Systematic studies on structure and physiological activity of cyclic alpha-keto enamines, a novel class of "cooling" compounds.
3-Methyl- and 5-methyl-2-(1-pyrrolidinyl)-2-cyclopenten-1-one were recently identified as intense cooling compounds in roasted dark malt. To gain more insights into the molecular requirements of these compounds for imparting a cooling sensation, 26 cyclic alpha-keto enamine derivatives were synthesized, and their physiological cooling activities were evaluated. Any modification of the amino moiety, the carbocyclic ring size, or incorporation of additional methyl groups led to a significant increase of the cooling threshold. Insertion of an oxygen atom into the 2-cyclopenten-1-one ring, however, increased the cooling activity, e.g., the cooling threshold of the 5-methyl-4-(1-pyrrolidinyl)-3(2H)-furanone was found to be 16-fold below the threshold concentration determined for the 3-methyl-2-(1-pyrrolidinyl)-2-cyclopenten-1-one. Shifting the oxygen atom from the 4- into the 5-position of the cyclopentenone ring resulted in a even more drastic increase in cooling activity, e.g., the 4-methyl-3-(1-pyrrolidinyl)-2(5H)-furanone exhibited the strongest cooling effect at the low oral threshold concentration of 0.02-0.06 mmol/L, which is 35-fold below the value determined for (-)-menthol. In contrast to the minty smelling (-)-menthol, most of the alpha-keto enamines were found to be virtually odorless but impart a sensation of "cooling" to the oral cavity as well as to the skin, thus illustrating that there is no physiological link between cooling activity and mint-like odors.
Ottinger
H
H
Deutsche Forschungsanstalt für Lebensmittelchemie, Lichtenbergstrasse 4, D-85748 Garching, Germany.
Soldo
T
T
Hofmann
T
T
D000588:Amines / Q000737:chemistry* / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D009682:Magnetic Resonance Spectroscopy; D015416:Maillard Reaction; D013329:Structure-Activity Relationship
D000588:Amines