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Acta Chim. Sinica ›› 2018, Vol. 76 ›› Issue (4): 278-285.DOI: 10.6023/A17120544 Previous Articles     Next Articles

Article

达玛烷皂苷Ginsenoside Re与Notoginsenoside R1的全合成

沈仁增, 曹鑫, 俞飚   

  1. 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
  • 投稿日期:2017-12-18 发布日期:2018-03-09
  • 通讯作者: 曹鑫, 俞飚 E-mail:caoxin@sioc.ac.cn;byu@sioc.ac.cn
  • 基金资助:

    项目受国家自然科学基金（Nos.21432012，21621002）、中国科学院先导B专项（No.XDB20020000）、中科院青年创新促进会（No.2017300）和王宽诚率先人才计划资助.

Total Synthesis of Dammarane-Type Saponins Ginsenoside Re and Notoginsenoside R1

Shen Renzeng, Cao Xin, Yu Biao   

  1. State Key Laboratory of Bio-organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032
  • Received:2017-12-18 Published:2018-03-09
  • Contact: 10.6023/A17120544 E-mail:caoxin@sioc.ac.cn;byu@sioc.ac.cn
  • Supported by:

    Project supported by the National Natural Science Foundation of China (Nos. 21432012, 21621002), the Strategic Priority Research Program of CAS (No. XDB20020000), Youth Innovation Promotion Association of CAS (No. 2017300) and the K. C. Wong Education Foundation.

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Supporting Info.

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Ginsenoside Re (1) and Notoginsenoside R1 (2) are two representative dammarane type protopanaxatriol-6,20-O-bisglycosides occurring widely founded in Panaxginseng. Ginsenoside Re (1) showed potent antioxidative, anti-inflammatory and antihyperlipemia activities, and Notoginsenoside R1 (2) showed potent antioxidative and antiinflammatory activities, so it would be helpful to synthesize these homogeneous natural products in appreciable amounts by accelerating their structure-activity relationship study. As a persistent effort on the chemical syntheses of the diverse ginsenosides in our group, we report herein the efficient syntheses of these two complex natural products. Thus, based on the reactivity sequence of the four hydroxyl groups (i.e., 12-OH > 3-OH > 6-OH >> 20-OH) of the protopanaxatriol aglycon, an orthogonal and efficient protecting group strategy was applied to distinguish these hydroxyl groups. The subsequent installation of the 6,20-O-bisglycosides are challenging, given the poor reactivity of the secondary 6-OH and tertiary 20-OH, moreover, with the latter being labile toward acidic conditions. Taking advantage of the neutral conditions of the Au(I)-catalyzed glycosylation reaction (0.3 equiv. Ph3PAuNTf2, 4 Å MS, CH2Cl2, r.t.), the glycosylation of the acid-labile 20-hydroxyl group was achieved effectively in a high 84% yield firstly. To be convergent for the syntheses of these two ginsenosides, the 6-O-disaccharide residues were installed in a stepwise manner. For the glycosylation of the 6-OH of protopanaxatriol, a higher loading of the catalyst Ph3PAuNTf2 (0.5 equiv.) was employed in order to increase the glycosylation yield while reduce the orthoester formation, thus, the desired 6β-O-glucosides were prepared in satisfactory yields (77%~83%). Both terminal α-L-Rha/β-D-Xyl moieties at the 2' position of 6-O-glc were installed efficiently under 0.2 equiv. Ph3PAuNTf2 catalyzing condition (ClCH2CH2Cl, 5 Å MS, 40℃) with 86% and 81% yields, respectively. After global deprotection, Ginsenoside Re (1) and Notoginsenoside R1 (2) were synthesized with the longest 13 linear steps in 5.1% and 4.5% overall yields, respectively.

Key words: dammarane-type saponin, Ginsenoside Re, Notoginsenoside R1, Au (I)-catalyzed glycosylation