Cymbopogon martinii, Roxb. Wats. var.
motia known as palmarosa which is commonly obtained from its leaves and
3
flowering tops. Besides being used as a scenting substance in soaps, perfumes and
cosmetics, palmarosa oil is a potent mosquito repellent, antiseptic and has also painꢀ
3
relieving properties. Various studies further show that 1 has antiꢀtumor activity
4, 5
against various cancer cells, both in vitro and in vivo. Geraniol, 1, has been
reported to exert several other pharmacological effects such as antimicrobial,
antibacterial, antiꢀinflammatory, and antiꢀoxidant effects, as well as neuroꢀprotectivity
6
and hepatoꢀprotectivity. 1 has also been shown to exert anticonvulsant effects
7
which has been proven to be independent of benzodiazepine receptors. Nerol, 3, or
(2Z)ꢀ3,7ꢀdimethyloctaꢀ2,6ꢀdienꢀ1ꢀol, is a monoterpene which can be found in various
medicinal plants such as Lippia spp and Melissa officinalis L. These species are
renowned for their antimicrobial, antioxidant and antiviral properties due to the
8
ꢀ10
presence of nerol.
It was also shown that 3, just like several other monoterpene
alcohols, exerts an anxiolytic effect in mice and can also be used for the treatment of
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anxiety and restlessness. In addition, nerol is not only applied as an odorant in
fragrances, soaps, and shampoos but is also added to household cleaners and
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detergents. Neryl acetate, 4, was found as one of the major compounds isolated
from the essential oil of the curry plant Helichrysum italicum (Asteraceae) which is
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known for its antiꢀinflammatory, antioxidant, fungicidal, and astringent effects.
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Moreover, the essential oil of H. italicum is used as an emollient and as a fixative in
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perfumes due to its intense odor. Still, the smell of neryl acetate is described in
literature as roseꢀlike, and not spicy, curryꢀlike as one might assume from its
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dominant presence in H. italicum essential oil.
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Apart from the natural occurrence of the aboveꢀmentioned compounds 1ꢀ4, a series
of derivatives has been observed both in plants and animals. After oral
administration of geraniol, 8ꢀhydroxygeraniol and 8ꢀcarboxygeraniol were isolated as
15
metabolic products from the urine of rats. Interestingly, the carbon 8ꢀhydroxylation
of geraniol and nerol is also the first step in the biosynthesis of indole alkaloids in the
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higher plant C. roseus. 8ꢀHydroxygeraniol and 8ꢀhydroxynerol were further found
as glycosidically bound monoterpenes in Shiraz and Muscat of Alexandria leaves
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and berries, and as aglycones in nectarines. 8ꢀCarboxygeraniol, also known as
foliamenthoic acid, was isolated in small amounts from Tongling white ginger, and
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was found as a secoiridoid derivative, foliamenthin, in Menyanthes trifoliata.
Geranyl and neryl acetates, 2, and 4, are also present in the peel and leaf oils of
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lemon and lime species belonging to the family of Rutaceae, as well as in the peel,
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flowers (neroli) and leaves (petitgrain) of bitter orange (Citrus aurantium L.).
Geranyl acetate can be further found in sweet flag leaves at different growing
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phases. Its odor was described in literature as woody, floral and rosy. Among the
oxidation products of the acetates, 2, and 4, the 8ꢀoxogeranyl acetate is the only
compound that was found as constituent of the attractant pheromone blend that is
2
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secreted by the Australian predaceous bug, Oechalia schellenbergii (Table 1).
Apart from that, no systematic data is available, on the odor characteristics of these
metabolites or derivatives, or of any other physiological effects of these compounds
on humans or animals. To close this gap, the aim of our study was to systematically
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evaluate the odor qualities and odor thresholds of these substances as we
previously did in a comparative approach for the related derivatives of linalool and
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linalyl acetate. To achieve this aim, we synthesized, starting from geraniol, nerol
and their acetates, reported metabolites and hypothetical derivatives of these acyclic
monoterpenes following the same study design as in our previous investigation. The
aim was to allow for a comprehensive analytical and olfactory evaluation, and to
establish an extended substance library aiding future analytical research, thereby
comprising data on retention indices (RI values) as well as mass spectrometric and
nuclear magnetic resonance data.
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Materials and Methods
Chemicals
Geraniol, nerol, geranyl acetate, neryl acetate, selenium dioxide, sodium
borohydride, methanol anhydrous, ethanol, dioxane, tertꢀbutyl alcohol, 2ꢀmethylꢀ2ꢀ
butene, sodium chlorite, sodium dihydrogen phosphate, ethyl acetate, hexane,
magnesium sulfate were purchased from Aldrich (Steinheim, Germany), and diethyl
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00 ether from Fisher Scientific (Loughborough, UK).
01 General methods
02 All reactions requiring anhydrous conditions were carried out under nitrogen and the
03 solvents were dried before use to remove moisture using appropriate drying agents.
04 All reactions were monitored by thinꢀlayer chromatography (TLC) using Kieselgel 60
05
06 was achieved using ultraviolet (UV) fluorescence (254 nm) and potassium
07 permanganate (KMnO ) staining. Column chromatography was carried out over
F254 plates (Merck, Darmstadt, Germany). Visualization of the reaction components
4
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08 silica gel 60. The yields reported are after purification. H and C nuclear magnetic
09 resonance (NMR) spectra were recorded in deuterated solvents and chemical shifts
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10 (δ) are quoted in parts per million (ppm) calibrated to tetramethylsilane (TMS) ( H
13
11 and C). Coupling constants (J) were measured in Hertz (Hz). The identity of all
12 intermediates and synthetic products was determined by electron ionization mass
13 spectrometry (EIꢀMS).
14 Nuclear Magnetic Resonance (NMR) Spectra
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H and C NMR spectra were recorded in deuterated chloroform (CDCl ) on Avance
3
16 360 and Avance 600 spectrometers (Bruker Biospin, Rheinstetten, Germany) at
1
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17 room temperature operated at 360 or 600 MHz ( H) and 90 or 150 MHz ( C),
18 respectively, with TMS as internal standard.
