There is an ongoing need in the fragrance industry to provide new chemicals to give perfumers and other persons ability to create new fragrances for perfumes, colognes and personal care products. Those with skill in the art appreciate how differences in the chemical structure of the molecule can result in significant differences in the odor, notes and characteristics of a molecule. These variations and the ongoing need to discover and use the new chemicals in the development of new fragrances allow perfumers to apply the new compounds in creating new fragrances.
One of the aims of the man skilled in the art of perfumery is to find new chemicals with improved performance than prior known compounds from an olfactive point of view, either because their odor qualities are more distinctive and original or because their odor is much stronger or yet, if he is lucky, as a result of both of these. Such a skilled man knows well enough that he cannot rely on structural closeness to predict whether a new chemical will be a more interesting fragrance ingredient or, even, whether it will be fragrant at all. Although he cannot be unaware of the role that the optical isomerism of a compound plays in determining its odor properties or, rather, its odor perception by the perfumer [see, for instance, W. Pickenhagen, in ACS Symposium Series 388, chapter 12, p. 151, ed. ACS, Washington D.C. (1989)], he often finds no motivation to prepare the optically active isomers, particularly when confronted with racemic compounds which possess a plurality of chiral centers, knowing that his task will be extremely difficult and unobvious, as the synthesis of the corresponding pure optical isomers not only requires particular expertise but is also costly. In addition, he may find no reward, as there is no way of predicting, even in the presence of a good racemate, whether his efforts will lead only to the discovery that none of the pure optically active components of said racemate is in any way superior to the latter, as a fragrance ingredient or, at least, not superior enough to justify its inevitably dearer industrial development.
In spite of such difficulties, the synthesis of novel chiral perfuming ingredients is an ever increasing need in this industry. The reason for this springs in an obvious manner from articles such as that of G. Ohloff in Experientia 42, 271 (1986), wherein the author not only impresses upon its reader the importance of every new discovery of fragrant chemicals towards completing an empirically set list of structural conditions or parameters, amongst which chiral activity, disclosed in this article and believed to influence odor perception, but also acknowledges the transient quality, at the present stage of the art, of such lists of structural parameters which, as he admits, every new compound behaving uncharacteristically may well contradict, leading to replacements or alterations. Yet, despite the necessity to continue preparing optically active species of known racemates, the outcome of such an endeavour is rendered all the more uncertain and unobvious by the fact that a racemate does not generally produce a fragrance effect which corresponds to a sum of the individual odor properties of the different optically active isomers present in the racemic mixture, both qualitatively and quantitatively, and this even when there are only two of such isomers in said mixture. The olfactive properties of the racemate can be, and often are, quite different from those of each optically active component of said racemate and, that is why it is impossible to predict the olfactive behaviour of any one isomer on the basis of the knowledge of the racemate, particularly when, as is the case here, there are several optically active isomers in the racemic mixture. The result of the chemist's research in this domain is therefore unpredictable.
It should be further noted that in the present case, the individual optically active isomers cannot be simply separated from the known racemic mixtures, but require specifically designed and sophisticated syntheses, as described further on.
The present invention is yet another example of this reality and it brings precisely a new and unexpected contribution into this field.
USPTO Backgrounds
USPTO Backgrounds