Physiological cooling agents continue to gain popularity for use in various consumer applications due to their recognized ability of improving desirable sensate properties in consumer products. These properties are generally explained by the chemical action of these agents on the nerve endings responsible for the sensation of cold. Common applications and uses for cooling agents include foods, beverages, flavors, pharmaceuticals, perfumes, and miscellaneous cosmetic goods.
One of the most well known physiological cooling agents is l-menthol, which has been used for a very long time in practically all of the above-mentioned applications. Menthol has an excellent cooling strength, low sensitivity threshold, and is relatively inexpensive. l-Menthol is available from natural sources such as cornmint oil from Mentha arvensis, as well as synthetically, primarily by the well-known methods practiced by Symrise (then Haarmann & Reimer) and Takasago.
On the other hand, l-menthol also exhibits some undesirable properties, such as strong “stinging” smell, a somewhat bitter taste and burning sensation in higher concentrations, and high volatility. These undesirable properties, to a certain extent, have limited l-menthol’s utility in many applications, and therefore have stimulated an intense search for suitable synthetic substitutes — physiological cooling agents that possess a low volatility and have a relatively weak odor or even no odor at all. Therefore, beginning in the 1960s, mainstream research into synthetic physiological cooling agents began to concentrate on the modifi cation of the l-menthol molecule in order to decrease its volatility by attaching a heavy group to the hydroxy group, or instead of the hydroxy group of menthol.