1
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19 Gas chromatography-olfactometry (GC/O) and GC-Electron Ionization -Mass
20 Spectrometry (GC-EI-MS)
121 GCꢀO analyses were performed with a Trace GC Ultra (Thermo Fisher Scientific
122 GmbH, Dreieich, Germany) by using the following capillaries: FFAP (30 m × 0.32
123 mm i.d. fused silica capillary, free fatty acid phase FFAP, film thickness 0.25 ꢁm;
124 Chrompack, Mühlheim, Germany) and DB5 (30 m × 0.32 mm i.d. fused silica
125 capillary DBꢀ5, film thickness 0.25 ꢁm; J&W Scientific, Fisons Instruments, Mainzꢀ
126 Kastel, Germany). The helium carrier gas flow was set for FFAP and DB5 capillary
127 columns at 2.5 mL/min and 1.2 mL/min, respectively. The compounds eluting at the
128 end of the capillaries were split with a Yꢀsplitter, ratio 1:1 (v/v) (J&W Scientific) and
129 transferred via two deactivated capillaries (0.5 m x 0.2 mm) (J&W Scientific) to a
130 flame ionization detector and a heated sniffing port (temperature: 250 °C). The
131 samples were applied onto the capillary using a coldꢀonꢀcolumn injector at 40 °C.
132 After 2 min, the oven was heated at a rate of 10 °C/min to 240 °C and held for 7 min
133 (DBꢀFFAP) or to 280 °C and held for 5 min (DBꢀ5), respectively.
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34 GCꢀEI MS analyses were performed with an MSD 5975C (Agilent Technologies,
35 Waldbronn, Germany) and an ITQ 900 (Thermo Fisher Scientific, Dreieich,
36 Germany) with the capillaries described above. Mass spectra in the electron impact
37 mode (EIꢀMS) were generated at 70 eV.
38 Retention indices (RI)
1
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39 Linear retention indices (Table 1) were determined by GCꢀO using mixtures of
40 individual odorants dissolved in dichloromethane together with a series of nꢀ
41 hydrocarbons (C6–C34) dissolved in nꢀpentane, according to the method previously
24
42 described.
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43 Evaluation of odor quality
44 The odor qualities were determined during GCꢀO evaluation with the aid of seven
45 panelists (one male, six females, aged 28ꢀ33) who were trained volunteers from the
46 University of Erlangen, exhibiting no known illness at the time of examination and
47 with audited olfactory function.
148 In preceding weekly training sessions the assessors were trained for at least half a
149 year in recognizing orthonasally about 140 selected known odorants such as linalool,
150 benzaldehyde, Eꢀ2ꢀnonenal, and vanillin at different concentrations according to their
151 odor qualities and in naming these according to an inꢀhouse developed flavor
152 language. The odorants were presented to the panel in 140 mL Weck jars (J. Weck
153 GmbH u. Co. KG, WehrꢀÖflingen, Germany) as aqueous solutions that were
154 prepared following two protocols: 1) Either an ethanolic stock solution of the odorant
155 was prepared by dissolving the reference compounds in ethanol abs. in given
156 concentrations, followed by dilution of the odorant stock solution with tap water to
157 reach about a tenꢀfold concentration of the odorant above its respective odor
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158 threshold in water, so that clear smell perception was ensured, thereby taking care,
159 that ethanol content remained limited to a minimum, or 2) the pure odorant was
160 directly weighed and dissolved in tap water, again with the goal of reaching about a
161 tenꢀfold concentration of the odor threshold value in water of the respective
162 compound.
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63 With regard to the GCꢀO experiments that were carried out on the synthesized
64 compounds, samples were evaluated by each panelist repeatedly on different days,
65 as they performed dilution analyses, as well as on different capillary columns (DBꢀ
66 FFAP and DBꢀ5). Thereby, panelists were informed about elution times of the
67 compounds to ensure that inhalation corresponded with substance elution from the
68 sniffing port, and were asked to relate the naming of their sensory impressions to
69 smell impressions that they recalled from training, if possible.
70 Determination of odor thresholds
71 Odor thresholds were determined in air following the procedure described by Czerny
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72 et al. using Eꢀdecꢀ2ꢀenal as an internal odor standard. According to this procedure,
73 Eꢀdecꢀ2ꢀenal and the respective target compound were dissolved in dichloromethane
74 at known concentrations, in each case providing one stock solution comprising both
75 odorants. This stock solution was diluted stepꢀwise by a factor 1:2 (v/v), and all
76 dilutions were applied to HRGC/O until no odor was perceivable. From the flavor
77 dilution (FD) factors and the relative concentrations of standard and target
78 compound, the odor threshold values in air were then calculated as previously
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79 described. The detection odor thresholds of the panel were calculated as the
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80 geometric mean of the individual thresholds according to Czerny et al.
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81 Syntheses, general procedures
82 Procedure 1.
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83 Generally, the method of Wakayama et al. was used (Figure 1). Compounds 1-4
84 and selenium dioxide (SeO ) (1 eq.) were dissolved in dioxane/ethanol (9:1, v/v), and
2
85 the solution was heated at 80 °C for 5 h. After removal of selenium deposit by double
86 filtration, the solvent was removed under reduced pressure using a rotary
87 evaporator. The residue was purified twice by flash chromatography on silica gel 60
88 (Merck), with a mobile phase of hexane/ethyl acetate, affording the crude
89 compounds 5-8.
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90 (2E, 6E)-8-Hydroxy-2,6-dimethylocta-2,6-dienal (5), 8-Oxogeraniol.
91 Compound 5 was prepared following procedure 1 from 1 (1.9 g, 12.9 mmol) and
2
92 SeO (1.4 g, 12.9 mmol) in 30 mL dioxane/ethanol (9:1, v/v). Flash chromatographic
93 purification with hexane/ethyl acetate (1:1, v/v) yielded 268 mg (12.4 %) of 5 as
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94 yellow oil. H NMR (360 MHz, CDCl
3
) δ ppm 9.38 (s, 1 H), 6.46 (t, J=6.70 Hz, 1 H),
95 5.45 (t, J=6.24 Hz, 1 H), 4.11 (d, J=7.04 Hz, 2 H), 2.49 (q, J=7.57 Hz, 2 H), 2.10 ꢀ
13
3
96 2.15 (m, 2 H), 1.75 (s, 3 H), 1.70 (s, 3 H). C NMR (90 MHz, CDCl ) δ ppm 194.7,
+
97 153.2, 139.1, 137.3, 124.1, 40.1, 27.0, 16.0, 8.8. MS (EI) m/z (%) (rel.int.): 168 [M ]
98 (1), 136(8), 135(81), 121(88), 105(66), 91(88), 79(100), 77(73), 67(26), 55(45).
