Perillartine

The binding specificity of d-[ C]glucose by the taste-papillae membranes, compared to that of control membranes isolated from epithelial tissue, has been confirmed in two studies. One inherent problem in the approach is that the stimuli, primarily carbohydrate sweeteners, are not ideal model compounds to use, as they are not active at low concentrations and do not show sufficiently high binding-constants. The use of other stimulus compounds that are at least several hundred times sweeter than sucrose, such as saccharin, dihydrochalcone sweeteners, dipeptide sweeteners, stevioside, perillartine and other sweet oximes, the 2-substituted 5-nitroanilines, and... 

It is of interest to point out in this context that a closely related analog of 46, peril-lartine (47), is used in Japan as artificial sweetner , and apparently is devoid of the physiological untoward effects of 46. Perillartine was used as a lead substance for systematic study of numerous combinations of an a,/ -unsaturation group and an aldoxime... 

Perillartine (25) is the syn-oxime of perillaldehyde isolated from Perilla arguta Benth., and was found to be about 2000 times as sweet as sucrose in 1920 in Japan 49). Acton and Stone prepared a number of related aldoximes (26) and determined their taste potency50,51). In quantitative analysis of their data, we have utilized steric parameters... 

Fig. 8. Definition of modified STERIMOL parameters the upper is for perillartine and related oximes and the lower is for substituted anilines 521 (reproduced with permission from the American Chemical Society)...

Perillartine, a-syn-oxime of perillaldehyde, is reported to be 2000 times sweeter than sucrose.48 49 Perillaldehyde is a principal volatile oil of Perilla frutescens (L.) Britton (Labiatae) and is reported to be only slightly sweet. Perillartine is used as a replacement for maple syrup and licorice for the sweetening of tobacco in Japan. However, due to its low solubility in water as well as a menthol-licorice off-taste, there is some limitation to its use. 

Two natural product derived semisynthetic compounds are utilized as a limited basis, namely, perillartine [28] and neohesperidin dihydrochalcone [45]. Perillartine is an a-jy -oxime and synthesized from perillaldehyde, a constituent of the volatile oil of Perilla frutescens (L.) Britton (Labiatae), and used in Japan as a sweetener for tobacco [28]. Neohesperidin dihydrochalcone is a dihydrochalcone glycoside prepared from a flavanone constituent of Citrus aurantium L. (Rutaceae), which is permitted for use in chewing gum and certain beverages in Belgium and elsewhere [45]. 

As mentioned earlier in this chapter, the a-syn-oxime, perillartine (10) is a semisynthetic compound prepared from a natural product, perillaldehyde, isolated fi om Perilla frutescens (L.) Britton (Labiatae). Although it is used commercially in Japan, its poor solubility and poor sweetness qualities have limited its further development [20,28]. 

Takahashi, Y., Miashita, Y., Tanaka, Y, Hayasaka, H., Abe, H. and Sasaki, S. (1985). Discriminative Structural Analysis Using Pattern Recognition Techniques in the Structure-Taste Problem of Perillartines. J.Pharm.ScL, 73,737-741. 

Monoterpenoids. It was mentioned earlier in this chapter that the semi-synthetic oxime, perillartine (1), is sweet and has some commercial use in Japan. In experiments designed to optimize the sensory attributes of the oxime sweeteners, it was found that the introduction of ether groups was advantageous, while hydroxyl groups and ring oxygen atoms tended to lower sweetness intensity and to destroy the sweet taste, respectively (16). Despite the discovery of cyclic derivatives of perillartine that are sweeter than this lead compound (20), the further development of this class of sweet substances is limited by poor water solubility and inappropriate hedonic qualities (20,21). 

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