Lycofargesiines A-F, further Lycopodium alkaloids from the club moss Huperzia fargesii

Juan Xiong; Wei-Jia Meng; Hai-Yan Zhang; Yike Zou; Wen-Xuan Wang; Xin-Yi Wang; Qi-Lian Yang; Ezzat E A Osman; Jin-Feng Hu

doi:10.1016/j.phytochem.2019.03.015

Lycofargesiines A-F, further Lycopodium alkaloids from the club moss Huperzia fargesii

Phytochemistry. 2019 Jun:162:183-192. doi: 10.1016/j.phytochem.2019.03.015. Epub 2019 Mar 29.

Authors

Juan Xiong¹, Wei-Jia Meng¹, Hai-Yan Zhang², Yike Zou³, Wen-Xuan Wang⁴, Xin-Yi Wang¹, Qi-Lian Yang⁵, Ezzat E A Osman⁶, Jin-Feng Hu⁷

Affiliations

¹ Minhang Hospital & Department of Natural Products Chemistry at School of Pharmacy, Fudan University, Shanghai, 201199, PR China.
² CAS Key Laboratory of Receptor Research, Shanghai Institute of Material Medica, Chinese Academy of Sciences, Shanghai, 201203, PR China. Electronic address: hzhang@simm.ac.cn.
³ Department of Chemistry, University of Pennsylvania, 231 S. 34 Street, Philadelphia, PA, 19104-6323, United States.
⁴ School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan, Hubei, 430074, PR China.
⁵ Minhang Hospital & Department of Natural Products Chemistry at School of Pharmacy, Fudan University, Shanghai, 201199, PR China. Electronic address: yangql@fudan.edu.cn.
⁶ Minhang Hospital & Department of Natural Products Chemistry at School of Pharmacy, Fudan University, Shanghai, 201199, PR China; Laboratory of Medicinal Chemistry, Theodor Bilharz Research Institute, Kornaish El-Nile St., Giza, 12411, Egypt.
⁷ Minhang Hospital & Department of Natural Products Chemistry at School of Pharmacy, Fudan University, Shanghai, 201199, PR China. Electronic address: jfhu@fudan.edu.cn.

PMID: 30928888
DOI: 10.1016/j.phytochem.2019.03.015

Abstract

Six undescribed Lycopodium alkaloids (LAs) comprising four lycodine-type (lycofargesiines A-D), one lycopodine-type (lycofargesiine E), and a phlegmarine-type (lycofargesiine F), together with 16 known ones were isolated from the club moss Huperzia fargesii. Their structures and absolute configurations were determined by extensive spectroscopic methods, electronic circular dichroism (ECD) analysis, and density functional theory (DFT) calculations. (7S,8R,12R,13R)-Lycofargesiine A is a rare naturally occurring LA possessing an exocyclic double bond between C-15 and C-16, with ring A being a rare 2,3-dihyropyridone motif. Lycofargesiine D is an uncommon lycodine-type alkaloid featuring a unique N-acetylated tetrahydropyridinyl segment (ring A), whereas lycofargesiine F is the first phlegmarane-type LA bearing two nitrone moieties. In addition to the isolated huperzine A in this study, another two isolates (lycofargesiine C and 16-hydroxyhuperzine A) were also found to show inhibitory activities against acetylcholinesterase (AChE), with IC₅₀ values of 8.63 and 5.18 μM, respectively.

Keywords: 6α-hydroxylycopodine (PubChem CID: 21576178); Huperzia fargesii; Lycofargesiines; Lycopodiaceae; Lycopodium alkaloids; N-methylhuperzine B (PubChem CID: 5489404); anti-AChE; flabelline (PubChem CID: 101289809); huperzine A (PubChem CID: 854026); luciduline (PubChem CID: 442480); lycopodine (PubChem CID: 5462445); lycoposerramine J (PubChem CID: 11021729); lycoposerramine X (PubChem CID: 101424895); lycoposerramine Z (PubChem CID: 44550887).

MeSH terms

Alkaloids / chemistry*
Alkaloids / pharmacology
Cholinesterase Inhibitors / chemistry*
Cholinesterase Inhibitors / pharmacology
Lycopodium / chemistry*
Models, Molecular
Molecular Conformation

Substances

Alkaloids
Cholinesterase Inhibitors