99 (2E, 6E)-3,7-Dimethyl-8-oxoocta-2,6-dien-1-yl acetate (6), 8-Oxogeranyl acetate.
00 Compound 6 was prepared following procedure 1 from 2 (2.1 g, 10.5 mmol) and
2
01 SeO (1.2 g, 10.5 mmol) in 30 mL dioxane/ethanol (9:1, v/v). Flash chromatographic
02 purification with hexane/ethyl acetate (3:1, v/v) yielded 438 mg (20 %) of 6 as pale
1
03 yellow oil. H NMR (360 MHz, CDCl ) δ ppm 9.37 (s, 1 H), 6.43 (t, J=7.20 Hz, 1 H),
3
04 5.37 (t, J=7.04 Hz, 1 H), 4.58 (d, J=7.04 Hz, 2 H), 2.48 (q, J=7.34 Hz, 2 H), 2.22 (t,
13
3
05 J=7.72 Hz, 2 H), 2.02 ꢀ 2.04 (m, 3 H), 1.73 (s, 6 H). C NMR (150 MHz, CDCl ) δ
06 ppm 195.1, 171.0, 153.3, 140.3, 140.0, 119.6, 61.1, 37.7, 27.0, 21.0, 16.4, 9.2.MS
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07 (EI) m/z (%) (rel.int.): 210 [M ] (1), 150(3), 135(56), 121(100), 107(39), 91(72),
08 79(55), 77(48), 67(16), 55(18).
09 (2E, 6Z)-8-Hydroxy-2,6-dimethylocta-2,6-dienal (7), 8-Oxonerol.
10 Compound 7 was prepared following procedure 1 from 3 (2.16 g, 14 mmol) and
2
11 SeO (3 g, 27 mmol) in 30 mL dioxane/ethanol (9:1, v/v). Flash chromatographic
12 purification with hexane/ethyl acetate (6:1 to 1:1, v/v) yielded 200 mg (8.5 %) of 7 as
1
13 yellow oil. H NMR (360 MHz, CDCl
3
) δ ppm 9.39 (s, 1 H), 6.46 (td, J=7.27, 1.14 Hz,
14 1 H), 5.50 (t, J=6.93 Hz, 1 H), 4.14 (d, J=7.00 Hz, 2 H), 2.45 ꢀ 2.48 (m, 2 H), 2.26 ꢀ
13
3
15 2.31 (m, 2 H), 1.78 (s, 3 H), 1.75 (s, 3 H). C NMR (90 MHz, CDCl ) δ ppm 195.1,
16 153.2, 139.8, 138.4, 125.5, 58.9, 30.5, 27.5, 23.2, 9.2. MS (EI) m/z (%) (rel.int.): 168
+
17 [M ] (1), 149(8), 135(38), 121(46), 107(33), 105(41), 91(93), 79(100), 77(89), 67(33),
18 55(55).
2
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2
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2
2
2
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2
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19 (2Z, 6E)-3,7-Dimethyl-8-oxoocta-2,6-dien-1-yl acetate (8), 8-Oxoneryl acetate.
20 Compound 8 was prepared following procedure 1 from 4 (2 g, 10.1 mmol) and SeO
2
21 (1.2 g, 10.3 mmol) in 20 mL dioxane/ethanol (9:1, v/v). Flash chromatographic
22 purification with hexane/ethyl acetate (6:1 to 1:1, v/v) yielded 171 mg (8 %) of 4 as
1
23 yellow oil. H NMR (600 MHz, CDCl ) δ ppm 9.39 (s, 1 H), 6.33 ꢀ 6.62 (m, 1 H), 5.43
3
24 (t, J=7.18 Hz, 1 H), 4.48 ꢀ 4.64 (m, 2 H), 2.48 (q, J=7.55 Hz, 2 H), 2.26 ꢀ 2.35 (m, 2
13
3
25 H), 2.04 (s, 3 H), 1.80 (s, 3 H), 1.75 (s, 3 H). C NMR (150 MHz, CDCl ) δ ppm
26 195.1, 170.9, 152.9, 140.8, 139.8, 120.5, 60.7, 30.5, 27.3, 23.2, 21.0, 9.2. MS (EI)
+
27 m/z (%) (rel.int.): 210 [M ] (1), 150(4), 135(63), 121(100), 105(45), 91(74), 79(67),
28 77(55), 67(16), 55(19).
2
2
2
29 Procedure 2.
28
30 Generally, the method of Liu et al. was used (Figure 1). Compounds 5-8 and
31 sodium borohydride (NaBH ) (2 eq.) were dissolved in dry methanol. The solution
4
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32 was stirred at ꢀ10 °C. After 1 h, water was added and the reaction mixture was
33 extracted with dichloromethane. The organic layer was dried over sodium sulfate.
34 After removal of the solvent, the residue was purified by flash chromatography on
35 silica gel 60 (Merck), with a mobile phase of hexane/ethyl acetate, affording the
36 crude compounds 9-12. As this approach has been previously reported as rather a
29
37 mildꢀselective procedure, all target compounds were specifically analyzed by GCꢀ
38 MS and NMR and compared to data reported in literature to exclude potential sideꢀ
39 reactions.
240 (2E,6E)-2,6-Dimethylocta-2,6-diene-1,8-diol (9), 8-Hydroxygeraniol.
