Structural Elucidation and Bioinspired Total Syntheses of Ascorbylated Diterpenoid Hongkonoids A-D

doi:10.1021/jacs.7b10135

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 天然药物化学研究室

	Structural Elucidation and Bioinspired Total Syntheses of Ascorbylated Diterpenoid Hongkonoids A-D
	Zhao, Jin-Xin 1; Yu, Yan-Yan 1,2; Wang, Sha-Sha 1; Huang, Su-Ling1 ; Shen, Yu 1; Gao, Xin-Hua 1,2; Sheng, Li 1; Li, Jing-Ya1 ; Leng, Ying1 ; Li, Jia1
刊名	JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
	2018-02-21
卷号	140 期号:7 页码:2485-2492
ISSN号	0002-7863
DOI	10.1021/jacs.7b10135
文献子类	Article
英文摘要	Hongkonoids A-D (1-4), the first example of ascorby-lated terpenoids featuring a unique 5,5,5-fused tricyclic spiroketal butyrolactone moiety and diterpenoid-derived long chain, were isolated from Dysoxylum hongkongense. Their structures were unambiguously assigned by a combination of spectroscopic data, chemical degradation, Xray crystallography, CD analysis, and total synthesis. The total syntheses of compounds 1-4 were effectively accomplished by a convergent strategy with the longest linear sequences of 12-14 steps and overall yields of 5.4-9.6%. Notably, we exploited a bioinspired one-pot method to construct the key intermediate 14 from an easily made compound 12 by involving the cascade reactions of an elaborate Claisen rearrangement, deprotections, and a 5-exo-trig cyclization. The desired major epimer 14a was then transformed to the main building block 21. Assembly of 21 and the long chain vinyl iodide 7 was made by an NHK coupling reaction to furnish the framework of 1-4. Some of the hongkonoids and/or synthetic analogs showed significant to moderate inhibitory activities against NF-kappa B, 11 beta-HSD1, and sterol synthesis. The most active NF-kappa B inhibitor 34 exhibited distinct inhibition on the LPS-induced inflammatory responses in RAW 246.7 and primary BMDM cells.
资助项目	National Natural Science Foundation[21532007] ; National Key Research and Development of the People's Republic of China[2016YFC1305500]
WOS关键词	NF-KAPPA-B ; L-ASCORBIC-ACID ; NATURAL-PRODUCTS ; DYSOXYLUM-MOLLISSIMUM ; ASYMMETRIC-SYNTHESIS ; SIGNALING PATHWAY ; ABSCISIC-ACID ; VITAMIN-C ; RING ; PART
WOS研究方向	Chemistry
语种	英语
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000426143800021
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279891]
专题	天然药物化学研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Yue, Jian-Min
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China; 2.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China
推荐引用方式 GB/T 7714	Zhao, Jin-Xin,Yu, Yan-Yan,Wang, Sha-Sha,et al. Structural Elucidation and Bioinspired Total Syntheses of Ascorbylated Diterpenoid Hongkonoids A-D[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,2018,140(7):2485-2492.
APA	Zhao, Jin-Xin.,Yu, Yan-Yan.,Wang, Sha-Sha.,Huang, Su-Ling.,Shen, Yu.,...&Yue, Jian-Min.(2018).Structural Elucidation and Bioinspired Total Syntheses of Ascorbylated Diterpenoid Hongkonoids A-D.JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,140(7),2485-2492.
MLA	Zhao, Jin-Xin,et al."Structural Elucidation and Bioinspired Total Syntheses of Ascorbylated Diterpenoid Hongkonoids A-D".JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 140.7(2018):2485-2492.