Citation: Shen Renzeng, Cao Xin, Yu Biao. Total Synthesis of Dammarane-Type Saponins Ginsenoside Re and Notoginsenoside R₁[J]. Acta Chimica Sinica, ;2018, 76(4): 278-285. doi: 10.6023/A17120544 shu

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

State Key Laboratory of Bio-organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032

Corresponding author: Cao Xin, caoxin@sioc.ac.cn Yu Biao, byu@sioc.ac.cn
Received Date: 18 December 2017
Available Online: 7 April 2018
Fund Project: 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 Foundationthe National Natural Science Foundation of China 21432012Innovation Promotion Association of CAS 2017300the National Natural Science Foundation of China 21621002the Strategic Priority Research Program of CAS XDB20020000

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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.
- dammarane-type saponin,
- Ginsenoside Re,
- Notoginsenoside R₁,
- Au (Ⅰ)-catalyzed glycosylation,
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Total Synthesis of Dammarane-Type Saponins Ginsenoside Re and Notoginsenoside R1

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