Hemandulcin

The first Mexican substance searched for, found, and isolated based on old traditions, was the sesquiterpene hemandulcin from Lippia dulcis Trev. It was determined by a human taste panel to be more than 1000 times sweeter than sucrose. The structure of this sesquiterpene was determined and confirmed by chemical synthesis. It was nontoxic when administered orally to mice, and did not induce bacterial mutation.5 Further work has been carried out with some of the plants more frequently used (Table 12.3). The sesquiterpene alkaloids hippocrateine I, hippocrateine II, and emarginatine were identified in Hippocratea excelsa used in Mexican traditional medicine, and antimicrobial abietane type diterpenes were isolated from Salvia albocaerulea.6 7... 

COMPADRE, C.M., PEZZUTO, J.M., KINGHORN, A.D., KAMATH, S.K., Hemandulcin An intensely sweet compound discovered by review of ancient literature., Science, 1985,227,417-419. 

Despite its high sweetness intensity, hemandulcin is limited as a potential sweetener because of its somewhat unpleasant hedonic attributes and its thermolability. In spite of this, a... 

Sauerwein, M., Flores, H.M., Yamazaki, T., and Shimomura, K. 1991. Lippia dulcis shoot cultures as a source of the sweet sesquiterpene hemandulcin. Plant Cell Rep., 9 663-666. 

The sesquiteipene hemandulcin (83) from Lippia dulcis (Verbenaceae), a plant used as a sweetener by the Aztecs, is more than 1000 times sweeter than sucrose (Compadre et al., 1985, 1987). 

Compadre, C. M., R. A. Hussain, R. L. L. de Compadre, J. M. Pezzuto, and A. D. Kinghorn, TTie intensely sweet sesquiterpene hemandulcin Isolation, synthesis, characterization, and preliminary safety evaluation, J. Agric. Food Chem., 35, 273-279 (1987). 

Hemandulcin is a sweet sesquiterpene from Lippia dulcis Trev. (Verhenaceae), with the structure 6-( 1,5-dimethyl-1 -hydroxy-hex-4-enyl)... 

In comparison with sucrose, the sweetening strength of this compound is /sac, mol (0-25) = 1250. Hemandulcin is somewhat less pleasant in taste than sucrose and exhibits some bitterness. The racemic compound was synthesized via a directed aldol-condensation reaction by adding 6-methyl-5-hepten-2-one to a mixture of 3-methyl-2-cyclohexen-l-one and lithium di-isopropylamide in tetrahydrofuran, followed by chromatographic separation of ( )-hemandulcin (I, 95%) from the diastereomeric counterpart ( )-epihemandulcin (II, 5%). Whereas I is sweet, II exhibits no sweet taste. 

Sweet sesquiterpenoids (-F)-hernandulcin, 6-(1,5-dimethyl-1-hydroxyhex-4-en-l-yl)-3-methylcyclohexen-2-one, and (-F)-4P-hydroxyhernandulcin (11-35) occur at a level of about 0.04% in the sweet herb Phyla dtdds (syn. Lippia dulcis, Verbenaceae) native to tropical Central and South America. Leaves with the sweet taste (hemandulcin is about 1250 times sweeter than saccharose) are used in traditional medicine. Because of its slightly bitter taste and minty after-taste, hemandulcin has only limited use as a sweetener. 

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