槲皮素衍生物的合成研究进展

doi:10.6023/cjoc202203016

摘要/Abstract

槲皮素是天然的抗氧化剂, 主要存在于蔬菜、水果等植物中, 可调节众多与疾病进展有关的细胞内外信号通路, 能抗炎、抗病毒、抗癌、预防和治疗心脑血管疾病等, 具有广泛的药理活性. 由于槲皮素的结构特征, 其生物利用度低, 限制了其在临床上的应用. 然而, 槲皮素的低分子质量和易修饰的化学基团, 使其具有药物开发的潜力. 因此, 研究人员通过各种方法设计合成新的槲皮素衍生物, 以改善其不利因素, 已经合成了许多性能优良、溶解性能好、生物利用度高、代谢稳定、毒副作用小且生物活性显著的槲皮素衍生物. 综述了近年来槲皮素衍生物的合成及其生物活性研究进展, 为槲皮素衍生物的进一步开发提供参考.

关键词: 槲皮素, 衍生物, 合成, 抗氧化, 抗癌, 生物活性

Quercetin, as a natural antioxidant, is mainly found in vegetables, fruits and other plants. It can regulate many intracellular and extracellular signaling pathways related to disease progression. It can be anti-inflammatory, antiviral, anticancer, prevention and treatment of cardiovascular and cerebrovascular diseases, thus has a wide range of pharmacological activities. Due to the structural characteristics of quercetin, its low bioavailability limits its clinical application. However, the low molecular mass and easily modifiable chemical groups of quercetin make it attractive for drug development. Therefore, researchers have designed and synthesized new quercetin derivatives through various methods to improve its unfavorable factors. Many quercetin derivatives with excellent properties, good solubility, high bioavailability, stable metabolism, low toxicity and significant biological activity have been synthesized. The recent progress in the synthesis of quercetin derivatives and their biological activities is reviewed, providing a reference for the further development of quercetin derivatives.

Key words: quercetin, derivative, synthesis, antioxidant, anticancer, biological activity

引用此文

毛雅君, 邵香敏, 李阳杰, 曹瑞梅, 冯亚莉, 翟广玉. 槲皮素衍生物的合成研究进展[J]. 有机化学, 2022, 42(11): 3588-3605.

Yajun Mao, Xiangmin Shao, Yangjie Li, Ruimei Cao, Yali Feng, Guangyu Zhai. Research Progress on the Synthesis of Quercetin Derivatives[J]. Chinese Journal of Organic Chemistry, 2022, 42(11): 3588-3605.

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图/表 22

图1. 槲皮素的结构及修饰

Figure 1. Structure and modification of quercetin

图式1. 槲皮素-3-O-或7-O-氨基酸衍生物的合成

Scheme 1. Synthesis of quercetin-3-O- or 7-O-amino acid derivatives

图式2. 槲皮素-3-O-氨基酸酯衍生物的合成

Scheme 2. Synthesis of quercetin-3-O-amino acid ester derivatives

图式3. 槲皮素-5-酰基酯的合成

Scheme 3. Synthesis of quercetin-5-acyl ester

图式4. 槲皮素-3-O-苯甲酸酯衍生物的合成

Scheme 4. Synthesis of quercetin-3-O-benzoate derivatives

图式5. 槲皮素硫辛酸酯的合成

Scheme 5. Synthesis of quercetin lipoate

图式6. 槲皮素磷酸酯的合成

Scheme 6. Synthesis of quercetin phosphate

图式7. 槲皮素硫酸酯的合成

Scheme 7. Synthesis of quercetin sulfate

图式8. 槲皮素四甲基烷基氨基醚的合成

Scheme 8. Synthesis of quercetin tetramethyl alkyl amino ether

图式9. 槲皮素-5-或-3'-醚基乙酸衍生物的合成

Scheme 9. Synthesis of quercetin 5, or 3'-ether acetic acid derivatives

图式10. 槲皮素-3-O-乙酰胺衍生物的合成

Scheme 10. Synthesis of quercetin-3-O-acetamide derivatives

图式11. 槲皮素-3-丙基醚的合成

Scheme11. Synthesis of quercetin-3-propyl ether

图式12. 含有1,4-戊二烯-3-酮槲皮素衍生物的合成

Scheme 12. Synthesis of quercetin derivatives containing 1,4-pentadien-3-one

图式13. 槲皮素-3-乙基醚衍生物的合成

Scheme 13. Synthesis of quercetin-3-ethyl ether derivatives

图式14. 槲皮素-8-甲基氨基衍生物的合成

Scheme 14. Synthesis of quercetin-8-methylamino derivatives

图15. C-8异戊烯基槲皮素的合成

Scheme 15. Synthesis of C-8 isopentenyl quercetin

图式16. C-5'异戊烯基槲皮素的合成

Scheme 16. Synthesis of C-5' isopentenyl quercetin

图式17. 8-芳基五甲基槲皮素衍生物的合成

Scheme 17. Synthesis of 8-aryl pentamethyl quercetin derivatives

图式18. 槲皮素羰基衍生物的合成

Scheme 18. Synthesis of quercetin carbonyl derivatives

图式19. 槲皮素羰基氧被硫或硒取代衍生物的合成

Scheme 19. Synthesis of quercetin carbonyl oxygen substituted by sulfur or selenium derivatives

图式20. 槲皮素金属配合物的合成

Scheme 20. Synthesis of quercetin metal complex

图2. 活性较好的槲皮素衍生物

Figure 2. More active quercetin derivatives

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