Acta Chimica Sinica ›› 2019, Vol. 77 ›› Issue (10): 999-1007.DOI: 10.6023/A19060233 Previous Articles     Next Articles

Article

灯盏花甲素、乙素等天然黄酮-7-O-糖苷的合成

邵文博a, 安泉林b, 曹鑫b*(), 俞飚a*()   

  1. a 中国科学院上海有机化学研究所 生命有机化学国家重点实验室 上海 200032
    b 复旦大学附属中山医院实验研究中心 上海 200032
  • 收稿日期:2019-06-25 出版日期:2019-10-15 发布日期:2019-07-17
  • 通讯作者: 曹鑫,俞飚 E-mail:caox@fudan.edu.cn;byu@sioc.ac.cn
  • 基金资助:
    项目受国家自然科学基金委基金(21432012);项目受国家自然科学基金委基金(21621002);中国科学院先导B专项(XDB20020200);中科院青年创新促进会(2017300);王宽诚率先人才计划资助

Efficient Synthesis of Representative Flavone-7-O-Glycosides

Shao, Wenboa, An, Quanlinb, Cao, Xinb*(), Yu, Biaoa*()   

  1. a State Key Laboratory of Bio-organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032
    b Institute of Clinical Science, Zhongshan Hospital, Shanghai Medical School, Fudan University, Shanghai 200032
  • Received:2019-06-25 Online:2019-10-15 Published:2019-07-17
  • Contact: Cao, Xin,Yu, Biao E-mail:caox@fudan.edu.cn;byu@sioc.ac.cn
  • Supported by:
    Project supported by the Funds from the National Natural Science Foundation of China(21432012);Project supported by the Funds from the National Natural Science Foundation of China(21621002);the Chinese Academy of Sciences(Strategic Priority Research Program)(XDB20020200);the Youth Innovation Promotion Association(2017300);the K.C. Wong Education Foundation.

Apigenin-7-O-β-D-glucuronide (1) and scutellarin (scutellarein-7-O-β-D-glucuronide, 2) are two major flavone glucuronide components occurring in breviscapines, which are prepared from the traditional Chinese herb Erigeron breviscapus. These two flavone glycosides show potent anti-oxidative, anti-inflammatory and neuroprotective activities in various evaluations. Synthesis of these natural glycosides in an efficiently manner would facilitate studies on their structure activity relationships. As a persistent effort on the chemical syntheses of the diverse glycoconjugates from traditional Chinese herbs in our group, we report herein the synthesis of these two representative flavone O-glucuronides. It is known that the solubility of flavone compounds is rather low and this property would greatly hinder their glycosylation reactions. In order to increase the solubility of the flavone derivatives in the glycosylation solvents, hexanoyl and benzyl groups were selected as the permanent protecting groups for the hydroxyl groups of apigenin (7) and scutellarein (8). The construction of the phenolic O-glucuronide is known to be a difficult task, especially the glycosylation of the poorly nucleophilic 7-hydroxyl group which locates at the para-position of the flavone carbonyl group. We achieved the glycosylation of the flavone 7-OH with 2,3,4-tri-O-benzoyl-6-O-TBDPS-glucopyranosyl ortho-alkynylbenzoate (9) under the catalysis of Ph3PAuNTf2 (0.2 equiv., 4 ? MS, CH2Cl2, r.t., 5 h) in excellent yields. After that, the 6-O-TBDPS groups were removed, and the requisite glucuronides were then elaborated by oxidation of the resulting 6-OH under the conditions of DAIB/TEMPO (CH2Cl2/H2O, VV=2∶1, r.t.) in good yields. After global deprotection, the desired products apigenin-7-O-β-D-glucuronide (1) and scutellarin (2) were obtained in overall yields of 36% (5 steps) and 7% (9 steps), respectively, from the starting flavone aglycones. Following the same strategy, four naturally occurring flavone-7-O-glycosides, namely apigetrin (3), plantaginin (4), apigenin 7-O-β-D-xylopyranoside (5) and apigenin 7-O-α-L-rhamnopyranoside (6), were smoothly synthesized in 4~7 steps with the overall yields of 61%, 13%, 58% and 61%, respectively.

Key words: apigenin-7-O-β-D-glucuronide, scutellarin, flavone glycoside, Au(I)-catalyzed glycosylation, synthesis