1. Regioselectivity of Odor Perception
an appropriate model, the dependance of the odor properties of an organic
compound on structural modifications can be readily demonstrated. In the
simplest case one can affect an odor change on an odorant by changing
the molecular environment of the functional group.
A simple transposition of the allyl function in an odorant can lead to drastic changes in odor quality. A good example in b-ionone 2 the odor of which after transposition into "roseketone" 3 changed from the typical violet character to a complex odor which very fruity, camphoraceous and green tonalities.
2. Stereochemistry and Odor
Functional groups play a determining part on the strengh and character
of odorants. The driving force of the odor receptor event is considered
to be a directed dipole-dipole interaction.
irones, in that a methyl group is in the ring are remarkable substances
possessing a powerful and most pleasant violet odor much superior to any
ionone and methylionone.
Diastereoselectivity:Small changes in the molecular srtucture of a stimulus can lead to drastic changes in the qualitative odor properties of an odorant.
the standpoint of aroma quality, cis-a-irone
has a clean iris oil odor, while the diasteromeric trans-a-irone
is less appreciated.
possesses a powerful and most pleasant violet odor much superior to trans-g-irone.
3. QSAR (Quantitative-Structure-Activity-Relationships)
Using connectivity parameters as selective descriptors, QSAR studies were done with several types of odorants like the sweaty odor of fatty acids, and compounds that are structurally related to benzaldehyde. The fact that the two of Amoore's "Primary Odors" such as etheral and floral could also be correlated to a corresponding standard compound reduces the value of this correlation procedure. Unfortunately, three dimensional connectivity increments are not known.
Methods that only use physico-chemical
data, as well as topological approaches that use only two dimensions, are
not suited for olfactory studies. A statistical method that is based on
the computer-assisted identification of the sensory active parts of a molecule
for calculating Structure-Activity Relationships (SAR) showed great results.
The value of this pattern recognition analysis depends on the number and
quality of the selected descriptors.
Computer-assisted molecular modeling handles the molecular properties of an active compound in three dimensions. Today, a number of commercially available programs can be used for computer-aided molecular graphics. The pharmaceuticalndustry also uses tailor-made, proprietary programs for this purpose.
The super-imposition of structurally modified compounds with active molecules not only allows the identification of the osmophoric structural parts but it can also, to a limited extent, lead to the prediction of new odorant that possess similar properties to the compound with which it was superimposed.
Recently , molecular modeling of b-ionone
showed that the steric bulk of the dimethyl substitution can be mimic
by fusing a six-membered ring. The remaining 5-methyl group was then found
to be best superimposed by a cyclooctene structure.
Combination of these structural features gave the bicyclic ketone 9.
9 was synthesized and the fruity-woody odor of the tailored molecular target 9 was indeed found to be very close to that of the parent b-ionone 2.