241 Compound 9 was prepared following procedure 2 from 5 (117 mg, 0.69 mmol) and
2
2
2
2
2
2
2
42 NaBH (78 mg, 2.1 mmol) in 10 mL dry methanol. Flash chromatographic purification
4
1
43 with hexane/ethyl acetate (3:1, v/v) yielded 83.6 mg (70 %) of 9 as colorless oil. H
44 NMR (360 MHz, CDCl
3
) δ ppm 5.34 ꢀ 5.46 (m, 2 H), 4.14 (d, J=6.81 Hz, 2 H), 3.99
13
45 (s, 2 H), 2.12 ꢀ 2.19 (m, 4 H), 1.68 (s, 3 H), 1.58 (s, 3 H). C NMR (90 MHz, CDCl
3
)
46 δ ppm 139.1, 135.2, 125.6, 124.0, 69.0, 59.3, 39.1, 27.1, 16.2, 13.8.MS (EI) m/z (%)
+
47 (rel.int.): 169 [M ꢀ1] (1), 151(5), 137(9), 121(20), 119(35), 105(24), 93(40), 91(100),
1
30
48 67(99), 55(22). The H NMR data fully agreed with an earlier report.
2
2
49 (2E, 6E)-8-Hydroxy-3,7-dimethylocta-2,6-dien-1-yl acetate (10), 8-
50 Hydroxygeranyl acetate.
2
2
2
2
2
2
51 Compound 10 was prepared following procedure 2 from 6 (17.5 mg, 0.083 mmol)
4
52 and NaBH (41 mg, 1.1 mmol) in 10 mL dry methanol. Flash chromatographic
53 purification with hexane/ethyl acetate (3:1, v/v) yielded 11.4 mg (64.5 %) of 10 as
1
54 colorless oil. H NMR (600 MHz, CDCl
3
) δ ppm 5.31 ꢀ 5.39 (m, 2 H), 4.58 (d, J=7.18
55 Hz, 2 H), 3.99 (d, J=4.91 Hz, 2 H), 2.17 (q, J=7.43 Hz, 2 H), 2.07 ꢀ 2.12 (m, 2 H),
13
3
56 2.05 (s, 3 H), 1.70 (s, 3 H), 1.66 (s, 3 H). C NMR (150 MHz, CDCl ) δ ppm 171.2,
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2
2
57 141.7, 135.3, 125.2, 118.7, 68.9, 61.4, 39.0, 25.6, 21.0, 16.4, 13.7. MS (EI) m/z (%)
+
58 (rel.int.): 212 [M ] (1), 152(5), 134(14), 121(8), 119(76), 105(24), 93(30), 91(100),
31
59 79(69), 67(82), 55(19). The NMR spectral data agreed with Holsclaw et al.
2
2
2
60 (2E, 6Z)-2,6-Dimethylocta-2,6-diene-1,8-diol (11), 8-Hydroxynerol.
61 Compound 11 was prepared following procedure 2 from 7 (25 mg, 0.15 mmol) and
62 NaBH (97 mg, 2.5 mmol) in 20 mL dry methanol. Flash chromatographic purification
4
2
2
2
2
2
2
2
63 with hexane/ethyl acetate (1:1, v/v) yielded 18.6 mg (72.9 %) of 11 as colorless oil.
1
64
3
H NMR (360 MHz, CDCl ) δ ppm 5.34 ꢀ 5.51 (m, 1 H), 4.83 ꢀ 4.91 (m, 1 H), 4.05 ꢀ
13
65 4.08 (m, 2 H), 3.98 (brs, 2 H), 2.12 ꢀ 2.17 (m, 4 H), 1.73 (s, 3 H), 1.65 (s, 3 H). C
66 NMR (150 MHz, CDCl
3
) δ ppm 138.6, 135.6, 125.0, 124.8, 68.6, 58.9, 25.3, 23.3,
+
67 13.7. MS (EI) m/z (%) (rel.int.): 171 [M +1] (1), 151(2), 137(10), 121(7), 119(26),
1
68 105(15), 93(28), 91(100), 79(88), 67(71), 55(16). The H NMR data agreed with Ono
32
69 et al.
2
2
70 (2Z, 6E)-8-Hydroxy-3,7-dimethylocta-2,6-dien-1-yl acetate (12), 8-Hydroxyneryl
71 acetate.
2
2
2
2
2
2
2
2
2
72 Compound 12 was prepared following procedure 2 from 8 (66 mg, 0.3 mmol) and
73 NaBH (29 mg, 0.7 mmol) in 10 mL dry methanol. Flash chromatographic purification
4
1
74 with hexane/ethyl acetate (2:1, v/v) yielded 32.5 mg (48 %) of 12 as colorless oil. H
75 NMR (600 MHz, CDCl
3
) δ ppm 5.39 (brs, 1 H), 5.34 ꢀ 5.38 (m, 2 H), 4.57 (d, J=7.18
76 Hz, 2 H), 3.99 (s, 2 H), 2.13 ꢀ 2.18 (m, 4 H), 2.05 (s, 3 H), 1.77 (s, 3 H), 1.67 (s, 3 H).
13
77
C NMR (150 MHz, CDCl
3
) δ ppm 171.1, 142.0, 135.6, 125.0, 119.6 , 68.7, 61.2,
+
78 31.7, 26.0, 23.4, 21.0, 13.63. MS (EI) m/z (%) (rel.int.): 212 [M ] (1), 137(10), 121(7),
79 119(74), 105(23), 93(26), 91(100), 79(67), 67(77), 55(14), 51(11). The NMR data
33
80 fully agreed with Tomooka et al.
281 Procedure 3.
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2
2
2
2
2
2
2
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2
2
82 Pinnick oxidation was used for the following syntheses (Figure 1). The aldehydes
83 5-8 were dissolved in tertꢀbutyl alcohol and 2ꢀmethylꢀ2ꢀbutene. A solution of sodium
2 2 4
84 chlorite (NaClO ) (9.2 eq., 80%) and sodium dihydrogen phosphate (NaH PO ) (6.9
85 eq.) in water was added dropꢀwise over a 10 min period. The reaction mixture was
86 stirred at room temperature (25ꢀ30 °C) overnight. Volatile components were then
87 removed under vacuum, the residue was dissolved in 30 mL water and this was
88 extracted twice with 15 mL portions of hexane. The aqueous layer was acidified to
89 pH 3 with HCl and extracted three times with 20 mL of ether. The combined ether
90 layers were washed with 50 mL cold water, dried, purified by flash chromatography
91 on silica gel 60 (Merck), with a mobile phase of hexane/ethyl acetate and
92 concentrated to give 13-16.
2
93 (2E, 6E)-8-Hydroxy-2,6-dimethylocta-2,6-dienoic acid (13), 8-Carboxygeraniol.
