As of April 6,
2010 You must have Java installed to view the
molecular visualization.
Chirality & Odour
Perception
It had been recognized by chemists in the flavor
& fragrance industry since the beginning of the
20th century that certain enantiomeric chemicals,
such as menthol and carvone had different &
differentiating organoleptic properties. Perhaps
the first rigorously definitive works were by
Julius von Braun culminating in the synthesis and
odor evaluation of the enantiomers of
3,5-dimethylcyclohexanone and the
3,5-dimethylcyclohexanols (see Geruch und
molekulare Asymmetrie, IV. Mitteilung: Die drei
1.3-Dimethylcyclohexanone-5 und die vier
1.3-Dimethyl-cyclohexanole-5, Berichte der
deutschen chemischen Gesellschaft (A and B Series),
Volume 60, Issue 11, Date: 7. Dezember 1927, Pages:
2438-2446).
By the 1960's, a number of processes had been
developed for the synthesis of the desired
(-)-menthol from optically active terpenoids and
both (-)-carvone and (+)-carvone were being
manufactured from (+)- and (-)-limonene
respectively by Norda (--> then Quest
International --> now Givaudan). However, the
premise that optical enantiomers could have
different odours was not generally accepted by
various academics (based partly on an erroneous
theory of olfaction proposed by Wright) until the
mid-1970's to 1980's's. Admittedly, prior to gas
chromatography and other measurments of
purification techniques, purity of the enantiomers
used for the odour evaluations was always a
question. In addition, a high enantiomeric excess
for the chemical is nearly always required for
organoleptic evaluations.
A number of reviews on this subject have been
written, notably those by Boelens1,
Ohloff 2 and Pickenhagen 3.
However, many new chemicals and their enantiomeric
odour descriptions have been reported since these
prior reviews were written. In this article, we
have compiled a list of chemicals for which
enantiomeric odour discrimination is known. Such
descrimination is defined as: differing odour
descriptors or/and odor strength as determined by
threshold measurements.
We greatly appreciate information provided to
us by Philip Kraft of Givaudan who along with his
associates (George Frater, Riccardo Cadalbert,
Caroline Denis, Jerzy Bajgrowicz, Markus Gautschi,
Roman Kaiser, Urs Muller & Walter Eichenberger)
have recently published a number of articles on
this subject.12-19 These references are
cited below. In addition, in January 2003,
Elisabetta Brenna, Claudio Fuganti and Stefano
Serra published an excellent review entitled
"Enantioselective perception of chiral odorants"
(Tetrahedron:
Asymmetry, 14 (1), 142, 2003)
Because of the very recent defining of the human
odour receptors by Lancet,
et. al, and Zozulya,
et. al, we thought that making available in
concise form, with accurate molecular structures
and molecular models (that are acknowledged
olfactorily as 3-D dependant) would be a benefit to
those working on the definititive concepts of
olfaction.
Introduction to
Chirality:
The concept of "chirality" has been known in
chemistry since the 1870's although it would be
nearly a hundred years before chemists began using
this term. In fact, in the first edition of Eliel's
"Stereochemistry of Carbon Compounds" in
19624, the word chiral is not mentioned,
although it would be prominant in later
editions5. In extremely simple terms,
chirality is "handedness," - that is, the existence
of left/right opposition. For example, your left
hand and right hand are mirror images and therefor
"chiral". The term Chiral is derived from the greek
name kheir meaning "hand" and apparently was coined
by Lord Kelvin in 1904, in his Baltimore Lectures
on Molecular Dynamics and the Wave Theory of Light
in which he stated ..."I call any geometrical
figure, or group of points, chiral, and say it has
chirality, if its image in a plane mirror, ideally
realized, cannot be brought to coincide with
itself."
For a simple video depiction see "Mirror
Molecule: Carvone" at NBC Learn.
While the concepts of "asymmetry" were developed
by J.H. vant Hoff 6 and J.A. Le
Bel7 in 1874 following the resolution by
Louis Pastuer of a mixture of tartaric acid salt
isomers during the period 1848-1853, in which he
picked out the differing crystal types by hand -
doing so on the basis of the differing physical
appearance of the salt crystals8.
Pastuer recognized that two of the isomers
polarized light differently (one to the left and
the other to the right) and that this must be due
to an asymmetric grouping of atoms in the optically
active molecules. Following Kekule's recognition in
1858 that carbon has a valence of 49,
vant' Hoff and Le Bel independently recognized that
when four different groups are attached to a carbon
atom, arrayed at the corners of a tetrahedron, then
the arrangements can be in two different forms, as
depicted schematically to the right.
As the number of carbons with assymetry
(chirality) increase in a molecule the number of
possible optical isomers (enantiomers) also
increases. With one asymmetric carbon, 2
isomers...with two asymmetric carbons, 4 isomers,
with three asymmetric carbons, 8 isomers...that is,
the number of isomers is 2n, where n =
number of asymmetric atoms.
