Phyllodulcin

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). 

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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. ... 

R)-l-[4-Methoxy-3-[(triisopropylsilyl)oxyphenyl)-2-[3-(methoxymethoxy)phenyl]ethanol 1123 undergoes selective hydrogen metal exchange followed by carbonylation to form the lithiated intermediate 1124, which undergoes cyclization in acid conditions to provide the dihydroisocoumarin 1125, a key intermediate during an enantioselective synthesis of phyllodulcin (Scheme 279) <1996JOC5371>. 

Phyllodulcin (3) Hydrangea macrophylla Seringe var. thunbergii (Siebold) Makino (Saxifragaceae) 400 28... 

The plant of origin may be crushed or fermented in order to generate phyllodulcin (3). 

A synthesis of phyllodulcin, which is a sweet component of the amacha plant in Japan that exhibits antimicrobial activity, relies on an AD reaction using commercially available AD-mix-a [95]. Another practical application of an AD reaction using A-methylmorpholine A-oxide as a reoxidant has been reported for the 2.5-kg scale synthesis of a chiral diol [96],... 

Naturally occurring phyllodulcin was orally administered to rats to investigate its metabolism using three-dimensional HPLC to analyze the urinary metabolites [97]. Potter et al. demonstrated that resveratrol (1) could be converted to piceatannol by the action of cytochrome P450 enzyme CYPIBI in vivo [379]. The fate of kobophenol A in rats has been studied and the major metabolites, koboquinone A (745), koboquinone B (746) and koboquinone C (767), have been characterized [338]. 

The dihydroisocoumarins phyllodulcin 39 and hydranginol 40 have been isolated from Hydrangea macrophylla leaves They have been synthesised as shown below... 

Among the 2-phenyl-2,3-dihydro-1,4-benzodioxins, one of them, 2-(3-hydroxy-4-methoxy-phenyl)-2,3-dihydro-1,4-benzodioxin, is 450 times sweeter than sucrose, with an aftertaste similar to that of Phyllodulcin <91JCS(P2)1399). 

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