94 Compound 13 was prepared following procedure 3 where compound 5 (2.3 g, 14.1
2
2
2
2
2
2
3
3
3
3
3
95 mmol) was dissolved in 50 mL tertꢀbutyl alcohol and 20 mL 2ꢀmethylꢀ2ꢀbutene. A
2 2 4
96 solution of NaClO (11.7 g, 161 mmol) and NaH PO (11.6 g, 97 mmol) in 40 mL
97 water was added dropwise over a 10 min period. Flash chromatographic purification
98 with hexane/ethyl acetate (6:1 to 1.5:2, v/v) yielded 832 mg (32 %) of 13 as pale
1
99 yellow oil. H NMR (600 MHz, CDCl
3
) δ ppm 6.76 (td, J=7.25, 1.50 Hz, 1 H), 5.43 (td,
00 J=7.00, 1.50 Hz, 1 H), 4.16 (d, J=7.00 Hz, 2H), 2.33 (q, J=7.50 Hz, 2H), 2.16 (t,
13
3
01 J=7.50 Hz, 2H), 1.81 (s, 3H), 1.64 (s, 3H). C NMR (150 MHz, CDCl ) δ ppm 172.1,
02 146.5, 139.4, 127.1, 124.6, 58.9, 40.4, 27.3, 16.4, 12.8. MS (EI) m/z (%) (rel.int.):
+
03 166 [M ꢀH
2
O] (1), 151(19), 148(100), 121(17), 117(16), 105(42), 91(77), 79(50),
04 77(61), 67(23), 65(30).
3
3
05 (2E, 6E)-8-Acetoxy-2,6-dimethylocta-2,6-dienoic acid (14), 8-Carboxygeranyl
06 acetate.
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07 Compound 14 was prepared following procedure 3 where compound 6 (175 mg,
08 0.83 mmol) was dissolved in 25 mL tertꢀbutyl alcohol and 6 mL 2ꢀmethylꢀ2ꢀbutene. A
2 2 4
09 solution of NaClO (694 mg, 9.5 mmol) and NaH PO (691 mg, 5.7 mmol) in 10 mL
10 water was added dropwise over a 10 min period. Flash chromatographic purification
11 with hexane/ethyl acetate (3:1, v/v) yielded 75.4 mg (40 %) of 14 as pale yellow oil.
1
12
3
H NMR (600 MHz, CDCl ) δ ppm 6.86 (td, J=7.27, 0.94 Hz, 1 H), 5.30 ꢀ 5.42 (m, 1
13 H), 4.59 (d, J=7.18 Hz, 2 H), 2.34 (q, J=7.43 Hz, 2 H), 2.14 ꢀ 2.22 (m, 2 H), 2.05 (s, 3
13
3
14 H), 1.83 (s, 3 H), 1.72 (s, 3 H). C NMR (150 MHz, CDCl ) δ ppm 173.4, 171.2,
15 143.9, 140.8, 127.5, 119.2, 61.2, 37.8, 27.0, 20.9, 16.4, 12.0.MS (EI) m/z (%)
+
16 (rel.int.): 226 [M ] (1), 166 (8), 150(7), 122(11), 121(100), 105(46), 91(37), 77(26),
17 67(10), 55(5).
3
18 (2E, 6Z)-8-Hydroxy-2,6-dimethylocta-2,6-dienoic acid (15), 8-Carboxynerol.
19 Compound 15 was prepared following procedure 3 where compound 7 (25 mg, 0.15
3
3
3
3
3
3
3
3
3
3
3
20 mmol) was dissolved in 20 mL tertꢀbutyl alcohol and 5 mL 2ꢀmethylꢀ2ꢀbutene. A
2 2 4
21 solution of NaClO (174 mg, 2.4 mmol) and NaH PO (210 mg, 2.3 mmol) in 10 mL
22 water was added dropwise over a 10 min period. Flash chromatographic purification
1
23 with hexane/ethyl acetate (1:1, v/v) yielded 10 mg (37 %) of 15 as yellow oil. H NMR
3
24 (360 MHz, CDCl ) δ ppm 6.83 (br. dt, J=6.70, 1.20, 1.20 Hz, 1 H), 5.48 (br. t, J=7.50,
25 7.50 Hz, 1 H), 4.12 (d, J=7.50 Hz, 2 H), 2.28 ꢀ 2.36 (m, 2 H), 2.20 ꢀ 2.27 (m, 2 H),
13
26 1.84 (s, 3 H), 1.73 ꢀ 1.78 (m, 3 H). C NMR (150 MHz, CDCl
3
) δ ppm 168.2, 141.4,
+
27 140.7, 127.1, 119.2, 60.5, 30.8, 27.2, 23.2, 12.4. MS (EI) m/z (%) (rel.int.): 166 [M ꢀ
28
2
H O] (1), 151(3), 148(100), 133(3), 121(8), 105(10), 91(12), 79(8), 77(11), 67(4),
29 65(5).
3
3
30 (2E, 6Z)-8-Acetoxy-2,6-dimethylocta-2,6-dienoic acid (16), 8-Carboxyneryl
31 acetate.
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32 Compound 16 was prepared following procedure 3 where compound 8 (65 mg, 0.31
33 mmol) was dissolved in 15 mL tertꢀbutyl alcohol and 5 mL 2ꢀmethylꢀ2ꢀbutene. A
2 2 4
34 solution of NaClO (290 mg, 4.0 mmol) and NaH PO (290 mg, 2.4 mmol) in 10 mL
35 water was added dropwise over a 10 min period. Flash chromatographic purification
1
36 with hexane/ethyl acetate (2:1, v/v) yielded 13.3 mg (19 %) of 16 as yellow oil. H
37 NMR (600 MHz, CDCl
3
) δ ppm 6.87 (t, J=6.99 Hz, 1 H), 5.42 (t, J=7.37 Hz, 1 H),
38 4.56 (d, J=7.18 Hz, 2 H), 2.33 (q, J=7.30 Hz, 2 H), 2.24 ꢀ 2.28 (m, 2 H), 2.05 (s, 3 H),
13
3
39 1.85 (s, 3 H), 1.79 (s, 3 H). C NMR (150 MHz, CDCl ) δ ppm 173.0, 171.1, 144.0,
40 141.2, 128.0, 120.2, 61.0, 31.2, 27.3, 23.3, 21.0, 12.0. MS (EI) m/z (%) (rel.int.): 226
+
41 [M ] (1), 166(8), 151 (7), 148(5), 121(100), 105(48), 91(40), 77(33), 67(11), 55(6).
