The estrogenic activity of a series of analogues of the daucane ester ferutinin (1a) modified at the acyl moiety was investigated in a yeast screen containing the human estrogen receptor alpha. Rather strict structure-activity relationships were observed. Thus, while the parent polyol (jaeschkeanadiol, 2a) was inactive, the presence of a p-hydroxybenzoyl moiety was necessary for activity in the yeast screen. Homologation and vinylation were both detrimental for activity, as were methylation of the p-hydroxyl substituent and the introduction of oxygen functions on the adjacent carbons.

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Finding new taste modifiers, particularly bitter-taste blockers (BTBs), is an important goal for pharmaceutical and food industries. Although BTBs have been much sought after, only a few possess a wide spectrum of activity. We prepared, on a gram scale, several macromolecular adducts in which β β β β β-and γ γ γ γ γ -CDs are linked to chitosan through succinyl or maleyl bridges. Their bitterness-masking power was evaluated on caffeine and bitter natural extracts (artichoke leaves, aloe and gentian) by a panel test using serial caffeine concentrations as a reference scale. The β β β β β-CD-chitosan adduct showed the highest efficacy and the bitterness attenuation was statistically significant.

Cascarilla is a commercially available and cheap source of polyfunctionalized diterpenoids belonging to the clerodane structural type. In addition to the bitter triol cascarillin, 10 additional new diterpenoids (eluterins A-J) have been isolated and characterized by spectroscopic means. Structural diversity within cascarilla clerodanes involves mainly the linkage between the carbocyclic and the heterocyclic moieties and the functionalization of C-3, C-4, and C-6 of the decalin core. Cascarillin was shown to be a mixture of interconverting gamma-lactols and not a gamma-hydroxyaldehyde as previously reported.

Esterification of p-hydroxybenzoic acid, a very weak estrogenic compound, with the daucane alcohol jaeschkeanadiol (1b) leads to a spectacular magnification of the estrogenic activity. To identify the structural elements responsible for this effect, the terpenoid core of jaeschkeanadiol p-hydroxybenzoate (ferutinin, 1a) was modified, capitalizing on the presence of two functionalities, the monoacylated, hydrogen-bonded 1,3-diol system and the double bond. The hydrogen bonding, while possibly useful, was not critical for activity, while hydrogenation and cyclopropanation of the double bond were tolerated. Conversely, oxidative modifications of the double bond that placed a hydroxyl on the alpha-face of the molecule proved detrimental. Taken together, these observations identified the substitution at C-8/C-9 as critical for activity.

This work is part of a plan to investigate the structure-bitterness relationship in sesquiterpene lactones of dietary origin. The major guaianolides from artichoke (Cynara scolimus L) were chosen for this study because of their exceedingly bitter taste and well-proven safety at concentrations currently employed in alcoholic beverages. Moreover they are available from horticultural left-overs and amenable to a wide range of chemical modifications. We isolated cynaropicrin and grosheimin from artichoke leaves and used either chemical modification or bioconversion by basidiomycetes to prepare a number of derivatives which were submitted to a panel test for sensory evaluation. Bitterness variations appeared to be related to changes in molecule polarity. Bitter taste was markedly abated by either the loss of exomethylenes or the opening of the lactone ring.

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