Dihydrochalcones—

The leaves of Hydrangea macrophylla contain a 3,4-dihydroisocoumarin derivative, phyllodulcin (Formula 8.8). Its sweetness matches that of dihydrochalcones and of licorice root. 

The taste perception builds relatively slowly and also fades away slowly. The sweetening strength is /sac (5) = 250. A study of a number of related isocoumarin derivatives shows that taste quality and strength are very much dependent on the substitution pattern of the molecule (cf. Table 8.7). 

The active substance from licorice root (Glycyrrhiza glabra) is a P, P -glucuronido-glucuronide of glycyrrhetic acid  

In different countries, this compound is used in chewing gum, mouthwashes, beverages, and various types of candy. The quality and strength of the sweet taste of dihydrochalcone are related particularly to the substitution pattern in ring B. The prerequsite for a sweet taste is the presence in ring B of at least one hydroxy group, but not three adjacent hydroxy and alkoxy substituents. 

The sweetening strength is /sac,g(4) = 50. The compound is utilized for production of hcorice (also spelled as liquorice). Its cortisone-like side effect limits its wide application. 

The bio availability of phloretin and its glucoside phloridzin was shown to be similar in rats, except that the kinetics of absorption was delayed for phloridzin (Crespy etal. 2001). About 10% of the ingested dose was excreted in the urine in 24 h, and plasma concentrations were returned to baseline at this timepoint. Plasma metabolites were glucuronidated and/or sulphated forms of phloretin. Intact phloridzin was not recovered. Phloretie acid was also detected in rat urine after phloretin gavage (Monge etal. 1984). 

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Fig. 2. Dihydrochalcone glycoside (49), where R = H, OH, or O—alkyl and R = glucosyl, mtinosyl, neohesperidosyl, or xylosyl.

Many other dihydrochalcones have been made, but most of the toxicological studies have been conducted using NHDC and thus (20) has been petitioned and allowed for use. Neohesperidin is best isolated from the bitter orange (Seville orange), but it can also be synthesized from (18) and isovanillin [621-59-0] (21) (Fig. 7) (98). 

Finally, some amphiphilic sweeteners, eg, aspartame, saccharin, and neohesperidin dihydrochalcone, have been shown to be capable of stimulating a purified G-protein direcdy in an in vitro assay (136). This suggests some sweeteners may be able to cross the plasma membrane and stimulate the G-protein without first binding to a receptor. This type of action could explain the relatively longer response times and the lingering of taste associated with many high potency sweeteners. 

Phlorizin, the glucoside of the dihydrochalcone phloretin, is a constituent of the tissues of the apple tree. Its distribution and bio-... 

The conversion of the bitter flavanone glycosides into those of the corresponding chalcones by alkali-catalyzed fission of the pyrone ring, and of the dihydrochalcone glycosides by hydrogenation thereof (see Scheme 1)... 

Scheme 1.—Conversion of a Flavone Glycoside into the Corresponding Chalcone and Dihydrochalcone Analogs.

It is known that the naturally occurring dihydrochalcone glycosides phloridzin (75) and glycyphillin (76), which are 2-yl glycosides, possess little or no sweetness, whereas phyllodulcin (77), which is not a glycoside, has the same taste properties as the dihydrochalcones it is 400 times sweeter than sucrose. ... 

It thus appears that the taste of the dihydrochalcones is not solely controlled by the sugar moiety, and subsequent studies 220 confirmed this. The flavanone 78 and the non-glycosidic dihydrochalcone 81 are intensely sweet. Furthermore, replacement of the bulky glycosyl residue by carboxyalkyl " (82) or sulfoalkyl (83) substituents did not significantly... 

Neohesperidin dihydrochalcone 2-O-a-L-rhamnosyl- -D-glucopyranoside substituted phloroglucinol, -QH, substituted phloroglucinol, -C2H4 phenyl OH and —OMe... 

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... 

These time-intensity effects are illustrated in Fig. 42 by a plot of perceived intensity vs. time, curve A being given by a stimulus molecule, such as sucrose, which exhibits rapid taste onset and cutoff, and curve B approximates the behavior of most dihydrochalcone sweeteners. 

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