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
42 Results and Discussion
43 The odor qualities of 1ꢀ4, and their synthesized oxygenated derivatives were
44 investigated by trained panelists using GCꢀO. The obtained odor attributes are
45 shown in Table 2. This procedure offers the advantage that compounds that might
46 be present as odorꢀactive impurities accompanying the reference compound are
47 separated from the target odorants during the chromatographic separation step.
48 Consequently, an influence of such components on the results is ruled out. Also,
49 odor thresholds can be compared to each other on an absolute basis without
50 interference with any matrix system as would be the case e.g. when determining
51 odor thresholds in water, oil or solid matrices. Potential pitfalls may arise in GCꢀO if
52 panelists do not take care to inhale at the time point of odorant elution from the GC
53 column so that they specifically need to be instructed on elution times as done in the
54 present study. Moreover, the chromatographic shape of the substances may vary
55 between different columns of different polarity. Accordingly, it is recommendable to
56 perform the experiments on capillaries with different polarities, as is done in the
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357 present study. Results obtained were reproducible and consistent as the
358 components were evaluated more than once on different columns at different days.
359 In addition, no changes in odor were observed when panelists olfactorily evaluated
360 different steps of concentration. It is worth mentioning that any impurity that might be
361 still present with our synthesized compounds did not interfere in the odor property
362 owing to the fact that elution by GCꢀO on different capillary columns revealed the
363 pure compounds without any interferences from even minute amounts that may
364 occur for example from organoꢀselenium byꢀproducts.
365 In general, geraniol, 1, geranyl acetate, 2, and nerol, 3, shared the main attributes
366 citrusꢀlike, floral, sweet and fruity with the sole exception of neryl acetate, 4, which
367 was described with unexpected odor attributes, namely cloveꢀlike and phenolic.
368 Panelists (three out of seven) specifically reported an olfactory similarity to the
369 characteristic clove constituent 4ꢀeugenol.
3
3
3
3
3
3
3
3
3
3
3
70 Geraniol, 1, was categorized by our panel as smelling citrusꢀlike as in previous
35
71 studies. However, this odor descriptor was more clearly specified by some
72 individuals to smell like orange peel and neroli. Additional odor attributes named for
73 1 were fresh and fatty as perceived by 43% of the subjects while only 29% gave the
74 attributes soapy and sweet. The odor of geranyl acetate, 2, was further described as
75 sweet and floral by 28% of the panel, while only two panelists used the terms soapy
76 and fruity. On the other hand, other odor attributes like soapy and floral were given to
77 nerol, 3, by 29% of the panel. Apart from that, 44ꢀ55% of the panel used the attribute
78 lemonꢀlike as a more precise descriptor for 3. The odor of neryl acetate, 4, was
79 perceived by 42% of the panel as floral, sweet and by 29% as cloveꢀlike, phenolic as
80 previously mentioned. Only one panelist perceived 4 as fattyꢀdusty. Despite being
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381 rated by the panelists as an intense odorant, one panelist was anosmic to 4 even
382 when directly smelling the substance in its pure oilꢀform from the bottle.
383 Regarding the odor qualities of the oxygenated derivatives, most of the 8ꢀoxo
384 derivatives were predominantly described by our panel as fatty, musty whereas the
385 8ꢀoxogeranyl acetate, 6, and the 8ꢀoxoneryl acetate, 8, were rated as citrusꢀlike by
386 42% and 57% of the panel, respectively. On the other hand, the 8ꢀhydroxy
387 derivatives showed odor attributes comparable to those of the respective parent
388 alcohols or acetates. Accordingly, these attributes comprised the main impressions
389 citrusꢀlike, floral, soapy and fruity. In addition to these smell impressions, half of the
390 panel rated the smell of 8ꢀhydroxynerol, 11, rather unexpectedly, as sweet and
391 vanillaꢀlike. Apart from that, it is interesting to note that 8ꢀhydroxyneryl acetate, 12,
392 was the sole substance that all panelists unequivocally agreed on as being citrusꢀ
393 like, with the exception of only one panelist who was anosmic to this substance.
394 In contrast to this, all 8ꢀcarboxy derivatives showed plasticineꢀlike, greasy and waxy
395 smells, with the sole exception of 8ꢀcarboxygeraniol, 13, which was unequivocally
396 perceived as odorless by all panelists, even at a concentration of 500 ꢁg/mL.
397 However, this plasticineꢀlike odor could not be further specified by the panel, as they
398 could not relate this impression to specific odor references. Nevertheless, this is
399 most likely due to the fact that the smell of plasticine as product of daily use is rather
400 a complex odorant mixture than a single compound.
401 Interestingly, one panelist described the smell of both 8ꢀcarboxynerol, 15, and 8ꢀ
402 carboxyneryl acetate, 16, as green and dillꢀlike. Moreover, these two attributes were
403 consistently reported by this panelist whenever smelling the two substances, even at
404 different concentrations and on different days. On the other hand, sweet and
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405 coconutꢀlike were recorded as attributes by 43% of the panel for the 8ꢀ
406 carboxygeranyl acetate, 14, while only one subject named coconutꢀlike for its isomer,
407 16. The same panelist who was anosmic to neryl acetate, 4, as mentioned earlier,
408 was also anosmic to the 8ꢀcarboxynerol 15 at the concentrations evaluated in this
409 study, i.e. a concentration of 220 ꢁg/mL.
4
4
4
4
4
4
4
10 With regard to the odor thresholds of the investigated compounds, it became clear,
11 as shown in Figure 2A, that geraniol is the most potent compound (14 ng/Lair
)
12 compared to its acetate, 2, and its corresponding oxygenated derivatives 5, 6, 9, 10
13 and 14. Thereby, 8ꢀhydroxygeraniol, 9, with an OT of 340 ng/Lair, was the least
14 potent compound in this substance group. In general, the OT values of geranyl
15 acetate, 2, and its oxygenated derivatives ranged between these OT values, and
16 predominantly between 22 ng/Lair and 66 ng/Lair
.
