摘要
采用汇聚式合成的方式,充分利用原人参三醇各羟基活性的差异,采用高效的区域选择性保护策略,并以Au(I)催化的糖苷化反应对达玛烷20位大位阻酸敏感羟基和6位羟基及6-O-Glc'糖基2位羟基连续三次糖苷化,以最长线性13步分别以5.1%和4.5%的收率合成了天然双糖基达玛烷皂苷Ginsenoside Re(1)和Notoginsenoside R1(2).
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, antiinflammatory and antihyperlipemia activities, and Notoginsenoside R1（2） showed potent antioxidative and antiinflammatory activities, soit would be helpful to synthesizethese 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 subsequentinstallation 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. Ph3 PAu NTf2, 4 ？ MS, CH2 Cl2, r.t.）, the glycosylation of the acid-labile 20-hydroxyl group was achieved effectivelyin a high84% yield firstly. To be convergent for the syntheses of these twoginsenosides, 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 Ph3 PAu NTf2（0.5 equiv.） was employed in order to increase the glycosylation yield while reduce the orthoester formation, thus, the desired 6β-O-glucosides were preparedin satisfactory yields（77%-83%）. Both terminal α-L-Rha/β-D-Xylmoieties at the 2＇ position of 6-O-glc were installed efficiently under 0.2 equiv. Ph3 PAu NTf2 catalyzing condition（Cl CH2 CH2 Cl, 5 A 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 in5.1% and 4.5% overall yields, respectively.
作者
沈仁增
曹鑫
俞飚
Shen Renzeng;Cao Xin;Yu Biao(State Key Laboratory of Bio-organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 20003)
出处
《化学学报》
SCIE
CAS
CSCD
北大核心
2018年第4期278-285,共8页
Acta Chimica Sinica
基金
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)
王宽诚率先人才计划资助~~
作者简介
E—mail：caoxin@sioc．ac．cn;E-mail：byu@sioc．ac．cn；Tel：021-54925131
