Synthetic Study on Bioactive Oligomeric and Polymeric Flavonoids

天然多酚作为酒、茶或草药的成分与人类生活有着传统的关系，这刺激了对与多酚相关的新候选药物的研究。然而，多酚的生物学研究常常受到难以以纯净和结构明确的形式分离出各自化合物的阻碍，因为主要的可用性依赖于天然来源，例如植物提取物，它们通常是密切相关化合物的混合物，即使借助现代分离和分析方法也很难处理。本研究的重点是开发一种能够获得各种儿茶素衍生物的通用合成方法，并利用其选择性寡聚。以1,3,5 -三氟苯为原料，经分子间与b环片段S_N2反应和分子内S_NAr反应合成单体儿茶素。单体的低聚化是基于正交合成策略进行的，得到的低聚物从3聚体到24聚体不等。该方法适用于从酸枣中分离得到的由表儿茶素、表没食子儿茶素和儿茶素组成的异质三聚体的合成。

Natural polyphenols have traditional relation to human life as ingredients of wine, tea or herbal medicines, which has stimulated the search for new pharmaceutical candidates relevant to polyphenols. However, the biological studies of polyphenols are often hampered by the difficulty in isolating respective compounds in pure and structurally-defined forms, because the major availability has relied on natural sources, e. g., plant extracts, which are generally a mixture of closely related compounds, hardly tractable even by the aid of modern separation and analytical methods.This study focused on development of general synthetic method enabling access to various catechin derivatives, and exploited its selective oligomerization. Monomeric catechins are synthesized from 1, 3, 5-trifluorobenzene via intermolecular S_N2 reaction with the B-ring fragment followed by intramolecular S_NAr reaction. Oligomerizations of monomers are conducted based on the orthogonal synthetic strategy, giving higher oligomers ranging from 3-mer to 24-mer. The method was applicable to the synthesis of the hetero-trimer, which was isolated from Ziziphus jujuba, composing of epiafzelechin, epigallocatechin, and catechin units.