The chemistry of flavours and fragrances is of great interest to academics and industrialists alike. Bringing together international contributors, this book presents the most recent research in this key area. Diverse topics such as structure-activity relationships; analytical techniques; natural products and essential oils; and organic and bioorganic chemistry are discussed, along with flavours and foods. Advances in Flavours and Fragrances: From the Sensation to the Synthesis will be a welcome addition to the bookshelves of all practitioners with a common interest in this fascinating area.
Advances in Flavours and Fragrances
From the Sensation to the Synthesis
By Karl A.D. SwiftThe Royal Society of Chemistry
Copyright © 2002 The Royal Society of Chemistry
All rights reserved.
ISBN: 978-0-85404-821-2Contents
Structure Activity Relationships,
Structure Activity Relationships and the Subjectivity of Odour Sensation Thomas Markert, 3,
Relationship of Odour and Chemical Structure in 1- and 2-Alkyl Alcohols and Thiols Y. Sakoda and S. Hayashi, 15,
Analytical,
New Developments in Sorptive Extraction for the Analysis of Flavours and Fragrances P. Sandra, F. David and J. Vercammen, 27,
Application of Chromotographic and Spectroscopic Methods for Solving Quality Problems in Several Flavour Aroma Chemicals Michael Zviely, Reuven Giger, Elias Abushkara, Alexander Ken, Horst Sommer, Heiz-Juergen Bertram, Gerhard E. Krammer, Claus Oliver Schmidt, Wolfgang Stumpe and Peter Werkhoff, 39,
Natural Products and Essential Oils,
Commercial Essential Oils: Truths and Consequences Brian Lawrence, 57,
Stable Isotopes for Determining the Origin of Flavour and Fragrance Components: Recent Findings Daniel Joulain, 84,
Fragrant Adventures in Madagascar: The Analysis of Fragrant Resin from Canarium madagascariense Robin Clery, 92,
The Effect of Microgravity on the Fragrance of a Miniature Rose, 'Overnight Scentsation' on Space Shuttle (STS-95) Braja D. Mookherjee, Subha Patel and Weijia Zhou, 99,
Organic and Bioorganic Chemistry,
Ambergris Fragrance Compounds from Labdanolic Acid and Larixol Aede de Groot, 113,
The Synthesis of Fragrant Cyclopentanone Systems Helen C. Hailes, 127,
Designing Damascone- and Ionone-like Odorants Philip Kraft, 138,
Creation of Flavours and the Synthesis of Raw Materials Inspired by Nature Mark L. Dewis and L. Kendrick, 147,
Flavours/Foods,
New Results on the Formation of Important Maillard Aroma Compounds Peter Schieberle and Thomas Hofmann, 163,
Out of Africa: The Chemistry and Flavour Properties of the Protein Thaumatin Steve Pearce and Hayley Roth, 178,
Stability of Thiols in an Aqueous Process Flavour Chris Winkel, Paul B. van Seeventer, Hugo Weenen and Josef Kerler, 194,
High Impact Aroma Chemicals David J. Rowe, 202,
Subject Index, 227,
CHAPTER 1
STRUCTURE ACTIVITY RELATIONSHIPS AND THE SUBJECTIVITY OF ODOUR SENSATION
Dr. Thomas Markert Cognis Deutschland GmbH, Henkelstr 67, D 40551 Duesseldorf, Germany
1 INTRODUCTION
Structure activity relationships (SAR) are one of the most useful sets of tools in both pharmaceutical and fragrance research. Ever since Amoore carried out his studies and formulated his theory of odour recognition, chemists have been looking at the shape of molecules and their associative possibilities to find clues that would explain perceived odour sensations. How difficult it is to go down this research path in finding new chemical entities with interesting odour qualities is clear from the broad variety of odours the human nose is able to detect and identify. I will now attempt to explain how complex the activity side of SAR can be and what the consequences of this complexity are.
In this context I will again follow up the question which Pieter Aarts recently put at the top of an article [1], although he was dealing with a totally different subject: "The Optimal Fragrance - Lucky Shot or Organised Hunt?"
The sense of smell is even able to discriminate between the antipodes of chemical structures like R- and S-carvone or R- and S-p-menthene-8-thiol [2]. When a perfume layman, like a chemist, tries to verify the reported odour descriptions, he becomes aware that the difference between the odours of chemically similar substances is dependent on purity, concentration in your nose, your sniffing technique, the way the air streams through your nose [3], and much more.
As Charles Sell tells us in a remarkable report about structure/odour correlations entitled "The Mechanism of Olfaction and the Design of Novel Fragrance Ingredients" [4], it is sometimes a trace impurity which fundamentally changes the scent of a substance or a mixture of substances.
2 AMOORE'S CONCEPT OF PRIMARY ODOURS
Let us start with John E. Amoore's [5] theory of odour reception (figure 1), which is based on specific anosmia and the concept of primary odours. What I understand about his idea is that he tried to find chemical structures by using the holes in the olfactory epithelium and a negative selection of substances that were reported as resulting in specific anosmia.
In terms of SAR, this would mean he was searching for chemicals with no activity. And from the shape of the molecules he found in this way he tried to reconstruct a receptor site which could in size and shape accept this chemical structure (figure 2). The goal of his studies was a classification of odours by collecting groups of similar molecules, which could fit, specifically into the same receptor. Amoore was limited in his approach to the choice of known substances and he was also dependent on the odour descriptions he was given by the experts. My opinion in this context is that Amoore could never definitely know whether a substance, which would bind to the same specific receptor, would cause the same odour sensations and associations. In other words, he grouped various chemicals together, guided by the similar odour descriptions for those materials.
3 SPECIFIC ANOSMIA AND THE CONCEPT OF PRIMARY ODOURS
I have to admit at this point that I have a problem. My problem is with specific anosmia, which is the basis of Amoore's theory of olfaction. The way Amoore measured specific anosmia demonstrated the usefulness of his approach and proved the reality of this phenomenon. However, the results are not useful to classify scents; they only caused chemists to focus on molecules for which there would probably be a specific receptor in the nasal mucous membrane. When a chemist looks at the structures found by Amoore they are surprised to find four small molecules like trimethylamine and isobutyric aldehyde, alongside two very large molecules like androstenone and pentadecanolide (figure 3).
Those who are able to smell androstenone with 19 carbon atoms describe it as reminding them of stale sweat. Isovaleric acid, a molecule with 5 carbon atoms, is almost officially said to smell sweaty. So, am I to believe that a molecule with 19 carbon atoms is bound to the same specific receptor as a similarly smelling compound containing 5 carbon atoms? The Amoore approach is most interesting because, when you think about it, in the end it doesn't tell you much about the structural side of SAR, nor does it tell you much about the activity on the side of the receptor, but it raises the question of what specific anosmia means. What is the sense of lacking receptors?
When we at Cognis were searching for new sandalwood substances, I noticed that I became anosmic to Sandelice®; first only on Fridays, then later all the time (figure 4).
Then I noticed that my anosmia was a hyperosmia. I was so sensitive to Sandelice® that I had the odour impression for a fraction of a second and then my nose had adapted. So adaptation can also look like anosmia. By contrast, I am truly anosmic to androstenone. True specific anosmics smell the impurities in the compounds. So, although I'm training on our androstenone sample, to me it smells a little bit cedar-woody but not at all like urine or stale sweat. Others nearly had their noses blasted off when they opened the...
