Synthesis of hupehenols A, B, and E from protopanaxadiol

doi:10.1039/c6ra04236h

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第一研究室

	Synthesis of hupehenols A, B, and E from protopanaxadiol
	Shao, Li-Dong 2; Xu, Jun 1,2; Li, Xiao-Nian 2; Zhang, Zhi-Jun 1,2; Shi, Xin 1,2; Ren, Jian 1,2; He, Juan 2; Zhao, Yu 2; Leng, Ying3 ; Xia, Chengfeng 2
刊名	RSC ADVANCES
	2016
卷号	6 期号:42 页码:35792-35803
ISSN号	2046-2069
DOI	10.1039/c6ra04236h
文献子类	Article
英文摘要	Hupehenols A-E (3-7) are bioactive octanordammarane triterpenoids, among which hupehenols B (4) and E (7) are the most potent and selective human 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) inhibitors (IC50 = 15 and 34 nM, respectively). Herein, the hupehenols were synthesized from protopanaxadiol, the main component of Panax notoginseng. The different synthetic attempts resulted in the stereoselective synthesis of hupehenols A, B, and E for further biological exploration. Notable features of the synthesis included a regioselective epoxide-opening reaction, regioselective acetylation, and a late-stage stereoselective oxa-Michael addition. Semi-synthetic derivatization of these natural products led to the determination of their absolute configurations, a better understanding of their inherent reactivity patterns, and the required C-17 configuration for murine 11 beta-HSD1 inhibition. These studies provide the basis for the synthesis of 11 beta-HSD1 inhibitors as potential targets for the treatment of type 2 diabetes.
资助项目	National Natural Science Foundation of China[U1502223] ; National Natural Science Foundation of China[81172941] ; National Basic Research Program of China (973 Program)[2011CB915503] ; Yunnan High-End Technology Professionals Introduction Program[2010CI117]
WOS关键词	11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-1 ; ENANTIOSELECTIVE TOTAL-SYNTHESIS ; BAEYER-VILLIGER OXIDATION ; 11-BETA-HSD1 INHIBITORS ; ALLYLIC OXIDATION ; INSULIN-RESISTANCE ; METABOLIC SYNDROME ; HYDROGEN-PEROXIDE ; ACID ; OBESITY
WOS研究方向	Chemistry
语种	英语
出版者	ROYAL SOC CHEMISTRY
WOS记录号	WOS:000374349600077
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276234]
专题	药理学第一研究室
通讯作者	Xia, Chengfeng; Zhao, Qin-Shi
作者单位	1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China; 2.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Shao, Li-Dong,Xu, Jun,Li, Xiao-Nian,et al. Synthesis of hupehenols A, B, and E from protopanaxadiol[J]. RSC ADVANCES,2016,6(42):35792-35803.
APA	Shao, Li-Dong.,Xu, Jun.,Li, Xiao-Nian.,Zhang, Zhi-Jun.,Shi, Xin.,...&Zhao, Qin-Shi.(2016).Synthesis of hupehenols A, B, and E from protopanaxadiol.RSC ADVANCES,6(42),35792-35803.
MLA	Shao, Li-Dong,et al."Synthesis of hupehenols A, B, and E from protopanaxadiol".RSC ADVANCES 6.42(2016):35792-35803.