In the early days, chemists often assigned
trivial names to differentiate isomers, and
enantiomers generally were specified by d- =
dextrorotary and l- = leavorotary based on which
direction the molecles polarized light. But Cahn,
Ingold and Prelog10 devised a system
based on assigning sequence rules based on
decreasing atomic number (and respective rate of
substitution for atoms of the same atomic number)
for projection formulas that allows the absolute
configuration assignments of R (for
rectus, Latin for right) and S (for
sinister, Latin for left). Tutorials on the
Cahn-Ingold-Prelog R/S notation are available on
the internet.11
These rules are incorporated in the chirality
monitor of Accelrys DS
Viewer and Discovery
Studio Visualizer (which is free). Very
occasionally, DS ViewerPro & Discovery Studio
Visualizer provides incorrect assignments (for
example, with the enantiomers of
gamma-dihydroionone, gamma-damascone, gamma-ionone
& methyl-gamma-cyclogeranate, etc.). However,
Cambridegsoft's
ChemDraw Ultra and ACD
Chemsketch (which is free) appear to
provide 100% correct C-I-P R,S assignments. Thus,
even without knowing the sequence rules, chemist's
today can rapidly establish the R/S configuration
at each asymmetric atom for a given molecular
structure in just a few minutes. The free version
of ACD
Chemsketch will verify C-I-P R,S assignments
for compounds having less than 50 atoms (the
commercial version handles more than 50 atoms).
The following tables link
to molecular visualizations of over 1,330
enantiomers (>665 enantiomeric pairs) with odour
descriptors and references. Note: Odour
thresholds are from evaluations in water unless
otherwise specified.
Technical Notes: The 2D-molecular
representations were built with the ACD Labs
"ChemSketch" or ChemDraw programs. The 3-D mol
models were prepared first by 3-D optimization in
ChemSketch or Chem3D Ultra which were then verified
in Accelrys DS
ViewerPro
or Discovery
Studio Visualizer. As this works poorly
(conformationally) for certain terpenoids and can
be totally inaccurate in absolute configuration for
some bicyclics and sesquiterpenoids, many of the
more complicated molecules were constructed and
energy minimized in Cambridegsoft's
Chem3D or AccuModel and then verified.
References:
1. Mans H. Boelens, Harrie Boelens & Leo J.
van Gemert, Perfumer & Flavorist, Vol.
18, No. 6, 1-15, (1993)
2. G. Ohloff, Scent and Fragrances,
Springer-Verlag (1994)
3. W. Pickenhagen, Enantioselectivity in Odor
Perception, in Flavor Chemistry - Trends &
Developments, ACS Symposium Series, Eds. R.
Teranishi, R.G. Buttery & F. Shahidi, American
Chemical Society, Washington (1989), pp.
151-157.
4. Stereochemistry of Carbon Compounds,
E. L. Eliel, (McGraw-Hill Book Company, Inc., New
York, 1962)
5. Stereochemistry of Organic Compounds,
Ernest L. Eliel and Samuel H. Wilen (Wiley, New
York, 1994)
6. J.H. van't Hoff, Bull. soc. chim.
France, [2]23, 295 (1875)
7. J.A. Le Bel, Bull. soc. chim. France,
[2]22, 337 (1874)
8. L. Pasteur, Two lecturesdelivered to the
Societe Chimique de Paris, Jan. 20 &
Feb. 3, 1860
9. A. Kekule, Ann., 106, 154 (1858)
10. R.S. Cahn, C.K. Ingold & V. Prelog,
Tetrahedron, 1, 119 (1961)
11.
http://www.chem.ucalgary.ca/courses/350/Carey/Ch07/ch7-6.html
12. Philip Kraft and Riccardo Cadalbert,
Constructing Conformationally Constrained
Macrobicyclic Musks, Chem. Eur. J., 7, No. 15, 3254
- 3262 (2001)
13. Philip Kraft, Caroline Denis, and Walter
Eichenberger, 5,6,7-Trimethylocta-2,5-dien-4-one 2
A Suspected Odorant with Surprising Olfactory
Properties, Eur. J. Org. Chem., 2363-2369
(2001)
14. Roman Kaiser & Philip Kraft, Neue und
ungewöhnliche Naturstoffe faszinierender
Blütendüfte, Chemie in unserer Zeit, 35,
No. 1, 8-23 (2001)
15. Markus Gautschi, Jerzy A. Bajgrowicz, and
Philip Kraft, Fragrance Chemistry - Milestones and
Perspectives, Chimia 55, 379387 (2001)
16. George Frater, Jerzy A. Bajgrowicz, and
Philip Kraft, Fragrance Chemistry, Tetrahedron, 54,
7633-7703 (1998)
17. Philip Kraft, Jerzy A. Bajgrowicz, Caroline
Denis and George Frater, Odds and Trends: Recent
Developments in the Chemistry of Odorants, Angew.
Chem. Int. Ed., 39, 2980-3010 (2000)
18. Philip Kraft and George Frater,
Enantioselectivity of the Musk Odor Sensation,
Chirality, 13, 388394 (2001)
19. Georg Frater, Urs Muller, and Philip Kraft,
Preparation and Olfactory Characterization of the
Enantiomerically Pure Isomers of the Perfumery
Synthetic Galaxolide, Helvetica Chimica Acta, Vol.
82, 1656-1665 (1999)
20. J.A. Bajgrowicz and G. Frater, Chiral
recognition of sandalwood odorants, Enantiomer,
5(3-4):225-34 (2000)
|
Two "chiral" forms
GO TO
Cyclic Terpenoid
Odorants
Bicyclic
Terpenoid Odorants
Acyclic
Terpenoid Odorants
Ionones, Irones,
Damascones & Structurally Related
Odorants
Acyclics (Alcohols,
Esters, Acids, Aldehydes)
Lactones &
Furanones
Sesquiterpenoid
Related Odorants
Steroid
Urine Type Odorants
Sandalwood
Type Odorants
Musk Odorants
Miscellaneous
|