Forrestiacids A and B, Pentaterpene Inhibitors of ACL and Lipogenesis: Extending the Limits of Computational NMR Methods in the Structure Assignment of Complex Natural Products

doi:10.1002/anie.202109082

	Forrestiacids A and B, Pentaterpene Inhibitors of ACL and Lipogenesis: Extending the Limits of Computational NMR Methods in the Structure Assignment of Complex Natural Products
	Xiong, Juan 1; Zhou, Peng-Jun 1; Jiang, Hao-Wen 2; Huang, Ting 1; He, Yu-Hang 1; Zhao, Ze-Yu 1; Zang, Yi 2; Choo, Yeun-Mun 3; Wang, Xiaojuan 4; Chittiboyina, Amar G.5
刊名	ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
	2021-09-02
页码	7
关键词	forrestiacids lipogenesis inhibitors natural products structure elucidation terpenoids
ISSN号	1433-7851
DOI	10.1002/anie.202109082
通讯作者	Hamann, Mark T.(hamannm@musc.edu) ; Li, Jia(jli@simm.ac.cn) ; Hu, Jin-Feng(jfhu@fudan.edu.cn)
英文摘要	Forrestiacids A (1) and B (2) are a novel class of [4+2] type pentaterpenoids derived from a rearranged lanostane moiety (dienophile) and an abietane unit (diene). These unprecedented molecules were isolated using guidance by molecular ion networking (MoIN) from Pseudotsuga forrestii, an endangered member of the Asian Douglas Fir Family. The intermolecular hetero-Diels-Alder adducts feature an unusual bicyclo[2.2.2]octene ring system. Their structures were elucidated by spectroscopic analysis, GIAO NMR calculations and DP4+ probability analyses, electronic circular dichroism calculations, and X-ray diffraction analysis. This unique addition to the pentaterpene family represents the largest and the most complex molecule successfully assigned using computational approaches to predict accurately chemical shift values. Compounds 1 and 2 exhibited potent inhibitory activities (IC(50)s mu M) of ATP-citrate lyase (ACL), a new drug target for the treatment of glycolipid metabolic disorders including hyperlipidemia. Validating this activity 1 effectively attenuated the de novo lipogenesis in HepG2 cells. These findings provide a new chemical class for developing potential therapeutic agents for ACL-related diseases with strong links to traditional medicines.
资助项目	National Natural Science Foundation of China[21937002] ; National Natural Science Foundation of China[81773599] ; National Natural Science Foundation of China[21772025]
WOS关键词	ATP-CITRATE LYASE ; DIELS-ALDER ADDUCTS
WOS研究方向	Chemistry
语种	英语
出版者	WILEY-V C H VERLAG GMBH
WOS记录号	WOS:000692020000001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/297706]
专题	中国科学院上海药物研究所
通讯作者	Hamann, Mark T.; Li, Jia; Hu, Jin-Feng
作者单位	1.Fudan Univ, Sch Pharm, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 3.Univ Malaya, Fac Sci, Dept Chem, Kuala Lumpur 50603, Malaysia 4.Lanzhou Univ, Sch Pharm, Lanzhou 730000, Gansu, Peoples R China 5.Univ Mississippi, Natl Ctr Nat Prod Res, Oxford, MS 38677 USA 6.Med Univ South Carolina, Coll Pharm & Med, Charleston, SC 29425 USA 7.Taizhou Univ, Sch Adv Study, Taizhou 318000, Zhejiang, Peoples R China
推荐引用方式 GB/T 7714	Xiong, Juan,Zhou, Peng-Jun,Jiang, Hao-Wen,et al. Forrestiacids A and B, Pentaterpene Inhibitors of ACL and Lipogenesis: Extending the Limits of Computational NMR Methods in the Structure Assignment of Complex Natural Products[J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,2021:7.
APA	Xiong, Juan.,Zhou, Peng-Jun.,Jiang, Hao-Wen.,Huang, Ting.,He, Yu-Hang.,...&Hu, Jin-Feng.(2021).Forrestiacids A and B, Pentaterpene Inhibitors of ACL and Lipogenesis: Extending the Limits of Computational NMR Methods in the Structure Assignment of Complex Natural Products.ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,7.
MLA	Xiong, Juan,et al."Forrestiacids A and B, Pentaterpene Inhibitors of ACL and Lipogenesis: Extending the Limits of Computational NMR Methods in the Structure Assignment of Complex Natural Products".ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2021):7.