4
4
4
4
4
4
4
4
4
4
4
4
17 It can be observed that oxidation of Cꢀ8 of geraniol to 8ꢀoxogeraniol led to an
18 increase in the odor threshold by a factor of 13 (194 ng/Lair), thereby turning the
19 citrusꢀlike odor of geraniol to a fattyꢀmusty smell. Reduction of the aldehyde group to
20 the corresponding alcohol, the 8ꢀhydroxygeraniol, retained the citrusꢀlike, fresh odor
21 but led to a further decline in odor potency (340 ng/Lair). Further oxidation of the 8ꢀ
22 oxogeraniol to the 8ꢀcarboxygeraniol resulted in total odor loss. This demonstrates
23 that an increase in polarity at Cꢀ8 obviously reduces odor potency. This finding is in
24 agreement with our observations in our previous structureꢀodor relationship study of
23
25 linalool and its Cꢀ8 oxygenated derivatives. Accordingly, it appears that not only the
26 presence of the OHꢀgroup at Cꢀ1 in geraniol or at Cꢀ3 in linalool defines the citrusy
27 character and high odor potency, but that modification at Cꢀ8 also influences both
28 odor quality and potency.
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29 Despite being isomers and having comparable smell, nerol, 3, was found to be less
30 potent than 1 by a factor of 4 (odor threshold: 60.5 ng/Lair). Still, it is the most potent
31 substance among its oxygenated derivatives, comparable to what we observed for
32 geraniol. Introduction of the aldehyde function at Cꢀ8 of nerol, giving 8ꢀoxonerol, not
33 only changed the smell from citrusꢀlike to musty but also increased the threshold to
34 493 ng/Lair. On the other hand, a hydroxyꢀfunction at Cꢀ8, giving 8ꢀhydroxynerol,
35 retained the citrusꢀlike main impression but additionally provoked a sweet, vanillaꢀ
36 like note that was perceived by almost half of the panel. The 8ꢀcarboxynerol was
37 found to be the most potent odorant amongst the nerol oxidation derivatives with a
38 threshold value of 268 ng/L ; however, it exhibited a greasy, waxy odor. Apparently,
air
39 increase of the polarity of the Cꢀ8 oxygenated functional group in nerol results in an
40 increase of potency which is opposite to the observations made for linalool and
41 geraniol and their derivatives. This consideration is, however, made regardless of the
42 odor quality of the respective compounds which also changed as discussed before.
443 Regarding the acetate derivatives, 8ꢀoxogeranyl acetate was found to be the most
444 potent compound (22 ng/Lair) among the geranyl acetate derivatives; it was
445 dominated by a musty, dusty odor character. The alcoholic derivative, 8ꢀ
446 hydroxygeranyl acetate, retained the citrusꢀlike odor but with a 3ꢀfold higher odor
447 threshold value (65 ng/Lair). Thus, the odor quality and threshold value of the 8ꢀ
448 hydroxygeranyl acetate are nearly similar to those of the geranyl acetate. An acid
449 moiety at Cꢀ8 in the 8ꢀcarboxygeranyl acetate produced a decrease in the odor
450 threshold value to 39 ng/Lair; however, the smell turned from citrusꢀlike to sweetꢀ
451 coconut and plasticineꢀlike.
4
52 Overall, the term musty was used as a main descriptor for the odor of all the 8ꢀoxo
53 derivatives, mainly 8ꢀoxogeraniol, 8ꢀoxogeranyl acetate and 8ꢀoxonerol. The panel
4
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4
54 was not able to further specify this musty odor by any other sensory terminology but
55 additionally reported the terms citrusꢀlike (two panelists) in case of 8ꢀoxoneryl
56 acetate, and fatty (all panelists) for all 8ꢀoxo derivatives. It has been previously
57 reported that the term musty is a general term comprising such divergent
3
6
58 impressions like dusty, papery, earthy or moldy. Interestingly, and in line with these
59 previous reports, the term musty was further specified by two panelists by the
60 additional term dusty in case of the 8ꢀoxogeranyl acetate, and by only one panelist in
61 case of the 8ꢀoxonerol. Although geosmin and 2ꢀmethylisoborneol are compounds
36
62 that are most commonly associated with musty odor, there are no common
63 structural features between these substances and the odorants investigated within
37
64 the present study. According to Jong and Birmingham 2ꢀoctanone and 3ꢀoctanone
65 are two compounds produced by mushrooms which also possess a musty odor.
66 However, none of these substances elicits a comparable musty impression as
67 perceived for the compounds of the present study. Nevertheless, one might
68 postulate that the carbonyl moiety is a common functional group of these 8ꢀcarbon
69 chain ketones and our 8ꢀoxo derivatives, and might be responsible for the musty
70 odor perceived by the panel. On the other hand, the same structural feature did not
71 affect the pleasant odors of the 8ꢀoxolinalool and 8ꢀoxolinalyl acetate as no musty
23
72 smell was recorded for these compounds.
4
4
4
4
4
4
73 As discussed above, neryl acetate, with a relatively high odor threshold among its
74 derivatives (96 ng/Lair), showed unexpected odor attributes, namely cloveꢀlike and
75 phenolic. These descriptors are not common among this substance group, and have
76 never been reported before for this substance. Interestingly, the smell of neryl
14
77 acetate has been previously described as roseꢀlike. However, the method of smell
78 determination was not detailed in this study, so that it is unclear where these
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79 differences originate. Potentially, the differing impressions of the previous study
80 arose from other sideꢀproducts or contaminations, as application of GCꢀO as
81 analytical strategy was not mentioned in the experimental part of the study.
82 Interestingly, cloveꢀlike and phenolic would relate to a completely different substance
38
83 class, namely guaiacol and phenol derivatives such as 4ꢀvinylguaiacol. One might
84 hypothesize that the presence of a 4ꢀcarbon chain with a double bond at Cꢀ2 and a
85 methoxy or an acetoxy group at Cꢀ1 might be the common structural feature
86 responsible for this smell impression as illustrated in Error! Reference source not
87 found..
