Stereochemistry‐Activity Relationships in Olfaction. Odorants containing a proton donor/proton acceptor unit

Abstract

SummaryA novel class of odorants is described where the odor is associated with the interaction of two functional groups, one being an H-donor (AH function), and the other an H-acceptor (B function). Generally, odor occurs only if the distance between the two structural elements (AH/B system) is less than 3 A. Bifunctional derivatives of the p-menthane and iridane series served as models for deriving this rule. The stereospecificity of odor perception was an important prerequisite for its establishment.It is known that hydroxycarbonyl compounds having a molecular weight up to about 250 may possess a pronounced odor. In other cases, however, bifunctional compounds of this type are completely odorless. No molecular explanation for this contrasting behaviour has been offered. While engaged in work on structure-activity relationships in olfaction we have been able to account for this discrepancy by invoking the stereochemistry of the molecules giving rise to the effects, as illustrated by the formulas below. The compounds in red are odorants, whereas the uncolored molecules were found to be virtually odorless. Examination of Dreiding models shows the distance between the hydrogen atom of the hydroxyl group and the carbonyl group to be less than 3 A in the odoriferous compounds, but more than 3 A in the odorless molecules. A single exception to this rule has been found.In the bifunctional unit of compound 1 the distance between the functional groups is 2.2 A, assuming a chair conformation for the ring and an axial conformation for the aldehyde group. In the diequatorial conformation of compound 2 the distance between the functional groups is about 6 A. Base-catalyzed equilibration showed the equilibrium between 1 and 2 to be mainly (92%) on the side of 2 with concomitant disappearance of the odor. The required distance for this particular type of fragrance already reaches the limit of about 3 A in odoriferous compound 3.This value is largely exceeded in the odorless hydroxyaldhyde 4. We presume that in the cyclohexene derivatives 5-8 the carbonyl group occupies an axial position since only in this case -independent of whether the ring is in a half-chair or a half-twist conformation -the bifunctional unit can be adjusted to the required distance oO18-0l9X/80/ 1/oO76-l9$01.00/0 0 1980 Schweizerische Chemische Gesellschaft

From the Linden Flower to Linden Honey – Volatile Constituents of Linden Nectar, the Extract of Bee‐Stomach and Ripe Honey

“…The isolation, identification, and spectral data of 14 and 15 will be discussed in a separate paper. The structures of these compounds, established by NMR (16), a known compound [14]. The content of linden ether (1) increased, and among the trace compounds, a series of further p-menthofuranoids, including dill ether and menthofuran, and rose oxide, are compounds with strong odor impacts (Fig.…”

Odds and Trends: Recent Developments in the Chemistry of Odorants

“…a-Dynascone (45), in a mixture with its weaker b isomer (62), had long been used as a captive material (that is, a material used only in-house and not sold to others) before it was introduced recently to the market. [30] Dynascone (45/62), allyl amyl glycolate (48), and Cyclogalbanate (49) are often used in perfumery, with or without natural galbanum oil. The more substantive galbanum odorant 46 can be obtained starting from cyclopentanone.…”

Total Synthesis and Olfactory Evaluation of (1R*,3S*,6S*,7S*,8S*)‐ 3‐Hydroxy‐6,8‐dimethyltricyclo[5.3.1.03,8]undecan‐2‐one: A New Synthetic Route to the Patchoulol Skeleton

“…This configuration was confirmed by an X-ray crystal structure (Figure 2), which indeed revealed a dihedral angle φ = -104.3°between the hydrogen bonds of C-2 and C-3. As was expected for ketols with an AH/B distance above 3 Å, [12] both isomers 13 and 2-epi-13 were devoid of any odor (distance OH/O = 4.84 Å in the X-ray crystal structure of 13). After removal of the C-2 hydroxy function, however, an odor should be detectable.…”

“…Due to its low price of around $ 40-50/kg, no other synthetic odorant has thus far been able to compete with patchouli oil. floral family, no intense bifunctional odorants with a proton-donor-proton-acceptor unit within a 3-Å distance [12] were known, and thus the ketol motive of 2 was a striking exception for a patchouli odorant. It was therefore tempting to superimpose the spirocyclic hydroxyketone 2 on the tricyclic alcohol 1, the odorous principle of patchouli oil.…”