Structure--activity relationships of the estrogenic sesquiterpene ester ferutinin. Modification of the terpenoid core.

Giovanni Appendino, Paola Spagliardi, Olov Sterner, Stuart Milligan

Dipartimento di Scienze Chimiche, Alimentari, Farmaceutiche e Farmacologiche, Università del Piemonte Orientale, Via Bovio 6, 28100 Novara, Italy. Giovanni.Appendino@pharm.unipmn.it

Journal of natural products 2004 Sep

filter terms:

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.

Citation

Giovanni Appendino, Paola Spagliardi, Olov Sterner, Stuart Milligan. Structure--activity relationships of the estrogenic sesquiterpene ester ferutinin. Modification of the terpenoid core. Journal of natural products. 2004 Sep;67(9):1557-64