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化学进展 2010, Vol. 22 Issue (11): 2147-2155 前一篇   后一篇

• 综述与评论 •

含5,4′-多羟基黄酮苷及苷元分子的结构修饰方法*

何方 李瑞霞  吴大诚*   

  1. (四川大学纺织研究所，成都，610065)
  • 收稿日期:2010-03-15 修回日期:2010-05-14 出版日期:2010-11-24 发布日期:2010-10-20
  • 通讯作者: 吴大诚 E-mail:wudacheng@scu.edu.cn
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Structural Modification Methods of 5,4′-hydroxyl-containing Flavonoid Glycoside and Aglycone Molecules

He Fang   LI Ruixia  Wu Da-cheng*   

  1. (Institute of Textile of Sichuan University, Chengdu 610065, China)
  • Received:2010-03-15 Revised:2010-05-14 Online:2010-11-24 Published:2010-10-20
  • Contact: Wu Dacheng E-mail:wudacheng@scu.edu.cn

多羟基黄酮苷及苷元类化合物具有多种生物活性与生理功能，但它们在体内的稳定性与生物利用度相对较弱，在药理学上也表现出非特异性作用。由于其在制药、食品与化妆品领域中的重要性， 本文根据其分子修饰的取代方式大致分为黄酮母核酚羟基的O-取代，苯环上C-取代与配糖羟基的酶促催化反应三类。以槲皮素（芦丁）及柚皮素（柚皮苷）等作为黄酮醇（苷）与二氢黄酮（苷）类化合物的典型代表，对酚羟基的保护方法进行了对比分析，并简述了这三类半合成反应的特点。重点探讨了Mannich 缩合应用于C-取代时，反应底物、单体以及体系酸碱度对反应的影响。研究指出，合理筛选黄酮母核羟基以及单体活性基团的保护方式是成功实现选择性半合成的重要途径。目前，对含有5,4′-多羟基黄酮醇与二氢黄酮类分子的O-取代以多取代产物为主，反应性能明显强于C-取代反应，区域选择性相对较弱。此外，这类活性分子与含长链烷基（C≥12）单体的反应一般属于单取代反应，其脂溶性取代产物在气/液界面上的物理化学行为具备重要的研究与应用价值。

关键词： 芦丁, 槲皮素, 柚皮素, 黄酮醇, 二氢黄酮, 结构修饰, Mannich

Multi-hydroxyl flavonoids (glycoside and their aglycones) are known to exhibit a variety of physiochemical properties and biological activities. But they are characterized by a low bioavailability and stability in vivo plus nonspecific action in pharmacology. Owing to their importance in pharmaceutics, food and cosmetics, the purpose of this work is an overview of valuable findings concerning hemisynthesis of multi-hydroxyl flavonol (e.g. rutin, quercetin) and dihydroflavone (e.g. Naringenin, Naringin) involving three types of substitutions (Ar-O-substitution, Ar (C)-substitution and glycoside-O-substitution catalyzed by enzymes). And wherein, the comparative analysis was made on the protection approaches for phenolic hydroxyls following by particular discussion for C-substitution by applying a Mannich-type reaction (including effects of substrate, monomer and systematic pH). The results indicate that a reasonable selection of the protection methods for hydroxyl groups and bioactive groups of monomers is critical to obtain desired products combining stability and target-specific bioactivity via selective hemisynthesis. Furthermore, O-substituted reactions for multi-hydroxyl flavonols and dihydroflavone exhibit comparably stronger reactivity than C-substitution but with poor regioselectivity once substitution occurs. In addition, their reactions with long alkyl-chain monomers (C≥12) in general belong to a monosubstitution, and the resultant hydrophobic substitution products, as a class of bisurfactants, exert a broad prospect for research and application.

Contents
1 Introduction
2 Characteristics of structural modification for flavonoids
2.1 Non-protection of phenolic hydroxyls
2.2 Protection and deprotection of phenolic hydroxyls
3 O-substituted flavonoid derivatives
3.1 Mono-O-substitution
3.2 Multi-O-substitution
4 C-substituted flavonoid derivatives
4.1 Effect of reactive substrate and monomer
4.2 Effect of systematic pH
5 Flavonoid glycoside-O-substituted derivatives
6 Conclusion and prospects

Key words: rutin, quercetin, naringenin, flavonol, dihydroflavone, structural modification, Mannich

中图分类号: 

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