RESUMO
Two trans-alpha,beta-dibenzyl-gamma-butyrolactone lignans carrying a hydroxyl group at the beta-benzylic carbon atom and a alpha-hydroxy alpha,beta-dibenzyl-gamma-butyrolactone lignan were synthesized in racemic form using the tandem conjugate addition reaction to construct the basic lignan skeleton. Subsequent reaction steps involved either a catalytic reduction of the regenerated keto group to the alcohol, or a hydrogenolysis to benzylic methylene followed by lactone enolate formation and oxidation to give the alpha-hydroxybutyrolactones. These procedures were applied for the synthesis of 7'-hydroxyenterolactones and 7'-hydroxymatairesinols, and 8-hydroxyenterolactones, respectively. The diastereomeric mixtures of these compounds were separated either by HPLC techniques or column chromatography and the structures were elucidated using NMR spectroscopy.
Assuntos
Álcoois/química , Lactonas/síntese química , Lignanas/síntese química , Extratos Vegetais/química , Antineoplásicos Fitogênicos/síntese química , Antineoplásicos Fitogênicos/química , Cromatografia , Cromatografia Líquida de Alta Pressão , Humanos , Lactonas/química , Lignanas/química , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Estereoisomerismo , Árvores/químicaRESUMO
A series of variably substituted derivatives of lignan lactones and diols were prepared using tandem conjugate addition reaction as a key step. These theoretical precursors of the mammalian lignans enterolactone 1 and enterodiol 3 are moderate or weak inhibitors of human aromatase activity.
Assuntos
4-Butirolactona/análogos & derivados , Inibidores da Aromatase , Catecóis/síntese química , Catecóis/farmacologia , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Fenóis/síntese química , Fenóis/farmacologia , 4-Butirolactona/síntese química , 4-Butirolactona/química , 4-Butirolactona/farmacologia , Humanos , Lignanas/químicaRESUMO
Because many Western diseases are hormone-dependent cancers, we have postulated that the Western diet, compared with a vegetarian or semi-vegetarian diet, may alter hormone production, metabolism or action at the cellular level. Recently, our interest has been focused on the cancer-protective role of some hormone-like diphenolic phytoestrogens of dietary origin, the lignans and isoflavonoids. The precursors of the biologically active compounds originate in soybean products (mainly isoflavonoids but also lignans), as well as whole grain cereals, seeds, probably berries and nuts (mainly lignans). The plant lignan and isoflavonoid glycosides are converted by intestinal bacteria to hormone-like compounds with weak estrogenic and antioxidative activity; they have now been shown to influence not only sex hormone metabolism and biological activity but also intracellular enzymes, protein synthesis, growth factor action, malignant cell proliferation, differentiation and angiogenesis, making them strong candidates for a role as natural cancer protective compounds. Epidemiological investigations support this hypothesis, because the highest levels of these compounds are found in countries or regions with low cancer incidence. This report is a review of results that suggest that the diphenolic isoflavonoids and lignans are natural cancer-protective compounds.