488 From the data compiled in Table 3, where all individual threshold values of the
489 participants are shown, it becomes evident that interꢀindividual variation in sensitivity
490 to these substances was pronounced. For example, 8ꢀoxogeraniol was found to
491 have the highest individual OT value (637 ng/Lair); yet, on average, it was not the
492 least potent compound amongst the geraniol derivatives. It is interesting to note that
493 no single panelist was especially sensitive to all compounds; however, one panelist
494 recorded the lowest OT values for three compounds, namely geraniol (2.8 ng/Lair),
495 geranyl acetate (18.8 ng/Lair) and 8ꢀhydroxygeranyl acetate (27 ng/Lair).
4
4
4
4
5
96 As can be seen from the data shown in Figure 2B, the lowest OT values were
97 determined in the nerol substance group with 8.8 ng/Lair for 8ꢀoxoneryl acetate and
98 27 ng/L for 8ꢀcarboxyneryl acetate, respectively, followed by nerol with a threshold
air
99 value of 60 ng/Lair. On the other hand, 8ꢀoxonerol was found to be the least potent
00 compound in this study, with a threshold value of 493 ng/Lair
.
5
01 When analyzing the data of individual panelists, the absolute lowest and highest
02 individual OT values were recorded for two nerol derivatives, with 0.41 ng/Lair for 8ꢀ
5
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503 oxoneryl acetate and 6480 ng/Lair, for 8ꢀoxonerol, respectively. Interestingly, these
504 two values were obtained from the same panelist; moreover, this panelist was also
505 exceptional in other terms, i.e. anosmic to 8ꢀhydroxyneryl acetate. Overall, the odor
506 threshold values showed that, for each substance, at least two panelists showed
507 comparable OT values regardless of the odor quality perceived. In addition, not more
508 than one subject was anosmic to each compound as previously mentioned, with a
509 total of five cases within the whole study.
5
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5
5
5
5
5
5
10 From the above results, several insights into structureꢀodor relationships can be
11 deduced for the investigated geraniol and nerol derivatives. With the exception of 8ꢀ
12 oxo and 8ꢀcarboxygeranyl acetate, all Eꢀisomer derivatives showed lower odor
13 threshold values than their respective Zꢀanalogues. Accordingly, the E/Z
14 configuration greatly affects the potency of the compounds regardless of the odor
15 quality. An aldehyde group at Cꢀ8 changed the odor completely from citrusꢀlike to
16 musty, with 8ꢀoxoneryl acetate showing somewhat exceptional behavior as this
17 substance retained the citrusꢀlike odor but was, in case of two panelists, associated
18 with a musty nuance. Comparing the results of this investigation with our previous
23
19 study on linalool and its derivatives, some links in structureꢀodor relationships
20 become obvious. First, substituting Cꢀ8 with an OHꢀgroup enhances the dominance
21 of the citrusꢀlike character; this is especially true for compounds bearing an acetate
22 moiety at Cꢀ1. In addition, 8ꢀhydroxy Cꢀ1 acetates are more potent than their
23 respective 8ꢀhydroxy Cꢀ1 alcohols. Next, a carboxyl group at Cꢀ8 is responsible for
24 plasticineꢀlike, greasy impressions as these were named for all odorꢀactive acid
25 derivatives. Last, it could be demonstrated that increase of the polarity of the
23
26 oxygenꢀbearing group at Cꢀ8 of geraniol or linalool decreases the odor potency
27 until the odor disappears. In contrast to this, the polarity is directly related to the odor
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528 potency for the oxygenated derivatives of nerol. More specifically, in this case a
529 carboxyl function at Cꢀ8 of nerol is more potent than an aldehyde group, regardless
530 of the odor quality.
531 To sum up, our study shows that geraniol, 1, nerol, 3, their acetates (2 and 4) and
532 their corresponding oxygenated derivatives, 5-16, were found to be odor active with
533 the sole exception of 8ꢀcarboxygeraniol. Odor threshold and odor quality
534 determinations revealed that structural changes on the basic skeleton of these
535 monoterpenes lead to derivatives that can be more potent or more pleasant with
536 regards to their smell character than the parent monoterpene itself. The 8ꢀoxo and 8ꢀ
537 hydroxy derivatives of geraniol, geranyl acetate and neryl acetate showed
538 comparable smells for all panelists whereas oxygenated derivatives of nerol showed
539 very divergent odor characteristics amongst panelists, with for example high
540 variations in odor thresholds for 8ꢀoxonerol and very divergent assignment of odor
541 attributes for 8ꢀcarboxynerol. Furthermore, cases of anosmia were recorded five
542 times for four panelists; three panelists for either 8ꢀhydroxygeraniol, 8ꢀ
543 carboxygeranyl acetate, or 8ꢀhydroxyneryl acetate, whereas one panelist showed
544 anosmia to both 8ꢀcarboxynerol and neryl acetate.
545 Overall, the structureꢀodor relationship of these monoterpene alcohols can be
546 summarized as follows; the OH group at C1 is the sole contributor to the odor quality
547 and potency of both isomers 1 and 3. Replacing this OH by an acetate group led
548 only to a remarkable decrease in the potency but not the odor quality, with the sole
549 exception of neryl acetate: for this substance the odor turned from the characteristic
550 citrusꢀ, lemonꢀlike impression of nerol to a cloveꢀlike, phenolic note. On the other
551 hand, an OH at Cꢀ8 preserved the common citrusꢀlike smell of the parent
552 monoterpenes, but not the potency, irrespective whether Cꢀ1 bears an OH or an
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553 acetate group. However, a carbonyl group at Cꢀ8 led to the appearance of a musty
554 note that was either relatively pure (8ꢀoxogeraniol) or accompanied by other odor
555 notes (8ꢀoxoneryl acetate). Last but not least, substitution of Cꢀ8 by a highly polar
556 functional group, the carboxy group, turned the odor of all derivatives to waxy,
557 greasy and plasticineꢀlike.
558 Accordingly, our study demonstrates that potentially naturally occurring nerol and
559 geraniol derivatives might be of sensory relevance as was previously demonstrated
560 for the corresponding linalool derivatives. Future studies will need to elucidate if
561 these substances contribute to certain smells in nature, or if they can impart other
562 physiological effects, apart from pure smell sensation.
5
5
5
63 Acknowledgments
64 We thank the members of our working group for their participation in the sensory
65 analyses.
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