Methyl derivatives, sweetness

Forty years after the initial proposal, Sweet and Fissekis proposed a more detailed pathway involving a carbenium ion species. According to these authors the first step involved an aldol condensation between ethyl acetoacetate (6) and benzaldehyde (5) to deliver the aldol adduct 11. Subsequent dehydration of 11 furnished the key carbenium ion 12 which was in equilibrium with enone 13. Nucleophilic attack of 12 by urea then delivered ureide 14. Intramolecular cyclization produced a hemiaminal which underwent dehydration to afford dihydropyrimidinone 15. These authors demonstrated that the carbenium species was viable through synthesis. After enone 13 was synthesized, it was allowed to react with N-methyl urea to deliver the mono-N-methylated derivative of DHPM 15. 

The sweet taste of the 3-O-methyl derivatives seems to conflict with the results obtained with deoxy sugars. However, the sweet taste of these... 

Lindley and Birch have attempted to ascertain why certain sugars are so sweet, recognizing that sweetness is a function of the hydroxy-groups. Using partially methylated derivatives of aa-trehalose, they were able to show that only half of the aa-trehalose molecule participates in the sensory response. It was also found that methyl ethers of methyl a-D-glucopyranoside are more bitter than the parent glycoside, presumably because of their increased lipophilicity. 

The simplest lactones are y-butyrolactone (butane-4-lactone, 8-96) and y-crotonolactone (but-2-eno-4-lactone, 8-100). These compounds are found as common constituents of many foods in small amounts. y-Butyrolactone has a faintly sweet odour reminiscent of rancid butter, and the smell of y-crotonolactone is Uke rancid fat. The methyl derivatives pent-3-eno-4-lactone (a-angeUca lactone, 8-101) and pent-2-eno-4-lactone ( -angeUca lactone, 8-102) are produced as degradation products of hexoses in acid solutions via laevulinic acid and have a sweet, herbal odour. 

A review of the relative reactivities of the hydroxy-groups of carbohydrates has dealt with esterification, etherification, acetalation, halogenation, and oxidation, and with the migration of substituents. Shallenberger s rationale is considered to explain satisfactorily the relative sweetness of sucrose, xylitol, arabinitol, ribitol, D-galacto-sucTOSG, and methylated derivatives of sucrose. ... 

Coum rinic Acid Compounds. These synthetic phyUoquinone derivatives and congeners have been employed as anticoagulants since the isolation of 3,3 -methylenebis(4-hydroxy-2H-l-benzopyran-2-one) [66-76-2] (bis-4-hydroxycoumarin or dicoumarol) (1) from spoiled sweet clover in 1939. The ingestion of the latter was responsible for widespread and extensive death of bovine animals at that time. The parent compound for the synthesis of many congeners is 4-hydrocoumarin, which is synthesized from methyl salicylate by acetylation and internal cyclization. The basic stmctures of these compounds are shown in Figure 2, and their properties Hsted in Table 6 (see Coumarin). 

All of the mono-O-methylated hexopyranosides are sweet, with only a trace of bitterness. The bitterness is more pronounced in the methyl glycoside derivatives, and this was attributed to the presence of two lipophilic centers (—OMe) in the methyl glycosides and only one in the a,a-trehalose analogs. ... 

The taste properties of the di-O-methylhexopyranosyl derivatives, like those of the corresponding deoxy sugars, are never sweet, and always bitter. As with the deoxy sugars, this is possibly the result of increased lipophilicity of the molecule. In sucrose, however, the presence of two methyl groups on the D-glucopyranosyl or the D-fructofuranosyl group does not seem to cause any marked bitterness (see Table XVIII). 

It is puzzling that the chlorine and other halogen substituents are not known to enhance the sweetness of other sugars, such as methyl -d-glycopyranosides, a,a-trehalose, maltose, or lactose. On the contrary, all of the deoxyhalo sugar derivatives tasted were extremely bitter. The high sweetness of the deoxyhalosucroses is clearly inexplicable in terms of either... 

The sweetest derivative included in Eq. 51 is L-aspartylaminomalonic acid methyl fencyl ester (32) which is 63000 times as sweet as sucrose59). This is understandable on the basis of the high coefficient of the a term of Eq. 51, a high a value itself of the N-substituent containing two ester carbonyl groups (estimated as 1.38) and the (W,)2 term due to the presence of methyl groups on the R2 cyclohexyl moiety. 

Acesulfame K is the generic name for the potassium salt of 6-methyl-1,2,3-oxathiazine-4(3H)-one-2,2,dioxide. Manufacture is by chemical derivation from acetoacetic acid. It is a white, non-hygroscopic crystalline product. Its solubility in water is good. The relative sweetness of acesulfame K varies from 100 to 200, depending on concentration and application (Von Ryinon Lipinsky, 1985). 

---